Diabetes

Study Overview

Objective. To update national trends in the treatment and risk factor control of diabetic patients from 1999 through 2018 in the US using data from the National Health and Nutrition Examination Survey (NHANES) with the goal of identifying population subgroups with the highest probability of having untreated risk factors.

Design. The authors conducted a cross-sectional analysis of data from NHANES focusing on adults with diabetes. They examined patient characteristics and medication use over time and estimated the prevalence of risk factor control and medication use. To minimize the effects of a small sample size, the survey years were pooled into 4-year intervals. The variables studied included glycated hemoglobin (HbA_1c), blood pressure, serum cholesterol, medication use, sociodemographic characteristics, and weight status. For statistical analysis, logistic and multinomial logistic regression models were used to examine factors associated with treatment in participants who did not achieve targets for glycemic, blood pressure, and lipid control. Temporal trends were estimated using 2-piece linear spline models with 1 knot at inflection points.

Setting and participants. The NHANES program began in the early 1960s to monitor the health of the US population. In 1999, the survey became a continuous program combining interviews and physical examinations. The survey examines a nationally representative sample of about 5000 persons each year. This study included 6653 participants who were nonpregnant, aged older than 20 years, reported a diagnosis of diabetes from a physician, and participated in NHANES from 1999 through 2018.

Main outcome measures. The main outcome measures were temporal trends in risk factor control (glycemic, blood pressure, or lipid levels) and medication use (glucose lowering, blood pressure lowering, or lipid lowering medications), and number as well as class of drug used, from 1999 through 2018 in diabetic adults from the US participating in NHANES.

Results. Sociodemographic characteristics of the studied diabetes population—The age and racial or ethnic distribution of participants with diabetes were stable from 1999 through 2018, whereas participants with a college degree, higher income, health insurance, obesity, or long-standing diabetes increased during the same period.

Trends in diabetes risk factor control—The trends for glycemic, blood pressure, and lipid control were nonlinear, with an inflection point around 2010. Glycemic control was defined as HbA_1c less than 7%, blood pressure was considered controlled if less than 140/90 mmHg, and lipid was controlled if non-HDL cholesterol level was less than 130 mg/dL. Although these chosen targets were based on the most recent clinical guidelines, the authors declared that they observed similar trends when alternative targets were used. The level of risk factor control improved in all diabetic patients from 1999 through 2010. However, the percentage of adult diabetic participants for whom glycemic control was achieved declined from 57.4% (95% CI, 52.9-61.8) in 2007-2010 to 50.5% (95% CI, 45.8-55.3) in 2015-2018. Blood pressure control was achieved in 74.2% of participants (95% CI, 70.7-77.4) in 2011-2014 but declined to 70.4% (95% CI, 66.7-73.8) in 2015-2018. Control in lipid levels improved during the entire study period; however, the rate of improvement heavily declined after 2007 with lipid target levels attained in 52.3% of participants (95% CI, 49.2-55.3) in 2007-2014 and 55.7% (95% CI, 50.8-60.5) in 2015-2018. Finally, the percentage of participants in whom targets for all 3 risk factors were simultaneously achieved plateaued after 2010 and was 22.2% (95% CI, 17.9-27.3) in 2015-2018.

Trends in diabetes treatment—The use of glucose lowering drugs increased from 74.1% in 1999-2002 to 82.7% in 2007-2010 and then stabilized. A shift toward a safer glucose lowering treatment choice was observed with a decline in the use of older glucose lowering medications such as sulfonylureas, which increases the risk of hypoglycemia, and an increase in the use of metformin, insulin, and newer agents such as sodium-glucose cotransporter 2 inhibitors.

Similarly, blood pressure lowering medication use rose from 1999-2002 to 2007-2010 and then stabilized, with increased use of first-line recommended treatments including angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Likewise, statin use rose from 28.4% in 1999-2002 to 56% in 2011-2014 and then stabilized. The total number of drugs used culminated in 2011-2014 with 60% of participants using more than 5 drugs and then leveled off to 57.2% in 2015-2018. Lastly, health insurance status and race or ethnicity impacted the likelihood of receiving monotherapy or combination drug therapy when targets for glycemic, blood pressure, or lipid control were not achieved.

Conclusion. Despite great progress in the control of diabetes and its associated risk factors between 1999 and 2010, this trend declined for glycemic and blood pressure control and leveled off for lipid control in adult NHANES participants with diabetes after 2010. First-line treatments for diabetes and associated risk factors remain underused, and treatment intensification may not be sufficiently considered in patients with uncontrolled risk factors despite clinical guideline recommendations. The findings of this study may portend a possible population-level increase in diabetes-related illnesses in the years to come.

Commentary

The thorough understanding of trends in management of diseases is critical to inform public health policies and planning. Well designed clinical studies heavily influence the development of public health policies and clinical guidelines, which in turn drive real-world clinical practice. In a recent analysis utilizing data from NHANES, Fang et al¹ showed evidence of a general shift toward less intensive treatment of diabetes, hypertension, and hypercholesterolemia in adults living in the US during the last decade.

Similarly, in a separate study using NHANES data collected between 1999 and 2018 published in JAMA just 2 weeks after the current report, Wang et al² confirms this declining trend in diabetes management with only 21.2% of diabetic adults simultaneously attaining glycemic, blood pressure, and lipid level targets during the same period. What led to the decline in more stringent risk factor and diabetes management since 2010 observed in these studies? One possible explanation, as suggested by Fang et al, is that major clinical trials from the late 2000s­—including Action to Control Cardiovascular Risk in Diabetes, UK Prospective Diabetes Study, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, and Veterans Affairs Diabetes Trial—that assessed the effects of intensive glycemic control (with target HbA_1c < 6.5%) found that intensive treatment of diabetes compared to standard care had no cardiovascular benefit albeit increasing the risk of hypoglycemia. Thus, these trial findings may have translated into suboptimal diabetes treatment observed in some NHANES participants. Wang et al propose that effective tailored approaches are needed to improve risk factor control in diabetic patients, such as enhance and maintain adherence to medications and healthy lifestyle behaviors, as well as better access to health care and therapeutic education.

The changes in recent trends in diabetes management have immense clinical implications. The authors of this study suggest a link between the recent relaxation of glycemic targets, as well as risk factor control, and a resurgence of diabetic complications such as lower limb amputation or stroke. Indeed, several recent studies indicate an upward trend or plateau in diabetic complications which had been decreasing in prevalence prior to 2010.³ For example, lower extremity amputation has surged by more than 25% between 2010 and 2015, especially in young and middle-aged adults.⁴ Among the arguments brought forward that this recent resurgence in amputations is directly linked to worsening glycemic control is the fact that between 2007 and 2010, when glucose levels were best controlled within the previous 30-year period, amputations were also at the lowest levels. Moreover, data from the Centers for Disease Control and Prevention also show a 55% increase in mortality (from 15.7 to 24.2 per 1000) among diabetic patients between 2010 and 2015.¹⁴ On the other hand, a growing number of studies show that an increase of inappropriate treatment intensification—reaching HbA_1c levels that are way below the recommended targets—is associated with adverse consequences in diabetic patients particularly in those aged more than 65 years.^5-7 These seemingly contradictory findings highlight the importance of a personalized and thoughtful approach to the management of diabetes and its risk factors. As an example, an increase in the use of newer and safer glucose lowering drugs (eg, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and dipeptidyl peptidase 4 inhibitors) can help achieve better HbA_1c goals with a reduced risk of hypoglycemic episodes as recently shown by a Danish study.⁸ In this study, the authors concluded that the reduction of the rate of hypoglycemic episodes leading to hospitalization in Denmark was directly linked to the use of these safer and newer glucose lowering drugs.

A discussion on the specifics of trends in diabetes treatment and control must include considerations in older adults aged more than 65 years who constitute more than 40% of the diabetic population. Despite the high prevalence of diabetes in this vulnerable population, such data are still insufficient in the literature and are critically needed to inform public health policies and clinical guidelines. In epidemiological studies focusing on diabetic complications from the last 10 years, concerning increases have been observed in younger⁹ and middle-aged adults while remaining stable in older adults. However, the risk of hypoglycemia or severe hypoglycemia remains high in older adults living in nursing facilities, even in those with an elevated HbA_1c of greater than 8%.⁷ Moreover, in light of more relaxed HbA_1c treatment goals for older frail adults as recommended by international guidelines since 2010,^10,11 recent findings from the French GERODIAB cohort show an increased mortality (hazard ratio, 1.76) in type 2 diabetics aged 70 years and older with HbA_1c greater than or equal to 8.6%.¹² Similarly, a 5-year retrospective British study from 2018 which included patients aged 70 years and older, shows an increased overall mortality in those with HbA_1c greater than 8.5%.¹³ Taken together, further age-stratified analysis utilizing data from large cohort studies including NHANES may help to clarify national trends in diabetes treatment and risk factor control as well as diabetic complications specific to the geriatric population. By being better informed of such trends, clinicians could then develop treatment strategies that minimize complications (eg, hypoglycemia, falls) while achieving favorable outcomes (eg, reduce hyperglycemic emergencies, improve survival) in frail older patients.

Applications for Clinical Practice

The understanding of population-wide trends in diabetes control is critical to planning public health approaches for the prevention and treatment of this disease and its complications. In older adults, the high risk of hypoglycemic events and insufficient epidemiological data on trends of diabetes control hinder diabetes management. Personalized treatment targets taking into account geriatric syndromes and general health status, as well as multidisciplinary management involving endocrinologists, geriatricians, and clinical pharmacists, are necessary to optimize care in older adults with diabetes.

Study Overview

Objective. To update national trends in the treatment and risk factor control of diabetic patients from 1999 through 2018 in the US using data from the National Health and Nutrition Examination Survey (NHANES) with the goal of identifying population subgroups with the highest probability of having untreated risk factors.

Design. The authors conducted a cross-sectional analysis of data from NHANES focusing on adults with diabetes. They examined patient characteristics and medication use over time and estimated the prevalence of risk factor control and medication use. To minimize the effects of a small sample size, the survey years were pooled into 4-year intervals. The variables studied included glycated hemoglobin (HbA_1c), blood pressure, serum cholesterol, medication use, sociodemographic characteristics, and weight status. For statistical analysis, logistic and multinomial logistic regression models were used to examine factors associated with treatment in participants who did not achieve targets for glycemic, blood pressure, and lipid control. Temporal trends were estimated using 2-piece linear spline models with 1 knot at inflection points.

Setting and participants. The NHANES program began in the early 1960s to monitor the health of the US population. In 1999, the survey became a continuous program combining interviews and physical examinations. The survey examines a nationally representative sample of about 5000 persons each year. This study included 6653 participants who were nonpregnant, aged older than 20 years, reported a diagnosis of diabetes from a physician, and participated in NHANES from 1999 through 2018.

Main outcome measures. The main outcome measures were temporal trends in risk factor control (glycemic, blood pressure, or lipid levels) and medication use (glucose lowering, blood pressure lowering, or lipid lowering medications), and number as well as class of drug used, from 1999 through 2018 in diabetic adults from the US participating in NHANES.

Results. Sociodemographic characteristics of the studied diabetes population—The age and racial or ethnic distribution of participants with diabetes were stable from 1999 through 2018, whereas participants with a college degree, higher income, health insurance, obesity, or long-standing diabetes increased during the same period.

Trends in diabetes risk factor control—The trends for glycemic, blood pressure, and lipid control were nonlinear, with an inflection point around 2010. Glycemic control was defined as HbA_1c less than 7%, blood pressure was considered controlled if less than 140/90 mmHg, and lipid was controlled if non-HDL cholesterol level was less than 130 mg/dL. Although these chosen targets were based on the most recent clinical guidelines, the authors declared that they observed similar trends when alternative targets were used. The level of risk factor control improved in all diabetic patients from 1999 through 2010. However, the percentage of adult diabetic participants for whom glycemic control was achieved declined from 57.4% (95% CI, 52.9-61.8) in 2007-2010 to 50.5% (95% CI, 45.8-55.3) in 2015-2018. Blood pressure control was achieved in 74.2% of participants (95% CI, 70.7-77.4) in 2011-2014 but declined to 70.4% (95% CI, 66.7-73.8) in 2015-2018. Control in lipid levels improved during the entire study period; however, the rate of improvement heavily declined after 2007 with lipid target levels attained in 52.3% of participants (95% CI, 49.2-55.3) in 2007-2014 and 55.7% (95% CI, 50.8-60.5) in 2015-2018. Finally, the percentage of participants in whom targets for all 3 risk factors were simultaneously achieved plateaued after 2010 and was 22.2% (95% CI, 17.9-27.3) in 2015-2018.

Trends in diabetes treatment—The use of glucose lowering drugs increased from 74.1% in 1999-2002 to 82.7% in 2007-2010 and then stabilized. A shift toward a safer glucose lowering treatment choice was observed with a decline in the use of older glucose lowering medications such as sulfonylureas, which increases the risk of hypoglycemia, and an increase in the use of metformin, insulin, and newer agents such as sodium-glucose cotransporter 2 inhibitors.

Similarly, blood pressure lowering medication use rose from 1999-2002 to 2007-2010 and then stabilized, with increased use of first-line recommended treatments including angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Likewise, statin use rose from 28.4% in 1999-2002 to 56% in 2011-2014 and then stabilized. The total number of drugs used culminated in 2011-2014 with 60% of participants using more than 5 drugs and then leveled off to 57.2% in 2015-2018. Lastly, health insurance status and race or ethnicity impacted the likelihood of receiving monotherapy or combination drug therapy when targets for glycemic, blood pressure, or lipid control were not achieved.

Conclusion. Despite great progress in the control of diabetes and its associated risk factors between 1999 and 2010, this trend declined for glycemic and blood pressure control and leveled off for lipid control in adult NHANES participants with diabetes after 2010. First-line treatments for diabetes and associated risk factors remain underused, and treatment intensification may not be sufficiently considered in patients with uncontrolled risk factors despite clinical guideline recommendations. The findings of this study may portend a possible population-level increase in diabetes-related illnesses in the years to come.

Commentary

The thorough understanding of trends in management of diseases is critical to inform public health policies and planning. Well designed clinical studies heavily influence the development of public health policies and clinical guidelines, which in turn drive real-world clinical practice. In a recent analysis utilizing data from NHANES, Fang et al¹ showed evidence of a general shift toward less intensive treatment of diabetes, hypertension, and hypercholesterolemia in adults living in the US during the last decade.

Similarly, in a separate study using NHANES data collected between 1999 and 2018 published in JAMA just 2 weeks after the current report, Wang et al² confirms this declining trend in diabetes management with only 21.2% of diabetic adults simultaneously attaining glycemic, blood pressure, and lipid level targets during the same period. What led to the decline in more stringent risk factor and diabetes management since 2010 observed in these studies? One possible explanation, as suggested by Fang et al, is that major clinical trials from the late 2000s­—including Action to Control Cardiovascular Risk in Diabetes, UK Prospective Diabetes Study, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, and Veterans Affairs Diabetes Trial—that assessed the effects of intensive glycemic control (with target HbA_1c < 6.5%) found that intensive treatment of diabetes compared to standard care had no cardiovascular benefit albeit increasing the risk of hypoglycemia. Thus, these trial findings may have translated into suboptimal diabetes treatment observed in some NHANES participants. Wang et al propose that effective tailored approaches are needed to improve risk factor control in diabetic patients, such as enhance and maintain adherence to medications and healthy lifestyle behaviors, as well as better access to health care and therapeutic education.

The changes in recent trends in diabetes management have immense clinical implications. The authors of this study suggest a link between the recent relaxation of glycemic targets, as well as risk factor control, and a resurgence of diabetic complications such as lower limb amputation or stroke. Indeed, several recent studies indicate an upward trend or plateau in diabetic complications which had been decreasing in prevalence prior to 2010.³ For example, lower extremity amputation has surged by more than 25% between 2010 and 2015, especially in young and middle-aged adults.⁴ Among the arguments brought forward that this recent resurgence in amputations is directly linked to worsening glycemic control is the fact that between 2007 and 2010, when glucose levels were best controlled within the previous 30-year period, amputations were also at the lowest levels. Moreover, data from the Centers for Disease Control and Prevention also show a 55% increase in mortality (from 15.7 to 24.2 per 1000) among diabetic patients between 2010 and 2015.¹⁴ On the other hand, a growing number of studies show that an increase of inappropriate treatment intensification—reaching HbA_1c levels that are way below the recommended targets—is associated with adverse consequences in diabetic patients particularly in those aged more than 65 years.^5-7 These seemingly contradictory findings highlight the importance of a personalized and thoughtful approach to the management of diabetes and its risk factors. As an example, an increase in the use of newer and safer glucose lowering drugs (eg, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and dipeptidyl peptidase 4 inhibitors) can help achieve better HbA_1c goals with a reduced risk of hypoglycemic episodes as recently shown by a Danish study.⁸ In this study, the authors concluded that the reduction of the rate of hypoglycemic episodes leading to hospitalization in Denmark was directly linked to the use of these safer and newer glucose lowering drugs.

A discussion on the specifics of trends in diabetes treatment and control must include considerations in older adults aged more than 65 years who constitute more than 40% of the diabetic population. Despite the high prevalence of diabetes in this vulnerable population, such data are still insufficient in the literature and are critically needed to inform public health policies and clinical guidelines. In epidemiological studies focusing on diabetic complications from the last 10 years, concerning increases have been observed in younger⁹ and middle-aged adults while remaining stable in older adults. However, the risk of hypoglycemia or severe hypoglycemia remains high in older adults living in nursing facilities, even in those with an elevated HbA_1c of greater than 8%.⁷ Moreover, in light of more relaxed HbA_1c treatment goals for older frail adults as recommended by international guidelines since 2010,^10,11 recent findings from the French GERODIAB cohort show an increased mortality (hazard ratio, 1.76) in type 2 diabetics aged 70 years and older with HbA_1c greater than or equal to 8.6%.¹² Similarly, a 5-year retrospective British study from 2018 which included patients aged 70 years and older, shows an increased overall mortality in those with HbA_1c greater than 8.5%.¹³ Taken together, further age-stratified analysis utilizing data from large cohort studies including NHANES may help to clarify national trends in diabetes treatment and risk factor control as well as diabetic complications specific to the geriatric population. By being better informed of such trends, clinicians could then develop treatment strategies that minimize complications (eg, hypoglycemia, falls) while achieving favorable outcomes (eg, reduce hyperglycemic emergencies, improve survival) in frail older patients.

Applications for Clinical Practice

The understanding of population-wide trends in diabetes control is critical to planning public health approaches for the prevention and treatment of this disease and its complications. In older adults, the high risk of hypoglycemic events and insufficient epidemiological data on trends of diabetes control hinder diabetes management. Personalized treatment targets taking into account geriatric syndromes and general health status, as well as multidisciplinary management involving endocrinologists, geriatricians, and clinical pharmacists, are necessary to optimize care in older adults with diabetes.

Study Overview

Objective. To update national trends in the treatment and risk factor control of diabetic patients from 1999 through 2018 in the US using data from the National Health and Nutrition Examination Survey (NHANES) with the goal of identifying population subgroups with the highest probability of having untreated risk factors.

Design. The authors conducted a cross-sectional analysis of data from NHANES focusing on adults with diabetes. They examined patient characteristics and medication use over time and estimated the prevalence of risk factor control and medication use. To minimize the effects of a small sample size, the survey years were pooled into 4-year intervals. The variables studied included glycated hemoglobin (HbA_1c), blood pressure, serum cholesterol, medication use, sociodemographic characteristics, and weight status. For statistical analysis, logistic and multinomial logistic regression models were used to examine factors associated with treatment in participants who did not achieve targets for glycemic, blood pressure, and lipid control. Temporal trends were estimated using 2-piece linear spline models with 1 knot at inflection points.

Setting and participants. The NHANES program began in the early 1960s to monitor the health of the US population. In 1999, the survey became a continuous program combining interviews and physical examinations. The survey examines a nationally representative sample of about 5000 persons each year. This study included 6653 participants who were nonpregnant, aged older than 20 years, reported a diagnosis of diabetes from a physician, and participated in NHANES from 1999 through 2018.

Main outcome measures. The main outcome measures were temporal trends in risk factor control (glycemic, blood pressure, or lipid levels) and medication use (glucose lowering, blood pressure lowering, or lipid lowering medications), and number as well as class of drug used, from 1999 through 2018 in diabetic adults from the US participating in NHANES.

Results. Sociodemographic characteristics of the studied diabetes population—The age and racial or ethnic distribution of participants with diabetes were stable from 1999 through 2018, whereas participants with a college degree, higher income, health insurance, obesity, or long-standing diabetes increased during the same period.

