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Lower is better for blood glucose to reduce heart disease
in a large, 12-year observational study of UK Biobank data.
The results highlight “the need for strategies to reduce risk of CVD across the [glycemic] spectrum,” Christopher T. Rentsch, MPH, PhD, and colleagues wrote in their study, which was published in the The Lancet Regional Health – Europe.
The findings suggest “that excess [CVD] risks in both men and women were largely explained by modifiable factors and could be ameliorated by attention to weight reduction strategies and greater use of antihypertensive and statin medications.
“Addressing these risk factors could reduce sex disparities in [glycemia]-related risks of CVD,” according to the researchers.
After the researchers accounted for age, the absolute rate of CVD events was higher among men than women (16.9 vs. 9.1 events per 1,000 person-years); however, the relative risk was higher among women than men.
Compared with men, women were more likely to have obesity (63% vs. 53%) and were less likely to be using antihypertensive medications (64% vs. 69%) or a statin (71% vs. 75%).
“This is the largest study to date to investigate sex differences in the risk of CVD across the glycemic spectrum,” the researchers noted.
“The lower the better”
“We uncovered compelling evidence that for blood sugar levels within the ‘normal’ range, it was a case of ‘the lower the better’ in protecting against heart disease,” Dr. Rentsch, assistant professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, told this news organization.
Compared with people with normal blood glucose levels, those with lower than normal levels were at 10% lower risk of developing any form of heart disease, he noted.
The study findings “support women being proactive in asking about medications like statins and antihypertensives as an option to help lower their [CVD] risk, if clinically appropriate,” Dr. Rentsch added.
“We found that men and women with diagnosed diabetes remained at elevated risk for three types of heart disease – coronary artery disease, stroke, and heart failure – even after accounting for a large number of sociodemographic, lifestyle, and clinical characteristics,” he pointed out.
However, “total cholesterol, family history of CVD, estimated glomerular filtration rate, and C-reactive protein had relatively little impact on explaining the risk of heart disease associated with blood sugar.”
“It is well established that being overweight can lead to higher blood sugar levels as well as higher blood pressure, these being factors that contribute to higher risk of heart attack and stroke,” Robert Storey, DM, professor of cardiology, University of Sheffield (England), told the UK Science Media Centre.
“This very large UK Biobank study,” he said, “shows that the higher heart risk associated with blood sugar can be detected at a very early stage along the path towards the abnormally high blood sugar levels associated with diabetes.
“The study provides support for a strategy of assessing cardiovascular risk in people who are overweight, including assessment of blood sugar, cholesterol, and blood pressure levels, all of which can be effectively managed to markedly reduce the risk of future heart attack and stroke,” according to Dr. Storey.
More than 400,000 men, women
The researchers enrolled men and women aged 40-69 between 2006 to 2010 who were living in England, Scotland, and Wales. After excluding people with type 1 diabetes or those whose A1c data were missing, the current study included 427,435 people (46% of whom were men).
The participants were classified as having low-normal A1c (< 35 mmol/mol or < 5.5%), normal A1c (35-41 mmol/mol or 5.5%-5.9%), prediabetes (42-47 mmol/mol or 6.0%-6.4%), undiagnosed diabetes (≥ 48 mmol/mol or ≥ 6.5%), or diagnosed type 2 diabetes (medical history and in receipt of glucose-lowering medication).
The researchers determined the incidence of six CVD outcomes during a median 11.8-year follow-up: coronary artery disease, atrial fibrillation, deep vein thrombosis, pulmonary embolism, stroke, and heart failure.
Few participants (5%) had any of these outcomes prior to study enrollment.
During the follow-up, there were 51,288 incident CVD events.
After adjustment for age, compared to having normal A1c, having prediabetes or undiagnosed diabetes was associated with an increased risk of CVD for women and men (hazard ratio [HR], 1.30-1.47).
Among individuals with diagnosed type 2 diabetes, the age-adjusted risk of CVD was greater for women (HR, 2.00) than for men (HR, 1.55).
After further adjustment for clinical and lifestyle factors, especially obesity and antihypertensive or statin use, the risk of CVD decreased and became similar among men and women. The fully adjusted HR for CVD was 1.17 for women and 1.06 for men with diagnosed diabetes.
Compared with having normal A1c, women and men with low-normal A1c were at decreased risk of CVD (HR, 0.86 for both).
The study was funded by Diabetes UK and the British Heart Foundation. Dr. Rentsch and Dr. Storey have disclosed no relevant financial relationships. The disclosures of the other study authors are listed in the original article.
A version of this article appeared on Medscape.com.
in a large, 12-year observational study of UK Biobank data.
The results highlight “the need for strategies to reduce risk of CVD across the [glycemic] spectrum,” Christopher T. Rentsch, MPH, PhD, and colleagues wrote in their study, which was published in the The Lancet Regional Health – Europe.
The findings suggest “that excess [CVD] risks in both men and women were largely explained by modifiable factors and could be ameliorated by attention to weight reduction strategies and greater use of antihypertensive and statin medications.
“Addressing these risk factors could reduce sex disparities in [glycemia]-related risks of CVD,” according to the researchers.
After the researchers accounted for age, the absolute rate of CVD events was higher among men than women (16.9 vs. 9.1 events per 1,000 person-years); however, the relative risk was higher among women than men.
Compared with men, women were more likely to have obesity (63% vs. 53%) and were less likely to be using antihypertensive medications (64% vs. 69%) or a statin (71% vs. 75%).
“This is the largest study to date to investigate sex differences in the risk of CVD across the glycemic spectrum,” the researchers noted.
“The lower the better”
“We uncovered compelling evidence that for blood sugar levels within the ‘normal’ range, it was a case of ‘the lower the better’ in protecting against heart disease,” Dr. Rentsch, assistant professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, told this news organization.
Compared with people with normal blood glucose levels, those with lower than normal levels were at 10% lower risk of developing any form of heart disease, he noted.
The study findings “support women being proactive in asking about medications like statins and antihypertensives as an option to help lower their [CVD] risk, if clinically appropriate,” Dr. Rentsch added.
“We found that men and women with diagnosed diabetes remained at elevated risk for three types of heart disease – coronary artery disease, stroke, and heart failure – even after accounting for a large number of sociodemographic, lifestyle, and clinical characteristics,” he pointed out.
However, “total cholesterol, family history of CVD, estimated glomerular filtration rate, and C-reactive protein had relatively little impact on explaining the risk of heart disease associated with blood sugar.”
“It is well established that being overweight can lead to higher blood sugar levels as well as higher blood pressure, these being factors that contribute to higher risk of heart attack and stroke,” Robert Storey, DM, professor of cardiology, University of Sheffield (England), told the UK Science Media Centre.
“This very large UK Biobank study,” he said, “shows that the higher heart risk associated with blood sugar can be detected at a very early stage along the path towards the abnormally high blood sugar levels associated with diabetes.
“The study provides support for a strategy of assessing cardiovascular risk in people who are overweight, including assessment of blood sugar, cholesterol, and blood pressure levels, all of which can be effectively managed to markedly reduce the risk of future heart attack and stroke,” according to Dr. Storey.
More than 400,000 men, women
The researchers enrolled men and women aged 40-69 between 2006 to 2010 who were living in England, Scotland, and Wales. After excluding people with type 1 diabetes or those whose A1c data were missing, the current study included 427,435 people (46% of whom were men).
The participants were classified as having low-normal A1c (< 35 mmol/mol or < 5.5%), normal A1c (35-41 mmol/mol or 5.5%-5.9%), prediabetes (42-47 mmol/mol or 6.0%-6.4%), undiagnosed diabetes (≥ 48 mmol/mol or ≥ 6.5%), or diagnosed type 2 diabetes (medical history and in receipt of glucose-lowering medication).
The researchers determined the incidence of six CVD outcomes during a median 11.8-year follow-up: coronary artery disease, atrial fibrillation, deep vein thrombosis, pulmonary embolism, stroke, and heart failure.
Few participants (5%) had any of these outcomes prior to study enrollment.
During the follow-up, there were 51,288 incident CVD events.
After adjustment for age, compared to having normal A1c, having prediabetes or undiagnosed diabetes was associated with an increased risk of CVD for women and men (hazard ratio [HR], 1.30-1.47).
Among individuals with diagnosed type 2 diabetes, the age-adjusted risk of CVD was greater for women (HR, 2.00) than for men (HR, 1.55).
After further adjustment for clinical and lifestyle factors, especially obesity and antihypertensive or statin use, the risk of CVD decreased and became similar among men and women. The fully adjusted HR for CVD was 1.17 for women and 1.06 for men with diagnosed diabetes.
Compared with having normal A1c, women and men with low-normal A1c were at decreased risk of CVD (HR, 0.86 for both).
The study was funded by Diabetes UK and the British Heart Foundation. Dr. Rentsch and Dr. Storey have disclosed no relevant financial relationships. The disclosures of the other study authors are listed in the original article.
A version of this article appeared on Medscape.com.
in a large, 12-year observational study of UK Biobank data.
The results highlight “the need for strategies to reduce risk of CVD across the [glycemic] spectrum,” Christopher T. Rentsch, MPH, PhD, and colleagues wrote in their study, which was published in the The Lancet Regional Health – Europe.
The findings suggest “that excess [CVD] risks in both men and women were largely explained by modifiable factors and could be ameliorated by attention to weight reduction strategies and greater use of antihypertensive and statin medications.
“Addressing these risk factors could reduce sex disparities in [glycemia]-related risks of CVD,” according to the researchers.
After the researchers accounted for age, the absolute rate of CVD events was higher among men than women (16.9 vs. 9.1 events per 1,000 person-years); however, the relative risk was higher among women than men.
Compared with men, women were more likely to have obesity (63% vs. 53%) and were less likely to be using antihypertensive medications (64% vs. 69%) or a statin (71% vs. 75%).
“This is the largest study to date to investigate sex differences in the risk of CVD across the glycemic spectrum,” the researchers noted.
“The lower the better”
“We uncovered compelling evidence that for blood sugar levels within the ‘normal’ range, it was a case of ‘the lower the better’ in protecting against heart disease,” Dr. Rentsch, assistant professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, told this news organization.
Compared with people with normal blood glucose levels, those with lower than normal levels were at 10% lower risk of developing any form of heart disease, he noted.
The study findings “support women being proactive in asking about medications like statins and antihypertensives as an option to help lower their [CVD] risk, if clinically appropriate,” Dr. Rentsch added.
“We found that men and women with diagnosed diabetes remained at elevated risk for three types of heart disease – coronary artery disease, stroke, and heart failure – even after accounting for a large number of sociodemographic, lifestyle, and clinical characteristics,” he pointed out.
However, “total cholesterol, family history of CVD, estimated glomerular filtration rate, and C-reactive protein had relatively little impact on explaining the risk of heart disease associated with blood sugar.”
“It is well established that being overweight can lead to higher blood sugar levels as well as higher blood pressure, these being factors that contribute to higher risk of heart attack and stroke,” Robert Storey, DM, professor of cardiology, University of Sheffield (England), told the UK Science Media Centre.
“This very large UK Biobank study,” he said, “shows that the higher heart risk associated with blood sugar can be detected at a very early stage along the path towards the abnormally high blood sugar levels associated with diabetes.
“The study provides support for a strategy of assessing cardiovascular risk in people who are overweight, including assessment of blood sugar, cholesterol, and blood pressure levels, all of which can be effectively managed to markedly reduce the risk of future heart attack and stroke,” according to Dr. Storey.
More than 400,000 men, women
The researchers enrolled men and women aged 40-69 between 2006 to 2010 who were living in England, Scotland, and Wales. After excluding people with type 1 diabetes or those whose A1c data were missing, the current study included 427,435 people (46% of whom were men).
The participants were classified as having low-normal A1c (< 35 mmol/mol or < 5.5%), normal A1c (35-41 mmol/mol or 5.5%-5.9%), prediabetes (42-47 mmol/mol or 6.0%-6.4%), undiagnosed diabetes (≥ 48 mmol/mol or ≥ 6.5%), or diagnosed type 2 diabetes (medical history and in receipt of glucose-lowering medication).
The researchers determined the incidence of six CVD outcomes during a median 11.8-year follow-up: coronary artery disease, atrial fibrillation, deep vein thrombosis, pulmonary embolism, stroke, and heart failure.
Few participants (5%) had any of these outcomes prior to study enrollment.
During the follow-up, there were 51,288 incident CVD events.
