Diabetes

A new statement from the Endocrine Society on hormones and aging highlights the differences between normal aging and disease, and when treatment is and isn’t appropriate.

The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.

The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.

“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.

During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”

The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.

“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
 

Not designed to be read all at once

In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.

“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.

In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.

Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”  

“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.

However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.

“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”

During the briefing, Dr. Cappola noted that the document need not be read all at once.

“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.

Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.

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

A new statement from the Endocrine Society on hormones and aging highlights the differences between normal aging and disease, and when treatment is and isn’t appropriate.

The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.

The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.

“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.

During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”

The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.

“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
 

Not designed to be read all at once

In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.

“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.

In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.

Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”  

“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.

However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.

“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”

During the briefing, Dr. Cappola noted that the document need not be read all at once.

“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.

Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.

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

A new statement from the Endocrine Society on hormones and aging highlights the differences between normal aging and disease, and when treatment is and isn’t appropriate.

The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.

The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.

“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.

During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”

The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.

“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
 

Not designed to be read all at once

In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.

“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.

In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.

Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”  

“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.

However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.

“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”

During the briefing, Dr. Cappola noted that the document need not be read all at once.

“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.

Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.

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

Baseline depression was significantly associated with recovered, incident, and persistent metabolic syndrome, based on data from more than 13,000 individuals.

Previous research has established a connection between metabolic syndrome and depression, but data on the increased risk for depressed individuals to develop metabolic syndrome (MetS) are lacking, wrote Lara Onofre Ferriani, PhD, of Federal University of Espírito Santo, Vitoria, Brazil, and colleagues.

“Individuals with MetS and depression have increased levels of inflammatory markers, and it is speculated that inflammation could mediate this comorbidity,” they said.

In a study published in the Journal of Psychiatric Research, the investigators reviewed data from 13,883 participants in the Brazilian Longitudinal Study of Adult Health; all were civil servants at universities in Brazil. The participants ranged from 35 to 74 years of age, with a mean age of 51.9 years; 54.3% were women; and 52.4% were white; the mean follow-up period was 3.8 years.

The primary outcome was the association between depression diagnosis and severity on components of MetS at baseline and over a 4-year period. Participants were classified by MetS trajectory as recovered, incident, or persistent, and classified by depression status as without depression or with a mild, moderate, or severe current depressive episode. Depression status was based on the Clinical Interview Schedule Revised. MetS components and diagnosis were based on the National Cholesterol Education Program Adult Treatment Panel III.

In a logistic regression analysis, baseline depression was positively associated with recovered, incident, and persistent MetS (odds ratios, 1.59, 1.45, and 1.70, respectively).

Depression at baseline also was significantly associated with separate components of MetS: large waist circumference, high triglycerides, low high-density lipoprotein cholesterol, and hyperglycemia, with odds ratios of 1.47, 1.23, 1.30, and 1.38, respectively.

Although not seen at baseline, a significant positive association between baseline depression and the presence of three or more MetS components was noted at follow-up, with a positive dose-response effect, the researchers wrote in their discussion.

Not all associations were statistically significant, but this was mainly because of the small number of cases of moderate and severe depression, they said. However, the magnitude of associations was greater in severe depression, when compared with moderate and mild, which suggests that the risk of MetS may be higher in this population, they added.

The study findings were limited by several factors including the possible misclassification of depression, inability to differentiate among depressive subtypes, and the potential lack of generalizability to other populations beyond Brazilian civil servants, the researchers noted.

However, the results were strengthened by the large sample size and support the role of depression as a risk factor for MetS, they said. More research is needed to determine a bidirectional relationship and to assess the trajectory of depression after MetS develops, but the findings “highlight the need to investigate and manage metabolic and cardiovascular alterations in the presence of depression in clinical settings,” they concluded.

The study was supported by the Brazilian Ministry of Health (Science and Technology Department) and the Brazilian Ministry of Science, Technology and Innovation FINEP and CNPq, and by the Coordenaçaõ de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES). The researchers had no financial conflicts to disclose.
 

Baseline depression was significantly associated with recovered, incident, and persistent metabolic syndrome, based on data from more than 13,000 individuals.

Previous research has established a connection between metabolic syndrome and depression, but data on the increased risk for depressed individuals to develop metabolic syndrome (MetS) are lacking, wrote Lara Onofre Ferriani, PhD, of Federal University of Espírito Santo, Vitoria, Brazil, and colleagues.

“Individuals with MetS and depression have increased levels of inflammatory markers, and it is speculated that inflammation could mediate this comorbidity,” they said.

In a study published in the Journal of Psychiatric Research, the investigators reviewed data from 13,883 participants in the Brazilian Longitudinal Study of Adult Health; all were civil servants at universities in Brazil. The participants ranged from 35 to 74 years of age, with a mean age of 51.9 years; 54.3% were women; and 52.4% were white; the mean follow-up period was 3.8 years.

The primary outcome was the association between depression diagnosis and severity on components of MetS at baseline and over a 4-year period. Participants were classified by MetS trajectory as recovered, incident, or persistent, and classified by depression status as without depression or with a mild, moderate, or severe current depressive episode. Depression status was based on the Clinical Interview Schedule Revised. MetS components and diagnosis were based on the National Cholesterol Education Program Adult Treatment Panel III.

In a logistic regression analysis, baseline depression was positively associated with recovered, incident, and persistent MetS (odds ratios, 1.59, 1.45, and 1.70, respectively).

Depression at baseline also was significantly associated with separate components of MetS: large waist circumference, high triglycerides, low high-density lipoprotein cholesterol, and hyperglycemia, with odds ratios of 1.47, 1.23, 1.30, and 1.38, respectively.

Although not seen at baseline, a significant positive association between baseline depression and the presence of three or more MetS components was noted at follow-up, with a positive dose-response effect, the researchers wrote in their discussion.

Not all associations were statistically significant, but this was mainly because of the small number of cases of moderate and severe depression, they said. However, the magnitude of associations was greater in severe depression, when compared with moderate and mild, which suggests that the risk of MetS may be higher in this population, they added.

The study findings were limited by several factors including the possible misclassification of depression, inability to differentiate among depressive subtypes, and the potential lack of generalizability to other populations beyond Brazilian civil servants, the researchers noted.

However, the results were strengthened by the large sample size and support the role of depression as a risk factor for MetS, they said. More research is needed to determine a bidirectional relationship and to assess the trajectory of depression after MetS develops, but the findings “highlight the need to investigate and manage metabolic and cardiovascular alterations in the presence of depression in clinical settings,” they concluded.

The study was supported by the Brazilian Ministry of Health (Science and Technology Department) and the Brazilian Ministry of Science, Technology and Innovation FINEP and CNPq, and by the Coordenaçaõ de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES). The researchers had no financial conflicts to disclose.
 

Baseline depression was significantly associated with recovered, incident, and persistent metabolic syndrome, based on data from more than 13,000 individuals.

Previous research has established a connection between metabolic syndrome and depression, but data on the increased risk for depressed individuals to develop metabolic syndrome (MetS) are lacking, wrote Lara Onofre Ferriani, PhD, of Federal University of Espírito Santo, Vitoria, Brazil, and colleagues.

“Individuals with MetS and depression have increased levels of inflammatory markers, and it is speculated that inflammation could mediate this comorbidity,” they said.

In a study published in the Journal of Psychiatric Research, the investigators reviewed data from 13,883 participants in the Brazilian Longitudinal Study of Adult Health; all were civil servants at universities in Brazil. The participants ranged from 35 to 74 years of age, with a mean age of 51.9 years; 54.3% were women; and 52.4% were white; the mean follow-up period was 3.8 years.

The primary outcome was the association between depression diagnosis and severity on components of MetS at baseline and over a 4-year period. Participants were classified by MetS trajectory as recovered, incident, or persistent, and classified by depression status as without depression or with a mild, moderate, or severe current depressive episode. Depression status was based on the Clinical Interview Schedule Revised. MetS components and diagnosis were based on the National Cholesterol Education Program Adult Treatment Panel III.

In a logistic regression analysis, baseline depression was positively associated with recovered, incident, and persistent MetS (odds ratios, 1.59, 1.45, and 1.70, respectively).

Depression at baseline also was significantly associated with separate components of MetS: large waist circumference, high triglycerides, low high-density lipoprotein cholesterol, and hyperglycemia, with odds ratios of 1.47, 1.23, 1.30, and 1.38, respectively.

Although not seen at baseline, a significant positive association between baseline depression and the presence of three or more MetS components was noted at follow-up, with a positive dose-response effect, the researchers wrote in their discussion.

Not all associations were statistically significant, but this was mainly because of the small number of cases of moderate and severe depression, they said. However, the magnitude of associations was greater in severe depression, when compared with moderate and mild, which suggests that the risk of MetS may be higher in this population, they added.

The study findings were limited by several factors including the possible misclassification of depression, inability to differentiate among depressive subtypes, and the potential lack of generalizability to other populations beyond Brazilian civil servants, the researchers noted.

However, the results were strengthened by the large sample size and support the role of depression as a risk factor for MetS, they said. More research is needed to determine a bidirectional relationship and to assess the trajectory of depression after MetS develops, but the findings “highlight the need to investigate and manage metabolic and cardiovascular alterations in the presence of depression in clinical settings,” they concluded.

The study was supported by the Brazilian Ministry of Health (Science and Technology Department) and the Brazilian Ministry of Science, Technology and Innovation FINEP and CNPq, and by the Coordenaçaõ de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES). The researchers had no financial conflicts to disclose.
 