Trends in diabetes risk factor control—The trends for glycemic, blood pressure, and lipid control were nonlinear, with an inflection point around 2010. Glycemic control was defined as HbA_1c less than 7%, blood pressure was considered controlled if less than 140/90 mmHg, and lipid was controlled if non-HDL cholesterol level was less than 130 mg/dL. Although these chosen targets were based on the most recent clinical guidelines, the authors declared that they observed similar trends when alternative targets were used. The level of risk factor control improved in all diabetic patients from 1999 through 2010. However, the percentage of adult diabetic participants for whom glycemic control was achieved declined from 57.4% (95% CI, 52.9-61.8) in 2007-2010 to 50.5% (95% CI, 45.8-55.3) in 2015-2018. Blood pressure control was achieved in 74.2% of participants (95% CI, 70.7-77.4) in 2011-2014 but declined to 70.4% (95% CI, 66.7-73.8) in 2015-2018. Control in lipid levels improved during the entire study period; however, the rate of improvement heavily declined after 2007 with lipid target levels attained in 52.3% of participants (95% CI, 49.2-55.3) in 2007-2014 and 55.7% (95% CI, 50.8-60.5) in 2015-2018. Finally, the percentage of participants in whom targets for all 3 risk factors were simultaneously achieved plateaued after 2010 and was 22.2% (95% CI, 17.9-27.3) in 2015-2018.

Trends in diabetes treatment—The use of glucose lowering drugs increased from 74.1% in 1999-2002 to 82.7% in 2007-2010 and then stabilized. A shift toward a safer glucose lowering treatment choice was observed with a decline in the use of older glucose lowering medications such as sulfonylureas, which increases the risk of hypoglycemia, and an increase in the use of metformin, insulin, and newer agents such as sodium-glucose cotransporter 2 inhibitors.

Similarly, blood pressure lowering medication use rose from 1999-2002 to 2007-2010 and then stabilized, with increased use of first-line recommended treatments including angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Likewise, statin use rose from 28.4% in 1999-2002 to 56% in 2011-2014 and then stabilized. The total number of drugs used culminated in 2011-2014 with 60% of participants using more than 5 drugs and then leveled off to 57.2% in 2015-2018. Lastly, health insurance status and race or ethnicity impacted the likelihood of receiving monotherapy or combination drug therapy when targets for glycemic, blood pressure, or lipid control were not achieved.

Conclusion. Despite great progress in the control of diabetes and its associated risk factors between 1999 and 2010, this trend declined for glycemic and blood pressure control and leveled off for lipid control in adult NHANES participants with diabetes after 2010. First-line treatments for diabetes and associated risk factors remain underused, and treatment intensification may not be sufficiently considered in patients with uncontrolled risk factors despite clinical guideline recommendations. The findings of this study may portend a possible population-level increase in diabetes-related illnesses in the years to come.

Commentary

The thorough understanding of trends in management of diseases is critical to inform public health policies and planning. Well designed clinical studies heavily influence the development of public health policies and clinical guidelines, which in turn drive real-world clinical practice. In a recent analysis utilizing data from NHANES, Fang et al¹ showed evidence of a general shift toward less intensive treatment of diabetes, hypertension, and hypercholesterolemia in adults living in the US during the last decade.

Similarly, in a separate study using NHANES data collected between 1999 and 2018 published in JAMA just 2 weeks after the current report, Wang et al² confirms this declining trend in diabetes management with only 21.2% of diabetic adults simultaneously attaining glycemic, blood pressure, and lipid level targets during the same period. What led to the decline in more stringent risk factor and diabetes management since 2010 observed in these studies? One possible explanation, as suggested by Fang et al, is that major clinical trials from the late 2000s­—including Action to Control Cardiovascular Risk in Diabetes, UK Prospective Diabetes Study, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, and Veterans Affairs Diabetes Trial—that assessed the effects of intensive glycemic control (with target HbA_1c < 6.5%) found that intensive treatment of diabetes compared to standard care had no cardiovascular benefit albeit increasing the risk of hypoglycemia. Thus, these trial findings may have translated into suboptimal diabetes treatment observed in some NHANES participants. Wang et al propose that effective tailored approaches are needed to improve risk factor control in diabetic patients, such as enhance and maintain adherence to medications and healthy lifestyle behaviors, as well as better access to health care and therapeutic education.

The changes in recent trends in diabetes management have immense clinical implications. The authors of this study suggest a link between the recent relaxation of glycemic targets, as well as risk factor control, and a resurgence of diabetic complications such as lower limb amputation or stroke. Indeed, several recent studies indicate an upward trend or plateau in diabetic complications which had been decreasing in prevalence prior to 2010.³ For example, lower extremity amputation has surged by more than 25% between 2010 and 2015, especially in young and middle-aged adults.⁴ Among the arguments brought forward that this recent resurgence in amputations is directly linked to worsening glycemic control is the fact that between 2007 and 2010, when glucose levels were best controlled within the previous 30-year period, amputations were also at the lowest levels. Moreover, data from the Centers for Disease Control and Prevention also show a 55% increase in mortality (from 15.7 to 24.2 per 1000) among diabetic patients between 2010 and 2015.¹⁴ On the other hand, a growing number of studies show that an increase of inappropriate treatment intensification—reaching HbA_1c levels that are way below the recommended targets—is associated with adverse consequences in diabetic patients particularly in those aged more than 65 years.^5-7 These seemingly contradictory findings highlight the importance of a personalized and thoughtful approach to the management of diabetes and its risk factors. As an example, an increase in the use of newer and safer glucose lowering drugs (eg, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and dipeptidyl peptidase 4 inhibitors) can help achieve better HbA_1c goals with a reduced risk of hypoglycemic episodes as recently shown by a Danish study.⁸ In this study, the authors concluded that the reduction of the rate of hypoglycemic episodes leading to hospitalization in Denmark was directly linked to the use of these safer and newer glucose lowering drugs.

A discussion on the specifics of trends in diabetes treatment and control must include considerations in older adults aged more than 65 years who constitute more than 40% of the diabetic population. Despite the high prevalence of diabetes in this vulnerable population, such data are still insufficient in the literature and are critically needed to inform public health policies and clinical guidelines. In epidemiological studies focusing on diabetic complications from the last 10 years, concerning increases have been observed in younger⁹ and middle-aged adults while remaining stable in older adults. However, the risk of hypoglycemia or severe hypoglycemia remains high in older adults living in nursing facilities, even in those with an elevated HbA_1c of greater than 8%.⁷ Moreover, in light of more relaxed HbA_1c treatment goals for older frail adults as recommended by international guidelines since 2010,^10,11 recent findings from the French GERODIAB cohort show an increased mortality (hazard ratio, 1.76) in type 2 diabetics aged 70 years and older with HbA_1c greater than or equal to 8.6%.¹² Similarly, a 5-year retrospective British study from 2018 which included patients aged 70 years and older, shows an increased overall mortality in those with HbA_1c greater than 8.5%.¹³ Taken together, further age-stratified analysis utilizing data from large cohort studies including NHANES may help to clarify national trends in diabetes treatment and risk factor control as well as diabetic complications specific to the geriatric population. By being better informed of such trends, clinicians could then develop treatment strategies that minimize complications (eg, hypoglycemia, falls) while achieving favorable outcomes (eg, reduce hyperglycemic emergencies, improve survival) in frail older patients.

Applications for Clinical Practice

The understanding of population-wide trends in diabetes control is critical to planning public health approaches for the prevention and treatment of this disease and its complications. In older adults, the high risk of hypoglycemic events and insufficient epidemiological data on trends of diabetes control hinder diabetes management. Personalized treatment targets taking into account geriatric syndromes and general health status, as well as multidisciplinary management involving endocrinologists, geriatricians, and clinical pharmacists, are necessary to optimize care in older adults with diabetes.

The streak of positive phase 3 trial results for the novel “twincretin” tirzepatide when treating patients with type 2 diabetes continued in a report in The Lancet on results from the SURPASS-3 trial, which compared weekly subcutaneous injections of tirzepatide against daily treatment with insulin degludec in patients inadequately controlled on metformin alone or on metformin plus a sodium-glucose cotransporter 2 inhibitor.

Despite positive results in SURPASS-3, as well as in four other pivotal trials that are in the process of releasing full results, the safety and efficacy picture of tirzepatide still includes several as-yet unresolved issues, including the true incidence rate of gastrointestinal adverse effects, the role these effects play in weight loss during tirzepatide treatment, and the drug’s effect on important endpoints beyond weight loss and glycemic control such as cardiovascular outcomes and renal function, said two Australian experts who coauthored a comment on the new SURPASS-3 report.

Tirzepatide is called a “twincretin” because the molecule acts as both a glucagonlike peptide–1 receptor agonist, the drug class that includes semaglutide (Ozempic, Rybelsus, Wegovy) and liraglutide (Saxenda, Victoza), and also as a glucose-dependent insulinotropic polypeptide (GIP). Trial results reported to date suggest that tirzepatide “might be more potent than available GLP-1 receptor agonists,” based on evidence of superior glycemic control it produced relative to semaglutide in results from the SURPASS-2 phase 3 trial reported in August 2021, wrote Christopher K. Rayner, MD, and Michael Horowitz, MD, in their comment.

Uncertainty about gastrointestinal adverse effects

“Limitations of SURPASS-3 include the relatively small number of Asian and Black” patients enrolled, “and an open-label design that carries a risk for bias” when tallying the incidence of gastrointestinal adverse effects, which the trial recorded based on self-reports by enrolled patients.

A better design would use validated questionnaires geared to discerning gastrointestinal symptoms like the ones used in trials involving patients with functional gastrointestinal disorders, wrote Dr. Rayner, a professor of gastroenterology at the University of Adelaide, and Dr. Horowitz, a professor at the same institution and also director of the endocrine and metabolic unit at Royal Adelaide Hospital.

This approach would “allow for more robust evaluation of whether gastrointestinal symptoms are associated with increased weight loss,” they proposed, a possible partial explanation for the weight loss of some patients treated with a GLP-1 receptor agonist.

Additional outstanding questions about tirzepatide include the contribution resulting from the drug’s stimulation of the GIP receptor, as well as the role of GLP-1 receptor stimulation by tirzepatide in slowing gastric emptying. And they also cite the still-unreported effects of tirzepatide on cardiovascular events, fatty liver disease, and kidney function, and its longer-term effects with chronic treatment beyond a year.

All five of the recently completed SURPASS trials ran for 40-52 weeks.

Tirzepatide surpasses insulin degludec’s glycemic control

SURPASS-3 enrolled 1,444 patients with type 2 diabetes at 122 sites in 13 countries during 2019. The study’s primary endpoint was mean change in hemoglobin A1c from baseline after 52 weeks on treatment. The results showed that the A1c reduction with tirzepatide treatment significantly exceeded the drop produced by insulin degludec by 0.59%, 0.86%, and 1.04%, respectively, across the three tirzepatide dosages tested in a dose-response fashion, according to the recent publication.

The most common treatment-emergent adverse effects were gastrointestinal, which decreased with continued treatment, and tirzepatide produced fewer episodes of hypoglycemia, compared with insulin degludec (Tresiba).

In addition to full reports now out from SURPASS-2 and SURPASS-3, researchers also recently published full primary results from SURPASS-1. Results from SURPASS-5 appeared in a poster presented at the American Diabetes Association scientific sessions in June 2021 but have not yet been published in a full report, and the primary results from SURPASS-4are expected in a report during the European Association for the Study of Diabetes in September 2021.

SURPASS-3 and the other trials of tirzepatide were funded by Lilly, the company developing the drug. Dr. Rayner has been an adviser to Allergen and Glyscend, and has received research funding from Sanofi and Novartis. Dr. Horowitz has received symposia fees from Lilly, as well as from AstraZeneca and Boehringer Ingelheim.

[email protected]

The streak of positive phase 3 trial results for the novel “twincretin” tirzepatide when treating patients with type 2 diabetes continued in a report in The Lancet on results from the SURPASS-3 trial, which compared weekly subcutaneous injections of tirzepatide against daily treatment with insulin degludec in patients inadequately controlled on metformin alone or on metformin plus a sodium-glucose cotransporter 2 inhibitor.

Despite positive results in SURPASS-3, as well as in four other pivotal trials that are in the process of releasing full results, the safety and efficacy picture of tirzepatide still includes several as-yet unresolved issues, including the true incidence rate of gastrointestinal adverse effects, the role these effects play in weight loss during tirzepatide treatment, and the drug’s effect on important endpoints beyond weight loss and glycemic control such as cardiovascular outcomes and renal function, said two Australian experts who coauthored a comment on the new SURPASS-3 report.

Tirzepatide is called a “twincretin” because the molecule acts as both a glucagonlike peptide–1 receptor agonist, the drug class that includes semaglutide (Ozempic, Rybelsus, Wegovy) and liraglutide (Saxenda, Victoza), and also as a glucose-dependent insulinotropic polypeptide (GIP). Trial results reported to date suggest that tirzepatide “might be more potent than available GLP-1 receptor agonists,” based on evidence of superior glycemic control it produced relative to semaglutide in results from the SURPASS-2 phase 3 trial reported in August 2021, wrote Christopher K. Rayner, MD, and Michael Horowitz, MD, in their comment.

Uncertainty about gastrointestinal adverse effects

“Limitations of SURPASS-3 include the relatively small number of Asian and Black” patients enrolled, “and an open-label design that carries a risk for bias” when tallying the incidence of gastrointestinal adverse effects, which the trial recorded based on self-reports by enrolled patients.

A better design would use validated questionnaires geared to discerning gastrointestinal symptoms like the ones used in trials involving patients with functional gastrointestinal disorders, wrote Dr. Rayner, a professor of gastroenterology at the University of Adelaide, and Dr. Horowitz, a professor at the same institution and also director of the endocrine and metabolic unit at Royal Adelaide Hospital.

This approach would “allow for more robust evaluation of whether gastrointestinal symptoms are associated with increased weight loss,” they proposed, a possible partial explanation for the weight loss of some patients treated with a GLP-1 receptor agonist.

Additional outstanding questions about tirzepatide include the contribution resulting from the drug’s stimulation of the GIP receptor, as well as the role of GLP-1 receptor stimulation by tirzepatide in slowing gastric emptying. And they also cite the still-unreported effects of tirzepatide on cardiovascular events, fatty liver disease, and kidney function, and its longer-term effects with chronic treatment beyond a year.

All five of the recently completed SURPASS trials ran for 40-52 weeks.

Tirzepatide surpasses insulin degludec’s glycemic control

SURPASS-3 enrolled 1,444 patients with type 2 diabetes at 122 sites in 13 countries during 2019. The study’s primary endpoint was mean change in hemoglobin A1c from baseline after 52 weeks on treatment. The results showed that the A1c reduction with tirzepatide treatment significantly exceeded the drop produced by insulin degludec by 0.59%, 0.86%, and 1.04%, respectively, across the three tirzepatide dosages tested in a dose-response fashion, according to the recent publication.

The most common treatment-emergent adverse effects were gastrointestinal, which decreased with continued treatment, and tirzepatide produced fewer episodes of hypoglycemia, compared with insulin degludec (Tresiba).

In addition to full reports now out from SURPASS-2 and SURPASS-3, researchers also recently published full primary results from SURPASS-1. Results from SURPASS-5 appeared in a poster presented at the American Diabetes Association scientific sessions in June 2021 but have not yet been published in a full report, and the primary results from SURPASS-4are expected in a report during the European Association for the Study of Diabetes in September 2021.

SURPASS-3 and the other trials of tirzepatide were funded by Lilly, the company developing the drug. Dr. Rayner has been an adviser to Allergen and Glyscend, and has received research funding from Sanofi and Novartis. Dr. Horowitz has received symposia fees from Lilly, as well as from AstraZeneca and Boehringer Ingelheim.

[email protected]

The streak of positive phase 3 trial results for the novel “twincretin” tirzepatide when treating patients with type 2 diabetes continued in a report in The Lancet on results from the SURPASS-3 trial, which compared weekly subcutaneous injections of tirzepatide against daily treatment with insulin degludec in patients inadequately controlled on metformin alone or on metformin plus a sodium-glucose cotransporter 2 inhibitor.

Despite positive results in SURPASS-3, as well as in four other pivotal trials that are in the process of releasing full results, the safety and efficacy picture of tirzepatide still includes several as-yet unresolved issues, including the true incidence rate of gastrointestinal adverse effects, the role these effects play in weight loss during tirzepatide treatment, and the drug’s effect on important endpoints beyond weight loss and glycemic control such as cardiovascular outcomes and renal function, said two Australian experts who coauthored a comment on the new SURPASS-3 report.

Tirzepatide is called a “twincretin” because the molecule acts as both a glucagonlike peptide–1 receptor agonist, the drug class that includes semaglutide (Ozempic, Rybelsus, Wegovy) and liraglutide (Saxenda, Victoza), and also as a glucose-dependent insulinotropic polypeptide (GIP). Trial results reported to date suggest that tirzepatide “might be more potent than available GLP-1 receptor agonists,” based on evidence of superior glycemic control it produced relative to semaglutide in results from the SURPASS-2 phase 3 trial reported in August 2021, wrote Christopher K. Rayner, MD, and Michael Horowitz, MD, in their comment.

Uncertainty about gastrointestinal adverse effects

“Limitations of SURPASS-3 include the relatively small number of Asian and Black” patients enrolled, “and an open-label design that carries a risk for bias” when tallying the incidence of gastrointestinal adverse effects, which the trial recorded based on self-reports by enrolled patients.

A better design would use validated questionnaires geared to discerning gastrointestinal symptoms like the ones used in trials involving patients with functional gastrointestinal disorders, wrote Dr. Rayner, a professor of gastroenterology at the University of Adelaide, and Dr. Horowitz, a professor at the same institution and also director of the endocrine and metabolic unit at Royal Adelaide Hospital.

This approach would “allow for more robust evaluation of whether gastrointestinal symptoms are associated with increased weight loss,” they proposed, a possible partial explanation for the weight loss of some patients treated with a GLP-1 receptor agonist.

Additional outstanding questions about tirzepatide include the contribution resulting from the drug’s stimulation of the GIP receptor, as well as the role of GLP-1 receptor stimulation by tirzepatide in slowing gastric emptying. And they also cite the still-unreported effects of tirzepatide on cardiovascular events, fatty liver disease, and kidney function, and its longer-term effects with chronic treatment beyond a year.

All five of the recently completed SURPASS trials ran for 40-52 weeks.

Tirzepatide surpasses insulin degludec’s glycemic control

SURPASS-3 enrolled 1,444 patients with type 2 diabetes at 122 sites in 13 countries during 2019. The study’s primary endpoint was mean change in hemoglobin A1c from baseline after 52 weeks on treatment. The results showed that the A1c reduction with tirzepatide treatment significantly exceeded the drop produced by insulin degludec by 0.59%, 0.86%, and 1.04%, respectively, across the three tirzepatide dosages tested in a dose-response fashion, according to the recent publication.

The most common treatment-emergent adverse effects were gastrointestinal, which decreased with continued treatment, and tirzepatide produced fewer episodes of hypoglycemia, compared with insulin degludec (Tresiba).

In addition to full reports now out from SURPASS-2 and SURPASS-3, researchers also recently published full primary results from SURPASS-1. Results from SURPASS-5 appeared in a poster presented at the American Diabetes Association scientific sessions in June 2021 but have not yet been published in a full report, and the primary results from SURPASS-4are expected in a report during the European Association for the Study of Diabetes in September 2021.

SURPASS-3 and the other trials of tirzepatide were funded by Lilly, the company developing the drug. Dr. Rayner has been an adviser to Allergen and Glyscend, and has received research funding from Sanofi and Novartis. Dr. Horowitz has received symposia fees from Lilly, as well as from AstraZeneca and Boehringer Ingelheim.

[email protected]

In the 2 decades from 1999 to 2018, ultraprocessed foods consistently accounted for the majority of energy intake by American young people, a large cross-sectional study of National Health and Nutrition Examination Survey (NHANES) data shows.

In young people aged 2-19 years, the estimated percentage of total energy from consumption of ultraprocessed foods increased from 61.4% to 67.0%, for a difference of 5.6% (95% confidence interval [CI] 3.5-7.7, P < .001 for trend), according to Lu Wang, PhD, MPH, a postdoctoral fellow at the Friedman School of Nutrition Science and Policy at Tufts University in Boston, and colleagues.

In contrast, total energy from non- or minimally processed foods decreased from 28.8% to 23.5% (difference −5.3%, 95% CI, −7.5 to −3.2, P < .001 for trend).

“The estimated percentage of energy consumed from ultraprocessed foods increased from 1999 to 2018, with an increasing trend in ready-to-heat and -eat mixed dishes and a decreasing trend in sugar-sweetened beverages,” the authors wrote. The report was published online Aug. 10 in JAMA.