After adjustment for age, compared to having normal A1c, having prediabetes or undiagnosed diabetes was associated with an increased risk of CVD for women and men (hazard ratio [HR], 1.30-1.47).
Among individuals with diagnosed type 2 diabetes, the age-adjusted risk of CVD was greater for women (HR, 2.00) than for men (HR, 1.55).
After further adjustment for clinical and lifestyle factors, especially obesity and antihypertensive or statin use, the risk of CVD decreased and became similar among men and women. The fully adjusted HR for CVD was 1.17 for women and 1.06 for men with diagnosed diabetes.
Compared with having normal A1c, women and men with low-normal A1c were at decreased risk of CVD (HR, 0.86 for both).
The study was funded by Diabetes UK and the British Heart Foundation. Dr. Rentsch and Dr. Storey have disclosed no relevant financial relationships. The disclosures of the other study authors are listed in the original article.
A version of this article appeared on Medscape.com.
FROM THE LANCET REGIONAL HEALTH – EUROPE
Morning vs. afternoon exercise debate: A false dichotomy
Should we be exercising in the morning or afternoon? Before a meal or after a meal?
Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But
Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.
But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.
But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.
The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).
But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).
I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.
Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!
It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.
A version of this article first appeared on Medscape.com.
Should we be exercising in the morning or afternoon? Before a meal or after a meal?
Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But
Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.
But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.
But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.
The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).
But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).
I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.
Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!
It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.
A version of this article first appeared on Medscape.com.
Should we be exercising in the morning or afternoon? Before a meal or after a meal?
Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But
Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.
But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.
But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.
The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).
But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).
I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.
Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!
It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.
A version of this article first appeared on Medscape.com.
First-line therapy in T2D: Has metformin been ‘dethroned’?
Initially approved by the U.S. Food and Drug Administration (FDA) in 1994, metformin has been the preferred first-line glucose-lowering agent for patients with type 2 diabetes (T2D) owing to its effectiveness, low hypoglycemia risk, weight neutrality, long clinical track record of safety, and affordability. However, the advent of newer glucose-lowering agents with evidence-based cardiovascular (CV) and renal benefits calls into question whether metformin should continue to be the initial pharmacotherapy for all patients with T2D.
Cardiovascular outcome trials transform standard of care
In 2008, the FDA issued guidance to industry to ensure that CV risk is more thoroughly addressed during development of T2D therapies. This guidance document required dedicated trials to establish CV safety of new glucose-lowering therapies. Findings from subsequent cardiovascular outcome trials (CVOTs) and subsequent large renal and heart failure (HF) outcome trials have since prompted frequent and substantial updates to major guidelines. On the basis of recent evidence from CVOT and renal trials, contemporary clinical practice guidelines have transitioned from a traditional glucocentric treatment approach to a holistic management approach that emphasizes organ protection through heart-kidney-metabolic risk reduction.
Per the 2008 FDA guidance, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagonlike peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors were evaluated in large dedicated CVOTs. Findings from several CVOTs established GLP-1 receptor agonist and SGLT2 inhibitor CV safety, and unexpectedly demonstrated reduced rates of major adverse cardiovascular events (MACE) relative to placebo. The LEADER and EMPA-REG OUTCOME trials were the first CVOTs to report cardioprotective benefits of the GLP-1 receptor agonist liraglutide and the SGLT2 inhibitor empagliflozin, respectively. The LEADER trial reported a 13% significant relative risk reduction for its primary composite MACE outcome, and the EMPA-REG OUTCOME trial similarly reported a 14% relative risk reduction for MACE. After CVOTs on other GLP-1 receptor agonists and SGLT2 inhibitors reported CV benefit, clinical practice guidelines began to recommend use of these agents in at-risk patients to mitigate CV risk.
During the period when most CVOTs were designed and conducted, a majority of trial participants were receiving metformin at baseline. Inclusion of a small subset of metformin-naive participants in these trials allowed for several post hoc and meta-analyses investigating the impact of background metformin use on the overall CV benefits reported. Depending on the trial, baseline metformin use in large GLP-1 receptor agonist CVOTs ranged from 66% to 81%. For instance, 76% of participants in the LEADER trial were receiving metformin at baseline, but a post hoc analysis found no heterogeneity for the observed CV benefit based on background metformin use. Similarly, a subgroup analysis of pooled data from the SUSTAIN-6 and PIONEER 6 trials of injectable and oral formulations of semaglutide, respectively, reported similar CV outcomes for participants, regardless of concomitant metformin use. When looking at the GLP-1 receptor agonist class overall, a meta-analysis of seven CVOTs, which included participants with established atherosclerotic cardiovascular disease (ASCVD) and those with multiple ASCVD risk factors, concluded that GLP-1 receptor agonist therapy reduced the overall incidence of MACE in participants not receiving concomitant metformin at baseline.
Similar analyses have examined the impact of background metformin use on CV outcomes with SGLT2 inhibitors. An analysis of EMPA-REG OUTCOME found that empagliflozin improved CV outcomes and reduced mortality irrespective of background metformin, sulfonylurea, or insulin use. Of note, this analysis suggested a greater risk reduction for incident or worsening nephropathy in patients not on concomitant metformin (hazard ratio, 0.47; 95% confidence interval, 0.37-0.59; P = .01), when compared with those taking metformin at baseline (HR, 0.68; 95% CI, 0.58-0.79; P = .01). In addition, a meta-analysis of six large outcome trials found consistent benefits of SGLT2 inhibition on CV, kidney, and mortality outcomes regardless of background metformin treatment. Therefore, although CVOTs on GLP-1 receptor agonists and SGLT2 inhibitors were not designed to assess the impact of background metformin use on CV outcomes, available evidence supports the CV benefits of these agents independent of metformin use.
Individualizing care to attain cardiorenal-metabolic goals
Three dedicated SGLT2 inhibitor renal outcome trials have been published to date: CREDENCE, DAPA-CKD, and EMPA-KIDNEY. All three studies confirmed the positive secondary renal outcomes observed in SGLT2 inhibitor CVOTs: reduced progression of kidney disease, HF-associated hospital admissions, and CV-related death. The observed renal and CV benefits from the CREDENCE trial were consistent across different levels of kidney function. Similarly, a meta-analysis of five SGLT2 inhibitor trials of patients with HF demonstrated a decreased risk for CV-related death and admission for HF, irrespective of baseline heart function. The ongoing FLOW is the first dedicated kidney-outcome trial to evaluate the effectiveness of a GLP-1 receptor agonist (semaglutide) in slowing the progression and worsening of chronic kidney disease (CKD) in patients with T2D.
As previously noted, findings from the LEADER and EMPA-REG OUTCOME trials demonstrated the beneficial effects of GLP-1 receptor agonists and SGLT2 inhibitors not only on MACE but also on secondary HF and kidney disease outcomes. These findings have supported a series of dedicated HF and kidney outcome trials further informing the standard of care for patients with these key comorbidities. Indeed, the American Diabetes Association’s 2023 Standards of Care in Diabetes updated its recommendations and algorithm for the use of glucose-lowering medications in the management of T2D. The current ADA recommendations stress cardiorenal risk reduction while concurrently achieving and maintaining glycemic and weight management goals. On the basis of evolving outcome trial data, GLP-1 receptor agonists and SGLT2 inhibitors with evidence of benefit are recommended for patients with established or at high risk for ASCVD. Further, the Standards preferentially recommend SGLT2 inhibitors for patients with HF and/or CKD. Because evidence suggests no heterogeneity of benefit based on hemoglobin A1c for MACE outcomes with GLP-1 receptor agonists and no heterogeneity of benefit for HF or CKD benefits with SGLT2 inhibitors, these agents are recommended for cardiorenal risk reduction regardless of the need to lower glucose.
The 2023 update to the American Association of Clinical Endocrinology Consensus Statement: Type 2 Diabetes Management Algorithm similarly recommends the use of GLP-1 receptor agonists and SGLT2 inhibitors to improve cardiorenal outcomes. To further emphasize the importance of prescribing agents with proven organ-protective benefits, the AACE consensus statement provides a complications-centric algorithm to guide therapeutic decisions for risk reduction in patients with key comorbidities (for instance, ASCVD, HF, CKD) and a separate glucocentric algorithm to guide selection and intensification of glucose-lowering agents in patients without key comorbidities to meet individualized glycemic targets. Within the complications-centric algorithm, AACE recommends GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment for cardiorenal risk reduction regardless of background metformin use or A1c level.
In addition to the emphasis on the use of GLP-1 receptor agonists and SGLT2 inhibitors for organ protection, guidelines now recommend SGLT2 inhibitors as the standard-of-care therapy in patients with T2D and CKD with an estimated glomerular filtration rate ≥ 20 mL/min per 1.73 m2, and irrespective of ejection fraction or a diagnosis of diabetes in the setting of HF. Overall, a common thread within current guidelines is the importance of individualized therapy based on patient- and medication-specific factors.
Optimizing guideline-directed medical therapy
Results from the DISCOVER trial found that GLP-1 receptor agonist and SGLT2 inhibitor use was less likely in the key patient subgroups most likely to benefit from therapy, including patients with peripheral artery disease and CKD. Factors contributing to underutilization of newer cardiorenal protective glucose-lowering therapies range from cost and access barriers to clinician-level barriers (for example, lack of knowledge on CKD, lack of familiarity with CKD practice guidelines). Addressing these issues and helping patients work through financial and other access barriers is essential to optimize the utilization of these therapies and improve cardiorenal and metabolic outcomes.
So, has metformin been “dethroned” as a first-line therapy for T2D? As is often the case in medicine, the answer depends on the individual patient and clinical situation. Metformin remains an important first-line treatment in combination with lifestyle interventions to help patients with T2D without key cardiorenal comorbidities achieve individualized glycemic targets. However, based on evidence demonstrating cardiorenal protective benefits and improved glycemia and weight loss, GLP-1 agonists and SGLT2 inhibitors may be considered as first-line treatment for patients with T2D with or at high risk for ASCVD, HF, or CKD, regardless of the need for additional glucose-lowering agents and independent of background metformin. Ultimately, the choice of first-line therapy for patients with T2D should be informed by individualized treatment goals, preferences, and cost-related access. Continued efforts to increase patient access to GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment when indicated are essential to ensure optimal treatment and outcomes.
Dr. Neumiller is professor, department of pharmacotherapy, Washington State University, Spokane. He disclosed ties with Bayer, Boehringer Ingelheim, and Eli Lilly. Dr. Alicic is clinical professor, department of medicine, University of Washington; and associate director of research, Inland Northwest Washington, Providence St. Joseph Health, Spokane. She disclosed ties with Providence St. Joseph Health, Boehringer Ingelheim/Lilly, and Bayer.
A version of this article appeared on Medscape.com.
Initially approved by the U.S. Food and Drug Administration (FDA) in 1994, metformin has been the preferred first-line glucose-lowering agent for patients with type 2 diabetes (T2D) owing to its effectiveness, low hypoglycemia risk, weight neutrality, long clinical track record of safety, and affordability. However, the advent of newer glucose-lowering agents with evidence-based cardiovascular (CV) and renal benefits calls into question whether metformin should continue to be the initial pharmacotherapy for all patients with T2D.
Cardiovascular outcome trials transform standard of care
In 2008, the FDA issued guidance to industry to ensure that CV risk is more thoroughly addressed during development of T2D therapies. This guidance document required dedicated trials to establish CV safety of new glucose-lowering therapies. Findings from subsequent cardiovascular outcome trials (CVOTs) and subsequent large renal and heart failure (HF) outcome trials have since prompted frequent and substantial updates to major guidelines. On the basis of recent evidence from CVOT and renal trials, contemporary clinical practice guidelines have transitioned from a traditional glucocentric treatment approach to a holistic management approach that emphasizes organ protection through heart-kidney-metabolic risk reduction.
Per the 2008 FDA guidance, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagonlike peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors were evaluated in large dedicated CVOTs. Findings from several CVOTs established GLP-1 receptor agonist and SGLT2 inhibitor CV safety, and unexpectedly demonstrated reduced rates of major adverse cardiovascular events (MACE) relative to placebo. The LEADER and EMPA-REG OUTCOME trials were the first CVOTs to report cardioprotective benefits of the GLP-1 receptor agonist liraglutide and the SGLT2 inhibitor empagliflozin, respectively. The LEADER trial reported a 13% significant relative risk reduction for its primary composite MACE outcome, and the EMPA-REG OUTCOME trial similarly reported a 14% relative risk reduction for MACE. After CVOTs on other GLP-1 receptor agonists and SGLT2 inhibitors reported CV benefit, clinical practice guidelines began to recommend use of these agents in at-risk patients to mitigate CV risk.