Could glucagonlike peptide–1 (GLP-1) receptor agonists such as semaglutide – approved as Ozempic to treat type 2 diabetes and as Wegovy to treat obesity, both from Novo Nordisk – also curb addictions and compulsive behaviors?

As demand for semaglutide for weight loss grew following approval of Wegovy by the U.S. Food and Drug Administration in 2021, anecdotal reports of unexpected potential added benefits also began to surface.

Some patients taking these drugs for type 2 diabetes or weight loss also lost interest in addictive and compulsive behaviors such as drinking alcohol, smoking, shopping, nail biting, and skin picking, as reported in articles in the New York Times and The Atlantic, among others.

There is also some preliminary research to support these observations.

This news organization invited three experts to weigh in.
 

Recent and upcoming studies

The senior author of a recent randomized controlled trial of 127 patients with alcohol use disorder (AUD), Anders Fink-Jensen, MD, said: “I hope that GLP-1 analogs in the future can be used against AUD, but before that can happen, several GLP-1 trials [are needed to] prove an effect on alcohol intake.”

His study involved patients who received exenatide (Byetta, Bydureon, AstraZeneca), the first-generation GLP-1 agonist approved for type 2 diabetes, over 26 weeks, but treatment did not reduce the number of heavy drinking days (the primary outcome), compared with placebo.  

However, in post hoc, exploratory analyses, heavy drinking days and total alcohol intake were significantly reduced in the subgroup of patients with AUD and obesity (body mass index > 30 kg/m²).

The participants were also shown pictures of alcohol or neutral subjects while they underwent functional magnetic resonance imaging. Those who had received exenatide, compared with placebo, had significantly less activation of brain reward centers when shown the pictures of alcohol.

“Something is happening in the brain and activation of the reward center is hampered by the GLP-1 compound,” Dr. Fink-Jensen, a clinical psychologist at the Psychiatric Centre Copenhagen, remarked in an email.

“If patients with AUD already fulfill the criteria for semaglutide (or other GLP-1 analogs) by having type 2 diabetes and/or a BMI over 30 kg/m², they can of course use the compound right now,” he noted.

His team is also beginning a study in patients with AUD and a BMI ≥ 30 kg/m² to investigate the effects on alcohol intake of semaglutide up to 2.4 mg weekly, the maximum dose currently approved for obesity in the United States.

“Based on the potency of exenatide and semaglutide,” Dr. Fink-Jensen said, “we expect that semaglutide will cause a stronger reduction in alcohol intake” than exenatide.

Animal studies have also shown that GLP-1 agonists suppress alcohol-induced reward, alcohol intake, motivation to consume alcohol, alcohol seeking, and relapse drinking of alcohol, Elisabet Jerlhag Holm, PhD, noted.

Interestingly, these agents also suppress the reward, intake, and motivation to consume other addictive drugs like cocaine, amphetamine, nicotine, and some opioids, Jerlhag Holm, professor, department of pharmacology, University of Gothenburg, Sweden, noted in an email.

In a recently published preclinical study, her group provides evidence to help explain anecdotal reports from patients with obesity treated with semaglutide who claim they also reduced their alcohol intake. In the study, semaglutide both reduced alcohol intake (and relapse-like drinking) and decreased body weight of rats of both sexes.

“Future research should explore the possibility of semaglutide decreasing alcohol intake in patients with AUD, particularly those who are overweight,” said Prof. Holm.

“AUD is a heterogenous disorder, and one medication is most likely not helpful for all AUD patients,” she added. “Therefore, an arsenal of different medications is beneficial when treating AUD.”

Janice J. Hwang, MD, MHS, echoed these thoughts: “Anecdotally, there are a lot of reports from patients (and in the news) that this class of medication [GLP-1 agonists] impacts cravings and could impact addictive behaviors.”

“I would say, overall, the jury is still out,” as to whether anecdotal reports of GLP-1 agonists curbing addictions will be borne out in randomized controlled trials.

“I think it is much too early to tell” whether these drugs might be approved for treating addictions without more solid clinical trial data, noted Dr. Hwang, who is an associate professor of medicine and chief, division of endocrinology and metabolism, at the University of North Carolina at Chapel Hill.

Meanwhile, another research group at the University of North Carolina at Chapel Hill, led by psychiatrist Christian Hendershot, PhD, is conducting a clinical trial in 48 participants with AUD who are also smokers.

They aim to determine if patients who receive semaglutide at escalating doses (0.25 mg to 1.0 mg per week via subcutaneous injection) over 9 weeks will consume less alcohol (the primary outcome) and smoke less (a secondary outcome) than those who receive a sham placebo injection. Results are expected in October 2023.

Dr. Fink-Jensen has received an unrestricted research grant from Novo Nordisk to investigate the effects of GLP-1 receptor stimulation on weight gain and metabolic disturbances in patients with schizophrenia treated with an antipsychotic.

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

Could glucagonlike peptide–1 (GLP-1) receptor agonists such as semaglutide – approved as Ozempic to treat type 2 diabetes and as Wegovy to treat obesity, both from Novo Nordisk – also curb addictions and compulsive behaviors?

As demand for semaglutide for weight loss grew following approval of Wegovy by the U.S. Food and Drug Administration in 2021, anecdotal reports of unexpected potential added benefits also began to surface.

Some patients taking these drugs for type 2 diabetes or weight loss also lost interest in addictive and compulsive behaviors such as drinking alcohol, smoking, shopping, nail biting, and skin picking, as reported in articles in the New York Times and The Atlantic, among others.

There is also some preliminary research to support these observations.

This news organization invited three experts to weigh in.
 

Recent and upcoming studies

The senior author of a recent randomized controlled trial of 127 patients with alcohol use disorder (AUD), Anders Fink-Jensen, MD, said: “I hope that GLP-1 analogs in the future can be used against AUD, but before that can happen, several GLP-1 trials [are needed to] prove an effect on alcohol intake.”

His study involved patients who received exenatide (Byetta, Bydureon, AstraZeneca), the first-generation GLP-1 agonist approved for type 2 diabetes, over 26 weeks, but treatment did not reduce the number of heavy drinking days (the primary outcome), compared with placebo.  

However, in post hoc, exploratory analyses, heavy drinking days and total alcohol intake were significantly reduced in the subgroup of patients with AUD and obesity (body mass index > 30 kg/m²).

The participants were also shown pictures of alcohol or neutral subjects while they underwent functional magnetic resonance imaging. Those who had received exenatide, compared with placebo, had significantly less activation of brain reward centers when shown the pictures of alcohol.

“Something is happening in the brain and activation of the reward center is hampered by the GLP-1 compound,” Dr. Fink-Jensen, a clinical psychologist at the Psychiatric Centre Copenhagen, remarked in an email.

“If patients with AUD already fulfill the criteria for semaglutide (or other GLP-1 analogs) by having type 2 diabetes and/or a BMI over 30 kg/m², they can of course use the compound right now,” he noted.

His team is also beginning a study in patients with AUD and a BMI ≥ 30 kg/m² to investigate the effects on alcohol intake of semaglutide up to 2.4 mg weekly, the maximum dose currently approved for obesity in the United States.

“Based on the potency of exenatide and semaglutide,” Dr. Fink-Jensen said, “we expect that semaglutide will cause a stronger reduction in alcohol intake” than exenatide.

Animal studies have also shown that GLP-1 agonists suppress alcohol-induced reward, alcohol intake, motivation to consume alcohol, alcohol seeking, and relapse drinking of alcohol, Elisabet Jerlhag Holm, PhD, noted.

Interestingly, these agents also suppress the reward, intake, and motivation to consume other addictive drugs like cocaine, amphetamine, nicotine, and some opioids, Jerlhag Holm, professor, department of pharmacology, University of Gothenburg, Sweden, noted in an email.

In a recently published preclinical study, her group provides evidence to help explain anecdotal reports from patients with obesity treated with semaglutide who claim they also reduced their alcohol intake. In the study, semaglutide both reduced alcohol intake (and relapse-like drinking) and decreased body weight of rats of both sexes.

“Future research should explore the possibility of semaglutide decreasing alcohol intake in patients with AUD, particularly those who are overweight,” said Prof. Holm.

“AUD is a heterogenous disorder, and one medication is most likely not helpful for all AUD patients,” she added. “Therefore, an arsenal of different medications is beneficial when treating AUD.”

Janice J. Hwang, MD, MHS, echoed these thoughts: “Anecdotally, there are a lot of reports from patients (and in the news) that this class of medication [GLP-1 agonists] impacts cravings and could impact addictive behaviors.”

“I would say, overall, the jury is still out,” as to whether anecdotal reports of GLP-1 agonists curbing addictions will be borne out in randomized controlled trials.

“I think it is much too early to tell” whether these drugs might be approved for treating addictions without more solid clinical trial data, noted Dr. Hwang, who is an associate professor of medicine and chief, division of endocrinology and metabolism, at the University of North Carolina at Chapel Hill.

Meanwhile, another research group at the University of North Carolina at Chapel Hill, led by psychiatrist Christian Hendershot, PhD, is conducting a clinical trial in 48 participants with AUD who are also smokers.

They aim to determine if patients who receive semaglutide at escalating doses (0.25 mg to 1.0 mg per week via subcutaneous injection) over 9 weeks will consume less alcohol (the primary outcome) and smoke less (a secondary outcome) than those who receive a sham placebo injection. Results are expected in October 2023.