The findings held regardless of the educational and socioeconomic status of the children’s parents.

Significant disparities by race and ethnicity emerged, however, with the ultraprocessed food phenomenon more marked in non-Hispanic Black youths and Mexican-American youths than in their non-Hispanic White counterparts. “Targeted marketing of junk foods toward racial/ethnic minority youths may partly contribute to such differences,” the authors wrote. “However, persistently lower consumption of ultraprocessed foods among Mexican-American youths may reflect more home cooking among Hispanic families.”

Among non-Hispanic Black youths consumption rose from 62.2% to 72.5% (difference 10.3%, 95% CI, 6.8-13.8) and among Mexican-American youths from 55.8% to 63.5% (difference 7.6%, 95% CI, 4.4-10.9). In non-Hispanic White youths intake rose from 63.4% to 68.6% (difference 5.2%, 95% CI, 2.1-8.3, P = .04 for trends).

In addition, a higher consumption of ultraprocessed foods among school-aged youths than among preschool children aged 2-5 years may reflect increased marketing, availability, and selection of ultraprocessed foods for older youths, the authors noted.

Food processing, with its potential adverse effects, may need to be considered as a food dimension in addition to nutrients and food groups in future dietary recommendations and food policies, they added.

“An increasing number of studies are showing a link between ultraprocessed food consumption and adverse health outcomes in children,” corresponding author Fang Fang Zhang, MD, PhD, Neely Family Professor and associate professor at Tufts’ Friedman School of Nutrition Science and Policy, said in an interview. “Health care providers can play a larger role in encouraging patients – and their parents – to replace unhealthy ultraprocessed foods such as ultraprocessed sweet bakery products with healthy unprocessed or minimally processed foods in their diet such as less processed whole grains. “

In Dr. Zhang’s view, teachers also have a part to play in promoting nutrition literacy. “Schools can play an important role in empowering children with knowledge and skills to make healthy food choices,” she said. “Nutrition literacy should be an integral part of the health education curriculum in all K-12 schools.”

Commenting on the study but not involved in it, Michelle Katzow, MD, a pediatrician/obesity medicine specialist and assistant professor at the Feinstein Institutes for Medical Research in Manhasset, N.Y., said the work highlights an often overlooked aspect of the modern American diet that may well be contributing to poor health outcomes in young people.

“It suggests that even as the science advances and we learn more about the adverse health effects of ultraprocessed foods, public health efforts to improve nutrition and food quality in children have not been successful,” she said in an interview. “This is because it is so hard for public health advocates to compete with the food industry, which stands to really benefit financially from hooking kids on processed foods that are not good for their health.”

Dr. Katzow added that the observed racial/ethnic disparities are not surprising in light of a growing body of evidence that racism exists in food marketing. “We need to put forward policies that regulate the food industry, particularly in relation to its most susceptible targets, our kids.”
 

Study details

The serial cross-sectional analysis used 24-hour dietary recall data from a nationally representative sample from 10 NHANES cycles for the range of 1999-2000 to 2017-2018. The weighted mean age of the cohort was 10.7 years and 49.1% were girls.

Among the subgroups of ultraprocessed foods, the estimated percentage of energy from ready-to-heat and ready-to-eat mixed dishes increased from 2.2% to 11.2% (difference 8.9%; 95%, CI, 7.7-10.2).

Energy from sweets and sweet snacks increased from 10.7% to 12.9% (difference 2.3%; 95% CI, 1.0-3.6), but the estimated percentage of energy decreased for sugar-sweetened beverages from 10.8% to 5.3% (difference −5.5%; 95% CI, −6.5 to −4.5).

In other categories, estimated energy intake from processed fats and oils, condiments, and sauces fell from 7.1% to 4.0% (difference −3.1%; 95% CI, −3.7 to −2.6, all P < .05 for trend).

Not surprisingly, ultraprocessed foods had an overall poorer nutrient profile than that of nonultraprocessed, although they often contained less saturated fat, and they also contained more carbohydrates, mostly from low-quality sources with added sugars and low levels of dietary fiber and protein.

And despite a higher total folate content in ultraprocessed foods because of fortification, higher-level consumers took in less total folate owing to their lower consumption of whole foods.

The authors cautioned that in addition to poor nutrient profiles, processing itself may harm health by changing the physical structure and chemical composition of food, which could lead to elevated glycemic response and reduced satiety. Furthermore, recent research has linked food additives such as emulsifiers, stabilizers, and artificial sweeteners to adverse metabolomic effects and obesity risk. Pointing to the recent success of efforts to reduce consumption of sugary beverages, Dr. Zhang said, “We need to mobilize the same energy and level of commitment when it comes to other unhealthy ultraprocessed foods such as cakes, cookies, doughnuts, and brownies.”

The trends identified by the Tufts study “are concerning and potentially have major public health significance,” according to an accompanying JAMA editorial.

“Better dietary assessment methods are needed to document trends and understand the unique role of ultraprocessed foods to inform future evidence-based policy and dietary recommendations,” wrote Katie A. Meyer, ScD, and Lindsey Smith Taillie, PhD, of the Gillings School of Global Public Health at the University of North Carolina in Chapel Hill.

The editorialists share the authors’ view that “a conceptual advancement would be to consider the level and characteristics of processing as just one of multiple dimensions (including nutrients and food groups) used to classify foods as healthy or unhealthy.” They pointed out that the Pan American Health Organization already recommends targeting products that are ultraprocessed and high in concerning add-in nutrients.

They cautioned, however, that the classification of ultraprocessed foods will not be easy because it requires data on a full list of ingredients, and the effects of processing generally cannot be separated from the composite nutrients of ultraprocessed foods.

This presents a challenge for national food consumption research “given that most large epidemiological studies rely on food frequency questionnaires that lack the information necessary to classify processing levels,” they wrote.

This study was supported by the National Institutes of Health and the São Paulo Research Foundation. Coauthor Dariush Mozaffarian, MD, a cardiologist at Tufts University, disclosed support from the Bill & Melinda Gates Foundation, the National Institutes of Health, and the Rockefeller Foundation as well as personal fees from several commercial companies. He has served on several scientific advisory boards and received royalties from UpToDate, all outside of the submitted work. Dr. Meyer reported a grant from choline manufacturer Balchem. Dr. Taillie reported funding from Bloomberg Philanthropies. Dr. Zhang had no disclosures. Dr. Katzow disclosed no competing interests.

In the 2 decades from 1999 to 2018, ultraprocessed foods consistently accounted for the majority of energy intake by American young people, a large cross-sectional study of National Health and Nutrition Examination Survey (NHANES) data shows.

In young people aged 2-19 years, the estimated percentage of total energy from consumption of ultraprocessed foods increased from 61.4% to 67.0%, for a difference of 5.6% (95% confidence interval [CI] 3.5-7.7, P < .001 for trend), according to Lu Wang, PhD, MPH, a postdoctoral fellow at the Friedman School of Nutrition Science and Policy at Tufts University in Boston, and colleagues.

In contrast, total energy from non- or minimally processed foods decreased from 28.8% to 23.5% (difference −5.3%, 95% CI, −7.5 to −3.2, P < .001 for trend).

“The estimated percentage of energy consumed from ultraprocessed foods increased from 1999 to 2018, with an increasing trend in ready-to-heat and -eat mixed dishes and a decreasing trend in sugar-sweetened beverages,” the authors wrote. The report was published online Aug. 10 in JAMA.

The findings held regardless of the educational and socioeconomic status of the children’s parents.

Significant disparities by race and ethnicity emerged, however, with the ultraprocessed food phenomenon more marked in non-Hispanic Black youths and Mexican-American youths than in their non-Hispanic White counterparts. “Targeted marketing of junk foods toward racial/ethnic minority youths may partly contribute to such differences,” the authors wrote. “However, persistently lower consumption of ultraprocessed foods among Mexican-American youths may reflect more home cooking among Hispanic families.”

Among non-Hispanic Black youths consumption rose from 62.2% to 72.5% (difference 10.3%, 95% CI, 6.8-13.8) and among Mexican-American youths from 55.8% to 63.5% (difference 7.6%, 95% CI, 4.4-10.9). In non-Hispanic White youths intake rose from 63.4% to 68.6% (difference 5.2%, 95% CI, 2.1-8.3, P = .04 for trends).

In addition, a higher consumption of ultraprocessed foods among school-aged youths than among preschool children aged 2-5 years may reflect increased marketing, availability, and selection of ultraprocessed foods for older youths, the authors noted.

Food processing, with its potential adverse effects, may need to be considered as a food dimension in addition to nutrients and food groups in future dietary recommendations and food policies, they added.

“An increasing number of studies are showing a link between ultraprocessed food consumption and adverse health outcomes in children,” corresponding author Fang Fang Zhang, MD, PhD, Neely Family Professor and associate professor at Tufts’ Friedman School of Nutrition Science and Policy, said in an interview. “Health care providers can play a larger role in encouraging patients – and their parents – to replace unhealthy ultraprocessed foods such as ultraprocessed sweet bakery products with healthy unprocessed or minimally processed foods in their diet such as less processed whole grains. “

In Dr. Zhang’s view, teachers also have a part to play in promoting nutrition literacy. “Schools can play an important role in empowering children with knowledge and skills to make healthy food choices,” she said. “Nutrition literacy should be an integral part of the health education curriculum in all K-12 schools.”

Commenting on the study but not involved in it, Michelle Katzow, MD, a pediatrician/obesity medicine specialist and assistant professor at the Feinstein Institutes for Medical Research in Manhasset, N.Y., said the work highlights an often overlooked aspect of the modern American diet that may well be contributing to poor health outcomes in young people.

“It suggests that even as the science advances and we learn more about the adverse health effects of ultraprocessed foods, public health efforts to improve nutrition and food quality in children have not been successful,” she said in an interview. “This is because it is so hard for public health advocates to compete with the food industry, which stands to really benefit financially from hooking kids on processed foods that are not good for their health.”

Dr. Katzow added that the observed racial/ethnic disparities are not surprising in light of a growing body of evidence that racism exists in food marketing. “We need to put forward policies that regulate the food industry, particularly in relation to its most susceptible targets, our kids.”
 

Study details

The serial cross-sectional analysis used 24-hour dietary recall data from a nationally representative sample from 10 NHANES cycles for the range of 1999-2000 to 2017-2018. The weighted mean age of the cohort was 10.7 years and 49.1% were girls.

Among the subgroups of ultraprocessed foods, the estimated percentage of energy from ready-to-heat and ready-to-eat mixed dishes increased from 2.2% to 11.2% (difference 8.9%; 95%, CI, 7.7-10.2).

Energy from sweets and sweet snacks increased from 10.7% to 12.9% (difference 2.3%; 95% CI, 1.0-3.6), but the estimated percentage of energy decreased for sugar-sweetened beverages from 10.8% to 5.3% (difference −5.5%; 95% CI, −6.5 to −4.5).

In other categories, estimated energy intake from processed fats and oils, condiments, and sauces fell from 7.1% to 4.0% (difference −3.1%; 95% CI, −3.7 to −2.6, all P < .05 for trend).

Not surprisingly, ultraprocessed foods had an overall poorer nutrient profile than that of nonultraprocessed, although they often contained less saturated fat, and they also contained more carbohydrates, mostly from low-quality sources with added sugars and low levels of dietary fiber and protein.

And despite a higher total folate content in ultraprocessed foods because of fortification, higher-level consumers took in less total folate owing to their lower consumption of whole foods.

The authors cautioned that in addition to poor nutrient profiles, processing itself may harm health by changing the physical structure and chemical composition of food, which could lead to elevated glycemic response and reduced satiety. Furthermore, recent research has linked food additives such as emulsifiers, stabilizers, and artificial sweeteners to adverse metabolomic effects and obesity risk. Pointing to the recent success of efforts to reduce consumption of sugary beverages, Dr. Zhang said, “We need to mobilize the same energy and level of commitment when it comes to other unhealthy ultraprocessed foods such as cakes, cookies, doughnuts, and brownies.”

The trends identified by the Tufts study “are concerning and potentially have major public health significance,” according to an accompanying JAMA editorial.

“Better dietary assessment methods are needed to document trends and understand the unique role of ultraprocessed foods to inform future evidence-based policy and dietary recommendations,” wrote Katie A. Meyer, ScD, and Lindsey Smith Taillie, PhD, of the Gillings School of Global Public Health at the University of North Carolina in Chapel Hill.

The editorialists share the authors’ view that “a conceptual advancement would be to consider the level and characteristics of processing as just one of multiple dimensions (including nutrients and food groups) used to classify foods as healthy or unhealthy.” They pointed out that the Pan American Health Organization already recommends targeting products that are ultraprocessed and high in concerning add-in nutrients.

They cautioned, however, that the classification of ultraprocessed foods will not be easy because it requires data on a full list of ingredients, and the effects of processing generally cannot be separated from the composite nutrients of ultraprocessed foods.

This presents a challenge for national food consumption research “given that most large epidemiological studies rely on food frequency questionnaires that lack the information necessary to classify processing levels,” they wrote.

This study was supported by the National Institutes of Health and the São Paulo Research Foundation. Coauthor Dariush Mozaffarian, MD, a cardiologist at Tufts University, disclosed support from the Bill & Melinda Gates Foundation, the National Institutes of Health, and the Rockefeller Foundation as well as personal fees from several commercial companies. He has served on several scientific advisory boards and received royalties from UpToDate, all outside of the submitted work. Dr. Meyer reported a grant from choline manufacturer Balchem. Dr. Taillie reported funding from Bloomberg Philanthropies. Dr. Zhang had no disclosures. Dr. Katzow disclosed no competing interests.

In the 2 decades from 1999 to 2018, ultraprocessed foods consistently accounted for the majority of energy intake by American young people, a large cross-sectional study of National Health and Nutrition Examination Survey (NHANES) data shows.

In young people aged 2-19 years, the estimated percentage of total energy from consumption of ultraprocessed foods increased from 61.4% to 67.0%, for a difference of 5.6% (95% confidence interval [CI] 3.5-7.7, P < .001 for trend), according to Lu Wang, PhD, MPH, a postdoctoral fellow at the Friedman School of Nutrition Science and Policy at Tufts University in Boston, and colleagues.

In contrast, total energy from non- or minimally processed foods decreased from 28.8% to 23.5% (difference −5.3%, 95% CI, −7.5 to −3.2, P < .001 for trend).

“The estimated percentage of energy consumed from ultraprocessed foods increased from 1999 to 2018, with an increasing trend in ready-to-heat and -eat mixed dishes and a decreasing trend in sugar-sweetened beverages,” the authors wrote. The report was published online Aug. 10 in JAMA.

The findings held regardless of the educational and socioeconomic status of the children’s parents.

Significant disparities by race and ethnicity emerged, however, with the ultraprocessed food phenomenon more marked in non-Hispanic Black youths and Mexican-American youths than in their non-Hispanic White counterparts. “Targeted marketing of junk foods toward racial/ethnic minority youths may partly contribute to such differences,” the authors wrote. “However, persistently lower consumption of ultraprocessed foods among Mexican-American youths may reflect more home cooking among Hispanic families.”

Among non-Hispanic Black youths consumption rose from 62.2% to 72.5% (difference 10.3%, 95% CI, 6.8-13.8) and among Mexican-American youths from 55.8% to 63.5% (difference 7.6%, 95% CI, 4.4-10.9). In non-Hispanic White youths intake rose from 63.4% to 68.6% (difference 5.2%, 95% CI, 2.1-8.3, P = .04 for trends).

In addition, a higher consumption of ultraprocessed foods among school-aged youths than among preschool children aged 2-5 years may reflect increased marketing, availability, and selection of ultraprocessed foods for older youths, the authors noted.

Food processing, with its potential adverse effects, may need to be considered as a food dimension in addition to nutrients and food groups in future dietary recommendations and food policies, they added.

“An increasing number of studies are showing a link between ultraprocessed food consumption and adverse health outcomes in children,” corresponding author Fang Fang Zhang, MD, PhD, Neely Family Professor and associate professor at Tufts’ Friedman School of Nutrition Science and Policy, said in an interview. “Health care providers can play a larger role in encouraging patients – and their parents – to replace unhealthy ultraprocessed foods such as ultraprocessed sweet bakery products with healthy unprocessed or minimally processed foods in their diet such as less processed whole grains. “

In Dr. Zhang’s view, teachers also have a part to play in promoting nutrition literacy. “Schools can play an important role in empowering children with knowledge and skills to make healthy food choices,” she said. “Nutrition literacy should be an integral part of the health education curriculum in all K-12 schools.”

Commenting on the study but not involved in it, Michelle Katzow, MD, a pediatrician/obesity medicine specialist and assistant professor at the Feinstein Institutes for Medical Research in Manhasset, N.Y., said the work highlights an often overlooked aspect of the modern American diet that may well be contributing to poor health outcomes in young people.

“It suggests that even as the science advances and we learn more about the adverse health effects of ultraprocessed foods, public health efforts to improve nutrition and food quality in children have not been successful,” she said in an interview. “This is because it is so hard for public health advocates to compete with the food industry, which stands to really benefit financially from hooking kids on processed foods that are not good for their health.”

Dr. Katzow added that the observed racial/ethnic disparities are not surprising in light of a growing body of evidence that racism exists in food marketing. “We need to put forward policies that regulate the food industry, particularly in relation to its most susceptible targets, our kids.”
 

Study details

The serial cross-sectional analysis used 24-hour dietary recall data from a nationally representative sample from 10 NHANES cycles for the range of 1999-2000 to 2017-2018. The weighted mean age of the cohort was 10.7 years and 49.1% were girls.

Among the subgroups of ultraprocessed foods, the estimated percentage of energy from ready-to-heat and ready-to-eat mixed dishes increased from 2.2% to 11.2% (difference 8.9%; 95%, CI, 7.7-10.2).

Energy from sweets and sweet snacks increased from 10.7% to 12.9% (difference 2.3%; 95% CI, 1.0-3.6), but the estimated percentage of energy decreased for sugar-sweetened beverages from 10.8% to 5.3% (difference −5.5%; 95% CI, −6.5 to −4.5).

In other categories, estimated energy intake from processed fats and oils, condiments, and sauces fell from 7.1% to 4.0% (difference −3.1%; 95% CI, −3.7 to −2.6, all P < .05 for trend).

Not surprisingly, ultraprocessed foods had an overall poorer nutrient profile than that of nonultraprocessed, although they often contained less saturated fat, and they also contained more carbohydrates, mostly from low-quality sources with added sugars and low levels of dietary fiber and protein.

And despite a higher total folate content in ultraprocessed foods because of fortification, higher-level consumers took in less total folate owing to their lower consumption of whole foods.

The authors cautioned that in addition to poor nutrient profiles, processing itself may harm health by changing the physical structure and chemical composition of food, which could lead to elevated glycemic response and reduced satiety. Furthermore, recent research has linked food additives such as emulsifiers, stabilizers, and artificial sweeteners to adverse metabolomic effects and obesity risk. Pointing to the recent success of efforts to reduce consumption of sugary beverages, Dr. Zhang said, “We need to mobilize the same energy and level of commitment when it comes to other unhealthy ultraprocessed foods such as cakes, cookies, doughnuts, and brownies.”

The trends identified by the Tufts study “are concerning and potentially have major public health significance,” according to an accompanying JAMA editorial.

“Better dietary assessment methods are needed to document trends and understand the unique role of ultraprocessed foods to inform future evidence-based policy and dietary recommendations,” wrote Katie A. Meyer, ScD, and Lindsey Smith Taillie, PhD, of the Gillings School of Global Public Health at the University of North Carolina in Chapel Hill.

The editorialists share the authors’ view that “a conceptual advancement would be to consider the level and characteristics of processing as just one of multiple dimensions (including nutrients and food groups) used to classify foods as healthy or unhealthy.” They pointed out that the Pan American Health Organization already recommends targeting products that are ultraprocessed and high in concerning add-in nutrients.

They cautioned, however, that the classification of ultraprocessed foods will not be easy because it requires data on a full list of ingredients, and the effects of processing generally cannot be separated from the composite nutrients of ultraprocessed foods.

This presents a challenge for national food consumption research “given that most large epidemiological studies rely on food frequency questionnaires that lack the information necessary to classify processing levels,” they wrote.

This study was supported by the National Institutes of Health and the São Paulo Research Foundation. Coauthor Dariush Mozaffarian, MD, a cardiologist at Tufts University, disclosed support from the Bill & Melinda Gates Foundation, the National Institutes of Health, and the Rockefeller Foundation as well as personal fees from several commercial companies. He has served on several scientific advisory boards and received royalties from UpToDate, all outside of the submitted work. Dr. Meyer reported a grant from choline manufacturer Balchem. Dr. Taillie reported funding from Bloomberg Philanthropies. Dr. Zhang had no disclosures. Dr. Katzow disclosed no competing interests.