During the period when most CVOTs were designed and conducted, a majority of trial participants were receiving metformin at baseline. Inclusion of a small subset of metformin-naive participants in these trials allowed for several post hoc and meta-analyses investigating the impact of background metformin use on the overall CV benefits reported. Depending on the trial, baseline metformin use in large GLP-1 receptor agonist CVOTs ranged from 66% to 81%. For instance, 76% of participants in the LEADER trial were receiving metformin at baseline, but a post hoc analysis found no heterogeneity for the observed CV benefit based on background metformin use. Similarly, a subgroup analysis of pooled data from the SUSTAIN-6 and PIONEER 6 trials of injectable and oral formulations of semaglutide, respectively, reported similar CV outcomes for participants, regardless of concomitant metformin use. When looking at the GLP-1 receptor agonist class overall, a meta-analysis of seven CVOTs, which included participants with established atherosclerotic cardiovascular disease (ASCVD) and those with multiple ASCVD risk factors, concluded that GLP-1 receptor agonist therapy reduced the overall incidence of MACE in participants not receiving concomitant metformin at baseline.
Similar analyses have examined the impact of background metformin use on CV outcomes with SGLT2 inhibitors. An analysis of EMPA-REG OUTCOME found that empagliflozin improved CV outcomes and reduced mortality irrespective of background metformin, sulfonylurea, or insulin use. Of note, this analysis suggested a greater risk reduction for incident or worsening nephropathy in patients not on concomitant metformin (hazard ratio, 0.47; 95% confidence interval, 0.37-0.59; P = .01), when compared with those taking metformin at baseline (HR, 0.68; 95% CI, 0.58-0.79; P = .01). In addition, a meta-analysis of six large outcome trials found consistent benefits of SGLT2 inhibition on CV, kidney, and mortality outcomes regardless of background metformin treatment. Therefore, although CVOTs on GLP-1 receptor agonists and SGLT2 inhibitors were not designed to assess the impact of background metformin use on CV outcomes, available evidence supports the CV benefits of these agents independent of metformin use.
Individualizing care to attain cardiorenal-metabolic goals
Three dedicated SGLT2 inhibitor renal outcome trials have been published to date: CREDENCE, DAPA-CKD, and EMPA-KIDNEY. All three studies confirmed the positive secondary renal outcomes observed in SGLT2 inhibitor CVOTs: reduced progression of kidney disease, HF-associated hospital admissions, and CV-related death. The observed renal and CV benefits from the CREDENCE trial were consistent across different levels of kidney function. Similarly, a meta-analysis of five SGLT2 inhibitor trials of patients with HF demonstrated a decreased risk for CV-related death and admission for HF, irrespective of baseline heart function. The ongoing FLOW is the first dedicated kidney-outcome trial to evaluate the effectiveness of a GLP-1 receptor agonist (semaglutide) in slowing the progression and worsening of chronic kidney disease (CKD) in patients with T2D.
As previously noted, findings from the LEADER and EMPA-REG OUTCOME trials demonstrated the beneficial effects of GLP-1 receptor agonists and SGLT2 inhibitors not only on MACE but also on secondary HF and kidney disease outcomes. These findings have supported a series of dedicated HF and kidney outcome trials further informing the standard of care for patients with these key comorbidities. Indeed, the American Diabetes Association’s 2023 Standards of Care in Diabetes updated its recommendations and algorithm for the use of glucose-lowering medications in the management of T2D. The current ADA recommendations stress cardiorenal risk reduction while concurrently achieving and maintaining glycemic and weight management goals. On the basis of evolving outcome trial data, GLP-1 receptor agonists and SGLT2 inhibitors with evidence of benefit are recommended for patients with established or at high risk for ASCVD. Further, the Standards preferentially recommend SGLT2 inhibitors for patients with HF and/or CKD. Because evidence suggests no heterogeneity of benefit based on hemoglobin A1c for MACE outcomes with GLP-1 receptor agonists and no heterogeneity of benefit for HF or CKD benefits with SGLT2 inhibitors, these agents are recommended for cardiorenal risk reduction regardless of the need to lower glucose.
The 2023 update to the American Association of Clinical Endocrinology Consensus Statement: Type 2 Diabetes Management Algorithm similarly recommends the use of GLP-1 receptor agonists and SGLT2 inhibitors to improve cardiorenal outcomes. To further emphasize the importance of prescribing agents with proven organ-protective benefits, the AACE consensus statement provides a complications-centric algorithm to guide therapeutic decisions for risk reduction in patients with key comorbidities (for instance, ASCVD, HF, CKD) and a separate glucocentric algorithm to guide selection and intensification of glucose-lowering agents in patients without key comorbidities to meet individualized glycemic targets. Within the complications-centric algorithm, AACE recommends GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment for cardiorenal risk reduction regardless of background metformin use or A1c level.
In addition to the emphasis on the use of GLP-1 receptor agonists and SGLT2 inhibitors for organ protection, guidelines now recommend SGLT2 inhibitors as the standard-of-care therapy in patients with T2D and CKD with an estimated glomerular filtration rate ≥ 20 mL/min per 1.73 m2, and irrespective of ejection fraction or a diagnosis of diabetes in the setting of HF. Overall, a common thread within current guidelines is the importance of individualized therapy based on patient- and medication-specific factors.
Optimizing guideline-directed medical therapy
Results from the DISCOVER trial found that GLP-1 receptor agonist and SGLT2 inhibitor use was less likely in the key patient subgroups most likely to benefit from therapy, including patients with peripheral artery disease and CKD. Factors contributing to underutilization of newer cardiorenal protective glucose-lowering therapies range from cost and access barriers to clinician-level barriers (for example, lack of knowledge on CKD, lack of familiarity with CKD practice guidelines). Addressing these issues and helping patients work through financial and other access barriers is essential to optimize the utilization of these therapies and improve cardiorenal and metabolic outcomes.
So, has metformin been “dethroned” as a first-line therapy for T2D? As is often the case in medicine, the answer depends on the individual patient and clinical situation. Metformin remains an important first-line treatment in combination with lifestyle interventions to help patients with T2D without key cardiorenal comorbidities achieve individualized glycemic targets. However, based on evidence demonstrating cardiorenal protective benefits and improved glycemia and weight loss, GLP-1 agonists and SGLT2 inhibitors may be considered as first-line treatment for patients with T2D with or at high risk for ASCVD, HF, or CKD, regardless of the need for additional glucose-lowering agents and independent of background metformin. Ultimately, the choice of first-line therapy for patients with T2D should be informed by individualized treatment goals, preferences, and cost-related access. Continued efforts to increase patient access to GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment when indicated are essential to ensure optimal treatment and outcomes.
Dr. Neumiller is professor, department of pharmacotherapy, Washington State University, Spokane. He disclosed ties with Bayer, Boehringer Ingelheim, and Eli Lilly. Dr. Alicic is clinical professor, department of medicine, University of Washington; and associate director of research, Inland Northwest Washington, Providence St. Joseph Health, Spokane. She disclosed ties with Providence St. Joseph Health, Boehringer Ingelheim/Lilly, and Bayer.
A version of this article appeared on Medscape.com.
Initially approved by the U.S. Food and Drug Administration (FDA) in 1994, metformin has been the preferred first-line glucose-lowering agent for patients with type 2 diabetes (T2D) owing to its effectiveness, low hypoglycemia risk, weight neutrality, long clinical track record of safety, and affordability. However, the advent of newer glucose-lowering agents with evidence-based cardiovascular (CV) and renal benefits calls into question whether metformin should continue to be the initial pharmacotherapy for all patients with T2D.
Cardiovascular outcome trials transform standard of care
In 2008, the FDA issued guidance to industry to ensure that CV risk is more thoroughly addressed during development of T2D therapies. This guidance document required dedicated trials to establish CV safety of new glucose-lowering therapies. Findings from subsequent cardiovascular outcome trials (CVOTs) and subsequent large renal and heart failure (HF) outcome trials have since prompted frequent and substantial updates to major guidelines. On the basis of recent evidence from CVOT and renal trials, contemporary clinical practice guidelines have transitioned from a traditional glucocentric treatment approach to a holistic management approach that emphasizes organ protection through heart-kidney-metabolic risk reduction.
Per the 2008 FDA guidance, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagonlike peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors were evaluated in large dedicated CVOTs. Findings from several CVOTs established GLP-1 receptor agonist and SGLT2 inhibitor CV safety, and unexpectedly demonstrated reduced rates of major adverse cardiovascular events (MACE) relative to placebo. The LEADER and EMPA-REG OUTCOME trials were the first CVOTs to report cardioprotective benefits of the GLP-1 receptor agonist liraglutide and the SGLT2 inhibitor empagliflozin, respectively. The LEADER trial reported a 13% significant relative risk reduction for its primary composite MACE outcome, and the EMPA-REG OUTCOME trial similarly reported a 14% relative risk reduction for MACE. After CVOTs on other GLP-1 receptor agonists and SGLT2 inhibitors reported CV benefit, clinical practice guidelines began to recommend use of these agents in at-risk patients to mitigate CV risk.
During the period when most CVOTs were designed and conducted, a majority of trial participants were receiving metformin at baseline. Inclusion of a small subset of metformin-naive participants in these trials allowed for several post hoc and meta-analyses investigating the impact of background metformin use on the overall CV benefits reported. Depending on the trial, baseline metformin use in large GLP-1 receptor agonist CVOTs ranged from 66% to 81%. For instance, 76% of participants in the LEADER trial were receiving metformin at baseline, but a post hoc analysis found no heterogeneity for the observed CV benefit based on background metformin use. Similarly, a subgroup analysis of pooled data from the SUSTAIN-6 and PIONEER 6 trials of injectable and oral formulations of semaglutide, respectively, reported similar CV outcomes for participants, regardless of concomitant metformin use. When looking at the GLP-1 receptor agonist class overall, a meta-analysis of seven CVOTs, which included participants with established atherosclerotic cardiovascular disease (ASCVD) and those with multiple ASCVD risk factors, concluded that GLP-1 receptor agonist therapy reduced the overall incidence of MACE in participants not receiving concomitant metformin at baseline.
Similar analyses have examined the impact of background metformin use on CV outcomes with SGLT2 inhibitors. An analysis of EMPA-REG OUTCOME found that empagliflozin improved CV outcomes and reduced mortality irrespective of background metformin, sulfonylurea, or insulin use. Of note, this analysis suggested a greater risk reduction for incident or worsening nephropathy in patients not on concomitant metformin (hazard ratio, 0.47; 95% confidence interval, 0.37-0.59; P = .01), when compared with those taking metformin at baseline (HR, 0.68; 95% CI, 0.58-0.79; P = .01). In addition, a meta-analysis of six large outcome trials found consistent benefits of SGLT2 inhibition on CV, kidney, and mortality outcomes regardless of background metformin treatment. Therefore, although CVOTs on GLP-1 receptor agonists and SGLT2 inhibitors were not designed to assess the impact of background metformin use on CV outcomes, available evidence supports the CV benefits of these agents independent of metformin use.
Individualizing care to attain cardiorenal-metabolic goals
Three dedicated SGLT2 inhibitor renal outcome trials have been published to date: CREDENCE, DAPA-CKD, and EMPA-KIDNEY. All three studies confirmed the positive secondary renal outcomes observed in SGLT2 inhibitor CVOTs: reduced progression of kidney disease, HF-associated hospital admissions, and CV-related death. The observed renal and CV benefits from the CREDENCE trial were consistent across different levels of kidney function. Similarly, a meta-analysis of five SGLT2 inhibitor trials of patients with HF demonstrated a decreased risk for CV-related death and admission for HF, irrespective of baseline heart function. The ongoing FLOW is the first dedicated kidney-outcome trial to evaluate the effectiveness of a GLP-1 receptor agonist (semaglutide) in slowing the progression and worsening of chronic kidney disease (CKD) in patients with T2D.