Dr. Fink-Jensen has received an unrestricted research grant from Novo Nordisk to investigate the effects of GLP-1 receptor stimulation on weight gain and metabolic disturbances in patients with schizophrenia treated with an antipsychotic.

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

Could glucagonlike peptide–1 (GLP-1) receptor agonists such as semaglutide – approved as Ozempic to treat type 2 diabetes and as Wegovy to treat obesity, both from Novo Nordisk – also curb addictions and compulsive behaviors?

As demand for semaglutide for weight loss grew following approval of Wegovy by the U.S. Food and Drug Administration in 2021, anecdotal reports of unexpected potential added benefits also began to surface.

Some patients taking these drugs for type 2 diabetes or weight loss also lost interest in addictive and compulsive behaviors such as drinking alcohol, smoking, shopping, nail biting, and skin picking, as reported in articles in the New York Times and The Atlantic, among others.

There is also some preliminary research to support these observations.

This news organization invited three experts to weigh in.
 

Recent and upcoming studies

The senior author of a recent randomized controlled trial of 127 patients with alcohol use disorder (AUD), Anders Fink-Jensen, MD, said: “I hope that GLP-1 analogs in the future can be used against AUD, but before that can happen, several GLP-1 trials [are needed to] prove an effect on alcohol intake.”

His study involved patients who received exenatide (Byetta, Bydureon, AstraZeneca), the first-generation GLP-1 agonist approved for type 2 diabetes, over 26 weeks, but treatment did not reduce the number of heavy drinking days (the primary outcome), compared with placebo.  

However, in post hoc, exploratory analyses, heavy drinking days and total alcohol intake were significantly reduced in the subgroup of patients with AUD and obesity (body mass index > 30 kg/m²).

The participants were also shown pictures of alcohol or neutral subjects while they underwent functional magnetic resonance imaging. Those who had received exenatide, compared with placebo, had significantly less activation of brain reward centers when shown the pictures of alcohol.

“Something is happening in the brain and activation of the reward center is hampered by the GLP-1 compound,” Dr. Fink-Jensen, a clinical psychologist at the Psychiatric Centre Copenhagen, remarked in an email.

“If patients with AUD already fulfill the criteria for semaglutide (or other GLP-1 analogs) by having type 2 diabetes and/or a BMI over 30 kg/m², they can of course use the compound right now,” he noted.

His team is also beginning a study in patients with AUD and a BMI ≥ 30 kg/m² to investigate the effects on alcohol intake of semaglutide up to 2.4 mg weekly, the maximum dose currently approved for obesity in the United States.

“Based on the potency of exenatide and semaglutide,” Dr. Fink-Jensen said, “we expect that semaglutide will cause a stronger reduction in alcohol intake” than exenatide.

Animal studies have also shown that GLP-1 agonists suppress alcohol-induced reward, alcohol intake, motivation to consume alcohol, alcohol seeking, and relapse drinking of alcohol, Elisabet Jerlhag Holm, PhD, noted.

Interestingly, these agents also suppress the reward, intake, and motivation to consume other addictive drugs like cocaine, amphetamine, nicotine, and some opioids, Jerlhag Holm, professor, department of pharmacology, University of Gothenburg, Sweden, noted in an email.

In a recently published preclinical study, her group provides evidence to help explain anecdotal reports from patients with obesity treated with semaglutide who claim they also reduced their alcohol intake. In the study, semaglutide both reduced alcohol intake (and relapse-like drinking) and decreased body weight of rats of both sexes.

“Future research should explore the possibility of semaglutide decreasing alcohol intake in patients with AUD, particularly those who are overweight,” said Prof. Holm.

“AUD is a heterogenous disorder, and one medication is most likely not helpful for all AUD patients,” she added. “Therefore, an arsenal of different medications is beneficial when treating AUD.”

Janice J. Hwang, MD, MHS, echoed these thoughts: “Anecdotally, there are a lot of reports from patients (and in the news) that this class of medication [GLP-1 agonists] impacts cravings and could impact addictive behaviors.”

“I would say, overall, the jury is still out,” as to whether anecdotal reports of GLP-1 agonists curbing addictions will be borne out in randomized controlled trials.

“I think it is much too early to tell” whether these drugs might be approved for treating addictions without more solid clinical trial data, noted Dr. Hwang, who is an associate professor of medicine and chief, division of endocrinology and metabolism, at the University of North Carolina at Chapel Hill.

Meanwhile, another research group at the University of North Carolina at Chapel Hill, led by psychiatrist Christian Hendershot, PhD, is conducting a clinical trial in 48 participants with AUD who are also smokers.

They aim to determine if patients who receive semaglutide at escalating doses (0.25 mg to 1.0 mg per week via subcutaneous injection) over 9 weeks will consume less alcohol (the primary outcome) and smoke less (a secondary outcome) than those who receive a sham placebo injection. Results are expected in October 2023.

Dr. Fink-Jensen has received an unrestricted research grant from Novo Nordisk to investigate the effects of GLP-1 receptor stimulation on weight gain and metabolic disturbances in patients with schizophrenia treated with an antipsychotic.

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

Nearly 40 antihyperglycemic agents have been approved by the US Food and Drug Administration (FDA) since the approval of human insulin in 1982.¹ In addition, existing antihyperglycemic medications are constantly gaining FDA approval for new indications for common type 2 diabetes (T2D) comorbidities. For example, in addition to their glycemic benefits, the sodium-glucose cotransporter-2 (SGLT2) inhibitors have been approved for use in patients with T2D and established atherosclerotic cardiovascular disease (ASCVD) to reduce the risk for major adverse cardiovascular events (MACE; canagliflozin), risk for hospitalization for heart failure (dapagliflozin), and cardiovascular death (empagliflozin).^2-4

The plethora of new agents and new data for existing agents, coupled with the annual release of guidelines from the American Diabetes Association (ADA) and practice recommendations from several other professional organizations,^5-7 make it challenging for family physicians to stay current and provide the most up-to-date, evidence-based care. In this article, we provide advice on how to approach the screening, diagnosis, and evaluation of T2D, and on how to manage newly diagnosed T2D.

Screening, Dx, and evaluation: A quick review

Screening

Screening recommendations vary among professional organizations (TABLE 1^5,6,8). The US Preventive Services Task Force (USPSTF) recommends screening adults ages 35 to 70 years who are overweight or obese. Clinicians also can consider screening patients with a higher risk for diabetes.⁵ The ADA suggests screening all adults starting at 35 years, regardless of risk factors.⁸ Asymptomatic adults of any age with overweight or obesity and 1 or more risk factors should be screened.⁸The American Association of Clinical Endocrinology (AACE) recommends screening adults of any age who have risk factors.⁶ If the screening result is normal, repeat testing in 3 years is appropriate, unless there is a change in symptoms or risks.^5,8 Annual testing can be considered in patients with ≥ 2 risk factors or with prediabetes (glycosylated hemoglobin [A1C] ≥ 5.7%).^6,8

Making the diagnosis

The initial diagnosis of diabetes can be made by a fasting plasma glucose level ≥ 126 mg/dL (7.0 mmol/L); a 2-hour plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) following an oral glucose tolerance test; or an A1C level ≥ 6.5%. Prioritize lab-drawn A1C measurements over point-of-care tests to diagnose T2D. In ­patients with classic symptoms of hyper­glycemia, a random plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) is also diagnostic. Generally, these tests are considered equally appropriate in screening for diabetes and may be used to detect prediabetes. In the absence of clear symptoms of hyperglycemia, the diagnosis of diabetes requires 2 abnormal screening test results, either via 1 blood sample (such as an abnormal A1C and glucose) or 2 separate blood samples of the same test. Further evaluation is advised if there is discordance between the 2 samples.⁸

Extended evaluations

Patients with newly diagnosed T2D require a thorough evaluation for comorbidities and complications of diabetes. Refer patients to an ophthalmologist for a dilated eye examination, with subsequent exams occurring every 1 to 2 years.^6,9 Additional referrals for diabetes education, family planning for women of reproductive age, and dental, social, or mental health services may be clinically appropriate.⁹

Setting goals for glycemic control

Glycemic control is commonly monitored by the A1C level and by blood glucose monitoring either through traditional point-of-care glucometers or continuous glucose monitors (CGMs).¹⁰ Generally, CGMs provide more glycemic data than traditional glucometers and may cue patients to choose healthier dietary options and engage in physical exercise.¹¹ Patients with T2D who use CGMs exhibit lower A1Cs, greater time in glycemic range, and reduced hypoglycemic episodes.¹¹ Generally, CGMs are reserved for patients with type 1 diabetes and patients with T2D who use multiple daily injections, subcutaneous insulin infusions, or basal insulin only.¹² Most professional organizations recommend that clinicians consider patient-specific factors to set individualized glycemic goals.^6,10,13,14 For example, more stringent glycemic goals could be pursued for patients with longer life expectancy, shorter disease duration, absence of complications (eg, nephropathy, neuropathy, or cardiovascular disease), fewer comorbid conditions, lower hypoglycemia risk, or higher cognitive function.⁶

With newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.