Asymptomatic pregnant women with no previous diagnosis of type 1 or 2 diabetes should be screened for gestational diabetes at 24 weeks’ gestation or later, according to an updated recommendation from the U.S. Preventive Services Task Force.

Pregnant individuals who develop gestational diabetes are at increased risk for complications including preeclampsia, fetal macrosomia, and neonatal hypoglycemia, as well as negative long-term outcomes for themselves and their children, wrote lead author Karina W. Davidson, PhD, of Feinstein Institute for Medical Research, Manhasset, N.Y., and colleagues. The statement was published online in JAMA.

The B recommendation and I statement reflect “moderate certainty” that current evidence supports the recommendation in terms of harms versus benefits, and is consistent with the 2014 USPSTF recommendation.

The statement calls for a one-time screening using a glucose tolerance test at or after 24 weeks’ gestation. Although most screening in the United States takes place prior to 28 weeks’ gestation, it can be performed later in patients who begin prenatal care after 28 weeks’ gestation, according to the statement. Data on the harms and benefits of gestational diabetes screening prior to 24 weeks’ gestation are limited, the authors noted. Gestational diabetes was defined as diabetes that develops during pregnancy that is not clearly overt diabetes.

To update the 2014 recommendation, the USPSTF commissioned a systematic review. In 45 prospective studies on the accuracy of gestational diabetes screening, several tests, included oral glucose challenge test, oral glucose tolerance test, and fasting plasma glucose using either a one- or two-step approach were accurate detectors of gestational diabetes; therefore, the USPSTF does not recommend a specific test.

In 13 trials on the impact of treating gestational diabetes on intermediate and health outcomes, treatment was associated with a reduced risk of outcomes, including primary cesarean delivery (but not total cesarean delivery) and preterm delivery, but not with a reduced risk of outcomes including preeclampsia, emergency cesarean delivery, induction of labor, or maternal birth trauma.

The task force also reviewed seven studies of harms associated with screening for gestational diabetes, including three on psychosocial harms, three on hospital experiences, and one of the odds of cesarean delivery after a diagnosis of gestational diabetes. No increase in anxiety or depression occurred following a positive diagnosis or false-positive test result, but data suggested that a gestational diabetes diagnosis may be associated with higher rates of cesarean delivery.

A total of 13 trials evaluated the harms associated with treatment of gestational diabetes, and found no association between treatment and increased risk of several outcomes including severe maternal hypoglycemia, low birth weight, and small for gestational age, and no effect was noted on the number of cesarean deliveries.

Evidence gaps that require additional research include randomized, controlled trials on the effects of gestational diabetes screening on health outcomes, as well as benefits versus harms of screening for pregnant individuals prior to 24 weeks, and studies on the effects of screening in subpopulations of race/ethnicity, age, and socioeconomic factors, according to the task force. Additional research also is needed in areas of maternal health outcomes, long-term outcomes, and the effect on outcomes of one-step versus two-step screening, the USPSTF said.

However, “screening for and detecting gestational diabetes provides a potential opportunity to control blood glucose levels (through lifestyle changes, pharmacological interventions, or both) and reduce the risk of macrosomia and LGA [large for gestational age] infants,” the task force wrote. “In turn, this can prevent associated complications such as primary cesarean delivery, shoulder dystocia, and [neonatal] ICU admissions.”
 

Support screening with counseling on risk reduction

The USPSTF recommendation is important at this time because “the prevalence of gestational diabetes is increasing secondary to rising rates of obesity,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“In 2014, based on a systematic review of literature, the USPSTF recommended screening all asymptomatic pregnant women for gestational diabetes mellitus [GDM] starting at 24 weeks’ gestation. The recommended gestational age for screening coincides with increasing insulin resistance during pregnancy with advancing gestational age,” Dr. Krishna said.

“An updated systematic review by the USPSTF concluded that existing literature continues to affirm current recommendations of universal screening for GDM at 24 weeks gestation or later. There continues, however, to be no consensus on the optimal approach to screening,” she noted.

“Screening can be performed as a two-step or one-step approach,” said Dr. Krishna. “The two-step approach is commonly used in the United States, and all pregnant women are first screened with a 50-gram oral glucose solution followed by a diagnostic test if they have a positive initial screening.

“Women with risk factors for diabetes, such as prior GDM, obesity, strong family history of diabetes, or history of fetal macrosomia, should be screened early in pregnancy for GDM and have the GDM screen repeated at 24 weeks’ gestation or later if normal in early pregnancy,” Dr. Krishna said. “Pregnant women should be counseled on the importance of diet and exercise and appropriate weight gain in pregnancy to reduce the risk of GDM. Overall, timely diagnosis of gestational diabetes is crucial to improving maternal and fetal pregnancy outcomes.”

The full recommendation statement is also available on the USPSTF website. The research was supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose. Dr. Krishna had no disclosures, but serves on the editorial advisory board of Ob.Gyn News.

Asymptomatic pregnant women with no previous diagnosis of type 1 or 2 diabetes should be screened for gestational diabetes at 24 weeks’ gestation or later, according to an updated recommendation from the U.S. Preventive Services Task Force.

Pregnant individuals who develop gestational diabetes are at increased risk for complications including preeclampsia, fetal macrosomia, and neonatal hypoglycemia, as well as negative long-term outcomes for themselves and their children, wrote lead author Karina W. Davidson, PhD, of Feinstein Institute for Medical Research, Manhasset, N.Y., and colleagues. The statement was published online in JAMA.

The B recommendation and I statement reflect “moderate certainty” that current evidence supports the recommendation in terms of harms versus benefits, and is consistent with the 2014 USPSTF recommendation.

The statement calls for a one-time screening using a glucose tolerance test at or after 24 weeks’ gestation. Although most screening in the United States takes place prior to 28 weeks’ gestation, it can be performed later in patients who begin prenatal care after 28 weeks’ gestation, according to the statement. Data on the harms and benefits of gestational diabetes screening prior to 24 weeks’ gestation are limited, the authors noted. Gestational diabetes was defined as diabetes that develops during pregnancy that is not clearly overt diabetes.

To update the 2014 recommendation, the USPSTF commissioned a systematic review. In 45 prospective studies on the accuracy of gestational diabetes screening, several tests, included oral glucose challenge test, oral glucose tolerance test, and fasting plasma glucose using either a one- or two-step approach were accurate detectors of gestational diabetes; therefore, the USPSTF does not recommend a specific test.

In 13 trials on the impact of treating gestational diabetes on intermediate and health outcomes, treatment was associated with a reduced risk of outcomes, including primary cesarean delivery (but not total cesarean delivery) and preterm delivery, but not with a reduced risk of outcomes including preeclampsia, emergency cesarean delivery, induction of labor, or maternal birth trauma.

The task force also reviewed seven studies of harms associated with screening for gestational diabetes, including three on psychosocial harms, three on hospital experiences, and one of the odds of cesarean delivery after a diagnosis of gestational diabetes. No increase in anxiety or depression occurred following a positive diagnosis or false-positive test result, but data suggested that a gestational diabetes diagnosis may be associated with higher rates of cesarean delivery.

A total of 13 trials evaluated the harms associated with treatment of gestational diabetes, and found no association between treatment and increased risk of several outcomes including severe maternal hypoglycemia, low birth weight, and small for gestational age, and no effect was noted on the number of cesarean deliveries.

Evidence gaps that require additional research include randomized, controlled trials on the effects of gestational diabetes screening on health outcomes, as well as benefits versus harms of screening for pregnant individuals prior to 24 weeks, and studies on the effects of screening in subpopulations of race/ethnicity, age, and socioeconomic factors, according to the task force. Additional research also is needed in areas of maternal health outcomes, long-term outcomes, and the effect on outcomes of one-step versus two-step screening, the USPSTF said.

However, “screening for and detecting gestational diabetes provides a potential opportunity to control blood glucose levels (through lifestyle changes, pharmacological interventions, or both) and reduce the risk of macrosomia and LGA [large for gestational age] infants,” the task force wrote. “In turn, this can prevent associated complications such as primary cesarean delivery, shoulder dystocia, and [neonatal] ICU admissions.”
 

Support screening with counseling on risk reduction

The USPSTF recommendation is important at this time because “the prevalence of gestational diabetes is increasing secondary to rising rates of obesity,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“In 2014, based on a systematic review of literature, the USPSTF recommended screening all asymptomatic pregnant women for gestational diabetes mellitus [GDM] starting at 24 weeks’ gestation. The recommended gestational age for screening coincides with increasing insulin resistance during pregnancy with advancing gestational age,” Dr. Krishna said.

“An updated systematic review by the USPSTF concluded that existing literature continues to affirm current recommendations of universal screening for GDM at 24 weeks gestation or later. There continues, however, to be no consensus on the optimal approach to screening,” she noted.

“Screening can be performed as a two-step or one-step approach,” said Dr. Krishna. “The two-step approach is commonly used in the United States, and all pregnant women are first screened with a 50-gram oral glucose solution followed by a diagnostic test if they have a positive initial screening.

“Women with risk factors for diabetes, such as prior GDM, obesity, strong family history of diabetes, or history of fetal macrosomia, should be screened early in pregnancy for GDM and have the GDM screen repeated at 24 weeks’ gestation or later if normal in early pregnancy,” Dr. Krishna said. “Pregnant women should be counseled on the importance of diet and exercise and appropriate weight gain in pregnancy to reduce the risk of GDM. Overall, timely diagnosis of gestational diabetes is crucial to improving maternal and fetal pregnancy outcomes.”

The full recommendation statement is also available on the USPSTF website. The research was supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose. Dr. Krishna had no disclosures, but serves on the editorial advisory board of Ob.Gyn News.

Asymptomatic pregnant women with no previous diagnosis of type 1 or 2 diabetes should be screened for gestational diabetes at 24 weeks’ gestation or later, according to an updated recommendation from the U.S. Preventive Services Task Force.

Pregnant individuals who develop gestational diabetes are at increased risk for complications including preeclampsia, fetal macrosomia, and neonatal hypoglycemia, as well as negative long-term outcomes for themselves and their children, wrote lead author Karina W. Davidson, PhD, of Feinstein Institute for Medical Research, Manhasset, N.Y., and colleagues. The statement was published online in JAMA.

The B recommendation and I statement reflect “moderate certainty” that current evidence supports the recommendation in terms of harms versus benefits, and is consistent with the 2014 USPSTF recommendation.

The statement calls for a one-time screening using a glucose tolerance test at or after 24 weeks’ gestation. Although most screening in the United States takes place prior to 28 weeks’ gestation, it can be performed later in patients who begin prenatal care after 28 weeks’ gestation, according to the statement. Data on the harms and benefits of gestational diabetes screening prior to 24 weeks’ gestation are limited, the authors noted. Gestational diabetes was defined as diabetes that develops during pregnancy that is not clearly overt diabetes.

To update the 2014 recommendation, the USPSTF commissioned a systematic review. In 45 prospective studies on the accuracy of gestational diabetes screening, several tests, included oral glucose challenge test, oral glucose tolerance test, and fasting plasma glucose using either a one- or two-step approach were accurate detectors of gestational diabetes; therefore, the USPSTF does not recommend a specific test.

In 13 trials on the impact of treating gestational diabetes on intermediate and health outcomes, treatment was associated with a reduced risk of outcomes, including primary cesarean delivery (but not total cesarean delivery) and preterm delivery, but not with a reduced risk of outcomes including preeclampsia, emergency cesarean delivery, induction of labor, or maternal birth trauma.

The task force also reviewed seven studies of harms associated with screening for gestational diabetes, including three on psychosocial harms, three on hospital experiences, and one of the odds of cesarean delivery after a diagnosis of gestational diabetes. No increase in anxiety or depression occurred following a positive diagnosis or false-positive test result, but data suggested that a gestational diabetes diagnosis may be associated with higher rates of cesarean delivery.

A total of 13 trials evaluated the harms associated with treatment of gestational diabetes, and found no association between treatment and increased risk of several outcomes including severe maternal hypoglycemia, low birth weight, and small for gestational age, and no effect was noted on the number of cesarean deliveries.

Evidence gaps that require additional research include randomized, controlled trials on the effects of gestational diabetes screening on health outcomes, as well as benefits versus harms of screening for pregnant individuals prior to 24 weeks, and studies on the effects of screening in subpopulations of race/ethnicity, age, and socioeconomic factors, according to the task force. Additional research also is needed in areas of maternal health outcomes, long-term outcomes, and the effect on outcomes of one-step versus two-step screening, the USPSTF said.

However, “screening for and detecting gestational diabetes provides a potential opportunity to control blood glucose levels (through lifestyle changes, pharmacological interventions, or both) and reduce the risk of macrosomia and LGA [large for gestational age] infants,” the task force wrote. “In turn, this can prevent associated complications such as primary cesarean delivery, shoulder dystocia, and [neonatal] ICU admissions.”
 

Support screening with counseling on risk reduction

The USPSTF recommendation is important at this time because “the prevalence of gestational diabetes is increasing secondary to rising rates of obesity,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“In 2014, based on a systematic review of literature, the USPSTF recommended screening all asymptomatic pregnant women for gestational diabetes mellitus [GDM] starting at 24 weeks’ gestation. The recommended gestational age for screening coincides with increasing insulin resistance during pregnancy with advancing gestational age,” Dr. Krishna said.

“An updated systematic review by the USPSTF concluded that existing literature continues to affirm current recommendations of universal screening for GDM at 24 weeks gestation or later. There continues, however, to be no consensus on the optimal approach to screening,” she noted.

“Screening can be performed as a two-step or one-step approach,” said Dr. Krishna. “The two-step approach is commonly used in the United States, and all pregnant women are first screened with a 50-gram oral glucose solution followed by a diagnostic test if they have a positive initial screening.

“Women with risk factors for diabetes, such as prior GDM, obesity, strong family history of diabetes, or history of fetal macrosomia, should be screened early in pregnancy for GDM and have the GDM screen repeated at 24 weeks’ gestation or later if normal in early pregnancy,” Dr. Krishna said. “Pregnant women should be counseled on the importance of diet and exercise and appropriate weight gain in pregnancy to reduce the risk of GDM. Overall, timely diagnosis of gestational diabetes is crucial to improving maternal and fetal pregnancy outcomes.”

The full recommendation statement is also available on the USPSTF website. The research was supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose. Dr. Krishna had no disclosures, but serves on the editorial advisory board of Ob.Gyn News.

Patients who had been hospitalized for heart attack or cardiovascular revascularization procedures commonly were overweight (46%) or had obesity (35%), but at a follow-up visit, few had lost weight or planned to do so, according to researchers who conduced a large European study.

Creatas Images/ThinkStockPhotos

The findings emphasize that obesity needs to be recognized as a disease that has to be optimally managed to lessen the risk for a secondary cardiovascular event, the authors stressed.

The study, by Dirk De Bacquer, PhD, professor, department of public health, Ghent (Belgium) University, and colleagues, was published recently in the European Heart Journal – Quality of Care and Clinical Outcomes.

The researchers analyzed data from more than 10,000 patients in the EUROASPIRE IV and V studies who were hospitalized for acute myocardial infarction (MI), coronary artery bypass graft (CABG), or percutaneous coronary intervention (PCI) and answered a survey 16 months later on average.

Although 20% of the patients with obesity had lost 5% or more of their initial weight, 16% had gained 5% or more of their initial weight.

Notably, “the discharge letter did not record the weight status in a quarter of [the patients with obesity] and a substantial proportion reported to have never been told by a healthcare professional [that they were] overweight,” the investigators wrote.

“It seems,” Dr. De Bacquer and colleagues noted, “that obesity is not considered by physicians as a serious medical problem, which requires attention, recommendations, and obvious advice on personal weight targets.”

However, “the benefits for patients who lost weight in our study, resulting in a healthier cardiovascular risk profile, are really worthwhile,” they pointed out.
 

Cardiovascular rehabilitation should include weight loss intervention

“The safest and most effective approach for managing body weight” in patients with coronary artery disease and obesity “is adopting a healthy eating pattern and increasing levels of physical activity,” they wrote.

Their findings that “patients who reported reducing their fat and sugar intake, consuming more fruit, vegetables, and fish and doing more regular physical activity, had significant weight loss,” support this.

Dr. De Bacquer and colleagues recommend that cardiovascular prevention and rehabilitation programs “should include weight loss intervention, including different forms of self-support, as a specific component of a comprehensive intervention to reduce total cardiovascular risk, extend life expectancy, and improve quality of life.”

Clinicians should “consider the incremental value of telehealth intervention as well as recently described pharmacological interventions,” they added, noting that the study did not look at these options or at metabolic surgery.

Invited to comment, one expert pointed out that two new observational studies of metabolic surgery in patients with obesity and coronary artery disease reported positive outcomes.

Another expert took issue with the “patient blaming” tone of the article and the lack of actionable ways to help patients lose weight. 
 

Medical therapy or bariatric surgery as other options?

“The study demonstrated how prevalent obesity is in patients with heart disease“ and “confirmed how difficult it is to achieve weight loss, in particular, in patients with heart disease, where weight loss would be beneficial,” Erik Näslund, MD, PhD, said in an interview.

Even though “current guidelines stress weight-loss counseling, some patients actually gained weight,” observed Dr. Näslund, of Danderyd Hospital and Karolinska Institutet, Stockholm.

On the other hand, patients who lost 5% or more of their initial weight had reduced comorbidities that are associated with cardiovascular disease.

“The best way to achieve long-term weight loss in patients with severe obesity is metabolic (bariatric) surgery,” noted Dr. Näslund, who was not involved in the study. “There are now two recent papers in the journal Circulation that demonstrate that metabolic surgery has a role in the secondary prevention of cardiovascular disease in patients with severe obesity” – one study from Dr. Näslund’s group (Circulation. 2021;143:1458-67), as previously reported, and one study from researchers in Ontario, Canada (Circulation. 2021;143:1468-80).

However, those were observational studies, and the findings would need to be confirmed in a randomized clinical trial before they could be used as recommended practice of care, he cautioned. In addition, most patients in the current study would not fulfill the minimum body weight criteria for metabolic surgery.

“Therefore, there is a need for intensified medical therapy for these patients,” as another treatment option, said Dr. Näslund.

“It would be interesting,” he speculated, “to study how the new glucagon-like peptide-1 (GLP-1) receptor agonist therapies could work in this setting as a weight loss agent and perhaps have a positive independent cardiovascular benefit.”
 

Obesity is a disease; clinicians need to be respectful

Meanwhile, Obesity Society fellow and spokesperson Fatima Cody Stanford, MD, said in an interview that she didn’t think the language and tone of the article was respectful for patients with obesity, and the researchers “talked about the old narrative of how we support patients with obesity.”

Lifestyle modification can be at the core of treatment, but medication or bariatric surgery may be other options to “help patients get to their best selves.

“Patients with obesity deserve to be cared for and treated with respect,” said Dr. Stanford, an obesity medicine physician scientist at Massachusetts General Hospital and Harvard Medical School, Boston.

Treatment needs to be individualized and clinicians need to listen to patient concerns. For example, a patient with obesity may not be able to follow advice to walk more. “I can barely stand up,” one patient with obesity and osteoarthritis told Dr. Stanford.

And patients’ insurance may not cover cardiac rehabilitation – especially patients from racial minorities or those with lower socioeconomic status, she noted.

“My feeling has always been that it is important to be respectful to all patients,” Dr. Näslund agreed. “I do agree that we need to recognize obesity as a chronic disease, and the paper in EHJ demonstrates this, as obesity was not registered in many of the discharge notes.

“If we as healthcare workers measured a weight of our patients the same way that we take a blood pressure,” he said, “perhaps the [stigma] of obesity would be reduced.”
 

Study findings

The researchers examined pooled data from EUROASPIRE IV (2012-13) and EUROASPIRE V (2016-17) surveys of patients who were overweight or had obesity who had been discharged from hospital after MI, CABG, or PCI to determine if they had received lifestyle advice for weight loss, if they had acted on this advice, and if losing weight altered their cardiovascular disease risk factors.

They identified 10,507 adult patients in 29 mainly European countries who had complete survey data.

The mean age of the patients was 63 at the time of their hospitalization; 25% were women. Many had hypertension (66%-88%), dyslipidemia (69%-80%), or diabetes (16%-37%).

The prevalence of obesity varied from 8% to 46% in men and from 18% to 57% in women, in different countries. Patients with obesity had a mean body weight of 97 kg (213 pounds).

One of the most “striking” findings was the “apparent lack of motivation” to lose weight, Dr. De Bacquer and colleagues wrote. Half of the patients with obesity had not attempted to lose weight in the month before the follow-up visit and most did not plan to do so in the following month.