As previously noted, findings from the LEADER and EMPA-REG OUTCOME trials demonstrated the beneficial effects of GLP-1 receptor agonists and SGLT2 inhibitors not only on MACE but also on secondary HF and kidney disease outcomes. These findings have supported a series of dedicated HF and kidney outcome trials further informing the standard of care for patients with these key comorbidities. Indeed, the American Diabetes Association’s 2023 Standards of Care in Diabetes updated its recommendations and algorithm for the use of glucose-lowering medications in the management of T2D. The current ADA recommendations stress cardiorenal risk reduction while concurrently achieving and maintaining glycemic and weight management goals. On the basis of evolving outcome trial data, GLP-1 receptor agonists and SGLT2 inhibitors with evidence of benefit are recommended for patients with established or at high risk for ASCVD. Further, the Standards preferentially recommend SGLT2 inhibitors for patients with HF and/or CKD. Because evidence suggests no heterogeneity of benefit based on hemoglobin A1c for MACE outcomes with GLP-1 receptor agonists and no heterogeneity of benefit for HF or CKD benefits with SGLT2 inhibitors, these agents are recommended for cardiorenal risk reduction regardless of the need to lower glucose.
The 2023 update to the American Association of Clinical Endocrinology Consensus Statement: Type 2 Diabetes Management Algorithm similarly recommends the use of GLP-1 receptor agonists and SGLT2 inhibitors to improve cardiorenal outcomes. To further emphasize the importance of prescribing agents with proven organ-protective benefits, the AACE consensus statement provides a complications-centric algorithm to guide therapeutic decisions for risk reduction in patients with key comorbidities (for instance, ASCVD, HF, CKD) and a separate glucocentric algorithm to guide selection and intensification of glucose-lowering agents in patients without key comorbidities to meet individualized glycemic targets. Within the complications-centric algorithm, AACE recommends GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment for cardiorenal risk reduction regardless of background metformin use or A1c level.
In addition to the emphasis on the use of GLP-1 receptor agonists and SGLT2 inhibitors for organ protection, guidelines now recommend SGLT2 inhibitors as the standard-of-care therapy in patients with T2D and CKD with an estimated glomerular filtration rate ≥ 20 mL/min per 1.73 m2, and irrespective of ejection fraction or a diagnosis of diabetes in the setting of HF. Overall, a common thread within current guidelines is the importance of individualized therapy based on patient- and medication-specific factors.
Optimizing guideline-directed medical therapy
Results from the DISCOVER trial found that GLP-1 receptor agonist and SGLT2 inhibitor use was less likely in the key patient subgroups most likely to benefit from therapy, including patients with peripheral artery disease and CKD. Factors contributing to underutilization of newer cardiorenal protective glucose-lowering therapies range from cost and access barriers to clinician-level barriers (for example, lack of knowledge on CKD, lack of familiarity with CKD practice guidelines). Addressing these issues and helping patients work through financial and other access barriers is essential to optimize the utilization of these therapies and improve cardiorenal and metabolic outcomes.
So, has metformin been “dethroned” as a first-line therapy for T2D? As is often the case in medicine, the answer depends on the individual patient and clinical situation. Metformin remains an important first-line treatment in combination with lifestyle interventions to help patients with T2D without key cardiorenal comorbidities achieve individualized glycemic targets. However, based on evidence demonstrating cardiorenal protective benefits and improved glycemia and weight loss, GLP-1 agonists and SGLT2 inhibitors may be considered as first-line treatment for patients with T2D with or at high risk for ASCVD, HF, or CKD, regardless of the need for additional glucose-lowering agents and independent of background metformin. Ultimately, the choice of first-line therapy for patients with T2D should be informed by individualized treatment goals, preferences, and cost-related access. Continued efforts to increase patient access to GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment when indicated are essential to ensure optimal treatment and outcomes.
Dr. Neumiller is professor, department of pharmacotherapy, Washington State University, Spokane. He disclosed ties with Bayer, Boehringer Ingelheim, and Eli Lilly. Dr. Alicic is clinical professor, department of medicine, University of Washington; and associate director of research, Inland Northwest Washington, Providence St. Joseph Health, Spokane. She disclosed ties with Providence St. Joseph Health, Boehringer Ingelheim/Lilly, and Bayer.
A version of this article appeared on Medscape.com.
Cause of common gastrointestinal symptoms in diabetes?
The condition – in which the pancreas fails to produce sufficient enzymes to fully digest food – can cause gastrointestinal symptoms, including steatorrhea or other stool changes, bloating, and/or abdominal pain. The preferred test for diagnosis is a 72-hour fecal fat quantification test, but fecal elastase-1 is a less invasive and reliable alternative; values of less than 200 mcg/g indicate EPI. Treatment is pancreatic enzyme replacement therapy (PERT), taken with every meal.
EPI occurs in up to 90% of people with cystic fibrosis and chronic pancreatitis and is commonly associated with acute pancreatitis, autoimmune pancreatitis, and pancreatic cancer. However, those conditions are relatively rare compared to diabetes, yet the EPI association with diabetes is less well-studied, Dana M. Lewis, BA, points out in her review article.
While the data vary across studies, owing to differences in inclusion and exclusion criteria, the overall median prevalence of EPI was 33% among patients with type 1 diabetes (range, 14%-77.5%) and 29% among patients with type 2 diabetes (range, 16.8%-49.2%), Ms. Lewis reports in the article, which was published in Diabetes Technology and Therapeutics.
“Cumulatively, this suggests there may be significant numbers of people with diabetes with EPI who are undiagnosed. People with diabetes who present with gastrointestinal symptoms – such as steatorrhea or changes in stool, bloating, and/or abdominal pain – should be screened for EPI. Diabetes specialists, gastroenterologists, and primary care providers should be aware of the high rates of prevalence of diabetes and EPI and recommend fecal elastase-1 screening for people with diabetes and GI symptoms,” Ms. Lewis writes.
Since the publication of her article, Ms. Lewis told this news organization, “I’ve gotten feedback from multiple diabetes and general providers that they will be changing their practice as a result of this paper, by screening people with diabetes who have GI symptoms for EPI, which is wonderful to hear.”
In addition, she noted that since she began blogging about EPI and diabetes last year following her own delayed diagnosis, “I have had at least half a dozen people with diabetes tell me that they’ve since sought screening for EPI after years of GI symptoms and ended up being diagnosed with EPI as well.”
Asked to comment, Romesh Khardori, MD, PhD, said in an interview, “it would be prudent to investigate EPI and treat it when confirmed. Consultation with a gastroenterologist colleague may be helpful. Treatment is quite rewarding.”
Data limitations; and don’t forget celiac disease and gastroparesis
However, as does Ms. Lewis, Dr. Khardori points to the limitations of the current literature.
“This review suffers from the lack of uniformity amongst the studies in terms of diagnosis and documentation of exocrine pancreatic insufficiency. Many studies lack a control group to draw any meaningful conclusions. Correlations with duration of diabetes, age of onset, symptoms, and glycemic control were mostly lacking,” says Dr. Khardori, now retired but formerly professor of medicine: endocrinology and metabolism at Eastern Virginia Medical School, Norfolk.
In general, the data suggest that PERT is safe and effective for people with diabetes and that it may reduce glycemic variability. However, “there are not many studies looking at glucose outcomes in detail, and only one study that has used CGM [continuous glucose monitoring] data, so this is a big area of need for future study,” Ms. Lewis told this news organization.
Ms. Lewis also reviewed the literature on the prevalence of two other diabetes-related gastrointestinal conditions, celiac disease and gastroparesis, “because anecdotally, it seems as though diabetes care providers and people with diabetes are more aware of those as causes of GI symptoms.”
In type 1 diabetes, the prevalence of both celiac disease and gastroparesis are reported at about 5%, in contrast to the 33% for EPI. Similarly, in type 2 diabetes, the reported prevalence of these two conditions are 1.3% and 1.6%, respectively, vs. 29% for EPI.
“This suggests to me that there is likely disproportionate screening for things like celiac [disease] and gastroparesis in diabetes, and that screening for EPI when people with diabetes present with GI symptoms is warranted,” Ms. Lewis said.
However, Dr. Khardori cautioned that those conditions may also be missed, noting, “Celiac disease often is undiagnosed and gastropathy or gastroparesis may be overlooked in a busy primary care clinic where most patients with diabetes mellitus get their care.”
Ms. Lewis and Dr. Khardori have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The condition – in which the pancreas fails to produce sufficient enzymes to fully digest food – can cause gastrointestinal symptoms, including steatorrhea or other stool changes, bloating, and/or abdominal pain. The preferred test for diagnosis is a 72-hour fecal fat quantification test, but fecal elastase-1 is a less invasive and reliable alternative; values of less than 200 mcg/g indicate EPI. Treatment is pancreatic enzyme replacement therapy (PERT), taken with every meal.
EPI occurs in up to 90% of people with cystic fibrosis and chronic pancreatitis and is commonly associated with acute pancreatitis, autoimmune pancreatitis, and pancreatic cancer. However, those conditions are relatively rare compared to diabetes, yet the EPI association with diabetes is less well-studied, Dana M. Lewis, BA, points out in her review article.
While the data vary across studies, owing to differences in inclusion and exclusion criteria, the overall median prevalence of EPI was 33% among patients with type 1 diabetes (range, 14%-77.5%) and 29% among patients with type 2 diabetes (range, 16.8%-49.2%), Ms. Lewis reports in the article, which was published in Diabetes Technology and Therapeutics.
“Cumulatively, this suggests there may be significant numbers of people with diabetes with EPI who are undiagnosed. People with diabetes who present with gastrointestinal symptoms – such as steatorrhea or changes in stool, bloating, and/or abdominal pain – should be screened for EPI. Diabetes specialists, gastroenterologists, and primary care providers should be aware of the high rates of prevalence of diabetes and EPI and recommend fecal elastase-1 screening for people with diabetes and GI symptoms,” Ms. Lewis writes.
Since the publication of her article, Ms. Lewis told this news organization, “I’ve gotten feedback from multiple diabetes and general providers that they will be changing their practice as a result of this paper, by screening people with diabetes who have GI symptoms for EPI, which is wonderful to hear.”
In addition, she noted that since she began blogging about EPI and diabetes last year following her own delayed diagnosis, “I have had at least half a dozen people with diabetes tell me that they’ve since sought screening for EPI after years of GI symptoms and ended up being diagnosed with EPI as well.”
Asked to comment, Romesh Khardori, MD, PhD, said in an interview, “it would be prudent to investigate EPI and treat it when confirmed. Consultation with a gastroenterologist colleague may be helpful. Treatment is quite rewarding.”
Data limitations; and don’t forget celiac disease and gastroparesis
However, as does Ms. Lewis, Dr. Khardori points to the limitations of the current literature.
“This review suffers from the lack of uniformity amongst the studies in terms of diagnosis and documentation of exocrine pancreatic insufficiency. Many studies lack a control group to draw any meaningful conclusions. Correlations with duration of diabetes, age of onset, symptoms, and glycemic control were mostly lacking,” says Dr. Khardori, now retired but formerly professor of medicine: endocrinology and metabolism at Eastern Virginia Medical School, Norfolk.
In general, the data suggest that PERT is safe and effective for people with diabetes and that it may reduce glycemic variability. However, “there are not many studies looking at glucose outcomes in detail, and only one study that has used CGM [continuous glucose monitoring] data, so this is a big area of need for future study,” Ms. Lewis told this news organization.
Ms. Lewis also reviewed the literature on the prevalence of two other diabetes-related gastrointestinal conditions, celiac disease and gastroparesis, “because anecdotally, it seems as though diabetes care providers and people with diabetes are more aware of those as causes of GI symptoms.”
In type 1 diabetes, the prevalence of both celiac disease and gastroparesis are reported at about 5%, in contrast to the 33% for EPI. Similarly, in type 2 diabetes, the reported prevalence of these two conditions are 1.3% and 1.6%, respectively, vs. 29% for EPI.
“This suggests to me that there is likely disproportionate screening for things like celiac [disease] and gastroparesis in diabetes, and that screening for EPI when people with diabetes present with GI symptoms is warranted,” Ms. Lewis said.
However, Dr. Khardori cautioned that those conditions may also be missed, noting, “Celiac disease often is undiagnosed and gastropathy or gastroparesis may be overlooked in a busy primary care clinic where most patients with diabetes mellitus get their care.”
Ms. Lewis and Dr. Khardori have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The condition – in which the pancreas fails to produce sufficient enzymes to fully digest food – can cause gastrointestinal symptoms, including steatorrhea or other stool changes, bloating, and/or abdominal pain. The preferred test for diagnosis is a 72-hour fecal fat quantification test, but fecal elastase-1 is a less invasive and reliable alternative; values of less than 200 mcg/g indicate EPI. Treatment is pancreatic enzyme replacement therapy (PERT), taken with every meal.