More specific A1C goals vary by professional organization. For nonpregnant adults, the ADA recommends an A1C goal of < 7% and a preprandial blood glucose level of 80 to 130 mg/dL (4.4-7.2 mmol/L).¹⁰ However, a lower A1C goal may be appropriate if it can be attained safely without causing hypoglycemia or other adverse effects.¹⁰ The AACE suggests an A1C goal of ≤ 6.5% and a fasting blood glucose level of < 110 mg/dL when it can be achieved safely.⁶ More stringent A1C goals may reduce long-term micro- and macrovascular complications—especially in patients with newly diagnosed T2D.¹⁰ While older studies such as the ACCORD trial found increased mortality in groups with more stringent glycemic targets, they did not include newer agents (SGLT2 inhibitors or glucagon-like peptide-1 [GLP-1] receptor agonists) that reduce cardiovascular events by mechanisms outside their glycemic-lowering effect. With these newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.¹⁰ Both the ADA and AACE recommend a less stringent A1C goal of 7% to 8% for patients with limited life expectancy or risks (eg, a history of hypoglycemia) that outweigh expected benefits.^6,10

Continue to: Lifestyle modifications

Nutrition

The energy-dense Western diet, combined with sedentary behavior, are thought to be a primary cause of T2D.¹⁵ Therefore, include lifestyle modifications in the initial management of newly diagnosed T2D. Diets that replace carbohydrates with saturated and trans fats are related to increased mortality in patients with T2D.¹⁶ Increased consumption of vegetables, fruits, legumes, nuts, fish, cereal, and oils reduces concentrations of saturated and trans fats and increases dietary intake of monounsaturated fatty acids, fiber, antioxidants, and polyphenols.¹⁷

Combined endurance and resistance training is superior for improving glycemic control, cardiorespiratory fitness, and body composition, compared with either type of training alone.

Increasing the intake of fiber, an undigestible carbohydrate, offers numerous benefits in T2D management. High-fiber diets can help regulate blood sugar and lipid levels, increase satiety, reduce inflammation, aid in weight management, and reduce premature mortality.¹⁸ Insoluble fiber, found in foods such as whole wheat flour, nuts, and cauliflower, helps food pass more quickly through the stomach and intestines and adds bulk to stool. Soluble fiber, found in foods such as chickpeas, lentils, and Brussels sprouts, absorbs water and forms a gel-like substance that protects nutrients from digestive enzymes and slows down digestion. The result is a more gradual rise in postprandial glucose levels and improved insulin sensitivity.¹⁹ Dietary fiber may produce short-chain fatty acids which in turn activate incretin secretion and stimulate a glucose-dependent release of insulin from the pancreas.²⁰

Simple dietary substitutions, such as whole grains and legumes for white rice, can reduce fasting blood glucose and A1C levels.²¹ In a randomized controlled trial (RCT), increasing whole grain oat intake improved measures of glycemic control, reducing A1C by 1% at 1-year follow-up.¹⁹ Encourage patients with T2D to increase consumption of high-fiber foods and replace animal fats and refined grains with vegetable fats (eg, nuts, avocados, olives).
Nutritional therapies should be individualized, taking into account personal preferences and cultural customs.²² Nutritional habits may be based on race/ethnicity, ­religion/spirituality, or even the city in which an individual resides. Nutrition recommendations should account for these differences as well as access to healthy foods. For instance, ethnic groups whose dietary patterns include tortillas could be counseled to choose high-fiber options such as corn instead of flour tortillas and to incorporate vegetables in place of high-fat foods. Additionally, ethnic groups who favor using animal fats in foods such as greens could be advised on ways to add flavor to vegetables without adding saturated fats. Taking this approach may lessen barriers to change and increase ability to make dietary modifications.²³

Exercise

Encourage all patients with T2D to exercise regularly. The atherosclerotic plaques found in patients with T2D have increased inflammatory properties and result in worse cardiovascular outcomes compared with plaques in individuals without T2D.²⁴ Regular exercise reduces levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-6, and tumor necrosis factor alpha—and increases levels of anti-­inflammatory markers (IL-4 and IL-10).²⁴ Regular exercise can improve body composition, physical fitness, lipid and glucose metabolism, and insulin sensitivity.^25,26

A meta-analysis of RCTs demonstrated that structured exercise > 150 minutes per week resulted in A1C reductions of 0.89%,²⁷ which is comparable to the effect of many oral antihyperglycemic medications.²⁶ The Health Benefits of Aerobic and Resistance Training in individuals with T2D (HART-D) and Diabetes Aerobic and Resistance Exercise (DARE) studies demonstrated that combining endurance and resistance training was superior for improving glycemic control, cardiorespiratory fitness, and body composition, than using either type of training alone.²⁵ Both the American College of Sports Medicine (ACSM) and the ADA recommend that adults engage in at least 150 total minutes of moderate-intensity aerobic activity per week and resistance training 2 to 3 times weekly.²⁶ ACSM defines moderate-intensity exercise as 65% to 75% of maximal heart rate, a rating of perceived exertion of 3 to 4, or a step rate of 100 steps per minute.²⁸

Continue to: Because of their longitudinal relationships...

Because of their longitudinal relationships with patients, family physicians are in an optimal position to assess a patient’s physical capacity level and provide individualized counseling. Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.²⁹ Encourage your patients with T2D to exercise regularly, considering each individual’s ability to engage in physical activity.

Weight loss

Include weight management in the initial treatment of patients with newly diagnosed T2D. Weight loss decreases hepatic glucose production and increases peripheral insulin sensitivity and insulin secretion.³⁰ Moderate decreases in weight (5%-10%) can reduce complications related to diabetes, and sustained significant weight loss (> 10%) can potentially cause T2D remission (A1C < 6.5% after stopping diabetes medications).^31,32

Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.

Diabetes self-management education supports patients by giving them tools for making and maintaining lifestyle changes. Understanding individual barriers to change and addressing these during motivational interviews is important. Through a qualitative interview study, participants in a diabetes self-management program revealed 4 factors that motivated them to maintain lifestyle changes: support from others, experiencing the impact of the changes they made, fear of T2D complications, and forming new habits.³³ Family physicians are key in helping patients acquire knowledge and support to make the lifestyle modifications needed to manage newly diagnosed T2D.

Individualized pharmacotherapy considerations

For decades, the initial pharmacotherapeutic regimen for patients with newly diagnosed T2D considered the patient’s baseline A1C as a major driver for therapy. Metformin has been the mainstay in T2D treatment due to its clinical efficacy, minimal risk for hypoglycemia, and low cost. Regardless of the regimen, pharmacotherapy should be initiated at the time of T2D diagnosis in conjunction with the aforementioned lifestyle modifications.³⁴

When selecting pharmacotherapy, practice guidelines recommend considering the efficacy and adverse effects of medications, patient-specific comorbidities, adherence, cost, and a patient’s lifestyle factors.³⁴ Drug classes with pertinent information are listed in TABLE 2.^34-54 After starting medication, monitor the A1C level every 3 months to determine whether therapy should be intensified. Patients should have their labs drawn ahead of the quarterly visit, or point-of-care measurements may be used to facilitate in-person patient–provider discussions.

Continue to: Consider patient-specific factors when starting pharmacotherapy

Consider patient-specific factors when starting pharmacotherapy

ASCVD. Regardless of baseline glycemic control, offer patients who have ASCVD, or who are at high risk for it, an SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or a long-acting GLP-1 receptor agonist (dulaglutide, liraglutide, or semaglutide).^34,35 SGLT2 inhibitors reduced the risk for MACE by 11% in patients with established ASCVD.⁵⁵ They also reduced a composite outcome of cardiovascular death or hospitalization for heart failure by 23% in patients with or without ASCVD or heart failure at baseline.⁵⁵ GLP-1 receptor agonists offer a similar reduction in MACE to SGLT2 inhibitors, but they do not have significant effects in heart failure.⁵⁶ Thiazolidinediones (TZDs), saxagliptin, and alogliptin should be avoided in patients with heart failure.⁵⁷ TZDs may reduce the risk for recurrent stroke in patients with T2D.⁵⁸

Chronic kidney disease (CKD). As with ASCVD, prioritize SGLT2 inhibitors and ­GLP-1 receptor agonists in patients with CKD. While both classes reduced the risk for progression of kidney disease such as macroalbuminuria, SGLT2 inhibitors offer additional benefits in their reduction of the worsening of estimated glomerular filtration rate, end-stage kidney disease, and renal death.⁵⁶

Obesity. Consider the effect of each drug class on weight when making initial treatment choices, taking special care to minimize weight gain and potentially promote weight loss.³⁴ The ADA prefers GLP-1 receptor agonists, but also suggests SGLT2 inhibitors in these patients. While all GLP-1 receptor agonists have an impact on weight, weekly subcutaneous semaglutide offers the most pronounced weight loss of 2 to 7 kg over 56 weeks.⁵⁹ SGLT2 inhibitors promote sustainable weight loss to a lesser degree, contributing to an average loss of 3 kg at 2 years.⁶⁰ Weight gain is common in patients taking sulfonylureas (2.01-2.3 kg)³¹ and insulin (3-9 kg weight gain in the first year)⁶¹ and should be avoided in patients with T2D and obesity.³⁴

Hypoglycemia risk. In addition to counseling patients on hypoglycemia management and prescribing glucagon rescue kits, offer medications with no or very low risk for hypoglycemia (eg, GLP-1 receptor agonists, SGLT2 inhibitors, dipeptidyl ­peptidase-4 inhibitors, and TZDs). Generally, avoid insulin and sulfonylureas in patients in whom hypoglycemia is a major concern (eg, older adults, individuals with labile blood glucose levels).³⁴ Patients with reduced renal function are at higher risk for hypoglycemia with insulin or sulfonylureas due to reduced drug clearance. However, insulin is often the only treatment for patients with advanced renal disease. Pay close attention to insulin dosing in patients with advanced renal disease, which may necessitate lower doses and smaller dose adjustments due to this risk.