Goal setting is an important aspect of behavior modification techniques, they wrote, yet 7% of the patients did not know their body weight and 21% did not have an optimal weight target.

Half of the patients had been advised to follow a cardiac rehabilitation program and two-thirds had been advised to follow dietary recommendations and move more.

Those who made positive dietary changes and were more physically active were more likely to lose at least 5% of their weight.

And patients who lost at least 5% of their initial weight were less likely to have hypertension, dyslipidemia, or diabetes compared with patients who had gained this much weight, which “is likely to translate into improved prognosis on the long term,” the authors wrote.

EUROASPIRE IV and V were supported through research grants to the European Society of Cardiology from Amgen, AstraZeneca, Bristol-Myers Squibb/Emea Sarl, GlaxoSmithKline, Hoffmann-La Roche, and Merck, Sharp & Dohme (EUROASPIRE IV) and Amarin, Amgen, Daiichi Sankyo, Eli Lilly, Pfizer, Sanofi, Ferrer, and Novo Nordisk (EUROASPIRE V). Dr. De Bacquer, Dr. Näslund, and Dr. Stanford have no disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients who had been hospitalized for heart attack or cardiovascular revascularization procedures commonly were overweight (46%) or had obesity (35%), but at a follow-up visit, few had lost weight or planned to do so, according to researchers who conduced a large European study.

Creatas Images/ThinkStockPhotos

The findings emphasize that obesity needs to be recognized as a disease that has to be optimally managed to lessen the risk for a secondary cardiovascular event, the authors stressed.

The study, by Dirk De Bacquer, PhD, professor, department of public health, Ghent (Belgium) University, and colleagues, was published recently in the European Heart Journal – Quality of Care and Clinical Outcomes.

The researchers analyzed data from more than 10,000 patients in the EUROASPIRE IV and V studies who were hospitalized for acute myocardial infarction (MI), coronary artery bypass graft (CABG), or percutaneous coronary intervention (PCI) and answered a survey 16 months later on average.

Although 20% of the patients with obesity had lost 5% or more of their initial weight, 16% had gained 5% or more of their initial weight.

Notably, “the discharge letter did not record the weight status in a quarter of [the patients with obesity] and a substantial proportion reported to have never been told by a healthcare professional [that they were] overweight,” the investigators wrote.

“It seems,” Dr. De Bacquer and colleagues noted, “that obesity is not considered by physicians as a serious medical problem, which requires attention, recommendations, and obvious advice on personal weight targets.”

However, “the benefits for patients who lost weight in our study, resulting in a healthier cardiovascular risk profile, are really worthwhile,” they pointed out.
 

Cardiovascular rehabilitation should include weight loss intervention

“The safest and most effective approach for managing body weight” in patients with coronary artery disease and obesity “is adopting a healthy eating pattern and increasing levels of physical activity,” they wrote.

Their findings that “patients who reported reducing their fat and sugar intake, consuming more fruit, vegetables, and fish and doing more regular physical activity, had significant weight loss,” support this.

Dr. De Bacquer and colleagues recommend that cardiovascular prevention and rehabilitation programs “should include weight loss intervention, including different forms of self-support, as a specific component of a comprehensive intervention to reduce total cardiovascular risk, extend life expectancy, and improve quality of life.”

Clinicians should “consider the incremental value of telehealth intervention as well as recently described pharmacological interventions,” they added, noting that the study did not look at these options or at metabolic surgery.

Invited to comment, one expert pointed out that two new observational studies of metabolic surgery in patients with obesity and coronary artery disease reported positive outcomes.

Another expert took issue with the “patient blaming” tone of the article and the lack of actionable ways to help patients lose weight. 
 

Medical therapy or bariatric surgery as other options?

“The study demonstrated how prevalent obesity is in patients with heart disease“ and “confirmed how difficult it is to achieve weight loss, in particular, in patients with heart disease, where weight loss would be beneficial,” Erik Näslund, MD, PhD, said in an interview.

Even though “current guidelines stress weight-loss counseling, some patients actually gained weight,” observed Dr. Näslund, of Danderyd Hospital and Karolinska Institutet, Stockholm.

On the other hand, patients who lost 5% or more of their initial weight had reduced comorbidities that are associated with cardiovascular disease.

“The best way to achieve long-term weight loss in patients with severe obesity is metabolic (bariatric) surgery,” noted Dr. Näslund, who was not involved in the study. “There are now two recent papers in the journal Circulation that demonstrate that metabolic surgery has a role in the secondary prevention of cardiovascular disease in patients with severe obesity” – one study from Dr. Näslund’s group (Circulation. 2021;143:1458-67), as previously reported, and one study from researchers in Ontario, Canada (Circulation. 2021;143:1468-80).

However, those were observational studies, and the findings would need to be confirmed in a randomized clinical trial before they could be used as recommended practice of care, he cautioned. In addition, most patients in the current study would not fulfill the minimum body weight criteria for metabolic surgery.

“Therefore, there is a need for intensified medical therapy for these patients,” as another treatment option, said Dr. Näslund.

“It would be interesting,” he speculated, “to study how the new glucagon-like peptide-1 (GLP-1) receptor agonist therapies could work in this setting as a weight loss agent and perhaps have a positive independent cardiovascular benefit.”
 

Obesity is a disease; clinicians need to be respectful

Meanwhile, Obesity Society fellow and spokesperson Fatima Cody Stanford, MD, said in an interview that she didn’t think the language and tone of the article was respectful for patients with obesity, and the researchers “talked about the old narrative of how we support patients with obesity.”

Lifestyle modification can be at the core of treatment, but medication or bariatric surgery may be other options to “help patients get to their best selves.

“Patients with obesity deserve to be cared for and treated with respect,” said Dr. Stanford, an obesity medicine physician scientist at Massachusetts General Hospital and Harvard Medical School, Boston.

Treatment needs to be individualized and clinicians need to listen to patient concerns. For example, a patient with obesity may not be able to follow advice to walk more. “I can barely stand up,” one patient with obesity and osteoarthritis told Dr. Stanford.

And patients’ insurance may not cover cardiac rehabilitation – especially patients from racial minorities or those with lower socioeconomic status, she noted.

“My feeling has always been that it is important to be respectful to all patients,” Dr. Näslund agreed. “I do agree that we need to recognize obesity as a chronic disease, and the paper in EHJ demonstrates this, as obesity was not registered in many of the discharge notes.

“If we as healthcare workers measured a weight of our patients the same way that we take a blood pressure,” he said, “perhaps the [stigma] of obesity would be reduced.”
 

Study findings

The researchers examined pooled data from EUROASPIRE IV (2012-13) and EUROASPIRE V (2016-17) surveys of patients who were overweight or had obesity who had been discharged from hospital after MI, CABG, or PCI to determine if they had received lifestyle advice for weight loss, if they had acted on this advice, and if losing weight altered their cardiovascular disease risk factors.

They identified 10,507 adult patients in 29 mainly European countries who had complete survey data.

The mean age of the patients was 63 at the time of their hospitalization; 25% were women. Many had hypertension (66%-88%), dyslipidemia (69%-80%), or diabetes (16%-37%).

The prevalence of obesity varied from 8% to 46% in men and from 18% to 57% in women, in different countries. Patients with obesity had a mean body weight of 97 kg (213 pounds).

One of the most “striking” findings was the “apparent lack of motivation” to lose weight, Dr. De Bacquer and colleagues wrote. Half of the patients with obesity had not attempted to lose weight in the month before the follow-up visit and most did not plan to do so in the following month.

Goal setting is an important aspect of behavior modification techniques, they wrote, yet 7% of the patients did not know their body weight and 21% did not have an optimal weight target.

Half of the patients had been advised to follow a cardiac rehabilitation program and two-thirds had been advised to follow dietary recommendations and move more.

Those who made positive dietary changes and were more physically active were more likely to lose at least 5% of their weight.

And patients who lost at least 5% of their initial weight were less likely to have hypertension, dyslipidemia, or diabetes compared with patients who had gained this much weight, which “is likely to translate into improved prognosis on the long term,” the authors wrote.

EUROASPIRE IV and V were supported through research grants to the European Society of Cardiology from Amgen, AstraZeneca, Bristol-Myers Squibb/Emea Sarl, GlaxoSmithKline, Hoffmann-La Roche, and Merck, Sharp & Dohme (EUROASPIRE IV) and Amarin, Amgen, Daiichi Sankyo, Eli Lilly, Pfizer, Sanofi, Ferrer, and Novo Nordisk (EUROASPIRE V). Dr. De Bacquer, Dr. Näslund, and Dr. Stanford have no disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients who had been hospitalized for heart attack or cardiovascular revascularization procedures commonly were overweight (46%) or had obesity (35%), but at a follow-up visit, few had lost weight or planned to do so, according to researchers who conduced a large European study.

Creatas Images/ThinkStockPhotos

The findings emphasize that obesity needs to be recognized as a disease that has to be optimally managed to lessen the risk for a secondary cardiovascular event, the authors stressed.

The study, by Dirk De Bacquer, PhD, professor, department of public health, Ghent (Belgium) University, and colleagues, was published recently in the European Heart Journal – Quality of Care and Clinical Outcomes.

The researchers analyzed data from more than 10,000 patients in the EUROASPIRE IV and V studies who were hospitalized for acute myocardial infarction (MI), coronary artery bypass graft (CABG), or percutaneous coronary intervention (PCI) and answered a survey 16 months later on average.

Although 20% of the patients with obesity had lost 5% or more of their initial weight, 16% had gained 5% or more of their initial weight.

Notably, “the discharge letter did not record the weight status in a quarter of [the patients with obesity] and a substantial proportion reported to have never been told by a healthcare professional [that they were] overweight,” the investigators wrote.

“It seems,” Dr. De Bacquer and colleagues noted, “that obesity is not considered by physicians as a serious medical problem, which requires attention, recommendations, and obvious advice on personal weight targets.”

However, “the benefits for patients who lost weight in our study, resulting in a healthier cardiovascular risk profile, are really worthwhile,” they pointed out.
 

Cardiovascular rehabilitation should include weight loss intervention

“The safest and most effective approach for managing body weight” in patients with coronary artery disease and obesity “is adopting a healthy eating pattern and increasing levels of physical activity,” they wrote.

Their findings that “patients who reported reducing their fat and sugar intake, consuming more fruit, vegetables, and fish and doing more regular physical activity, had significant weight loss,” support this.

Dr. De Bacquer and colleagues recommend that cardiovascular prevention and rehabilitation programs “should include weight loss intervention, including different forms of self-support, as a specific component of a comprehensive intervention to reduce total cardiovascular risk, extend life expectancy, and improve quality of life.”

Clinicians should “consider the incremental value of telehealth intervention as well as recently described pharmacological interventions,” they added, noting that the study did not look at these options or at metabolic surgery.

Invited to comment, one expert pointed out that two new observational studies of metabolic surgery in patients with obesity and coronary artery disease reported positive outcomes.

Another expert took issue with the “patient blaming” tone of the article and the lack of actionable ways to help patients lose weight. 
 

Medical therapy or bariatric surgery as other options?

“The study demonstrated how prevalent obesity is in patients with heart disease“ and “confirmed how difficult it is to achieve weight loss, in particular, in patients with heart disease, where weight loss would be beneficial,” Erik Näslund, MD, PhD, said in an interview.

Even though “current guidelines stress weight-loss counseling, some patients actually gained weight,” observed Dr. Näslund, of Danderyd Hospital and Karolinska Institutet, Stockholm.

On the other hand, patients who lost 5% or more of their initial weight had reduced comorbidities that are associated with cardiovascular disease.

“The best way to achieve long-term weight loss in patients with severe obesity is metabolic (bariatric) surgery,” noted Dr. Näslund, who was not involved in the study. “There are now two recent papers in the journal Circulation that demonstrate that metabolic surgery has a role in the secondary prevention of cardiovascular disease in patients with severe obesity” – one study from Dr. Näslund’s group (Circulation. 2021;143:1458-67), as previously reported, and one study from researchers in Ontario, Canada (Circulation. 2021;143:1468-80).

However, those were observational studies, and the findings would need to be confirmed in a randomized clinical trial before they could be used as recommended practice of care, he cautioned. In addition, most patients in the current study would not fulfill the minimum body weight criteria for metabolic surgery.

“Therefore, there is a need for intensified medical therapy for these patients,” as another treatment option, said Dr. Näslund.

“It would be interesting,” he speculated, “to study how the new glucagon-like peptide-1 (GLP-1) receptor agonist therapies could work in this setting as a weight loss agent and perhaps have a positive independent cardiovascular benefit.”
 

Obesity is a disease; clinicians need to be respectful

Meanwhile, Obesity Society fellow and spokesperson Fatima Cody Stanford, MD, said in an interview that she didn’t think the language and tone of the article was respectful for patients with obesity, and the researchers “talked about the old narrative of how we support patients with obesity.”

Lifestyle modification can be at the core of treatment, but medication or bariatric surgery may be other options to “help patients get to their best selves.

“Patients with obesity deserve to be cared for and treated with respect,” said Dr. Stanford, an obesity medicine physician scientist at Massachusetts General Hospital and Harvard Medical School, Boston.

Treatment needs to be individualized and clinicians need to listen to patient concerns. For example, a patient with obesity may not be able to follow advice to walk more. “I can barely stand up,” one patient with obesity and osteoarthritis told Dr. Stanford.

And patients’ insurance may not cover cardiac rehabilitation – especially patients from racial minorities or those with lower socioeconomic status, she noted.

“My feeling has always been that it is important to be respectful to all patients,” Dr. Näslund agreed. “I do agree that we need to recognize obesity as a chronic disease, and the paper in EHJ demonstrates this, as obesity was not registered in many of the discharge notes.

“If we as healthcare workers measured a weight of our patients the same way that we take a blood pressure,” he said, “perhaps the [stigma] of obesity would be reduced.”
 

Study findings

The researchers examined pooled data from EUROASPIRE IV (2012-13) and EUROASPIRE V (2016-17) surveys of patients who were overweight or had obesity who had been discharged from hospital after MI, CABG, or PCI to determine if they had received lifestyle advice for weight loss, if they had acted on this advice, and if losing weight altered their cardiovascular disease risk factors.

They identified 10,507 adult patients in 29 mainly European countries who had complete survey data.

The mean age of the patients was 63 at the time of their hospitalization; 25% were women. Many had hypertension (66%-88%), dyslipidemia (69%-80%), or diabetes (16%-37%).

The prevalence of obesity varied from 8% to 46% in men and from 18% to 57% in women, in different countries. Patients with obesity had a mean body weight of 97 kg (213 pounds).

One of the most “striking” findings was the “apparent lack of motivation” to lose weight, Dr. De Bacquer and colleagues wrote. Half of the patients with obesity had not attempted to lose weight in the month before the follow-up visit and most did not plan to do so in the following month.

Goal setting is an important aspect of behavior modification techniques, they wrote, yet 7% of the patients did not know their body weight and 21% did not have an optimal weight target.

Half of the patients had been advised to follow a cardiac rehabilitation program and two-thirds had been advised to follow dietary recommendations and move more.

Those who made positive dietary changes and were more physically active were more likely to lose at least 5% of their weight.

And patients who lost at least 5% of their initial weight were less likely to have hypertension, dyslipidemia, or diabetes compared with patients who had gained this much weight, which “is likely to translate into improved prognosis on the long term,” the authors wrote.

EUROASPIRE IV and V were supported through research grants to the European Society of Cardiology from Amgen, AstraZeneca, Bristol-Myers Squibb/Emea Sarl, GlaxoSmithKline, Hoffmann-La Roche, and Merck, Sharp & Dohme (EUROASPIRE IV) and Amarin, Amgen, Daiichi Sankyo, Eli Lilly, Pfizer, Sanofi, Ferrer, and Novo Nordisk (EUROASPIRE V). Dr. De Bacquer, Dr. Näslund, and Dr. Stanford have no disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Consumption of a plant-based diet rich in lignans is associated with a lower risk of coronary heart disease (CHD), new research suggests.

Kirby Hamilton/iStockphoto

In a prospective cohort study that followed almost 214,108 men and women who were free of CHD and cancer at baseline, increased long-term intake of lignans, polyphenolic substances produced by plants, was associated with significantly lower risk of total CHD in both men and women.

The benefit was increased in participants with a greater intake of fiber, suggesting that synergistic effects between the two might exist in relation to CHD reduction.

The results were published online in the Journal of the American College of Cardiology.

“Lignan is an estrogen-like molecule, so it exerts some estrogenic effects which are cardioprotective. It also has anti-inflammatory properties,” first author Yang Hu, ScD, a research fellow at the Harvard School of Public Health, Boston, said in an interview.

“Our results that showed an inverse association between lignan consumption and heart disease risk were expected, because it is known that lignans, which are predominantly from plant-based foods, like whole grains, fruit, vegetables, red wine, and coffee, are all associated with lower CHD risk,” Dr. Hu said.

What is novel about the current study is that it established a threshold for lignan consumption, above which there is no CHD benefit, he said.

“It is not a matter of the more you consume, the lower your risk. There is a certain amount of lignan you have to reach, after which there is no more benefit,” Dr. Hu said.

Dr. Hu and associates prospectively followed 214,108 men and women in three cohorts who did not have cardiovascular disease or cancer at baseline. The cohorts were the Health Professionals Follow-Up Study, Nurses’ Health Study, and Nurses’ Health Study II.

Diets were assessed using the Food Frequency Questionnaire every 2-4 years at follow-up visits.

During 5.5 million person-years of follow-up, Dr. Hu and associates documented 10,244 CHD cases, including 6,283 nonfatal myocardial infarctions and 3,961 fatal CHD cases.

The results showed that higher total lignan intake, and all individual lignan intake as well, were associated with significantly lower risk of total CHD.

Participants with higher total lignan intake were older and had more favorable health and lifestyle profiles including lower body mass index, lower prevalence of hypertension and hypercholesterolemia, high levels of physical activity, and better diet quality.

Overall, the pooled hazard ratios of CHD were 0.85 (95% confidence interval, 0.79-0.92) for total lignans, 0.76 (95% CI, 0.71-0.82) for matairesinol, 0.87 (95% CI, 0.81-0.93) for secoisolariciresinol, 0.89 (95% CI, 0.83-0.95) for pinoresinol, and 0.89 (95% CI: 0.83- 0.95) for lariciresinol (all P values for trend ≤ .003).

In addition, nonlinear relationships were found for total lignan, matairesinol, and secoisolariciresinol: The risk reduction plateaued at intakes above approximately 300 mcg/d for total lignan; 10 mcg/d for matairesinol, and 100 mcg/d for secoisolariciresinol.

The inverse associations for total lignan intake were more apparent among participants with higher total fiber intake.

In addition, lignan intake was more strongly associated with plasma concentrations of enterolactone when fiber intake was higher.

Dr. Hu said a next avenue of research will explore the synergistic association between lignans and fiber in further lowering CHD risk.

Lignans are exclusively metabolized by gut microbiota, Dr. Hu noted. “This opens another avenue of research because we can take further steps to see how the gut microbiota compositions and fiber interact with the production of lignans and how these might affect disease risk for other conditions, such as diabetes.”
 

An important study

“The evidence is building that there is an association between polyphenol intake and chronic disease, especially for CVD [cardiovascular disease],” David J.A. Jenkins, MD, PhD, and colleagues wrote in an accompanying editorial.

“Plant polyphenols may be important components of healthy plant-based diets that contribute to freedom from chronic diseases such as CVD, diabetes, and possibly cancer and so are associated with a reduction in all-cause mortality,” they wrote.

“I think this is an important study even though the results are not unexpected,” Dr. Jenkins, professor in the departments of medicine and nutritional sciences at the University of Toronto, said in an interview.

“We do know that plant polyphenols are important sources of antioxidants and may have many protective roles in preventing destruction of proteins and DNA destruction, so the results here reinforce very strongly the concept of plant foods and their importance in the diet,” he said.

The data reaffirmed the value of eating a variety of plant foods and eating them in a less processed form, because they have higher amounts of their phenolic compounds, Dr. Jenkins said.

“Things like wheat, oats, barley, [and] whole grain foods will have more phenolic components with them, as do fruits and vegetables,” he said.

Dr. Hu and Dr. Jenkins disclosed no relevant financial relationships.  

Aversion of this article first appeared on Medscape.com.

Consumption of a plant-based diet rich in lignans is associated with a lower risk of coronary heart disease (CHD), new research suggests.

Kirby Hamilton/iStockphoto

In a prospective cohort study that followed almost 214,108 men and women who were free of CHD and cancer at baseline, increased long-term intake of lignans, polyphenolic substances produced by plants, was associated with significantly lower risk of total CHD in both men and women.