EPI occurs in up to 90% of people with cystic fibrosis and chronic pancreatitis and is commonly associated with acute pancreatitis, autoimmune pancreatitis, and pancreatic cancer. However, those conditions are relatively rare compared to diabetes, yet the EPI association with diabetes is less well-studied, Dana M. Lewis, BA, points out in her review article.
While the data vary across studies, owing to differences in inclusion and exclusion criteria, the overall median prevalence of EPI was 33% among patients with type 1 diabetes (range, 14%-77.5%) and 29% among patients with type 2 diabetes (range, 16.8%-49.2%), Ms. Lewis reports in the article, which was published in Diabetes Technology and Therapeutics.
“Cumulatively, this suggests there may be significant numbers of people with diabetes with EPI who are undiagnosed. People with diabetes who present with gastrointestinal symptoms – such as steatorrhea or changes in stool, bloating, and/or abdominal pain – should be screened for EPI. Diabetes specialists, gastroenterologists, and primary care providers should be aware of the high rates of prevalence of diabetes and EPI and recommend fecal elastase-1 screening for people with diabetes and GI symptoms,” Ms. Lewis writes.
Since the publication of her article, Ms. Lewis told this news organization, “I’ve gotten feedback from multiple diabetes and general providers that they will be changing their practice as a result of this paper, by screening people with diabetes who have GI symptoms for EPI, which is wonderful to hear.”
In addition, she noted that since she began blogging about EPI and diabetes last year following her own delayed diagnosis, “I have had at least half a dozen people with diabetes tell me that they’ve since sought screening for EPI after years of GI symptoms and ended up being diagnosed with EPI as well.”
Asked to comment, Romesh Khardori, MD, PhD, said in an interview, “it would be prudent to investigate EPI and treat it when confirmed. Consultation with a gastroenterologist colleague may be helpful. Treatment is quite rewarding.”
Data limitations; and don’t forget celiac disease and gastroparesis
However, as does Ms. Lewis, Dr. Khardori points to the limitations of the current literature.
“This review suffers from the lack of uniformity amongst the studies in terms of diagnosis and documentation of exocrine pancreatic insufficiency. Many studies lack a control group to draw any meaningful conclusions. Correlations with duration of diabetes, age of onset, symptoms, and glycemic control were mostly lacking,” says Dr. Khardori, now retired but formerly professor of medicine: endocrinology and metabolism at Eastern Virginia Medical School, Norfolk.
In general, the data suggest that PERT is safe and effective for people with diabetes and that it may reduce glycemic variability. However, “there are not many studies looking at glucose outcomes in detail, and only one study that has used CGM [continuous glucose monitoring] data, so this is a big area of need for future study,” Ms. Lewis told this news organization.
Ms. Lewis also reviewed the literature on the prevalence of two other diabetes-related gastrointestinal conditions, celiac disease and gastroparesis, “because anecdotally, it seems as though diabetes care providers and people with diabetes are more aware of those as causes of GI symptoms.”
In type 1 diabetes, the prevalence of both celiac disease and gastroparesis are reported at about 5%, in contrast to the 33% for EPI. Similarly, in type 2 diabetes, the reported prevalence of these two conditions are 1.3% and 1.6%, respectively, vs. 29% for EPI.
“This suggests to me that there is likely disproportionate screening for things like celiac [disease] and gastroparesis in diabetes, and that screening for EPI when people with diabetes present with GI symptoms is warranted,” Ms. Lewis said.
However, Dr. Khardori cautioned that those conditions may also be missed, noting, “Celiac disease often is undiagnosed and gastropathy or gastroparesis may be overlooked in a busy primary care clinic where most patients with diabetes mellitus get their care.”
Ms. Lewis and Dr. Khardori have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM DIABETES TECHNOLOGY AND THERAPEUTICS
A1c not linked to postop complications in kids with diabetes
TOPLINE:
- Delaying elective surgeries until A1c is consistently normalized may not be warranted, particularly because this is challenging to accomplish rapidly.
METHODOLOGY:
- A retrospective analysis was done of data from surgery and endocrinology medical records of 438 children aged 1-18 years with type 1 (72%) or type 2 diabetes (28%) undergoing elective noncardiac surgery at Texas Children’s Hospital, January 2011 to June 2021.
- Overall, 28% had an A1c less than 7.0%, 42% had A1c 7%-9%, and 30% had A1c greater than 9%.
- The primary outcome was defined as a new-onset postoperative systemic infection, wound complication, or ketosis.
TAKEAWAY:
- The incidence of any postoperative systemic infections was 0.91% (n = 4); postoperative wound disruption, 3.33% (n = 19); and postoperative ketosis, 3.89% (n = 17).
- A1c levels were not associated with any postoperative systemic infections, wound complications, or ketosis.
- No other preoperative factors, including diabetes type, body mass index, or procedure type, were association with these complications.
IN PRACTICE:
“Current recommendations suggest consulting with the diabetes team before surgery and if glycemic status is suboptimal to consider delaying surgery and, if surgery cannot be delayed, considering admission to the hospital before surgery for acute optimization of glycemia, However, there is no guidance on the level of elevated A1c that should prompt consideration of delaying surgery. This issue is of crucial importance because necessary elective surgery or diagnostic procedures may be delayed unnecessarily or for longer than needed in children with elevated A1c because of the difficulty of improving A1c levels rapidly.”
STUDY DETAILS:
The study was led by Grace Kim, MD, of the division of diabetes and endocrinology, Texas Children’s Hospital, Houston. It was published online August 1, 2023, in Diabetes Care.
LIMITATIONS:
- The postoperative complication rate was low.
- Only elective procedures were included.
DISCLOSURES:
The authors have no disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
- Delaying elective surgeries until A1c is consistently normalized may not be warranted, particularly because this is challenging to accomplish rapidly.
METHODOLOGY:
- A retrospective analysis was done of data from surgery and endocrinology medical records of 438 children aged 1-18 years with type 1 (72%) or type 2 diabetes (28%) undergoing elective noncardiac surgery at Texas Children’s Hospital, January 2011 to June 2021.
- Overall, 28% had an A1c less than 7.0%, 42% had A1c 7%-9%, and 30% had A1c greater than 9%.
- The primary outcome was defined as a new-onset postoperative systemic infection, wound complication, or ketosis.
TAKEAWAY:
- The incidence of any postoperative systemic infections was 0.91% (n = 4); postoperative wound disruption, 3.33% (n = 19); and postoperative ketosis, 3.89% (n = 17).
- A1c levels were not associated with any postoperative systemic infections, wound complications, or ketosis.
- No other preoperative factors, including diabetes type, body mass index, or procedure type, were association with these complications.
IN PRACTICE:
“Current recommendations suggest consulting with the diabetes team before surgery and if glycemic status is suboptimal to consider delaying surgery and, if surgery cannot be delayed, considering admission to the hospital before surgery for acute optimization of glycemia, However, there is no guidance on the level of elevated A1c that should prompt consideration of delaying surgery. This issue is of crucial importance because necessary elective surgery or diagnostic procedures may be delayed unnecessarily or for longer than needed in children with elevated A1c because of the difficulty of improving A1c levels rapidly.”
STUDY DETAILS:
The study was led by Grace Kim, MD, of the division of diabetes and endocrinology, Texas Children’s Hospital, Houston. It was published online August 1, 2023, in Diabetes Care.
LIMITATIONS:
- The postoperative complication rate was low.
- Only elective procedures were included.
DISCLOSURES:
The authors have no disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
- Delaying elective surgeries until A1c is consistently normalized may not be warranted, particularly because this is challenging to accomplish rapidly.
METHODOLOGY:
- A retrospective analysis was done of data from surgery and endocrinology medical records of 438 children aged 1-18 years with type 1 (72%) or type 2 diabetes (28%) undergoing elective noncardiac surgery at Texas Children’s Hospital, January 2011 to June 2021.
- Overall, 28% had an A1c less than 7.0%, 42% had A1c 7%-9%, and 30% had A1c greater than 9%.
- The primary outcome was defined as a new-onset postoperative systemic infection, wound complication, or ketosis.
TAKEAWAY:
- The incidence of any postoperative systemic infections was 0.91% (n = 4); postoperative wound disruption, 3.33% (n = 19); and postoperative ketosis, 3.89% (n = 17).
- A1c levels were not associated with any postoperative systemic infections, wound complications, or ketosis.
- No other preoperative factors, including diabetes type, body mass index, or procedure type, were association with these complications.
IN PRACTICE:
“Current recommendations suggest consulting with the diabetes team before surgery and if glycemic status is suboptimal to consider delaying surgery and, if surgery cannot be delayed, considering admission to the hospital before surgery for acute optimization of glycemia, However, there is no guidance on the level of elevated A1c that should prompt consideration of delaying surgery. This issue is of crucial importance because necessary elective surgery or diagnostic procedures may be delayed unnecessarily or for longer than needed in children with elevated A1c because of the difficulty of improving A1c levels rapidly.”
STUDY DETAILS:
The study was led by Grace Kim, MD, of the division of diabetes and endocrinology, Texas Children’s Hospital, Houston. It was published online August 1, 2023, in Diabetes Care.
LIMITATIONS:
- The postoperative complication rate was low.
- Only elective procedures were included.
DISCLOSURES:
The authors have no disclosures.
A version of this article first appeared on Medscape.com.
FROM DIABETES CARE
Growth hormone links with worse T2D control in adolescents
SAN DIEGO – Plasma levels of three proteins involved in growth hormone activity showed significant links to the controllability of type 2 diabetes in children, a finding that suggests these proteins may serve as risk markers for incident type 2 diabetes and help identify adolescents who could benefit from aggressive preventive care.
“Plasma growth hormone mediators are associated with glycemic failure in youth with type 2 diabetes,” Chang Lu, MD, said at the at the annual scientific sessions of the American Diabetes Association. “Our hope is that these mediators could be biomarkers for predicting type 2 diabetes onset,” she added in an interview.
Another potential application is to “leverage these data to find predictive markers” that could identify adolescents with type 2 diabetes “at risk for particularly aggressive disease and target them for more intervention,” added Elvira M. Isganaitis, MD, senior author of the report and a pediatric endocrinologist at the Joslin Diabetes Center in Boston.
Does growth hormone cause incident T2D at puberty?
Changes in levels of growth hormone–associated peptides during puberty “could potentially explain why children with type 2 diabetes have a more aggressive course” of the disorder, added Dr. Lu, a pediatric endocrinologist at Joslin and at Boston’s Children’s Hospital.
Puberty-associated changes in growth hormone and related peptides “could be why type 2 diabetes starts during puberty. Type 2 diabetes is almost unheard of before children reach about age 10,” Dr. Isganaitis said in an interview.
A current hypothesis is that “high levels of growth hormone is a cause of insulin resistance during puberty, but in healthy children their beta cells overcome this by making more insulin and so they do not develop diabetes,” said Kristen J. Nadeau, MD, a pediatric endocrinologist and professor at Children’s Hospital Colorado in Denver.
“But this is a stress situation, and if someone has poor beta-cell function they may develop diabetes. The increase in growth hormone [during puberty] can unmask a physiologic and genetic predisposition” to developing type 2 diabetes, Dr. Nadeau said in an interview.
The analyses run by Dr. Lu, Dr. Isganaitis, and their coauthors used data collected in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which randomized 699 children aged 10-17 years with type 2 diabetes to one of three antidiabetes treatment regimens and tallied the subsequent incidence of glycemic failure. The study defined the latter as either 6 months with a hemoglobin A1c level of at least 8% or need for insulin treatment.
The primary outcome showed a 39%-52% incidence of failure during 5 years of follow-up depending on the specific treatments the study participants received.
Growth hormone correlates of glycemic failure
The new analyses focused on 310 study participants from TODAY who had plasma specimens available from baseline and a second specimen obtained after 3 years of follow-up. The researchers compared the levels of three peptides that mediate growth hormone signaling at baseline and after 3 years, and assessed these changes relative to the endpoint of glycemic failure.
The results showed that an increase in insulin-like growth factor-1 significantly linked with a reduced incidence of glycemic failure and improved glycemia and beta-cell function.
In contrast, Also, an increase in insulin-like growth factor binding protein-1 significantly linked with glycemic failure and hyperglycemia at 36 months, and with higher insulin sensitivity at baseline. All these analyses adjusted for baseline differences in several demographic and clinical variables.