Social determinants of health. Medication access and cost is a major burden in T2D management and should be considered for every patient. Compared with the period of 2005 to 2007, the annual cost of diabetes medications for an individual in 2015 to 2017 increased by 147%, rising from $1106 to $2727 per year.⁶² This increase is driven by the cost of insulin and newer medications without generic options.⁶² Identify local resources in your community, such as patient assistance programs and pharmacies with reduced-price generic prescription programs, which may be useful for patients who are underinsured or uninsured.

Continue to: Even if cost weren't an issue...

Even if cost weren’t an issue, many ­medications such as insulin and GLP-1 receptor agonists should be kept refrigerated and are only stable at room temperature for a limited time. Medications that are stable at room temperature should be prioritized in patients with limited or inconsistent access to refrigeration or unstable housing who may find it difficult to store their medications ­appropriately.

Do not delay insulin initiation in patients with high baseline A1C

Whenever possible, a GLP-1 receptor agonist is the preferred injectable medication to insulin. Starting insulin introduces numerous risks, including hypoglycemia, weight gain, and stigma. However, in the patient with newly diagnosed T2D, choose basal insulin when the baseline hyperglycemia is severe,³⁴ as indicated by:

• blood glucose > 300 mg/dL (16.7 mmol/L),
• A1C > 10% (86 mmol/mol),
• symptoms of hyperglycemia (polyuria or polydipsia), or
• evidence of catabolism (weight loss, hypertriglyceridemia, ketosis).

Basal insulin analogs are preferred over NPH given their reduced variability, dosing, and hypoglycemic risk.³⁵ Mixed insulins may be used if a patient is unable to afford an insulin analog, which can be quite costly. However, extensive counseling on dosing and management of hypoglycemia is crucial to patient safety with these agents. The ADA ­recommends initiating 0.1 to 0.2 units/kg of basal insulin daily or 10 units daily.³⁴ The AACE follows this recommendation for ­patients with baseline A1C < 8%, but it proposes a more aggressive initiation of 0.2 to 0.3 units/kg/d for patients with baseline A1C > 8%.³⁵ Titrate the dose by 2 units every 3 days to reach the target fasting blood glucose level. As hyperglycemia resolves, simplify the regimen and transition to noninsulin options per the previously discussed considerations.

It’s not just about glycemic control

In addition to the direct effects of hyperglycemia, a T2D diagnosis introduces an increased risk for ASCVD, a reduced ability to fight infection, and heightened risk for depression. Order a lipid panel at the time of T2D diagnosis and initiate lipid management as needed (TABLE 3^35,63,64). Both the ADA and the American Heart Association recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.⁶³ The AACE uses specific lipid targets and recommends moderate- to high-intensity statin therapy for patients with T2D.³⁵ All recommendations by professional organizations list high-intensity statins for patients with established ASCVD.

Both the ADA and the AHA recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.

It is also vital to recommend that patients with newly diagnosed T2D remain up to date on all indicated vaccinations. They should promptly receive the hepatitis B and pneumococcal vaccines if they have not already done so for a previous indication. COVID-19 and annual influenza vaccines also should be prioritized for these patients.⁶⁵

Finally, patients with diabetes are twice as likely to develop depression than patients without diabetes.⁶⁶ Individuals with T2D and depression exhibit poorer medication adherence, lifestyle choices, and glycemic control.⁶⁶ Screen for and treat these issues in all patients with T2D across the course of the disease.

Overall, work closely with patients to support them in managing their new diagnosis with evidence-based pharmacologic and nonpharmacologic approaches. The importance of lifestyle changes including high-fiber diets, regular exercise, and weight loss should not be overlooked. Do not delay starting pharmacotherapy after diagnosing T2D and consider medication-specific and patient-specific factors to individualize therapy, improve adherence, and prevent complications.

CORRESPONDENCE
Jennie B. Jarrett, PharmD, MMedEd, 833 South Wood Street (MC 886), Chicago, IL 60612; [email protected]

Nearly 40 antihyperglycemic agents have been approved by the US Food and Drug Administration (FDA) since the approval of human insulin in 1982.¹ In addition, existing antihyperglycemic medications are constantly gaining FDA approval for new indications for common type 2 diabetes (T2D) comorbidities. For example, in addition to their glycemic benefits, the sodium-glucose cotransporter-2 (SGLT2) inhibitors have been approved for use in patients with T2D and established atherosclerotic cardiovascular disease (ASCVD) to reduce the risk for major adverse cardiovascular events (MACE; canagliflozin), risk for hospitalization for heart failure (dapagliflozin), and cardiovascular death (empagliflozin).^2-4

The plethora of new agents and new data for existing agents, coupled with the annual release of guidelines from the American Diabetes Association (ADA) and practice recommendations from several other professional organizations,^5-7 make it challenging for family physicians to stay current and provide the most up-to-date, evidence-based care. In this article, we provide advice on how to approach the screening, diagnosis, and evaluation of T2D, and on how to manage newly diagnosed T2D.

Screening, Dx, and evaluation: A quick review

Screening

Screening recommendations vary among professional organizations (TABLE 1^5,6,8). The US Preventive Services Task Force (USPSTF) recommends screening adults ages 35 to 70 years who are overweight or obese. Clinicians also can consider screening patients with a higher risk for diabetes.⁵ The ADA suggests screening all adults starting at 35 years, regardless of risk factors.⁸ Asymptomatic adults of any age with overweight or obesity and 1 or more risk factors should be screened.⁸The American Association of Clinical Endocrinology (AACE) recommends screening adults of any age who have risk factors.⁶ If the screening result is normal, repeat testing in 3 years is appropriate, unless there is a change in symptoms or risks.^5,8 Annual testing can be considered in patients with ≥ 2 risk factors or with prediabetes (glycosylated hemoglobin [A1C] ≥ 5.7%).^6,8

Making the diagnosis

The initial diagnosis of diabetes can be made by a fasting plasma glucose level ≥ 126 mg/dL (7.0 mmol/L); a 2-hour plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) following an oral glucose tolerance test; or an A1C level ≥ 6.5%. Prioritize lab-drawn A1C measurements over point-of-care tests to diagnose T2D. In ­patients with classic symptoms of hyper­glycemia, a random plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) is also diagnostic. Generally, these tests are considered equally appropriate in screening for diabetes and may be used to detect prediabetes. In the absence of clear symptoms of hyperglycemia, the diagnosis of diabetes requires 2 abnormal screening test results, either via 1 blood sample (such as an abnormal A1C and glucose) or 2 separate blood samples of the same test. Further evaluation is advised if there is discordance between the 2 samples.⁸

Extended evaluations

Patients with newly diagnosed T2D require a thorough evaluation for comorbidities and complications of diabetes. Refer patients to an ophthalmologist for a dilated eye examination, with subsequent exams occurring every 1 to 2 years.^6,9 Additional referrals for diabetes education, family planning for women of reproductive age, and dental, social, or mental health services may be clinically appropriate.⁹

Setting goals for glycemic control

Glycemic control is commonly monitored by the A1C level and by blood glucose monitoring either through traditional point-of-care glucometers or continuous glucose monitors (CGMs).¹⁰ Generally, CGMs provide more glycemic data than traditional glucometers and may cue patients to choose healthier dietary options and engage in physical exercise.¹¹ Patients with T2D who use CGMs exhibit lower A1Cs, greater time in glycemic range, and reduced hypoglycemic episodes.¹¹ Generally, CGMs are reserved for patients with type 1 diabetes and patients with T2D who use multiple daily injections, subcutaneous insulin infusions, or basal insulin only.¹² Most professional organizations recommend that clinicians consider patient-specific factors to set individualized glycemic goals.^6,10,13,14 For example, more stringent glycemic goals could be pursued for patients with longer life expectancy, shorter disease duration, absence of complications (eg, nephropathy, neuropathy, or cardiovascular disease), fewer comorbid conditions, lower hypoglycemia risk, or higher cognitive function.⁶

With newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.

More specific A1C goals vary by professional organization. For nonpregnant adults, the ADA recommends an A1C goal of < 7% and a preprandial blood glucose level of 80 to 130 mg/dL (4.4-7.2 mmol/L).¹⁰ However, a lower A1C goal may be appropriate if it can be attained safely without causing hypoglycemia or other adverse effects.¹⁰ The AACE suggests an A1C goal of ≤ 6.5% and a fasting blood glucose level of < 110 mg/dL when it can be achieved safely.⁶ More stringent A1C goals may reduce long-term micro- and macrovascular complications—especially in patients with newly diagnosed T2D.¹⁰ While older studies such as the ACCORD trial found increased mortality in groups with more stringent glycemic targets, they did not include newer agents (SGLT2 inhibitors or glucagon-like peptide-1 [GLP-1] receptor agonists) that reduce cardiovascular events by mechanisms outside their glycemic-lowering effect. With these newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.¹⁰ Both the ADA and AACE recommend a less stringent A1C goal of 7% to 8% for patients with limited life expectancy or risks (eg, a history of hypoglycemia) that outweigh expected benefits.^6,10

Continue to: Lifestyle modifications

Nutrition

The energy-dense Western diet, combined with sedentary behavior, are thought to be a primary cause of T2D.¹⁵ Therefore, include lifestyle modifications in the initial management of newly diagnosed T2D. Diets that replace carbohydrates with saturated and trans fats are related to increased mortality in patients with T2D.¹⁶ Increased consumption of vegetables, fruits, legumes, nuts, fish, cereal, and oils reduces concentrations of saturated and trans fats and increases dietary intake of monounsaturated fatty acids, fiber, antioxidants, and polyphenols.¹⁷

Combined endurance and resistance training is superior for improving glycemic control, cardiorespiratory fitness, and body composition, compared with either type of training alone.