The benefit was increased in participants with a greater intake of fiber, suggesting that synergistic effects between the two might exist in relation to CHD reduction.

The results were published online in the Journal of the American College of Cardiology.

“Lignan is an estrogen-like molecule, so it exerts some estrogenic effects which are cardioprotective. It also has anti-inflammatory properties,” first author Yang Hu, ScD, a research fellow at the Harvard School of Public Health, Boston, said in an interview.

“Our results that showed an inverse association between lignan consumption and heart disease risk were expected, because it is known that lignans, which are predominantly from plant-based foods, like whole grains, fruit, vegetables, red wine, and coffee, are all associated with lower CHD risk,” Dr. Hu said.

What is novel about the current study is that it established a threshold for lignan consumption, above which there is no CHD benefit, he said.

“It is not a matter of the more you consume, the lower your risk. There is a certain amount of lignan you have to reach, after which there is no more benefit,” Dr. Hu said.

Dr. Hu and associates prospectively followed 214,108 men and women in three cohorts who did not have cardiovascular disease or cancer at baseline. The cohorts were the Health Professionals Follow-Up Study, Nurses’ Health Study, and Nurses’ Health Study II.

Diets were assessed using the Food Frequency Questionnaire every 2-4 years at follow-up visits.

During 5.5 million person-years of follow-up, Dr. Hu and associates documented 10,244 CHD cases, including 6,283 nonfatal myocardial infarctions and 3,961 fatal CHD cases.

The results showed that higher total lignan intake, and all individual lignan intake as well, were associated with significantly lower risk of total CHD.

Participants with higher total lignan intake were older and had more favorable health and lifestyle profiles including lower body mass index, lower prevalence of hypertension and hypercholesterolemia, high levels of physical activity, and better diet quality.

Overall, the pooled hazard ratios of CHD were 0.85 (95% confidence interval, 0.79-0.92) for total lignans, 0.76 (95% CI, 0.71-0.82) for matairesinol, 0.87 (95% CI, 0.81-0.93) for secoisolariciresinol, 0.89 (95% CI, 0.83-0.95) for pinoresinol, and 0.89 (95% CI: 0.83- 0.95) for lariciresinol (all P values for trend ≤ .003).

In addition, nonlinear relationships were found for total lignan, matairesinol, and secoisolariciresinol: The risk reduction plateaued at intakes above approximately 300 mcg/d for total lignan; 10 mcg/d for matairesinol, and 100 mcg/d for secoisolariciresinol.

The inverse associations for total lignan intake were more apparent among participants with higher total fiber intake.

In addition, lignan intake was more strongly associated with plasma concentrations of enterolactone when fiber intake was higher.

Dr. Hu said a next avenue of research will explore the synergistic association between lignans and fiber in further lowering CHD risk.

Lignans are exclusively metabolized by gut microbiota, Dr. Hu noted. “This opens another avenue of research because we can take further steps to see how the gut microbiota compositions and fiber interact with the production of lignans and how these might affect disease risk for other conditions, such as diabetes.”
 

An important study

“The evidence is building that there is an association between polyphenol intake and chronic disease, especially for CVD [cardiovascular disease],” David J.A. Jenkins, MD, PhD, and colleagues wrote in an accompanying editorial.

“Plant polyphenols may be important components of healthy plant-based diets that contribute to freedom from chronic diseases such as CVD, diabetes, and possibly cancer and so are associated with a reduction in all-cause mortality,” they wrote.

“I think this is an important study even though the results are not unexpected,” Dr. Jenkins, professor in the departments of medicine and nutritional sciences at the University of Toronto, said in an interview.

“We do know that plant polyphenols are important sources of antioxidants and may have many protective roles in preventing destruction of proteins and DNA destruction, so the results here reinforce very strongly the concept of plant foods and their importance in the diet,” he said.

The data reaffirmed the value of eating a variety of plant foods and eating them in a less processed form, because they have higher amounts of their phenolic compounds, Dr. Jenkins said.

“Things like wheat, oats, barley, [and] whole grain foods will have more phenolic components with them, as do fruits and vegetables,” he said.

Dr. Hu and Dr. Jenkins disclosed no relevant financial relationships.  

Aversion of this article first appeared on Medscape.com.

Consumption of a plant-based diet rich in lignans is associated with a lower risk of coronary heart disease (CHD), new research suggests.

Kirby Hamilton/iStockphoto

In a prospective cohort study that followed almost 214,108 men and women who were free of CHD and cancer at baseline, increased long-term intake of lignans, polyphenolic substances produced by plants, was associated with significantly lower risk of total CHD in both men and women.

The benefit was increased in participants with a greater intake of fiber, suggesting that synergistic effects between the two might exist in relation to CHD reduction.

The results were published online in the Journal of the American College of Cardiology.

“Lignan is an estrogen-like molecule, so it exerts some estrogenic effects which are cardioprotective. It also has anti-inflammatory properties,” first author Yang Hu, ScD, a research fellow at the Harvard School of Public Health, Boston, said in an interview.

“Our results that showed an inverse association between lignan consumption and heart disease risk were expected, because it is known that lignans, which are predominantly from plant-based foods, like whole grains, fruit, vegetables, red wine, and coffee, are all associated with lower CHD risk,” Dr. Hu said.

What is novel about the current study is that it established a threshold for lignan consumption, above which there is no CHD benefit, he said.

“It is not a matter of the more you consume, the lower your risk. There is a certain amount of lignan you have to reach, after which there is no more benefit,” Dr. Hu said.

Dr. Hu and associates prospectively followed 214,108 men and women in three cohorts who did not have cardiovascular disease or cancer at baseline. The cohorts were the Health Professionals Follow-Up Study, Nurses’ Health Study, and Nurses’ Health Study II.

Diets were assessed using the Food Frequency Questionnaire every 2-4 years at follow-up visits.

During 5.5 million person-years of follow-up, Dr. Hu and associates documented 10,244 CHD cases, including 6,283 nonfatal myocardial infarctions and 3,961 fatal CHD cases.

The results showed that higher total lignan intake, and all individual lignan intake as well, were associated with significantly lower risk of total CHD.

Participants with higher total lignan intake were older and had more favorable health and lifestyle profiles including lower body mass index, lower prevalence of hypertension and hypercholesterolemia, high levels of physical activity, and better diet quality.

Overall, the pooled hazard ratios of CHD were 0.85 (95% confidence interval, 0.79-0.92) for total lignans, 0.76 (95% CI, 0.71-0.82) for matairesinol, 0.87 (95% CI, 0.81-0.93) for secoisolariciresinol, 0.89 (95% CI, 0.83-0.95) for pinoresinol, and 0.89 (95% CI: 0.83- 0.95) for lariciresinol (all P values for trend ≤ .003).

In addition, nonlinear relationships were found for total lignan, matairesinol, and secoisolariciresinol: The risk reduction plateaued at intakes above approximately 300 mcg/d for total lignan; 10 mcg/d for matairesinol, and 100 mcg/d for secoisolariciresinol.

The inverse associations for total lignan intake were more apparent among participants with higher total fiber intake.

In addition, lignan intake was more strongly associated with plasma concentrations of enterolactone when fiber intake was higher.

Dr. Hu said a next avenue of research will explore the synergistic association between lignans and fiber in further lowering CHD risk.

Lignans are exclusively metabolized by gut microbiota, Dr. Hu noted. “This opens another avenue of research because we can take further steps to see how the gut microbiota compositions and fiber interact with the production of lignans and how these might affect disease risk for other conditions, such as diabetes.”
 

An important study

“The evidence is building that there is an association between polyphenol intake and chronic disease, especially for CVD [cardiovascular disease],” David J.A. Jenkins, MD, PhD, and colleagues wrote in an accompanying editorial.

“Plant polyphenols may be important components of healthy plant-based diets that contribute to freedom from chronic diseases such as CVD, diabetes, and possibly cancer and so are associated with a reduction in all-cause mortality,” they wrote.

“I think this is an important study even though the results are not unexpected,” Dr. Jenkins, professor in the departments of medicine and nutritional sciences at the University of Toronto, said in an interview.

“We do know that plant polyphenols are important sources of antioxidants and may have many protective roles in preventing destruction of proteins and DNA destruction, so the results here reinforce very strongly the concept of plant foods and their importance in the diet,” he said.

The data reaffirmed the value of eating a variety of plant foods and eating them in a less processed form, because they have higher amounts of their phenolic compounds, Dr. Jenkins said.

“Things like wheat, oats, barley, [and] whole grain foods will have more phenolic components with them, as do fruits and vegetables,” he said.

Dr. Hu and Dr. Jenkins disclosed no relevant financial relationships.  

Aversion of this article first appeared on Medscape.com.

People with diabetes are at increased risk of hospitalization for infection, as well as infection-related mortality, shows a large U.S. study that suggests the risk is even higher in younger and Black individuals.

Michael Fang, PhD, Johns Hopkins University, Baltimore, and colleagues studied more than 12,000 participants in a community cohort study who were followed for an average of 24 years, between 1987-1989 and 2019.

Participants with diabetes faced a 67% increase risk of infection-related hospitalization, compared with those without diabetes.

Of particular note, the risk of hospitalization with foot infection was almost sixfold higher for people with diabetes than those without.

The research, published in Diabetologia on August 4, also suggests that diabetes may be associated with a 72% increased risk of infection-related mortality, although the absolute numbers were small.

Dr. Fang explained to this news organization that they focused on infection-related hospitalization and mortality “because these are comprehensively tracked in administrative data and ... are the most severe types of outcomes.”

However, this is probably just the tip of the iceberg, as people with diabetes are “likely at increased risk for milder infection too,” which can have a “significant adverse impact on people’s well-being and quality of life.”

As a result of their findings, the authors call for “broader guidance on infection prevention and management” in people with diabetes. To achieve this, Dr. Fang said, “we need to better understand why diabetes is associated with an increased risk of infection-related complications.”

“One likely factor is glycemic control: Emerging research suggests patients with diabetes with better glycemic control may be at significantly lower risk of infection-related complications.”

He continued that, in younger patients, a factor for worse outcomes could be that “diabetes tends to be more aggressive when it emerges early in life,” while in Black patients “there is research highlighting Black-White differences in glycemic control, access to care, and beliefs around vaccines.”

Overall, their findings – coupled with recent data showing that diabetes is an important risk factor for adverse outcomes with COVID-19 infection – paint “a common picture,” Dr. Fang said.

“People with diabetes are much more susceptible to infection-related complications, including COVID-related hospitalization and mortality,” which suggests people with diabetes “may need to be especially cautious.”
 

Adds to existing literature; amputations begin with infections

Robert A. Gabbay, MD, PhD, chief scientific and medical officer for the American Diabetes Association (ADA), said the study “does add to the existing literature by having followed a larger number of people over time and linking them to serious complications from infections.”

“Sadly, we have seen this play out in real-time during the COVID-19 pandemic.”

“One of the sobering bits of data is the significant health disparities that exist in Black Americans and the fact that foot infections remain a significant problem,” he said in an interview.

“Given that amputation rates for [Black Americans] are three times higher than White Americans, amputations begin with infections,” Dr. Gabbay added, noting the ADA “has been taking a strong stand to prevent amputations and address the inequities in health that exist.”

Jamie Hartmann-Boyce, PhD, from the University of Oxford, U.K., who was not involved in the study, commented that diabetes is a “well-known risk factor for worse outcomes from all kinds of infection,” which is why they “are prioritized for flu vaccination every year.”

She told this news organization that the current study “further confirms that people with diabetes are more likely to be hospitalized for infection of any type and most markedly for foot infection.”

“These new data further highlight the need for public health interventions to prevent type 2 diabetes, and for preventive health care in people with diabetes, including access to diabetes medications and support and to vaccinations to prevent infection,” added Dr. Hartmann-Boyce, who is a senior research fellow in health behaviors.

Diabetes is thought to be associated with susceptibility to infection via mechanisms such as impaired neutrophil functioning and humoral immune responses, and studies have shown a link with both common and rare infections.

However, the authors point out that “most” of those included “small clinical populations and were cross-sectional or had short follow-up.”

Guidelines for diabetes management, they note, also “pay less attention” to infectious diseases than they do to the prevention of micro- and macrovascular complications.
 

ARIC data mined for infections in those with diabetes

The team analyzed data from the ongoing U.S. community-based Atherosclerosis Risk in Communities (ARIC) study.

The National Heart, Lung, and Blood Institute–sponsored cohort was comprised of adults aged 45-64 years from four U.S. communities, recruited between 1987 and 1989 for clinical examinations, medical interviews, and laboratory tests, repeated over five more visits up to 2018-2019.

For the current analysis, the team included 12,739 individuals with a mean age of 54.5 years, of whom 54.3% were female and 24.7% were Black.

Patients were defined as having diabetes if their baseline fasting blood glucose was greater than or equal to 7 mmol/L, or nonfasting glucose was greater than or equal to 11.1 mmol/l, they self-reported a diagnosis of diabetes by a physician, or they were taking glucose-lowering medication at the first study visit. The researchers weren’t able to distinguish between type 1 and type 2 diabetes.

In total, 1,485 individuals had diabetes at baseline. They were more likely to be older, Black, have a low socioeconomic status, and have worse cardiometabolic health than participants without diabetes.

Over an average follow-up of 23.8 years, there were 4,229 incident hospitalizations for infection, at an overall rate of 15.9 per 1,000 person-years.

Individuals with diabetes at baseline had a higher rate of hospitalizations than those without, at 25.4 per 1,000 person-years versus 15.2 per 1,000 person-years.

After taking into account sociodemographic characteristics, socioeconomic status, and cardiometabolic risk factors, this equated to a hazard ratio for hospitalization with any infection of 1.67 (P < .001).

The risk of hospitalization for any infection was significantly higher for younger patients with diabetes, defined as aged less than 55 years (P = .005), and for Black patients (P < .001).

While the increased risk was generally consistent across infection types, it was markedly increased for foot infection, at a hazard ratio of 5.99 (P < .001).

Overall, there were few deaths due to infection in the study, at just 362. The risk of infection mortality was nevertheless significantly increased in people with diabetes, at an adjusted hazard ratio of 1.72 (P < .001).

Dr. Fang has reported being supported by a grant from the National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Selvin has reported being supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Selvin is an associate editor for Diabetologia and had no role in the peer review of the manuscript.

A version of this article first appeared on Medscape.com.

People with diabetes are at increased risk of hospitalization for infection, as well as infection-related mortality, shows a large U.S. study that suggests the risk is even higher in younger and Black individuals.

Michael Fang, PhD, Johns Hopkins University, Baltimore, and colleagues studied more than 12,000 participants in a community cohort study who were followed for an average of 24 years, between 1987-1989 and 2019.

Participants with diabetes faced a 67% increase risk of infection-related hospitalization, compared with those without diabetes.

Of particular note, the risk of hospitalization with foot infection was almost sixfold higher for people with diabetes than those without.

The research, published in Diabetologia on August 4, also suggests that diabetes may be associated with a 72% increased risk of infection-related mortality, although the absolute numbers were small.

Dr. Fang explained to this news organization that they focused on infection-related hospitalization and mortality “because these are comprehensively tracked in administrative data and ... are the most severe types of outcomes.”

However, this is probably just the tip of the iceberg, as people with diabetes are “likely at increased risk for milder infection too,” which can have a “significant adverse impact on people’s well-being and quality of life.”

As a result of their findings, the authors call for “broader guidance on infection prevention and management” in people with diabetes. To achieve this, Dr. Fang said, “we need to better understand why diabetes is associated with an increased risk of infection-related complications.”

“One likely factor is glycemic control: Emerging research suggests patients with diabetes with better glycemic control may be at significantly lower risk of infection-related complications.”

He continued that, in younger patients, a factor for worse outcomes could be that “diabetes tends to be more aggressive when it emerges early in life,” while in Black patients “there is research highlighting Black-White differences in glycemic control, access to care, and beliefs around vaccines.”

Overall, their findings – coupled with recent data showing that diabetes is an important risk factor for adverse outcomes with COVID-19 infection – paint “a common picture,” Dr. Fang said.

“People with diabetes are much more susceptible to infection-related complications, including COVID-related hospitalization and mortality,” which suggests people with diabetes “may need to be especially cautious.”
 

Adds to existing literature; amputations begin with infections

Robert A. Gabbay, MD, PhD, chief scientific and medical officer for the American Diabetes Association (ADA), said the study “does add to the existing literature by having followed a larger number of people over time and linking them to serious complications from infections.”

“Sadly, we have seen this play out in real-time during the COVID-19 pandemic.”

“One of the sobering bits of data is the significant health disparities that exist in Black Americans and the fact that foot infections remain a significant problem,” he said in an interview.

“Given that amputation rates for [Black Americans] are three times higher than White Americans, amputations begin with infections,” Dr. Gabbay added, noting the ADA “has been taking a strong stand to prevent amputations and address the inequities in health that exist.”

Jamie Hartmann-Boyce, PhD, from the University of Oxford, U.K., who was not involved in the study, commented that diabetes is a “well-known risk factor for worse outcomes from all kinds of infection,” which is why they “are prioritized for flu vaccination every year.”

She told this news organization that the current study “further confirms that people with diabetes are more likely to be hospitalized for infection of any type and most markedly for foot infection.”

“These new data further highlight the need for public health interventions to prevent type 2 diabetes, and for preventive health care in people with diabetes, including access to diabetes medications and support and to vaccinations to prevent infection,” added Dr. Hartmann-Boyce, who is a senior research fellow in health behaviors.

Diabetes is thought to be associated with susceptibility to infection via mechanisms such as impaired neutrophil functioning and humoral immune responses, and studies have shown a link with both common and rare infections.

However, the authors point out that “most” of those included “small clinical populations and were cross-sectional or had short follow-up.”

Guidelines for diabetes management, they note, also “pay less attention” to infectious diseases than they do to the prevention of micro- and macrovascular complications.
 

ARIC data mined for infections in those with diabetes

The team analyzed data from the ongoing U.S. community-based Atherosclerosis Risk in Communities (ARIC) study.

The National Heart, Lung, and Blood Institute–sponsored cohort was comprised of adults aged 45-64 years from four U.S. communities, recruited between 1987 and 1989 for clinical examinations, medical interviews, and laboratory tests, repeated over five more visits up to 2018-2019.

For the current analysis, the team included 12,739 individuals with a mean age of 54.5 years, of whom 54.3% were female and 24.7% were Black.

Patients were defined as having diabetes if their baseline fasting blood glucose was greater than or equal to 7 mmol/L, or nonfasting glucose was greater than or equal to 11.1 mmol/l, they self-reported a diagnosis of diabetes by a physician, or they were taking glucose-lowering medication at the first study visit. The researchers weren’t able to distinguish between type 1 and type 2 diabetes.

In total, 1,485 individuals had diabetes at baseline. They were more likely to be older, Black, have a low socioeconomic status, and have worse cardiometabolic health than participants without diabetes.

Over an average follow-up of 23.8 years, there were 4,229 incident hospitalizations for infection, at an overall rate of 15.9 per 1,000 person-years.

Individuals with diabetes at baseline had a higher rate of hospitalizations than those without, at 25.4 per 1,000 person-years versus 15.2 per 1,000 person-years.

After taking into account sociodemographic characteristics, socioeconomic status, and cardiometabolic risk factors, this equated to a hazard ratio for hospitalization with any infection of 1.67 (P < .001).

The risk of hospitalization for any infection was significantly higher for younger patients with diabetes, defined as aged less than 55 years (P = .005), and for Black patients (P < .001).

While the increased risk was generally consistent across infection types, it was markedly increased for foot infection, at a hazard ratio of 5.99 (P < .001).

Overall, there were few deaths due to infection in the study, at just 362. The risk of infection mortality was nevertheless significantly increased in people with diabetes, at an adjusted hazard ratio of 1.72 (P < .001).

Dr. Fang has reported being supported by a grant from the National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Selvin has reported being supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Selvin is an associate editor for Diabetologia and had no role in the peer review of the manuscript.

A version of this article first appeared on Medscape.com.

People with diabetes are at increased risk of hospitalization for infection, as well as infection-related mortality, shows a large U.S. study that suggests the risk is even higher in younger and Black individuals.

Michael Fang, PhD, Johns Hopkins University, Baltimore, and colleagues studied more than 12,000 participants in a community cohort study who were followed for an average of 24 years, between 1987-1989 and 2019.

Participants with diabetes faced a 67% increase risk of infection-related hospitalization, compared with those without diabetes.

Of particular note, the risk of hospitalization with foot infection was almost sixfold higher for people with diabetes than those without.

The research, published in Diabetologia on August 4, also suggests that diabetes may be associated with a 72% increased risk of infection-related mortality, although the absolute numbers were small.