But these post hoc analyses could not determine whether these associations resulted from, or had a causal role in, treatment failure, cautioned Dr. Lu.
Future studies should examine the relationship of growth hormone signaling and the course of glycemic control in children and adolescents with prediabetes and obesity, Dr. Lu said.
Confirming that these growth hormone-related proteins are reliable predictors of future glycemic dysfunction would open the door to studies of interventions to slow or prevent progression to type 2 diabetes in children identified as high risk.
Potential interventions include early initiation of insulin treatment, which could help preserve beta-cell function, or treatment with a glucagon-like peptide-1 (GLP-1) agonist, a class of agents that may interact with the insulin-like growth factor-1 receptors on beta cells, Dr. Lu said.
The study received no commercial funding. Dr. Lu, Dr. Isganaitis, and Dr. Nadeau reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO – Plasma levels of three proteins involved in growth hormone activity showed significant links to the controllability of type 2 diabetes in children, a finding that suggests these proteins may serve as risk markers for incident type 2 diabetes and help identify adolescents who could benefit from aggressive preventive care.
“Plasma growth hormone mediators are associated with glycemic failure in youth with type 2 diabetes,” Chang Lu, MD, said at the at the annual scientific sessions of the American Diabetes Association. “Our hope is that these mediators could be biomarkers for predicting type 2 diabetes onset,” she added in an interview.
Another potential application is to “leverage these data to find predictive markers” that could identify adolescents with type 2 diabetes “at risk for particularly aggressive disease and target them for more intervention,” added Elvira M. Isganaitis, MD, senior author of the report and a pediatric endocrinologist at the Joslin Diabetes Center in Boston.
Does growth hormone cause incident T2D at puberty?
Changes in levels of growth hormone–associated peptides during puberty “could potentially explain why children with type 2 diabetes have a more aggressive course” of the disorder, added Dr. Lu, a pediatric endocrinologist at Joslin and at Boston’s Children’s Hospital.
Puberty-associated changes in growth hormone and related peptides “could be why type 2 diabetes starts during puberty. Type 2 diabetes is almost unheard of before children reach about age 10,” Dr. Isganaitis said in an interview.
A current hypothesis is that “high levels of growth hormone is a cause of insulin resistance during puberty, but in healthy children their beta cells overcome this by making more insulin and so they do not develop diabetes,” said Kristen J. Nadeau, MD, a pediatric endocrinologist and professor at Children’s Hospital Colorado in Denver.
“But this is a stress situation, and if someone has poor beta-cell function they may develop diabetes. The increase in growth hormone [during puberty] can unmask a physiologic and genetic predisposition” to developing type 2 diabetes, Dr. Nadeau said in an interview.
The analyses run by Dr. Lu, Dr. Isganaitis, and their coauthors used data collected in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which randomized 699 children aged 10-17 years with type 2 diabetes to one of three antidiabetes treatment regimens and tallied the subsequent incidence of glycemic failure. The study defined the latter as either 6 months with a hemoglobin A1c level of at least 8% or need for insulin treatment.
The primary outcome showed a 39%-52% incidence of failure during 5 years of follow-up depending on the specific treatments the study participants received.
Growth hormone correlates of glycemic failure
The new analyses focused on 310 study participants from TODAY who had plasma specimens available from baseline and a second specimen obtained after 3 years of follow-up. The researchers compared the levels of three peptides that mediate growth hormone signaling at baseline and after 3 years, and assessed these changes relative to the endpoint of glycemic failure.
The results showed that an increase in insulin-like growth factor-1 significantly linked with a reduced incidence of glycemic failure and improved glycemia and beta-cell function.
In contrast, Also, an increase in insulin-like growth factor binding protein-1 significantly linked with glycemic failure and hyperglycemia at 36 months, and with higher insulin sensitivity at baseline. All these analyses adjusted for baseline differences in several demographic and clinical variables.
But these post hoc analyses could not determine whether these associations resulted from, or had a causal role in, treatment failure, cautioned Dr. Lu.
Future studies should examine the relationship of growth hormone signaling and the course of glycemic control in children and adolescents with prediabetes and obesity, Dr. Lu said.
Confirming that these growth hormone-related proteins are reliable predictors of future glycemic dysfunction would open the door to studies of interventions to slow or prevent progression to type 2 diabetes in children identified as high risk.
Potential interventions include early initiation of insulin treatment, which could help preserve beta-cell function, or treatment with a glucagon-like peptide-1 (GLP-1) agonist, a class of agents that may interact with the insulin-like growth factor-1 receptors on beta cells, Dr. Lu said.
The study received no commercial funding. Dr. Lu, Dr. Isganaitis, and Dr. Nadeau reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO – Plasma levels of three proteins involved in growth hormone activity showed significant links to the controllability of type 2 diabetes in children, a finding that suggests these proteins may serve as risk markers for incident type 2 diabetes and help identify adolescents who could benefit from aggressive preventive care.
“Plasma growth hormone mediators are associated with glycemic failure in youth with type 2 diabetes,” Chang Lu, MD, said at the at the annual scientific sessions of the American Diabetes Association. “Our hope is that these mediators could be biomarkers for predicting type 2 diabetes onset,” she added in an interview.
Another potential application is to “leverage these data to find predictive markers” that could identify adolescents with type 2 diabetes “at risk for particularly aggressive disease and target them for more intervention,” added Elvira M. Isganaitis, MD, senior author of the report and a pediatric endocrinologist at the Joslin Diabetes Center in Boston.
Does growth hormone cause incident T2D at puberty?
Changes in levels of growth hormone–associated peptides during puberty “could potentially explain why children with type 2 diabetes have a more aggressive course” of the disorder, added Dr. Lu, a pediatric endocrinologist at Joslin and at Boston’s Children’s Hospital.
Puberty-associated changes in growth hormone and related peptides “could be why type 2 diabetes starts during puberty. Type 2 diabetes is almost unheard of before children reach about age 10,” Dr. Isganaitis said in an interview.
A current hypothesis is that “high levels of growth hormone is a cause of insulin resistance during puberty, but in healthy children their beta cells overcome this by making more insulin and so they do not develop diabetes,” said Kristen J. Nadeau, MD, a pediatric endocrinologist and professor at Children’s Hospital Colorado in Denver.
“But this is a stress situation, and if someone has poor beta-cell function they may develop diabetes. The increase in growth hormone [during puberty] can unmask a physiologic and genetic predisposition” to developing type 2 diabetes, Dr. Nadeau said in an interview.
The analyses run by Dr. Lu, Dr. Isganaitis, and their coauthors used data collected in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which randomized 699 children aged 10-17 years with type 2 diabetes to one of three antidiabetes treatment regimens and tallied the subsequent incidence of glycemic failure. The study defined the latter as either 6 months with a hemoglobin A1c level of at least 8% or need for insulin treatment.
The primary outcome showed a 39%-52% incidence of failure during 5 years of follow-up depending on the specific treatments the study participants received.
Growth hormone correlates of glycemic failure
The new analyses focused on 310 study participants from TODAY who had plasma specimens available from baseline and a second specimen obtained after 3 years of follow-up. The researchers compared the levels of three peptides that mediate growth hormone signaling at baseline and after 3 years, and assessed these changes relative to the endpoint of glycemic failure.
The results showed that an increase in insulin-like growth factor-1 significantly linked with a reduced incidence of glycemic failure and improved glycemia and beta-cell function.
In contrast, Also, an increase in insulin-like growth factor binding protein-1 significantly linked with glycemic failure and hyperglycemia at 36 months, and with higher insulin sensitivity at baseline. All these analyses adjusted for baseline differences in several demographic and clinical variables.
But these post hoc analyses could not determine whether these associations resulted from, or had a causal role in, treatment failure, cautioned Dr. Lu.
Future studies should examine the relationship of growth hormone signaling and the course of glycemic control in children and adolescents with prediabetes and obesity, Dr. Lu said.
Confirming that these growth hormone-related proteins are reliable predictors of future glycemic dysfunction would open the door to studies of interventions to slow or prevent progression to type 2 diabetes in children identified as high risk.
Potential interventions include early initiation of insulin treatment, which could help preserve beta-cell function, or treatment with a glucagon-like peptide-1 (GLP-1) agonist, a class of agents that may interact with the insulin-like growth factor-1 receptors on beta cells, Dr. Lu said.
The study received no commercial funding. Dr. Lu, Dr. Isganaitis, and Dr. Nadeau reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
AT ADA 2023
A step forward in diabetic foot disease management
As we navigate the ever-evolving landscape of diabetic foot disease management,
The goal is to create a common language of risk that is easily related from clinician to clinician to patient.Whatever language we use, though, the problem we face is vast:
- Diabetic foot ulcers affect approximately 18.6 million people worldwide and 1.6 million in the United States each year.
- They are associated with high rates of premature death, with a 5-year mortality rate of 30%. This rate is greater than 70% for those with above-foot amputations, worse than all but the most aggressive cancers.
- The direct costs of treating diabetic foot ulcers in the United States is estimated at $9 billion-$13 billion annually.
- Over 550 million people worldwide have diabetes, with 18.6 million developing foot ulcers annually. Up to 34% of those with diabetes will develop a foot ulcer.
- About 20% of those with a diabetic foot ulcer will undergo amputation, a major cause of which is infection, which affects 50% of foot ulcers.
- Up to 20% of those with a foot ulcer require hospitalization, with 15%-20% undergoing amputation. Inequities exist in diabetes-related foot complications:
- –Rates of major amputation are higher in non-Hispanic Black, Hispanic, and Native American populations, compared with non-Hispanic White populations.
- –Non-Hispanic Black and Hispanic populations present with more advanced ulcers and peripheral artery disease, and are more likely to undergo amputation without revascularization attempt.
The IWGDF, a multidisciplinary team of international experts, has recently updated its guidelines. This team, comprising endocrinologists, internal medicine physicians, physiatrists, podiatrists, and vascular surgeons from across the globe, has worked tirelessly to provide us with a comprehensive guide to managing diabetes-related foot ulcers.
The updated guidelines address five critical clinical questions, each with up to 13 important outcomes. The systematic review that underpins these guidelines identified 149 eligible studies, assessing 28 different systems. This exhaustive research has led to the development of seven key recommendations that address the clinical questions and consider the existence of different clinical settings.
One of the significant updates in the 2023 guidelines is the recommendation of SINBAD – site, ischemia, neuropathy, bacterial infection, area, and depth – as the priority wound classification system for people with diabetes and a foot ulcer. This system is particularly useful for interprofessional communication, describing each composite variable, and conducting clinical audits using the full score. However, the guidelines also recommend the use of other, more specific assessment systems for infection and peripheral artery disease from the Infectious Diseases Society of America/IWGDF when resources and an appropriate level of expertise exist.
The introduction of the Wound, Ischemia and Foot Infection (WIfI) classification system in the guidelines is also a noteworthy development. This system is crucial in assessing perfusion and the likely benefit of revascularization in a person with diabetes and a foot ulcer. By assessing the level of wound ischemia and infection, we can make informed decisions about the need for vascular intervention, which can significantly affect the patient’s outcome. This can be done simply by classifying each of the three categories of wound, ischemia, or foot infection as none, mild, moderate, or severe. By simplifying the very dynamic comorbidities of tissue loss, ischemia, and infection into a usable and predictive scale, it helps us to communicate risk across disciplines. This has been found to be highly predictive of healing, amputation, and mortality.
We use WIfI every day across our system. An example might include a patient we recently treated:
A 76-year-old woman presented with a wound to her left foot. Her past medical history revealed type 2 diabetes, peripheral neuropathy, and documented peripheral artery disease with prior bilateral femoral-popliteal bypass conducted at an external facility. In addition to gangrenous changes to her fourth toe, she displayed erythema and lymphangitic streaking up her dorsal foot. While she was afebrile, her white cell count was 13,000/mcL. Radiographic examinations did not show signs of osteomyelitis. Noninvasive vascular evaluations revealed an ankle brachial index of 0.4 and a toe pressure of 10 mm Hg. An aortogram with a lower-extremity runoff arteriogram confirmed the obstruction of her left femoral-popliteal bypass.
Taking these results into account, her WIfI score was determined as: wound 2 (moderate), ischemia 3 (severe), foot infection 2 (moderate, no sepsis), translating to a clinical stage 4. This denotes a high risk for major amputation.