Increasing the intake of fiber, an undigestible carbohydrate, offers numerous benefits in T2D management. High-fiber diets can help regulate blood sugar and lipid levels, increase satiety, reduce inflammation, aid in weight management, and reduce premature mortality.¹⁸ Insoluble fiber, found in foods such as whole wheat flour, nuts, and cauliflower, helps food pass more quickly through the stomach and intestines and adds bulk to stool. Soluble fiber, found in foods such as chickpeas, lentils, and Brussels sprouts, absorbs water and forms a gel-like substance that protects nutrients from digestive enzymes and slows down digestion. The result is a more gradual rise in postprandial glucose levels and improved insulin sensitivity.¹⁹ Dietary fiber may produce short-chain fatty acids which in turn activate incretin secretion and stimulate a glucose-dependent release of insulin from the pancreas.²⁰

Simple dietary substitutions, such as whole grains and legumes for white rice, can reduce fasting blood glucose and A1C levels.²¹ In a randomized controlled trial (RCT), increasing whole grain oat intake improved measures of glycemic control, reducing A1C by 1% at 1-year follow-up.¹⁹ Encourage patients with T2D to increase consumption of high-fiber foods and replace animal fats and refined grains with vegetable fats (eg, nuts, avocados, olives).
Nutritional therapies should be individualized, taking into account personal preferences and cultural customs.²² Nutritional habits may be based on race/ethnicity, ­religion/spirituality, or even the city in which an individual resides. Nutrition recommendations should account for these differences as well as access to healthy foods. For instance, ethnic groups whose dietary patterns include tortillas could be counseled to choose high-fiber options such as corn instead of flour tortillas and to incorporate vegetables in place of high-fat foods. Additionally, ethnic groups who favor using animal fats in foods such as greens could be advised on ways to add flavor to vegetables without adding saturated fats. Taking this approach may lessen barriers to change and increase ability to make dietary modifications.²³

Exercise

Encourage all patients with T2D to exercise regularly. The atherosclerotic plaques found in patients with T2D have increased inflammatory properties and result in worse cardiovascular outcomes compared with plaques in individuals without T2D.²⁴ Regular exercise reduces levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-6, and tumor necrosis factor alpha—and increases levels of anti-­inflammatory markers (IL-4 and IL-10).²⁴ Regular exercise can improve body composition, physical fitness, lipid and glucose metabolism, and insulin sensitivity.^25,26

A meta-analysis of RCTs demonstrated that structured exercise > 150 minutes per week resulted in A1C reductions of 0.89%,²⁷ which is comparable to the effect of many oral antihyperglycemic medications.²⁶ The Health Benefits of Aerobic and Resistance Training in individuals with T2D (HART-D) and Diabetes Aerobic and Resistance Exercise (DARE) studies demonstrated that combining endurance and resistance training was superior for improving glycemic control, cardiorespiratory fitness, and body composition, than using either type of training alone.²⁵ Both the American College of Sports Medicine (ACSM) and the ADA recommend that adults engage in at least 150 total minutes of moderate-intensity aerobic activity per week and resistance training 2 to 3 times weekly.²⁶ ACSM defines moderate-intensity exercise as 65% to 75% of maximal heart rate, a rating of perceived exertion of 3 to 4, or a step rate of 100 steps per minute.²⁸

Continue to: Because of their longitudinal relationships...

Because of their longitudinal relationships with patients, family physicians are in an optimal position to assess a patient’s physical capacity level and provide individualized counseling. Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.²⁹ Encourage your patients with T2D to exercise regularly, considering each individual’s ability to engage in physical activity.

Weight loss

Include weight management in the initial treatment of patients with newly diagnosed T2D. Weight loss decreases hepatic glucose production and increases peripheral insulin sensitivity and insulin secretion.³⁰ Moderate decreases in weight (5%-10%) can reduce complications related to diabetes, and sustained significant weight loss (> 10%) can potentially cause T2D remission (A1C < 6.5% after stopping diabetes medications).^31,32

Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.

Diabetes self-management education supports patients by giving them tools for making and maintaining lifestyle changes. Understanding individual barriers to change and addressing these during motivational interviews is important. Through a qualitative interview study, participants in a diabetes self-management program revealed 4 factors that motivated them to maintain lifestyle changes: support from others, experiencing the impact of the changes they made, fear of T2D complications, and forming new habits.³³ Family physicians are key in helping patients acquire knowledge and support to make the lifestyle modifications needed to manage newly diagnosed T2D.

Individualized pharmacotherapy considerations

For decades, the initial pharmacotherapeutic regimen for patients with newly diagnosed T2D considered the patient’s baseline A1C as a major driver for therapy. Metformin has been the mainstay in T2D treatment due to its clinical efficacy, minimal risk for hypoglycemia, and low cost. Regardless of the regimen, pharmacotherapy should be initiated at the time of T2D diagnosis in conjunction with the aforementioned lifestyle modifications.³⁴

When selecting pharmacotherapy, practice guidelines recommend considering the efficacy and adverse effects of medications, patient-specific comorbidities, adherence, cost, and a patient’s lifestyle factors.³⁴ Drug classes with pertinent information are listed in TABLE 2.^34-54 After starting medication, monitor the A1C level every 3 months to determine whether therapy should be intensified. Patients should have their labs drawn ahead of the quarterly visit, or point-of-care measurements may be used to facilitate in-person patient–provider discussions.

Continue to: Consider patient-specific factors when starting pharmacotherapy

Consider patient-specific factors when starting pharmacotherapy

ASCVD. Regardless of baseline glycemic control, offer patients who have ASCVD, or who are at high risk for it, an SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or a long-acting GLP-1 receptor agonist (dulaglutide, liraglutide, or semaglutide).^34,35 SGLT2 inhibitors reduced the risk for MACE by 11% in patients with established ASCVD.⁵⁵ They also reduced a composite outcome of cardiovascular death or hospitalization for heart failure by 23% in patients with or without ASCVD or heart failure at baseline.⁵⁵ GLP-1 receptor agonists offer a similar reduction in MACE to SGLT2 inhibitors, but they do not have significant effects in heart failure.⁵⁶ Thiazolidinediones (TZDs), saxagliptin, and alogliptin should be avoided in patients with heart failure.⁵⁷ TZDs may reduce the risk for recurrent stroke in patients with T2D.⁵⁸

Chronic kidney disease (CKD). As with ASCVD, prioritize SGLT2 inhibitors and ­GLP-1 receptor agonists in patients with CKD. While both classes reduced the risk for progression of kidney disease such as macroalbuminuria, SGLT2 inhibitors offer additional benefits in their reduction of the worsening of estimated glomerular filtration rate, end-stage kidney disease, and renal death.⁵⁶

Obesity. Consider the effect of each drug class on weight when making initial treatment choices, taking special care to minimize weight gain and potentially promote weight loss.³⁴ The ADA prefers GLP-1 receptor agonists, but also suggests SGLT2 inhibitors in these patients. While all GLP-1 receptor agonists have an impact on weight, weekly subcutaneous semaglutide offers the most pronounced weight loss of 2 to 7 kg over 56 weeks.⁵⁹ SGLT2 inhibitors promote sustainable weight loss to a lesser degree, contributing to an average loss of 3 kg at 2 years.⁶⁰ Weight gain is common in patients taking sulfonylureas (2.01-2.3 kg)³¹ and insulin (3-9 kg weight gain in the first year)⁶¹ and should be avoided in patients with T2D and obesity.³⁴

Hypoglycemia risk. In addition to counseling patients on hypoglycemia management and prescribing glucagon rescue kits, offer medications with no or very low risk for hypoglycemia (eg, GLP-1 receptor agonists, SGLT2 inhibitors, dipeptidyl ­peptidase-4 inhibitors, and TZDs). Generally, avoid insulin and sulfonylureas in patients in whom hypoglycemia is a major concern (eg, older adults, individuals with labile blood glucose levels).³⁴ Patients with reduced renal function are at higher risk for hypoglycemia with insulin or sulfonylureas due to reduced drug clearance. However, insulin is often the only treatment for patients with advanced renal disease. Pay close attention to insulin dosing in patients with advanced renal disease, which may necessitate lower doses and smaller dose adjustments due to this risk.

Social determinants of health. Medication access and cost is a major burden in T2D management and should be considered for every patient. Compared with the period of 2005 to 2007, the annual cost of diabetes medications for an individual in 2015 to 2017 increased by 147%, rising from $1106 to $2727 per year.⁶² This increase is driven by the cost of insulin and newer medications without generic options.⁶² Identify local resources in your community, such as patient assistance programs and pharmacies with reduced-price generic prescription programs, which may be useful for patients who are underinsured or uninsured.

Continue to: Even if cost weren't an issue...

Even if cost weren’t an issue, many ­medications such as insulin and GLP-1 receptor agonists should be kept refrigerated and are only stable at room temperature for a limited time. Medications that are stable at room temperature should be prioritized in patients with limited or inconsistent access to refrigeration or unstable housing who may find it difficult to store their medications ­appropriately.