Dr. Fang explained to this news organization that they focused on infection-related hospitalization and mortality “because these are comprehensively tracked in administrative data and ... are the most severe types of outcomes.”

However, this is probably just the tip of the iceberg, as people with diabetes are “likely at increased risk for milder infection too,” which can have a “significant adverse impact on people’s well-being and quality of life.”

As a result of their findings, the authors call for “broader guidance on infection prevention and management” in people with diabetes. To achieve this, Dr. Fang said, “we need to better understand why diabetes is associated with an increased risk of infection-related complications.”

“One likely factor is glycemic control: Emerging research suggests patients with diabetes with better glycemic control may be at significantly lower risk of infection-related complications.”

He continued that, in younger patients, a factor for worse outcomes could be that “diabetes tends to be more aggressive when it emerges early in life,” while in Black patients “there is research highlighting Black-White differences in glycemic control, access to care, and beliefs around vaccines.”

Overall, their findings – coupled with recent data showing that diabetes is an important risk factor for adverse outcomes with COVID-19 infection – paint “a common picture,” Dr. Fang said.

“People with diabetes are much more susceptible to infection-related complications, including COVID-related hospitalization and mortality,” which suggests people with diabetes “may need to be especially cautious.”
 

Adds to existing literature; amputations begin with infections

Robert A. Gabbay, MD, PhD, chief scientific and medical officer for the American Diabetes Association (ADA), said the study “does add to the existing literature by having followed a larger number of people over time and linking them to serious complications from infections.”

“Sadly, we have seen this play out in real-time during the COVID-19 pandemic.”

“One of the sobering bits of data is the significant health disparities that exist in Black Americans and the fact that foot infections remain a significant problem,” he said in an interview.

“Given that amputation rates for [Black Americans] are three times higher than White Americans, amputations begin with infections,” Dr. Gabbay added, noting the ADA “has been taking a strong stand to prevent amputations and address the inequities in health that exist.”

Jamie Hartmann-Boyce, PhD, from the University of Oxford, U.K., who was not involved in the study, commented that diabetes is a “well-known risk factor for worse outcomes from all kinds of infection,” which is why they “are prioritized for flu vaccination every year.”

She told this news organization that the current study “further confirms that people with diabetes are more likely to be hospitalized for infection of any type and most markedly for foot infection.”

“These new data further highlight the need for public health interventions to prevent type 2 diabetes, and for preventive health care in people with diabetes, including access to diabetes medications and support and to vaccinations to prevent infection,” added Dr. Hartmann-Boyce, who is a senior research fellow in health behaviors.

Diabetes is thought to be associated with susceptibility to infection via mechanisms such as impaired neutrophil functioning and humoral immune responses, and studies have shown a link with both common and rare infections.

However, the authors point out that “most” of those included “small clinical populations and were cross-sectional or had short follow-up.”

Guidelines for diabetes management, they note, also “pay less attention” to infectious diseases than they do to the prevention of micro- and macrovascular complications.
 

ARIC data mined for infections in those with diabetes

The team analyzed data from the ongoing U.S. community-based Atherosclerosis Risk in Communities (ARIC) study.

The National Heart, Lung, and Blood Institute–sponsored cohort was comprised of adults aged 45-64 years from four U.S. communities, recruited between 1987 and 1989 for clinical examinations, medical interviews, and laboratory tests, repeated over five more visits up to 2018-2019.

For the current analysis, the team included 12,739 individuals with a mean age of 54.5 years, of whom 54.3% were female and 24.7% were Black.

Patients were defined as having diabetes if their baseline fasting blood glucose was greater than or equal to 7 mmol/L, or nonfasting glucose was greater than or equal to 11.1 mmol/l, they self-reported a diagnosis of diabetes by a physician, or they were taking glucose-lowering medication at the first study visit. The researchers weren’t able to distinguish between type 1 and type 2 diabetes.

In total, 1,485 individuals had diabetes at baseline. They were more likely to be older, Black, have a low socioeconomic status, and have worse cardiometabolic health than participants without diabetes.

Over an average follow-up of 23.8 years, there were 4,229 incident hospitalizations for infection, at an overall rate of 15.9 per 1,000 person-years.

Individuals with diabetes at baseline had a higher rate of hospitalizations than those without, at 25.4 per 1,000 person-years versus 15.2 per 1,000 person-years.

After taking into account sociodemographic characteristics, socioeconomic status, and cardiometabolic risk factors, this equated to a hazard ratio for hospitalization with any infection of 1.67 (P < .001).

The risk of hospitalization for any infection was significantly higher for younger patients with diabetes, defined as aged less than 55 years (P = .005), and for Black patients (P < .001).

While the increased risk was generally consistent across infection types, it was markedly increased for foot infection, at a hazard ratio of 5.99 (P < .001).

Overall, there were few deaths due to infection in the study, at just 362. The risk of infection mortality was nevertheless significantly increased in people with diabetes, at an adjusted hazard ratio of 1.72 (P < .001).

Dr. Fang has reported being supported by a grant from the National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Selvin has reported being supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Selvin is an associate editor for Diabetologia and had no role in the peer review of the manuscript.

A version of this article first appeared on Medscape.com.

Nearly half of adults prescribed metformin after a new diagnosis of type 2 diabetes have stopped taking it by 1 year, new data show.

SDI Productions/E+

The findings, from a retrospective analysis of administrative data from Alberta, Canada, during 2012-2017, also show that the fall-off in metformin adherence was most dramatic during the first 30 days, and in most cases, there was no concomitant substitution of another glucose-lowering drug.

While the majority with newly diagnosed type 2 diabetes were prescribed metformin as first-line therapy, patients started on other agents incurred far higher medication and health care costs.

The data were recently published online in Diabetic Medicine by David J. T. Campbell, MD, PhD, of the University of Calgary (Alta.), and colleagues.

“We realized that even if someone is prescribed metformin that doesn’t mean they’re staying on metformin even for a year ... the drop-off rate is really quite abrupt,” Dr. Campbell said in an interview. Most who discontinued had A1c levels above 7.5%, so it wasn’t that they no longer needed glucose-lowering medication, he noted.
 

People don’t understand chronic use; meds don’t make you feel better

One reason for the discontinuations, he said, is that patients might not realize they need to keep taking the medication.

“When a physician is seeing a person with newly diagnosed diabetes, I think it’s important to remember that they might not know the implications of having a chronic condition. A lot of times we’re quick to prescribe metformin and forget about it. ... Physicians might write a script for 3 months and three refills and not see the patient again for a year ... We may need to keep a closer eye on these folks and have more regular follow-up, and make sure they’re getting early diabetes education.”

Side effects are an issue, but not for most. “Any clinician who prescribes metformin knows there are side effects, such as upset stomach, diarrhea, and nausea. But certainly, it’s not half [who experience these]. ... A lot of people just aren’t accepting of having to take it lifelong, especially since they probably don’t feel any better on it,” Dr. Campbell said.  

James Flory, MD, an endocrinologist at Memorial Sloan Kettering Cancer Center, New York, said in an interview that about 25% of patients taking metformin experience gastrointestinal side effects.

Moreover, he noted that the drop-off in adherence is also seen with antihypertensive and lipid-lowering drugs that have fewer side effects than those of metformin. He pointed to a “striking example” of this, a 2011 randomized trial published in the New England Journal of Medicine, and as reported by this news organization, showing overall rates of adherence to these medications was around 50%, even among people who had already had a myocardial infarction.   

“People really don’t want to be on these medications. ... They have an aversion to being medicalized and taking pills. If they’re not being pretty consistently prompted and reminded and urged to take them, I think people will find rationalizations, reasons for stopping. ... I think people want to handle things through lifestyle and not be on a drug,” noted Dr. Flory, who has published on the subject of metformin adherence.

“These drugs don’t make people feel better. None of them do. At best they don’t make you feel worse. You have to really believe in the chronic condition and believe that it’s hurting you and that you can’t handle it without the drugs to motivate you to keep taking them,” Dr. Flory explained.

Communication with the patient is key, he added.

“I don’t have empirical data to support this, but I feel it’s helpful to acknowledge the downsides to patients. I tell them to let me know [if they’re having side effects] and we’ll work on it. Don’t just stop taking the drug and never circle back.” At the same time, he added, “I think it’s important to emphasize metformin’s safety and effectiveness.”

For patients experiencing gastrointestinal side effects, options including switching to extended-release metformin or lowering the dose.

Also, while patients are typically advised to take metformin with food, some experience diarrhea when they do that and prefer to take it at bedtime than with dinner. “If that’s what works for people, that’s what they should do,” Dr. Flory advised.

“It doesn’t take a lot of time to emphasize to patients the safety and this level of flexibility and control they should be able to exercise over how much they take and when. These things should really help.”  
 

Metformin usually prescribed, but not always taken

Dr. Campbell and colleagues analyzed 17,932 individuals with incident type 2 diabetes diagnosed between April 1, 2012, and March 31, 2017. Overall, 89% received metformin monotherapy as their initial diabetes prescription, 7.6% started metformin in combination with another glucose-lowering drug, and 3.3% were prescribed a nonmetformin diabetes medication. (Those prescribed insulin as their first diabetes medication were excluded.) 

The most commonly coprescribed drugs with metformin were sulfonylureas (in 47%) and DPP-4 inhibitors (28%). Of those initiated with only nonmetformin medications, sulfonylureas were also the most common (53%) and dipeptidyl peptidase-4 (DPP-4) inhibitors second (21%).

The metformin prescribing rate of 89% reflects current guidelines, Dr. Campbell noted.

“In hypertension, clinicians weren’t really following the guidelines ... they were prescribing more expensive drugs than the guidelines say. ... We showed that in diabetes, contrary to hypertension, clinicians really are generally following the clinical practice guidelines. ... The vast majority who are started on metformin are started on monotherapy. That was reassuring to us. We’re not paying for a bunch of expensive drugs when metformin would do just as well,” he said.

However, the proportion who had been dispensed metformin to cover the prescribed number of days dropped by about 10% after 30 days, by a further 10% after 90 days, and yet again after 100 days, resulting in just 54% remaining on the drug by 1 year.

Factors associated with higher adherence included older age, presence of comorbidities, and highest versus lowest neighborhood income quintile.

Those who had been prescribed nonmetformin monotherapy had about twice the total health care costs of those initially prescribed metformin monotherapy. Higher health care costs were seen among patients who were younger, had lower incomes, had higher baseline A1c, had more comorbidities, and were men.

How will the newer type 2 diabetes drugs change prescribing?

Dr. Campbell noted that “a lot has changed since 2017. ... At least in Canada, the sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists were supposed to be reserved as second-line agents in patients with cardiovascular disease, but more and more they’re being thought of as first-line agents in high-risk patients.”

“I suspect as those guidelines are transmitted to primary care colleagues who are doing the bulk of the prescribing we’ll see more and more uptake of these agents.”

Indeed, Dr. Flory said, “The metformin data at this point are very dated and the body of trials showing health benefits for it is actually very weak compared to the big trials that have been done for the newer agents, to the point where you can imagine a consensus gradually forming where people start to recommend something other than metformin for nearly everybody with type 2 diabetes. The cost implications are just huge, and I think the safety implications as well.”

According to Dr. Flory, the SGLT2 inhibitors “are fundamentally not as safe as metformin. I think they’re very safe drugs – large good studies have established that – but if you’re going to give drugs to a large number of people who are pretty healthy at baseline the safety standards have to be pretty high.”

Just the elevated risk of euglycemic diabetic ketoacidosis alone is reason for pause, Dr. Flory said. “Even though it’s manageable ... metformin just doesn’t have a safety problem like that. I’m very comfortable prescribing SGLT2 inhibitors, but If I’m going to give a drug to a million people and have nothing go wrong with any of them, that would be metformin, not an SGLT2 [inhibitor].”

Dr. Campbell and colleagues will be conducting a follow-up of prescribing data through 2019, which will of course include the newer agents. They’ll also investigate reasons for drug discontinuation and outcomes of those who discontinue versus continue metformin.

Dr. Campbell has reported no relevant financial relationships. Dr. Flory consults for a legal firm on litigation related to insulin analog pricing issues, not for or pertaining to a specific company.

A version of this article first appeared on Medscape.com.

Nearly half of adults prescribed metformin after a new diagnosis of type 2 diabetes have stopped taking it by 1 year, new data show.

SDI Productions/E+

The findings, from a retrospective analysis of administrative data from Alberta, Canada, during 2012-2017, also show that the fall-off in metformin adherence was most dramatic during the first 30 days, and in most cases, there was no concomitant substitution of another glucose-lowering drug.

While the majority with newly diagnosed type 2 diabetes were prescribed metformin as first-line therapy, patients started on other agents incurred far higher medication and health care costs.

The data were recently published online in Diabetic Medicine by David J. T. Campbell, MD, PhD, of the University of Calgary (Alta.), and colleagues.

“We realized that even if someone is prescribed metformin that doesn’t mean they’re staying on metformin even for a year ... the drop-off rate is really quite abrupt,” Dr. Campbell said in an interview. Most who discontinued had A1c levels above 7.5%, so it wasn’t that they no longer needed glucose-lowering medication, he noted.
 

People don’t understand chronic use; meds don’t make you feel better

One reason for the discontinuations, he said, is that patients might not realize they need to keep taking the medication.

“When a physician is seeing a person with newly diagnosed diabetes, I think it’s important to remember that they might not know the implications of having a chronic condition. A lot of times we’re quick to prescribe metformin and forget about it. ... Physicians might write a script for 3 months and three refills and not see the patient again for a year ... We may need to keep a closer eye on these folks and have more regular follow-up, and make sure they’re getting early diabetes education.”

Side effects are an issue, but not for most. “Any clinician who prescribes metformin knows there are side effects, such as upset stomach, diarrhea, and nausea. But certainly, it’s not half [who experience these]. ... A lot of people just aren’t accepting of having to take it lifelong, especially since they probably don’t feel any better on it,” Dr. Campbell said.  

James Flory, MD, an endocrinologist at Memorial Sloan Kettering Cancer Center, New York, said in an interview that about 25% of patients taking metformin experience gastrointestinal side effects.

Moreover, he noted that the drop-off in adherence is also seen with antihypertensive and lipid-lowering drugs that have fewer side effects than those of metformin. He pointed to a “striking example” of this, a 2011 randomized trial published in the New England Journal of Medicine, and as reported by this news organization, showing overall rates of adherence to these medications was around 50%, even among people who had already had a myocardial infarction.   

“People really don’t want to be on these medications. ... They have an aversion to being medicalized and taking pills. If they’re not being pretty consistently prompted and reminded and urged to take them, I think people will find rationalizations, reasons for stopping. ... I think people want to handle things through lifestyle and not be on a drug,” noted Dr. Flory, who has published on the subject of metformin adherence.

“These drugs don’t make people feel better. None of them do. At best they don’t make you feel worse. You have to really believe in the chronic condition and believe that it’s hurting you and that you can’t handle it without the drugs to motivate you to keep taking them,” Dr. Flory explained.

Communication with the patient is key, he added.

“I don’t have empirical data to support this, but I feel it’s helpful to acknowledge the downsides to patients. I tell them to let me know [if they’re having side effects] and we’ll work on it. Don’t just stop taking the drug and never circle back.” At the same time, he added, “I think it’s important to emphasize metformin’s safety and effectiveness.”

For patients experiencing gastrointestinal side effects, options including switching to extended-release metformin or lowering the dose.

Also, while patients are typically advised to take metformin with food, some experience diarrhea when they do that and prefer to take it at bedtime than with dinner. “If that’s what works for people, that’s what they should do,” Dr. Flory advised.

“It doesn’t take a lot of time to emphasize to patients the safety and this level of flexibility and control they should be able to exercise over how much they take and when. These things should really help.”  
 

Metformin usually prescribed, but not always taken

Dr. Campbell and colleagues analyzed 17,932 individuals with incident type 2 diabetes diagnosed between April 1, 2012, and March 31, 2017. Overall, 89% received metformin monotherapy as their initial diabetes prescription, 7.6% started metformin in combination with another glucose-lowering drug, and 3.3% were prescribed a nonmetformin diabetes medication. (Those prescribed insulin as their first diabetes medication were excluded.) 

The most commonly coprescribed drugs with metformin were sulfonylureas (in 47%) and DPP-4 inhibitors (28%). Of those initiated with only nonmetformin medications, sulfonylureas were also the most common (53%) and dipeptidyl peptidase-4 (DPP-4) inhibitors second (21%).

The metformin prescribing rate of 89% reflects current guidelines, Dr. Campbell noted.

“In hypertension, clinicians weren’t really following the guidelines ... they were prescribing more expensive drugs than the guidelines say. ... We showed that in diabetes, contrary to hypertension, clinicians really are generally following the clinical practice guidelines. ... The vast majority who are started on metformin are started on monotherapy. That was reassuring to us. We’re not paying for a bunch of expensive drugs when metformin would do just as well,” he said.

However, the proportion who had been dispensed metformin to cover the prescribed number of days dropped by about 10% after 30 days, by a further 10% after 90 days, and yet again after 100 days, resulting in just 54% remaining on the drug by 1 year.

Factors associated with higher adherence included older age, presence of comorbidities, and highest versus lowest neighborhood income quintile.

Those who had been prescribed nonmetformin monotherapy had about twice the total health care costs of those initially prescribed metformin monotherapy. Higher health care costs were seen among patients who were younger, had lower incomes, had higher baseline A1c, had more comorbidities, and were men.

How will the newer type 2 diabetes drugs change prescribing?

Dr. Campbell noted that “a lot has changed since 2017. ... At least in Canada, the sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists were supposed to be reserved as second-line agents in patients with cardiovascular disease, but more and more they’re being thought of as first-line agents in high-risk patients.”

“I suspect as those guidelines are transmitted to primary care colleagues who are doing the bulk of the prescribing we’ll see more and more uptake of these agents.”

Indeed, Dr. Flory said, “The metformin data at this point are very dated and the body of trials showing health benefits for it is actually very weak compared to the big trials that have been done for the newer agents, to the point where you can imagine a consensus gradually forming where people start to recommend something other than metformin for nearly everybody with type 2 diabetes. The cost implications are just huge, and I think the safety implications as well.”

According to Dr. Flory, the SGLT2 inhibitors “are fundamentally not as safe as metformin. I think they’re very safe drugs – large good studies have established that – but if you’re going to give drugs to a large number of people who are pretty healthy at baseline the safety standards have to be pretty high.”

Just the elevated risk of euglycemic diabetic ketoacidosis alone is reason for pause, Dr. Flory said. “Even though it’s manageable ... metformin just doesn’t have a safety problem like that. I’m very comfortable prescribing SGLT2 inhibitors, but If I’m going to give a drug to a million people and have nothing go wrong with any of them, that would be metformin, not an SGLT2 [inhibitor].”

Dr. Campbell and colleagues will be conducting a follow-up of prescribing data through 2019, which will of course include the newer agents. They’ll also investigate reasons for drug discontinuation and outcomes of those who discontinue versus continue metformin.

Dr. Campbell has reported no relevant financial relationships. Dr. Flory consults for a legal firm on litigation related to insulin analog pricing issues, not for or pertaining to a specific company.

A version of this article first appeared on Medscape.com.

Nearly half of adults prescribed metformin after a new diagnosis of type 2 diabetes have stopped taking it by 1 year, new data show.

SDI Productions/E+

The findings, from a retrospective analysis of administrative data from Alberta, Canada, during 2012-2017, also show that the fall-off in metformin adherence was most dramatic during the first 30 days, and in most cases, there was no concomitant substitution of another glucose-lowering drug.

While the majority with newly diagnosed type 2 diabetes were prescribed metformin as first-line therapy, patients started on other agents incurred far higher medication and health care costs.

The data were recently published online in Diabetic Medicine by David J. T. Campbell, MD, PhD, of the University of Calgary (Alta.), and colleagues.

“We realized that even if someone is prescribed metformin that doesn’t mean they’re staying on metformin even for a year ... the drop-off rate is really quite abrupt,” Dr. Campbell said in an interview. Most who discontinued had A1c levels above 7.5%, so it wasn’t that they no longer needed glucose-lowering medication, he noted.
 

People don’t understand chronic use; meds don’t make you feel better

One reason for the discontinuations, he said, is that patients might not realize they need to keep taking the medication.

“When a physician is seeing a person with newly diagnosed diabetes, I think it’s important to remember that they might not know the implications of having a chronic condition. A lot of times we’re quick to prescribe metformin and forget about it. ... Physicians might write a script for 3 months and three refills and not see the patient again for a year ... We may need to keep a closer eye on these folks and have more regular follow-up, and make sure they’re getting early diabetes education.”