Following a team discussion, she was taken to the operating room for an initial debridement of her infection which consisted of a partial fourth ray resection to the level of the mid-metatarsal. Following control of the infection, she received a vascular assessment which ultimately constituted a femoral to distal anterior tibial bypass. Following both of these, she was discharged on a negative-pressure wound therapy device, receiving a split-thickness skin graft 4 weeks later.
The guidelines also emphasize the need for specific training, skills, and experience to ensure the accuracy of the recommended systems for characterizing foot ulcers. The person applying these systems should be appropriately trained and, according to their national or regional standards, should have the knowledge, expertise, and skills necessary to manage people with a diabetes-related foot ulcer.
As we continue to navigate the complexities of diabetes-related foot disease, these guidelines serve as a valuable compass, guiding our decisions and actions. They remind us of the importance of continuous learning, collaboration, and the application of evidence-based practice in our work.
I encourage you to delve into these guidelines. Let’s use them to improve our practice, enhance our communication, and, ultimately, provide better care for our patients.
Dr. Armstrong is professor of surgery, director of limb preservation, University of Southern California, Los Angeles. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
As we navigate the ever-evolving landscape of diabetic foot disease management,
The goal is to create a common language of risk that is easily related from clinician to clinician to patient.Whatever language we use, though, the problem we face is vast:
- Diabetic foot ulcers affect approximately 18.6 million people worldwide and 1.6 million in the United States each year.
- They are associated with high rates of premature death, with a 5-year mortality rate of 30%. This rate is greater than 70% for those with above-foot amputations, worse than all but the most aggressive cancers.
- The direct costs of treating diabetic foot ulcers in the United States is estimated at $9 billion-$13 billion annually.
- Over 550 million people worldwide have diabetes, with 18.6 million developing foot ulcers annually. Up to 34% of those with diabetes will develop a foot ulcer.
- About 20% of those with a diabetic foot ulcer will undergo amputation, a major cause of which is infection, which affects 50% of foot ulcers.
- Up to 20% of those with a foot ulcer require hospitalization, with 15%-20% undergoing amputation. Inequities exist in diabetes-related foot complications:
- –Rates of major amputation are higher in non-Hispanic Black, Hispanic, and Native American populations, compared with non-Hispanic White populations.
- –Non-Hispanic Black and Hispanic populations present with more advanced ulcers and peripheral artery disease, and are more likely to undergo amputation without revascularization attempt.
The IWGDF, a multidisciplinary team of international experts, has recently updated its guidelines. This team, comprising endocrinologists, internal medicine physicians, physiatrists, podiatrists, and vascular surgeons from across the globe, has worked tirelessly to provide us with a comprehensive guide to managing diabetes-related foot ulcers.
The updated guidelines address five critical clinical questions, each with up to 13 important outcomes. The systematic review that underpins these guidelines identified 149 eligible studies, assessing 28 different systems. This exhaustive research has led to the development of seven key recommendations that address the clinical questions and consider the existence of different clinical settings.
One of the significant updates in the 2023 guidelines is the recommendation of SINBAD – site, ischemia, neuropathy, bacterial infection, area, and depth – as the priority wound classification system for people with diabetes and a foot ulcer. This system is particularly useful for interprofessional communication, describing each composite variable, and conducting clinical audits using the full score. However, the guidelines also recommend the use of other, more specific assessment systems for infection and peripheral artery disease from the Infectious Diseases Society of America/IWGDF when resources and an appropriate level of expertise exist.
The introduction of the Wound, Ischemia and Foot Infection (WIfI) classification system in the guidelines is also a noteworthy development. This system is crucial in assessing perfusion and the likely benefit of revascularization in a person with diabetes and a foot ulcer. By assessing the level of wound ischemia and infection, we can make informed decisions about the need for vascular intervention, which can significantly affect the patient’s outcome. This can be done simply by classifying each of the three categories of wound, ischemia, or foot infection as none, mild, moderate, or severe. By simplifying the very dynamic comorbidities of tissue loss, ischemia, and infection into a usable and predictive scale, it helps us to communicate risk across disciplines. This has been found to be highly predictive of healing, amputation, and mortality.
We use WIfI every day across our system. An example might include a patient we recently treated:
A 76-year-old woman presented with a wound to her left foot. Her past medical history revealed type 2 diabetes, peripheral neuropathy, and documented peripheral artery disease with prior bilateral femoral-popliteal bypass conducted at an external facility. In addition to gangrenous changes to her fourth toe, she displayed erythema and lymphangitic streaking up her dorsal foot. While she was afebrile, her white cell count was 13,000/mcL. Radiographic examinations did not show signs of osteomyelitis. Noninvasive vascular evaluations revealed an ankle brachial index of 0.4 and a toe pressure of 10 mm Hg. An aortogram with a lower-extremity runoff arteriogram confirmed the obstruction of her left femoral-popliteal bypass.
Taking these results into account, her WIfI score was determined as: wound 2 (moderate), ischemia 3 (severe), foot infection 2 (moderate, no sepsis), translating to a clinical stage 4. This denotes a high risk for major amputation.
Following a team discussion, she was taken to the operating room for an initial debridement of her infection which consisted of a partial fourth ray resection to the level of the mid-metatarsal. Following control of the infection, she received a vascular assessment which ultimately constituted a femoral to distal anterior tibial bypass. Following both of these, she was discharged on a negative-pressure wound therapy device, receiving a split-thickness skin graft 4 weeks later.
The guidelines also emphasize the need for specific training, skills, and experience to ensure the accuracy of the recommended systems for characterizing foot ulcers. The person applying these systems should be appropriately trained and, according to their national or regional standards, should have the knowledge, expertise, and skills necessary to manage people with a diabetes-related foot ulcer.
As we continue to navigate the complexities of diabetes-related foot disease, these guidelines serve as a valuable compass, guiding our decisions and actions. They remind us of the importance of continuous learning, collaboration, and the application of evidence-based practice in our work.
I encourage you to delve into these guidelines. Let’s use them to improve our practice, enhance our communication, and, ultimately, provide better care for our patients.
Dr. Armstrong is professor of surgery, director of limb preservation, University of Southern California, Los Angeles. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
As we navigate the ever-evolving landscape of diabetic foot disease management,
The goal is to create a common language of risk that is easily related from clinician to clinician to patient.Whatever language we use, though, the problem we face is vast:
- Diabetic foot ulcers affect approximately 18.6 million people worldwide and 1.6 million in the United States each year.
- They are associated with high rates of premature death, with a 5-year mortality rate of 30%. This rate is greater than 70% for those with above-foot amputations, worse than all but the most aggressive cancers.
- The direct costs of treating diabetic foot ulcers in the United States is estimated at $9 billion-$13 billion annually.
- Over 550 million people worldwide have diabetes, with 18.6 million developing foot ulcers annually. Up to 34% of those with diabetes will develop a foot ulcer.
- About 20% of those with a diabetic foot ulcer will undergo amputation, a major cause of which is infection, which affects 50% of foot ulcers.
- Up to 20% of those with a foot ulcer require hospitalization, with 15%-20% undergoing amputation. Inequities exist in diabetes-related foot complications:
- –Rates of major amputation are higher in non-Hispanic Black, Hispanic, and Native American populations, compared with non-Hispanic White populations.
- –Non-Hispanic Black and Hispanic populations present with more advanced ulcers and peripheral artery disease, and are more likely to undergo amputation without revascularization attempt.
The IWGDF, a multidisciplinary team of international experts, has recently updated its guidelines. This team, comprising endocrinologists, internal medicine physicians, physiatrists, podiatrists, and vascular surgeons from across the globe, has worked tirelessly to provide us with a comprehensive guide to managing diabetes-related foot ulcers.
The updated guidelines address five critical clinical questions, each with up to 13 important outcomes. The systematic review that underpins these guidelines identified 149 eligible studies, assessing 28 different systems. This exhaustive research has led to the development of seven key recommendations that address the clinical questions and consider the existence of different clinical settings.
One of the significant updates in the 2023 guidelines is the recommendation of SINBAD – site, ischemia, neuropathy, bacterial infection, area, and depth – as the priority wound classification system for people with diabetes and a foot ulcer. This system is particularly useful for interprofessional communication, describing each composite variable, and conducting clinical audits using the full score. However, the guidelines also recommend the use of other, more specific assessment systems for infection and peripheral artery disease from the Infectious Diseases Society of America/IWGDF when resources and an appropriate level of expertise exist.
The introduction of the Wound, Ischemia and Foot Infection (WIfI) classification system in the guidelines is also a noteworthy development. This system is crucial in assessing perfusion and the likely benefit of revascularization in a person with diabetes and a foot ulcer. By assessing the level of wound ischemia and infection, we can make informed decisions about the need for vascular intervention, which can significantly affect the patient’s outcome. This can be done simply by classifying each of the three categories of wound, ischemia, or foot infection as none, mild, moderate, or severe. By simplifying the very dynamic comorbidities of tissue loss, ischemia, and infection into a usable and predictive scale, it helps us to communicate risk across disciplines. This has been found to be highly predictive of healing, amputation, and mortality.
We use WIfI every day across our system. An example might include a patient we recently treated:
A 76-year-old woman presented with a wound to her left foot. Her past medical history revealed type 2 diabetes, peripheral neuropathy, and documented peripheral artery disease with prior bilateral femoral-popliteal bypass conducted at an external facility. In addition to gangrenous changes to her fourth toe, she displayed erythema and lymphangitic streaking up her dorsal foot. While she was afebrile, her white cell count was 13,000/mcL. Radiographic examinations did not show signs of osteomyelitis. Noninvasive vascular evaluations revealed an ankle brachial index of 0.4 and a toe pressure of 10 mm Hg. An aortogram with a lower-extremity runoff arteriogram confirmed the obstruction of her left femoral-popliteal bypass.
Taking these results into account, her WIfI score was determined as: wound 2 (moderate), ischemia 3 (severe), foot infection 2 (moderate, no sepsis), translating to a clinical stage 4. This denotes a high risk for major amputation.
Following a team discussion, she was taken to the operating room for an initial debridement of her infection which consisted of a partial fourth ray resection to the level of the mid-metatarsal. Following control of the infection, she received a vascular assessment which ultimately constituted a femoral to distal anterior tibial bypass. Following both of these, she was discharged on a negative-pressure wound therapy device, receiving a split-thickness skin graft 4 weeks later.
The guidelines also emphasize the need for specific training, skills, and experience to ensure the accuracy of the recommended systems for characterizing foot ulcers. The person applying these systems should be appropriately trained and, according to their national or regional standards, should have the knowledge, expertise, and skills necessary to manage people with a diabetes-related foot ulcer.
As we continue to navigate the complexities of diabetes-related foot disease, these guidelines serve as a valuable compass, guiding our decisions and actions. They remind us of the importance of continuous learning, collaboration, and the application of evidence-based practice in our work.
I encourage you to delve into these guidelines. Let’s use them to improve our practice, enhance our communication, and, ultimately, provide better care for our patients.
Dr. Armstrong is professor of surgery, director of limb preservation, University of Southern California, Los Angeles. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Studies link GLP-1 agonists to progression of diabetic retinopathy
SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.
Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that
Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.
Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.
GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.
Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).
Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.
Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.
People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
Albiglutide the key culprit?
In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).
Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.
“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
What causes progression?
Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.
“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”
The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.
Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that
Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.
Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.
GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.
Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).
Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.
Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.
People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
Albiglutide the key culprit?
In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).
Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.
“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
What causes progression?
Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.
“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”
The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.
Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that
Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.
Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.
GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.
Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).
Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.
Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.
People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
Albiglutide the key culprit?
In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).
Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.
“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
What causes progression?
Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.
“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”
The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM ASRS 2023
Time-restricted eating gains for weight and glycemic control
Time-restricted eating (TRE) can be a practical, easy-to-follow way for some people to control their daily food intake and lose weight. It precludes a person’s need to pay close attention to how much they eat as long as they confine consumption to a limited time window. Plus, results from several recent studies show TRE can further benefit people with type 2 diabetes as well as obesity via mechanisms beyond weight loss.
The most tested and recommended eating window is 8 hours long, although periods up to roughly 10 hours may provide some benefits. Results from multiple studies document that TRE produces modest but consistent weight loss of less than 5% in many people. A recent meta-analysis of 17 randomized controlled studies involving 899 people showed an overall incremental weight loss, compared with controls of 1.60 kg on a TRE regimen.