Do not delay insulin initiation in patients with high baseline A1C

Whenever possible, a GLP-1 receptor agonist is the preferred injectable medication to insulin. Starting insulin introduces numerous risks, including hypoglycemia, weight gain, and stigma. However, in the patient with newly diagnosed T2D, choose basal insulin when the baseline hyperglycemia is severe,³⁴ as indicated by:

• blood glucose > 300 mg/dL (16.7 mmol/L),
• A1C > 10% (86 mmol/mol),
• symptoms of hyperglycemia (polyuria or polydipsia), or
• evidence of catabolism (weight loss, hypertriglyceridemia, ketosis).

Basal insulin analogs are preferred over NPH given their reduced variability, dosing, and hypoglycemic risk.³⁵ Mixed insulins may be used if a patient is unable to afford an insulin analog, which can be quite costly. However, extensive counseling on dosing and management of hypoglycemia is crucial to patient safety with these agents. The ADA ­recommends initiating 0.1 to 0.2 units/kg of basal insulin daily or 10 units daily.³⁴ The AACE follows this recommendation for ­patients with baseline A1C < 8%, but it proposes a more aggressive initiation of 0.2 to 0.3 units/kg/d for patients with baseline A1C > 8%.³⁵ Titrate the dose by 2 units every 3 days to reach the target fasting blood glucose level. As hyperglycemia resolves, simplify the regimen and transition to noninsulin options per the previously discussed considerations.

It’s not just about glycemic control

In addition to the direct effects of hyperglycemia, a T2D diagnosis introduces an increased risk for ASCVD, a reduced ability to fight infection, and heightened risk for depression. Order a lipid panel at the time of T2D diagnosis and initiate lipid management as needed (TABLE 3^35,63,64). Both the ADA and the American Heart Association recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.⁶³ The AACE uses specific lipid targets and recommends moderate- to high-intensity statin therapy for patients with T2D.³⁵ All recommendations by professional organizations list high-intensity statins for patients with established ASCVD.

Both the ADA and the AHA recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.

It is also vital to recommend that patients with newly diagnosed T2D remain up to date on all indicated vaccinations. They should promptly receive the hepatitis B and pneumococcal vaccines if they have not already done so for a previous indication. COVID-19 and annual influenza vaccines also should be prioritized for these patients.⁶⁵

Finally, patients with diabetes are twice as likely to develop depression than patients without diabetes.⁶⁶ Individuals with T2D and depression exhibit poorer medication adherence, lifestyle choices, and glycemic control.⁶⁶ Screen for and treat these issues in all patients with T2D across the course of the disease.

Overall, work closely with patients to support them in managing their new diagnosis with evidence-based pharmacologic and nonpharmacologic approaches. The importance of lifestyle changes including high-fiber diets, regular exercise, and weight loss should not be overlooked. Do not delay starting pharmacotherapy after diagnosing T2D and consider medication-specific and patient-specific factors to individualize therapy, improve adherence, and prevent complications.

CORRESPONDENCE
Jennie B. Jarrett, PharmD, MMedEd, 833 South Wood Street (MC 886), Chicago, IL 60612; [email protected]

Nearly 40 antihyperglycemic agents have been approved by the US Food and Drug Administration (FDA) since the approval of human insulin in 1982.¹ In addition, existing antihyperglycemic medications are constantly gaining FDA approval for new indications for common type 2 diabetes (T2D) comorbidities. For example, in addition to their glycemic benefits, the sodium-glucose cotransporter-2 (SGLT2) inhibitors have been approved for use in patients with T2D and established atherosclerotic cardiovascular disease (ASCVD) to reduce the risk for major adverse cardiovascular events (MACE; canagliflozin), risk for hospitalization for heart failure (dapagliflozin), and cardiovascular death (empagliflozin).^2-4

The plethora of new agents and new data for existing agents, coupled with the annual release of guidelines from the American Diabetes Association (ADA) and practice recommendations from several other professional organizations,^5-7 make it challenging for family physicians to stay current and provide the most up-to-date, evidence-based care. In this article, we provide advice on how to approach the screening, diagnosis, and evaluation of T2D, and on how to manage newly diagnosed T2D.

Screening, Dx, and evaluation: A quick review

Screening

Screening recommendations vary among professional organizations (TABLE 1^5,6,8). The US Preventive Services Task Force (USPSTF) recommends screening adults ages 35 to 70 years who are overweight or obese. Clinicians also can consider screening patients with a higher risk for diabetes.⁵ The ADA suggests screening all adults starting at 35 years, regardless of risk factors.⁸ Asymptomatic adults of any age with overweight or obesity and 1 or more risk factors should be screened.⁸The American Association of Clinical Endocrinology (AACE) recommends screening adults of any age who have risk factors.⁶ If the screening result is normal, repeat testing in 3 years is appropriate, unless there is a change in symptoms or risks.^5,8 Annual testing can be considered in patients with ≥ 2 risk factors or with prediabetes (glycosylated hemoglobin [A1C] ≥ 5.7%).^6,8

Making the diagnosis

The initial diagnosis of diabetes can be made by a fasting plasma glucose level ≥ 126 mg/dL (7.0 mmol/L); a 2-hour plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) following an oral glucose tolerance test; or an A1C level ≥ 6.5%. Prioritize lab-drawn A1C measurements over point-of-care tests to diagnose T2D. In ­patients with classic symptoms of hyper­glycemia, a random plasma glucose level ≥ 200 mg/dL (11.0 mmol/L) is also diagnostic. Generally, these tests are considered equally appropriate in screening for diabetes and may be used to detect prediabetes. In the absence of clear symptoms of hyperglycemia, the diagnosis of diabetes requires 2 abnormal screening test results, either via 1 blood sample (such as an abnormal A1C and glucose) or 2 separate blood samples of the same test. Further evaluation is advised if there is discordance between the 2 samples.⁸

Extended evaluations

Patients with newly diagnosed T2D require a thorough evaluation for comorbidities and complications of diabetes. Refer patients to an ophthalmologist for a dilated eye examination, with subsequent exams occurring every 1 to 2 years.^6,9 Additional referrals for diabetes education, family planning for women of reproductive age, and dental, social, or mental health services may be clinically appropriate.⁹

Setting goals for glycemic control

Glycemic control is commonly monitored by the A1C level and by blood glucose monitoring either through traditional point-of-care glucometers or continuous glucose monitors (CGMs).¹⁰ Generally, CGMs provide more glycemic data than traditional glucometers and may cue patients to choose healthier dietary options and engage in physical exercise.¹¹ Patients with T2D who use CGMs exhibit lower A1Cs, greater time in glycemic range, and reduced hypoglycemic episodes.¹¹ Generally, CGMs are reserved for patients with type 1 diabetes and patients with T2D who use multiple daily injections, subcutaneous insulin infusions, or basal insulin only.¹² Most professional organizations recommend that clinicians consider patient-specific factors to set individualized glycemic goals.^6,10,13,14 For example, more stringent glycemic goals could be pursued for patients with longer life expectancy, shorter disease duration, absence of complications (eg, nephropathy, neuropathy, or cardiovascular disease), fewer comorbid conditions, lower hypoglycemia risk, or higher cognitive function.⁶

With newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.

More specific A1C goals vary by professional organization. For nonpregnant adults, the ADA recommends an A1C goal of < 7% and a preprandial blood glucose level of 80 to 130 mg/dL (4.4-7.2 mmol/L).¹⁰ However, a lower A1C goal may be appropriate if it can be attained safely without causing hypoglycemia or other adverse effects.¹⁰ The AACE suggests an A1C goal of ≤ 6.5% and a fasting blood glucose level of < 110 mg/dL when it can be achieved safely.⁶ More stringent A1C goals may reduce long-term micro- and macrovascular complications—especially in patients with newly diagnosed T2D.¹⁰ While older studies such as the ACCORD trial found increased mortality in groups with more stringent glycemic targets, they did not include newer agents (SGLT2 inhibitors or glucagon-like peptide-1 [GLP-1] receptor agonists) that reduce cardiovascular events by mechanisms outside their glycemic-lowering effect. With these newer agents, more aggressive A1C goals can be targeted safely in select patients, particularly those with long life expectancy.¹⁰ Both the ADA and AACE recommend a less stringent A1C goal of 7% to 8% for patients with limited life expectancy or risks (eg, a history of hypoglycemia) that outweigh expected benefits.^6,10

Continue to: Lifestyle modifications

Nutrition

The energy-dense Western diet, combined with sedentary behavior, are thought to be a primary cause of T2D.¹⁵ Therefore, include lifestyle modifications in the initial management of newly diagnosed T2D. Diets that replace carbohydrates with saturated and trans fats are related to increased mortality in patients with T2D.¹⁶ Increased consumption of vegetables, fruits, legumes, nuts, fish, cereal, and oils reduces concentrations of saturated and trans fats and increases dietary intake of monounsaturated fatty acids, fiber, antioxidants, and polyphenols.¹⁷

Combined endurance and resistance training is superior for improving glycemic control, cardiorespiratory fitness, and body composition, compared with either type of training alone.