Side effects are an issue, but not for most. “Any clinician who prescribes metformin knows there are side effects, such as upset stomach, diarrhea, and nausea. But certainly, it’s not half [who experience these]. ... A lot of people just aren’t accepting of having to take it lifelong, especially since they probably don’t feel any better on it,” Dr. Campbell said.  

James Flory, MD, an endocrinologist at Memorial Sloan Kettering Cancer Center, New York, said in an interview that about 25% of patients taking metformin experience gastrointestinal side effects.

Moreover, he noted that the drop-off in adherence is also seen with antihypertensive and lipid-lowering drugs that have fewer side effects than those of metformin. He pointed to a “striking example” of this, a 2011 randomized trial published in the New England Journal of Medicine, and as reported by this news organization, showing overall rates of adherence to these medications was around 50%, even among people who had already had a myocardial infarction.   

“People really don’t want to be on these medications. ... They have an aversion to being medicalized and taking pills. If they’re not being pretty consistently prompted and reminded and urged to take them, I think people will find rationalizations, reasons for stopping. ... I think people want to handle things through lifestyle and not be on a drug,” noted Dr. Flory, who has published on the subject of metformin adherence.

“These drugs don’t make people feel better. None of them do. At best they don’t make you feel worse. You have to really believe in the chronic condition and believe that it’s hurting you and that you can’t handle it without the drugs to motivate you to keep taking them,” Dr. Flory explained.

Communication with the patient is key, he added.

“I don’t have empirical data to support this, but I feel it’s helpful to acknowledge the downsides to patients. I tell them to let me know [if they’re having side effects] and we’ll work on it. Don’t just stop taking the drug and never circle back.” At the same time, he added, “I think it’s important to emphasize metformin’s safety and effectiveness.”

For patients experiencing gastrointestinal side effects, options including switching to extended-release metformin or lowering the dose.

Also, while patients are typically advised to take metformin with food, some experience diarrhea when they do that and prefer to take it at bedtime than with dinner. “If that’s what works for people, that’s what they should do,” Dr. Flory advised.

“It doesn’t take a lot of time to emphasize to patients the safety and this level of flexibility and control they should be able to exercise over how much they take and when. These things should really help.”  
 

Metformin usually prescribed, but not always taken

Dr. Campbell and colleagues analyzed 17,932 individuals with incident type 2 diabetes diagnosed between April 1, 2012, and March 31, 2017. Overall, 89% received metformin monotherapy as their initial diabetes prescription, 7.6% started metformin in combination with another glucose-lowering drug, and 3.3% were prescribed a nonmetformin diabetes medication. (Those prescribed insulin as their first diabetes medication were excluded.) 

The most commonly coprescribed drugs with metformin were sulfonylureas (in 47%) and DPP-4 inhibitors (28%). Of those initiated with only nonmetformin medications, sulfonylureas were also the most common (53%) and dipeptidyl peptidase-4 (DPP-4) inhibitors second (21%).

The metformin prescribing rate of 89% reflects current guidelines, Dr. Campbell noted.

“In hypertension, clinicians weren’t really following the guidelines ... they were prescribing more expensive drugs than the guidelines say. ... We showed that in diabetes, contrary to hypertension, clinicians really are generally following the clinical practice guidelines. ... The vast majority who are started on metformin are started on monotherapy. That was reassuring to us. We’re not paying for a bunch of expensive drugs when metformin would do just as well,” he said.

However, the proportion who had been dispensed metformin to cover the prescribed number of days dropped by about 10% after 30 days, by a further 10% after 90 days, and yet again after 100 days, resulting in just 54% remaining on the drug by 1 year.

Factors associated with higher adherence included older age, presence of comorbidities, and highest versus lowest neighborhood income quintile.

Those who had been prescribed nonmetformin monotherapy had about twice the total health care costs of those initially prescribed metformin monotherapy. Higher health care costs were seen among patients who were younger, had lower incomes, had higher baseline A1c, had more comorbidities, and were men.

How will the newer type 2 diabetes drugs change prescribing?

Dr. Campbell noted that “a lot has changed since 2017. ... At least in Canada, the sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists were supposed to be reserved as second-line agents in patients with cardiovascular disease, but more and more they’re being thought of as first-line agents in high-risk patients.”

“I suspect as those guidelines are transmitted to primary care colleagues who are doing the bulk of the prescribing we’ll see more and more uptake of these agents.”

Indeed, Dr. Flory said, “The metformin data at this point are very dated and the body of trials showing health benefits for it is actually very weak compared to the big trials that have been done for the newer agents, to the point where you can imagine a consensus gradually forming where people start to recommend something other than metformin for nearly everybody with type 2 diabetes. The cost implications are just huge, and I think the safety implications as well.”

According to Dr. Flory, the SGLT2 inhibitors “are fundamentally not as safe as metformin. I think they’re very safe drugs – large good studies have established that – but if you’re going to give drugs to a large number of people who are pretty healthy at baseline the safety standards have to be pretty high.”

Just the elevated risk of euglycemic diabetic ketoacidosis alone is reason for pause, Dr. Flory said. “Even though it’s manageable ... metformin just doesn’t have a safety problem like that. I’m very comfortable prescribing SGLT2 inhibitors, but If I’m going to give a drug to a million people and have nothing go wrong with any of them, that would be metformin, not an SGLT2 [inhibitor].”

Dr. Campbell and colleagues will be conducting a follow-up of prescribing data through 2019, which will of course include the newer agents. They’ll also investigate reasons for drug discontinuation and outcomes of those who discontinue versus continue metformin.

Dr. Campbell has reported no relevant financial relationships. Dr. Flory consults for a legal firm on litigation related to insulin analog pricing issues, not for or pertaining to a specific company.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

A version of this article first appeared on Medscape.com.

Having more diverse gut bacteria (greater microbiome richness) and specifically a greater abundance of 12 types of butyrate-producing bacteria were both associated with less insulin resistance and less type 2 diabetes, in a population-based observational study from the Netherlands.

Several studies have reported that there is less microbiome diversity in type 2 diabetes, Zhangling Chen, MD, PhD, of Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues note.

Their study also identified a dozen types of bacteria that ferment dietary fiber (undigested carbohydrates) in the gut to produce butyrate, a short-chain fatty acid, which may play a role in protection against type 2 diabetes.

“The current study is the first, to our knowledge, to comprehensively investigate the associations between gut microbiome composition [and] type 2 diabetes in a large population-based sample … which we adjusted for a series of key confounders,” the researchers write.

“These findings suggest that higher gut microbial diversity, along with specifically more butyrate-producing bacteria, may play a role in the development of type 2 diabetes, which may help guide future prevention and treatment strategies,” they conclude in their study published online July 29 in JAMA Network Open.
 

Confirmation of previous work, plus some new findings

The study confirms what many smaller ones have repeatedly shown – that low gut microbiome diversity is associated with increased risks of obesity and type 2 diabetes, Nanette I. Steinle, MD, RDN, who was not involved in the research, said in an interview.

A diet rich in fiber and prebiotics promotes gut biome diversity, added Dr. Steinle, chief of the endocrinology and diabetes section at Maryland Veterans Affairs Medical Center in Baltimore.

The findings add to other research, she noted, such as a prospective trial in which a high-fiber diet induced changes in the gut microbe that were linked to better glycemic regulation (Science. 2018;359:1151-6) and a study of a promising probiotic formula to treat diabetes.

“An important next step,” according to Dr. Steinle, “is to provide interventions like healthy diet or specific fiber types to see what can be done to produce lasting shifts in the gut microbiome and if these shifts result in improved metabolic health.”

Natalia Shulzhenko, MD, PhD, said: “Some of associations of taxa [bacteria groupings] with type 2 diabetes reported by this study are new.”

Dr. Shulzhenko and colleagues recently published a review of the role of gut microbiota in type 2 diabetes pathophysiology that summarized evidence from 42 human studies as well as preclinical studies and clinical trials of probiotic treatments (EBioMedicine. 2020;51:102590).

“Besides adding new microbes to the list of potential pathobionts [organisms that can cause harm] and beneficial microbes for type 2 diabetes,” the findings by Dr. Chen and colleagues “support a notion that different members of the gut microbial community may have similar effects on type 2 diabetes in different individuals,” commonly known as “functional redundancy,” Dr. Shulzhenko, associate professor, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, pointed out in an email.

Also “in line with previous studies,” the study shows that butyrate-producing bacteria are associated with type 2 diabetes.

She speculated that “these results will probably contribute to the body of knowledge that is needed to develop microbiota-based therapy and diagnostics.”
 

Which gut bacteria are linked with diabetes?

It is unclear which gut bacteria are associated with the development of type 2 diabetes, Dr. Chen and colleagues write.

To investigate this, they identified 1,418 participants from the Rotterdam Study and 748 participants from the LifeLines-DEEP study enrolled from January 2018 to December 2020. Of these participants, 193 had type 2 diabetes.

The participants provided stool samples that were used to measure gut microbiome composition using the 16S ribosomal RNA method. They also had blood tests to measure glucose and insulin, and researchers collected other demographic and medical data.

Participants in the Rotterdam study were older than in the LifeLines Deep study (mean age, 62 vs. 45 years). Both cohorts included slightly more men than women (58%).

Dr. Chen and colleagues identified 126 (bacteria) genera in the gut microbiome in the Rotterdam study and 184 genera in the LifeLines Deep study.

After correcting for age, sex, smoking, education, physical activity, alcohol intake, daily calories, body mass index, and use of lipid-lowering medication or proton pump inhibitors, higher microbiome diversity was associated with lower insulin resistance and a lower prevalence of type 2 diabetes.

A higher abundance of each of seven types of butyrate-producing bacteria – Christensenellaceae, Christensenellaceae R7 group, Marvinbryantia, Ruminococcaceae UCG-005, Ruminococcaceae UCG-008, Ruminococcaceae UCG-010, and Ruminococcaceae NK4A214 group – was associated with lower insulin resistance, after adjusting for confounders such as diet and medications (all P < .001).

And a higher abundance of each of five other types of butyrate-producing bacteria – Clostridiaceae 1, Peptostreptococcaceae, Clostridium sensu stricto 1, Intestinibacter, and Romboutsia – was associated with less type 2 diabetes (all P < .001). 

Study limitations include that gut microbiome composition was determined from stool (fecal) samples, whereas the actual composition varies in different locations along the intestine, and the study also lacked information about butyrate concentrations in stool or blood, the researchers note.

They call for “future research [to] validate the hypothesis of butyrate-producing bacteria affecting glucose metabolism and diabetes risk via production of butyrate.”

The authors and Dr. Shulzhenko have reported no relevant financial relationships. Dr. Steinle has reported receiving funding from the National Institutes of Health and conducting a study funded by Kowa through the VA.

A version of this article first appeared on Medscape.com.

Having more diverse gut bacteria (greater microbiome richness) and specifically a greater abundance of 12 types of butyrate-producing bacteria were both associated with less insulin resistance and less type 2 diabetes, in a population-based observational study from the Netherlands.

Several studies have reported that there is less microbiome diversity in type 2 diabetes, Zhangling Chen, MD, PhD, of Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues note.

Their study also identified a dozen types of bacteria that ferment dietary fiber (undigested carbohydrates) in the gut to produce butyrate, a short-chain fatty acid, which may play a role in protection against type 2 diabetes.

“The current study is the first, to our knowledge, to comprehensively investigate the associations between gut microbiome composition [and] type 2 diabetes in a large population-based sample … which we adjusted for a series of key confounders,” the researchers write.

“These findings suggest that higher gut microbial diversity, along with specifically more butyrate-producing bacteria, may play a role in the development of type 2 diabetes, which may help guide future prevention and treatment strategies,” they conclude in their study published online July 29 in JAMA Network Open.
 

Confirmation of previous work, plus some new findings

The study confirms what many smaller ones have repeatedly shown – that low gut microbiome diversity is associated with increased risks of obesity and type 2 diabetes, Nanette I. Steinle, MD, RDN, who was not involved in the research, said in an interview.

A diet rich in fiber and prebiotics promotes gut biome diversity, added Dr. Steinle, chief of the endocrinology and diabetes section at Maryland Veterans Affairs Medical Center in Baltimore.

The findings add to other research, she noted, such as a prospective trial in which a high-fiber diet induced changes in the gut microbe that were linked to better glycemic regulation (Science. 2018;359:1151-6) and a study of a promising probiotic formula to treat diabetes.

“An important next step,” according to Dr. Steinle, “is to provide interventions like healthy diet or specific fiber types to see what can be done to produce lasting shifts in the gut microbiome and if these shifts result in improved metabolic health.”

Natalia Shulzhenko, MD, PhD, said: “Some of associations of taxa [bacteria groupings] with type 2 diabetes reported by this study are new.”

Dr. Shulzhenko and colleagues recently published a review of the role of gut microbiota in type 2 diabetes pathophysiology that summarized evidence from 42 human studies as well as preclinical studies and clinical trials of probiotic treatments (EBioMedicine. 2020;51:102590).

“Besides adding new microbes to the list of potential pathobionts [organisms that can cause harm] and beneficial microbes for type 2 diabetes,” the findings by Dr. Chen and colleagues “support a notion that different members of the gut microbial community may have similar effects on type 2 diabetes in different individuals,” commonly known as “functional redundancy,” Dr. Shulzhenko, associate professor, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, pointed out in an email.

Also “in line with previous studies,” the study shows that butyrate-producing bacteria are associated with type 2 diabetes.

She speculated that “these results will probably contribute to the body of knowledge that is needed to develop microbiota-based therapy and diagnostics.”
 

Which gut bacteria are linked with diabetes?

It is unclear which gut bacteria are associated with the development of type 2 diabetes, Dr. Chen and colleagues write.

To investigate this, they identified 1,418 participants from the Rotterdam Study and 748 participants from the LifeLines-DEEP study enrolled from January 2018 to December 2020. Of these participants, 193 had type 2 diabetes.

The participants provided stool samples that were used to measure gut microbiome composition using the 16S ribosomal RNA method. They also had blood tests to measure glucose and insulin, and researchers collected other demographic and medical data.

Participants in the Rotterdam study were older than in the LifeLines Deep study (mean age, 62 vs. 45 years). Both cohorts included slightly more men than women (58%).

Dr. Chen and colleagues identified 126 (bacteria) genera in the gut microbiome in the Rotterdam study and 184 genera in the LifeLines Deep study.

After correcting for age, sex, smoking, education, physical activity, alcohol intake, daily calories, body mass index, and use of lipid-lowering medication or proton pump inhibitors, higher microbiome diversity was associated with lower insulin resistance and a lower prevalence of type 2 diabetes.

A higher abundance of each of seven types of butyrate-producing bacteria – Christensenellaceae, Christensenellaceae R7 group, Marvinbryantia, Ruminococcaceae UCG-005, Ruminococcaceae UCG-008, Ruminococcaceae UCG-010, and Ruminococcaceae NK4A214 group – was associated with lower insulin resistance, after adjusting for confounders such as diet and medications (all P < .001).

And a higher abundance of each of five other types of butyrate-producing bacteria – Clostridiaceae 1, Peptostreptococcaceae, Clostridium sensu stricto 1, Intestinibacter, and Romboutsia – was associated with less type 2 diabetes (all P < .001). 

Study limitations include that gut microbiome composition was determined from stool (fecal) samples, whereas the actual composition varies in different locations along the intestine, and the study also lacked information about butyrate concentrations in stool or blood, the researchers note.

They call for “future research [to] validate the hypothesis of butyrate-producing bacteria affecting glucose metabolism and diabetes risk via production of butyrate.”

The authors and Dr. Shulzhenko have reported no relevant financial relationships. Dr. Steinle has reported receiving funding from the National Institutes of Health and conducting a study funded by Kowa through the VA.

A version of this article first appeared on Medscape.com.

Having more diverse gut bacteria (greater microbiome richness) and specifically a greater abundance of 12 types of butyrate-producing bacteria were both associated with less insulin resistance and less type 2 diabetes, in a population-based observational study from the Netherlands.

Several studies have reported that there is less microbiome diversity in type 2 diabetes, Zhangling Chen, MD, PhD, of Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues note.

Their study also identified a dozen types of bacteria that ferment dietary fiber (undigested carbohydrates) in the gut to produce butyrate, a short-chain fatty acid, which may play a role in protection against type 2 diabetes.

“The current study is the first, to our knowledge, to comprehensively investigate the associations between gut microbiome composition [and] type 2 diabetes in a large population-based sample … which we adjusted for a series of key confounders,” the researchers write.

“These findings suggest that higher gut microbial diversity, along with specifically more butyrate-producing bacteria, may play a role in the development of type 2 diabetes, which may help guide future prevention and treatment strategies,” they conclude in their study published online July 29 in JAMA Network Open.
 

Confirmation of previous work, plus some new findings

The study confirms what many smaller ones have repeatedly shown – that low gut microbiome diversity is associated with increased risks of obesity and type 2 diabetes, Nanette I. Steinle, MD, RDN, who was not involved in the research, said in an interview.

A diet rich in fiber and prebiotics promotes gut biome diversity, added Dr. Steinle, chief of the endocrinology and diabetes section at Maryland Veterans Affairs Medical Center in Baltimore.

The findings add to other research, she noted, such as a prospective trial in which a high-fiber diet induced changes in the gut microbe that were linked to better glycemic regulation (Science. 2018;359:1151-6) and a study of a promising probiotic formula to treat diabetes.

“An important next step,” according to Dr. Steinle, “is to provide interventions like healthy diet or specific fiber types to see what can be done to produce lasting shifts in the gut microbiome and if these shifts result in improved metabolic health.”

Natalia Shulzhenko, MD, PhD, said: “Some of associations of taxa [bacteria groupings] with type 2 diabetes reported by this study are new.”

Dr. Shulzhenko and colleagues recently published a review of the role of gut microbiota in type 2 diabetes pathophysiology that summarized evidence from 42 human studies as well as preclinical studies and clinical trials of probiotic treatments (EBioMedicine. 2020;51:102590).

“Besides adding new microbes to the list of potential pathobionts [organisms that can cause harm] and beneficial microbes for type 2 diabetes,” the findings by Dr. Chen and colleagues “support a notion that different members of the gut microbial community may have similar effects on type 2 diabetes in different individuals,” commonly known as “functional redundancy,” Dr. Shulzhenko, associate professor, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, pointed out in an email.

Also “in line with previous studies,” the study shows that butyrate-producing bacteria are associated with type 2 diabetes.

She speculated that “these results will probably contribute to the body of knowledge that is needed to develop microbiota-based therapy and diagnostics.”
 

Which gut bacteria are linked with diabetes?

It is unclear which gut bacteria are associated with the development of type 2 diabetes, Dr. Chen and colleagues write.

To investigate this, they identified 1,418 participants from the Rotterdam Study and 748 participants from the LifeLines-DEEP study enrolled from January 2018 to December 2020. Of these participants, 193 had type 2 diabetes.

The participants provided stool samples that were used to measure gut microbiome composition using the 16S ribosomal RNA method. They also had blood tests to measure glucose and insulin, and researchers collected other demographic and medical data.

Participants in the Rotterdam study were older than in the LifeLines Deep study (mean age, 62 vs. 45 years). Both cohorts included slightly more men than women (58%).

Dr. Chen and colleagues identified 126 (bacteria) genera in the gut microbiome in the Rotterdam study and 184 genera in the LifeLines Deep study.

After correcting for age, sex, smoking, education, physical activity, alcohol intake, daily calories, body mass index, and use of lipid-lowering medication or proton pump inhibitors, higher microbiome diversity was associated with lower insulin resistance and a lower prevalence of type 2 diabetes.

A higher abundance of each of seven types of butyrate-producing bacteria – Christensenellaceae, Christensenellaceae R7 group, Marvinbryantia, Ruminococcaceae UCG-005, Ruminococcaceae UCG-008, Ruminococcaceae UCG-010, and Ruminococcaceae NK4A214 group – was associated with lower insulin resistance, after adjusting for confounders such as diet and medications (all P < .001).

And a higher abundance of each of five other types of butyrate-producing bacteria – Clostridiaceae 1, Peptostreptococcaceae, Clostridium sensu stricto 1, Intestinibacter, and Romboutsia – was associated with less type 2 diabetes (all P < .001). 

Study limitations include that gut microbiome composition was determined from stool (fecal) samples, whereas the actual composition varies in different locations along the intestine, and the study also lacked information about butyrate concentrations in stool or blood, the researchers note.

They call for “future research [to] validate the hypothesis of butyrate-producing bacteria affecting glucose metabolism and diabetes risk via production of butyrate.”

The authors and Dr. Shulzhenko have reported no relevant financial relationships. Dr. Steinle has reported receiving funding from the National Institutes of Health and conducting a study funded by Kowa through the VA.

A version of this article first appeared on Medscape.com.