The more limited data collected so far in people with type 2 diabetes show additional metabolic benefits from TRE, including improved beta-cell responsiveness, increased insulin sensitivity, nonoxidative glucose disposal, increased time in glycemic range, and virtually no hypoglycemic events, Courtney Peterson, PhD, said at the annual scientific sessions of the American Diabetes Association.
said Dr. Peterson, a researcher in the department of nutrition sciences at the University of Alabama, Birmingham.
‘Eating earlier is better’
An advantage of TRE is that it is “agnostic to food preferences and quality,” said Lisa S. Chow, MD, during a separate session at the meeting. TRE “may have benefits beyond calorie restriction” that appear related to “the timing of eating and the extent of the eating window restriction. Eating earlier [in the day] is better” for markers of metabolic health regardless of how much weight a person may lose on a TRE regimen, noted Dr. Chow, an endocrinologist and professor at the University of Minnesota Medical School, Minneapolis.
But the TRE paradigm seems amenable to some flexibility on the timing for the eating window while still having benefit.
“Self-selected eating windows are usually late,” Dr. Chow observed, and because compliance with a constrained eating window matters, it may be worth allowing people to choose whichever time window for eating works best for them.
“If you let people pick their eating window, they typically include dinner,” said Dr. Chow, who has run a small TRE study that showed this.
“To maximize the effects [of TRE] people should use the eating window that best fits their life,” agreed Kelsey Gabel, PhD, who also gave a TRE talk during the meeting. “Eating most of your [daily] calories first thing in the morning would have the best cardiometabolic benefit, but reduced adherence would mitigate the benefit,” said Dr. Gabel, a nutrition researcher at the University of Illinois.
‘Meeting people where they’re at’
“We can have a larger public health impact by meeting people where they’re at. People should position their eating window where it best fits so they can achieve calorie restriction without even knowing it,” Dr. Gabel advised.
She cited a report as evidence that most people prefer a later eating window. The report reviewed observational data from nearly 800,000 people who used either of two different TRE phone apps. The data showed that most people opted to start their daily eating during 11:00 AM-1:00 PM, and then stop during 6:00 PM-8:00 PM.
“TRE will not solve all of our obesity problems, but it’s a good place to start,” Dr. Gabel declared.
For people who include dinner at a typical evening time in their TRE window, a key message is that “dinner is your last food of the day. There’s no snacking later,” said Dr. Chow.
“The biggest challenge is adherence,” said Dr. Peterson. “Fewer people want to do TRE than you think. We know that calorie restriction works. We just need a way for people to do it,” and for at least some people, TRE is that way. While no evidence clearly shows that 8 hours is the best eating-window duration, “we think 8 hours is a good sweet-spot for motivated people,” she said.
Sparser data on TRE in people with T2D
Fewer studies have examined the impact of TRE on glycemic control, insulin sensitivity, and related effects in people with type 2 diabetes. According to Dr. Peterson, published reports currently include two randomized controlled studies and three single-arm studies in people with type 2 diabetes and an additional two studies in people with prediabetes.
The largest of these reports randomized 120 adults in China with type 2 diabetes and overweight to TRE using a 10-hour eating window (8:00 AM-6:00 PM) or unrestricted eating for 12 weeks. By the end of the study, those on the TRE regimen had an average reduction in their hemoglobin A1c from baseline that was 0.88 percentage points greater than among the controls, and the TRE arm had also lost an average of nearly 2.15 kg more from baseline than the controls.
Dr. Peterson highlighted the importance of expanding research using TRE in people with type 2 diabetes.
Dr. Peterson and Dr. Gabel report no relevant financial relationships. Dr. Chow has received research support from Dexcom.
A version of this article first appeared on Medscape.com.
Time-restricted eating (TRE) can be a practical, easy-to-follow way for some people to control their daily food intake and lose weight. It precludes a person’s need to pay close attention to how much they eat as long as they confine consumption to a limited time window. Plus, results from several recent studies show TRE can further benefit people with type 2 diabetes as well as obesity via mechanisms beyond weight loss.
The most tested and recommended eating window is 8 hours long, although periods up to roughly 10 hours may provide some benefits. Results from multiple studies document that TRE produces modest but consistent weight loss of less than 5% in many people. A recent meta-analysis of 17 randomized controlled studies involving 899 people showed an overall incremental weight loss, compared with controls of 1.60 kg on a TRE regimen.
The more limited data collected so far in people with type 2 diabetes show additional metabolic benefits from TRE, including improved beta-cell responsiveness, increased insulin sensitivity, nonoxidative glucose disposal, increased time in glycemic range, and virtually no hypoglycemic events, Courtney Peterson, PhD, said at the annual scientific sessions of the American Diabetes Association.
said Dr. Peterson, a researcher in the department of nutrition sciences at the University of Alabama, Birmingham.
‘Eating earlier is better’
An advantage of TRE is that it is “agnostic to food preferences and quality,” said Lisa S. Chow, MD, during a separate session at the meeting. TRE “may have benefits beyond calorie restriction” that appear related to “the timing of eating and the extent of the eating window restriction. Eating earlier [in the day] is better” for markers of metabolic health regardless of how much weight a person may lose on a TRE regimen, noted Dr. Chow, an endocrinologist and professor at the University of Minnesota Medical School, Minneapolis.
But the TRE paradigm seems amenable to some flexibility on the timing for the eating window while still having benefit.
“Self-selected eating windows are usually late,” Dr. Chow observed, and because compliance with a constrained eating window matters, it may be worth allowing people to choose whichever time window for eating works best for them.
“If you let people pick their eating window, they typically include dinner,” said Dr. Chow, who has run a small TRE study that showed this.
“To maximize the effects [of TRE] people should use the eating window that best fits their life,” agreed Kelsey Gabel, PhD, who also gave a TRE talk during the meeting. “Eating most of your [daily] calories first thing in the morning would have the best cardiometabolic benefit, but reduced adherence would mitigate the benefit,” said Dr. Gabel, a nutrition researcher at the University of Illinois.
‘Meeting people where they’re at’
“We can have a larger public health impact by meeting people where they’re at. People should position their eating window where it best fits so they can achieve calorie restriction without even knowing it,” Dr. Gabel advised.
She cited a report as evidence that most people prefer a later eating window. The report reviewed observational data from nearly 800,000 people who used either of two different TRE phone apps. The data showed that most people opted to start their daily eating during 11:00 AM-1:00 PM, and then stop during 6:00 PM-8:00 PM.
“TRE will not solve all of our obesity problems, but it’s a good place to start,” Dr. Gabel declared.
For people who include dinner at a typical evening time in their TRE window, a key message is that “dinner is your last food of the day. There’s no snacking later,” said Dr. Chow.
“The biggest challenge is adherence,” said Dr. Peterson. “Fewer people want to do TRE than you think. We know that calorie restriction works. We just need a way for people to do it,” and for at least some people, TRE is that way. While no evidence clearly shows that 8 hours is the best eating-window duration, “we think 8 hours is a good sweet-spot for motivated people,” she said.
Sparser data on TRE in people with T2D
Fewer studies have examined the impact of TRE on glycemic control, insulin sensitivity, and related effects in people with type 2 diabetes. According to Dr. Peterson, published reports currently include two randomized controlled studies and three single-arm studies in people with type 2 diabetes and an additional two studies in people with prediabetes.
The largest of these reports randomized 120 adults in China with type 2 diabetes and overweight to TRE using a 10-hour eating window (8:00 AM-6:00 PM) or unrestricted eating for 12 weeks. By the end of the study, those on the TRE regimen had an average reduction in their hemoglobin A1c from baseline that was 0.88 percentage points greater than among the controls, and the TRE arm had also lost an average of nearly 2.15 kg more from baseline than the controls.
Dr. Peterson highlighted the importance of expanding research using TRE in people with type 2 diabetes.
Dr. Peterson and Dr. Gabel report no relevant financial relationships. Dr. Chow has received research support from Dexcom.
A version of this article first appeared on Medscape.com.
Time-restricted eating (TRE) can be a practical, easy-to-follow way for some people to control their daily food intake and lose weight. It precludes a person’s need to pay close attention to how much they eat as long as they confine consumption to a limited time window. Plus, results from several recent studies show TRE can further benefit people with type 2 diabetes as well as obesity via mechanisms beyond weight loss.
The most tested and recommended eating window is 8 hours long, although periods up to roughly 10 hours may provide some benefits. Results from multiple studies document that TRE produces modest but consistent weight loss of less than 5% in many people. A recent meta-analysis of 17 randomized controlled studies involving 899 people showed an overall incremental weight loss, compared with controls of 1.60 kg on a TRE regimen.
The more limited data collected so far in people with type 2 diabetes show additional metabolic benefits from TRE, including improved beta-cell responsiveness, increased insulin sensitivity, nonoxidative glucose disposal, increased time in glycemic range, and virtually no hypoglycemic events, Courtney Peterson, PhD, said at the annual scientific sessions of the American Diabetes Association.
said Dr. Peterson, a researcher in the department of nutrition sciences at the University of Alabama, Birmingham.
‘Eating earlier is better’
An advantage of TRE is that it is “agnostic to food preferences and quality,” said Lisa S. Chow, MD, during a separate session at the meeting. TRE “may have benefits beyond calorie restriction” that appear related to “the timing of eating and the extent of the eating window restriction. Eating earlier [in the day] is better” for markers of metabolic health regardless of how much weight a person may lose on a TRE regimen, noted Dr. Chow, an endocrinologist and professor at the University of Minnesota Medical School, Minneapolis.
But the TRE paradigm seems amenable to some flexibility on the timing for the eating window while still having benefit.
“Self-selected eating windows are usually late,” Dr. Chow observed, and because compliance with a constrained eating window matters, it may be worth allowing people to choose whichever time window for eating works best for them.
“If you let people pick their eating window, they typically include dinner,” said Dr. Chow, who has run a small TRE study that showed this.
“To maximize the effects [of TRE] people should use the eating window that best fits their life,” agreed Kelsey Gabel, PhD, who also gave a TRE talk during the meeting. “Eating most of your [daily] calories first thing in the morning would have the best cardiometabolic benefit, but reduced adherence would mitigate the benefit,” said Dr. Gabel, a nutrition researcher at the University of Illinois.
‘Meeting people where they’re at’
“We can have a larger public health impact by meeting people where they’re at. People should position their eating window where it best fits so they can achieve calorie restriction without even knowing it,” Dr. Gabel advised.
She cited a report as evidence that most people prefer a later eating window. The report reviewed observational data from nearly 800,000 people who used either of two different TRE phone apps. The data showed that most people opted to start their daily eating during 11:00 AM-1:00 PM, and then stop during 6:00 PM-8:00 PM.
“TRE will not solve all of our obesity problems, but it’s a good place to start,” Dr. Gabel declared.
For people who include dinner at a typical evening time in their TRE window, a key message is that “dinner is your last food of the day. There’s no snacking later,” said Dr. Chow.
“The biggest challenge is adherence,” said Dr. Peterson. “Fewer people want to do TRE than you think. We know that calorie restriction works. We just need a way for people to do it,” and for at least some people, TRE is that way. While no evidence clearly shows that 8 hours is the best eating-window duration, “we think 8 hours is a good sweet-spot for motivated people,” she said.
Sparser data on TRE in people with T2D
Fewer studies have examined the impact of TRE on glycemic control, insulin sensitivity, and related effects in people with type 2 diabetes. According to Dr. Peterson, published reports currently include two randomized controlled studies and three single-arm studies in people with type 2 diabetes and an additional two studies in people with prediabetes.
The largest of these reports randomized 120 adults in China with type 2 diabetes and overweight to TRE using a 10-hour eating window (8:00 AM-6:00 PM) or unrestricted eating for 12 weeks. By the end of the study, those on the TRE regimen had an average reduction in their hemoglobin A1c from baseline that was 0.88 percentage points greater than among the controls, and the TRE arm had also lost an average of nearly 2.15 kg more from baseline than the controls.
Dr. Peterson highlighted the importance of expanding research using TRE in people with type 2 diabetes.
Dr. Peterson and Dr. Gabel report no relevant financial relationships. Dr. Chow has received research support from Dexcom.
A version of this article first appeared on Medscape.com.
FROM ADA 2023
Lawsuit alleges undisclosed stomach risks from Ozempic, Mounjaro
The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.
In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.
The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it.
Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.
Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”
Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
A version of this article first appeared on WebMD.com.
The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.
In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.
The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it.
Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.
Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”
Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
A version of this article first appeared on WebMD.com.
The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.
In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.
The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it.
Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.
Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”
Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
A version of this article first appeared on WebMD.com.