Increasing the intake of fiber, an undigestible carbohydrate, offers numerous benefits in T2D management. High-fiber diets can help regulate blood sugar and lipid levels, increase satiety, reduce inflammation, aid in weight management, and reduce premature mortality.¹⁸ Insoluble fiber, found in foods such as whole wheat flour, nuts, and cauliflower, helps food pass more quickly through the stomach and intestines and adds bulk to stool. Soluble fiber, found in foods such as chickpeas, lentils, and Brussels sprouts, absorbs water and forms a gel-like substance that protects nutrients from digestive enzymes and slows down digestion. The result is a more gradual rise in postprandial glucose levels and improved insulin sensitivity.¹⁹ Dietary fiber may produce short-chain fatty acids which in turn activate incretin secretion and stimulate a glucose-dependent release of insulin from the pancreas.²⁰

Simple dietary substitutions, such as whole grains and legumes for white rice, can reduce fasting blood glucose and A1C levels.²¹ In a randomized controlled trial (RCT), increasing whole grain oat intake improved measures of glycemic control, reducing A1C by 1% at 1-year follow-up.¹⁹ Encourage patients with T2D to increase consumption of high-fiber foods and replace animal fats and refined grains with vegetable fats (eg, nuts, avocados, olives).
Nutritional therapies should be individualized, taking into account personal preferences and cultural customs.²² Nutritional habits may be based on race/ethnicity, ­religion/spirituality, or even the city in which an individual resides. Nutrition recommendations should account for these differences as well as access to healthy foods. For instance, ethnic groups whose dietary patterns include tortillas could be counseled to choose high-fiber options such as corn instead of flour tortillas and to incorporate vegetables in place of high-fat foods. Additionally, ethnic groups who favor using animal fats in foods such as greens could be advised on ways to add flavor to vegetables without adding saturated fats. Taking this approach may lessen barriers to change and increase ability to make dietary modifications.²³

Exercise

Encourage all patients with T2D to exercise regularly. The atherosclerotic plaques found in patients with T2D have increased inflammatory properties and result in worse cardiovascular outcomes compared with plaques in individuals without T2D.²⁴ Regular exercise reduces levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-6, and tumor necrosis factor alpha—and increases levels of anti-­inflammatory markers (IL-4 and IL-10).²⁴ Regular exercise can improve body composition, physical fitness, lipid and glucose metabolism, and insulin sensitivity.^25,26

A meta-analysis of RCTs demonstrated that structured exercise > 150 minutes per week resulted in A1C reductions of 0.89%,²⁷ which is comparable to the effect of many oral antihyperglycemic medications.²⁶ The Health Benefits of Aerobic and Resistance Training in individuals with T2D (HART-D) and Diabetes Aerobic and Resistance Exercise (DARE) studies demonstrated that combining endurance and resistance training was superior for improving glycemic control, cardiorespiratory fitness, and body composition, than using either type of training alone.²⁵ Both the American College of Sports Medicine (ACSM) and the ADA recommend that adults engage in at least 150 total minutes of moderate-intensity aerobic activity per week and resistance training 2 to 3 times weekly.²⁶ ACSM defines moderate-intensity exercise as 65% to 75% of maximal heart rate, a rating of perceived exertion of 3 to 4, or a step rate of 100 steps per minute.²⁸

Continue to: Because of their longitudinal relationships...

Because of their longitudinal relationships with patients, family physicians are in an optimal position to assess a patient’s physical capacity level and provide individualized counseling. Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.²⁹ Encourage your patients with T2D to exercise regularly, considering each individual’s ability to engage in physical activity.

Weight loss

Include weight management in the initial treatment of patients with newly diagnosed T2D. Weight loss decreases hepatic glucose production and increases peripheral insulin sensitivity and insulin secretion.³⁰ Moderate decreases in weight (5%-10%) can reduce complications related to diabetes, and sustained significant weight loss (> 10%) can potentially cause T2D remission (A1C < 6.5% after stopping diabetes medications).^31,32

Several systematic reviews have demonstrated that counseling on exercise increases patients’ participation in physical activity.

Diabetes self-management education supports patients by giving them tools for making and maintaining lifestyle changes. Understanding individual barriers to change and addressing these during motivational interviews is important. Through a qualitative interview study, participants in a diabetes self-management program revealed 4 factors that motivated them to maintain lifestyle changes: support from others, experiencing the impact of the changes they made, fear of T2D complications, and forming new habits.³³ Family physicians are key in helping patients acquire knowledge and support to make the lifestyle modifications needed to manage newly diagnosed T2D.

Individualized pharmacotherapy considerations

For decades, the initial pharmacotherapeutic regimen for patients with newly diagnosed T2D considered the patient’s baseline A1C as a major driver for therapy. Metformin has been the mainstay in T2D treatment due to its clinical efficacy, minimal risk for hypoglycemia, and low cost. Regardless of the regimen, pharmacotherapy should be initiated at the time of T2D diagnosis in conjunction with the aforementioned lifestyle modifications.³⁴

When selecting pharmacotherapy, practice guidelines recommend considering the efficacy and adverse effects of medications, patient-specific comorbidities, adherence, cost, and a patient’s lifestyle factors.³⁴ Drug classes with pertinent information are listed in TABLE 2.^34-54 After starting medication, monitor the A1C level every 3 months to determine whether therapy should be intensified. Patients should have their labs drawn ahead of the quarterly visit, or point-of-care measurements may be used to facilitate in-person patient–provider discussions.

Continue to: Consider patient-specific factors when starting pharmacotherapy

Consider patient-specific factors when starting pharmacotherapy

ASCVD. Regardless of baseline glycemic control, offer patients who have ASCVD, or who are at high risk for it, an SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or a long-acting GLP-1 receptor agonist (dulaglutide, liraglutide, or semaglutide).^34,35 SGLT2 inhibitors reduced the risk for MACE by 11% in patients with established ASCVD.⁵⁵ They also reduced a composite outcome of cardiovascular death or hospitalization for heart failure by 23% in patients with or without ASCVD or heart failure at baseline.⁵⁵ GLP-1 receptor agonists offer a similar reduction in MACE to SGLT2 inhibitors, but they do not have significant effects in heart failure.⁵⁶ Thiazolidinediones (TZDs), saxagliptin, and alogliptin should be avoided in patients with heart failure.⁵⁷ TZDs may reduce the risk for recurrent stroke in patients with T2D.⁵⁸

Chronic kidney disease (CKD). As with ASCVD, prioritize SGLT2 inhibitors and ­GLP-1 receptor agonists in patients with CKD. While both classes reduced the risk for progression of kidney disease such as macroalbuminuria, SGLT2 inhibitors offer additional benefits in their reduction of the worsening of estimated glomerular filtration rate, end-stage kidney disease, and renal death.⁵⁶

Obesity. Consider the effect of each drug class on weight when making initial treatment choices, taking special care to minimize weight gain and potentially promote weight loss.³⁴ The ADA prefers GLP-1 receptor agonists, but also suggests SGLT2 inhibitors in these patients. While all GLP-1 receptor agonists have an impact on weight, weekly subcutaneous semaglutide offers the most pronounced weight loss of 2 to 7 kg over 56 weeks.⁵⁹ SGLT2 inhibitors promote sustainable weight loss to a lesser degree, contributing to an average loss of 3 kg at 2 years.⁶⁰ Weight gain is common in patients taking sulfonylureas (2.01-2.3 kg)³¹ and insulin (3-9 kg weight gain in the first year)⁶¹ and should be avoided in patients with T2D and obesity.³⁴

Hypoglycemia risk. In addition to counseling patients on hypoglycemia management and prescribing glucagon rescue kits, offer medications with no or very low risk for hypoglycemia (eg, GLP-1 receptor agonists, SGLT2 inhibitors, dipeptidyl ­peptidase-4 inhibitors, and TZDs). Generally, avoid insulin and sulfonylureas in patients in whom hypoglycemia is a major concern (eg, older adults, individuals with labile blood glucose levels).³⁴ Patients with reduced renal function are at higher risk for hypoglycemia with insulin or sulfonylureas due to reduced drug clearance. However, insulin is often the only treatment for patients with advanced renal disease. Pay close attention to insulin dosing in patients with advanced renal disease, which may necessitate lower doses and smaller dose adjustments due to this risk.

Social determinants of health. Medication access and cost is a major burden in T2D management and should be considered for every patient. Compared with the period of 2005 to 2007, the annual cost of diabetes medications for an individual in 2015 to 2017 increased by 147%, rising from $1106 to $2727 per year.⁶² This increase is driven by the cost of insulin and newer medications without generic options.⁶² Identify local resources in your community, such as patient assistance programs and pharmacies with reduced-price generic prescription programs, which may be useful for patients who are underinsured or uninsured.

Continue to: Even if cost weren't an issue...

Even if cost weren’t an issue, many ­medications such as insulin and GLP-1 receptor agonists should be kept refrigerated and are only stable at room temperature for a limited time. Medications that are stable at room temperature should be prioritized in patients with limited or inconsistent access to refrigeration or unstable housing who may find it difficult to store their medications ­appropriately.

Do not delay insulin initiation in patients with high baseline A1C

Whenever possible, a GLP-1 receptor agonist is the preferred injectable medication to insulin. Starting insulin introduces numerous risks, including hypoglycemia, weight gain, and stigma. However, in the patient with newly diagnosed T2D, choose basal insulin when the baseline hyperglycemia is severe,³⁴ as indicated by:

• blood glucose > 300 mg/dL (16.7 mmol/L),
• A1C > 10% (86 mmol/mol),
• symptoms of hyperglycemia (polyuria or polydipsia), or
• evidence of catabolism (weight loss, hypertriglyceridemia, ketosis).

Basal insulin analogs are preferred over NPH given their reduced variability, dosing, and hypoglycemic risk.³⁵ Mixed insulins may be used if a patient is unable to afford an insulin analog, which can be quite costly. However, extensive counseling on dosing and management of hypoglycemia is crucial to patient safety with these agents. The ADA ­recommends initiating 0.1 to 0.2 units/kg of basal insulin daily or 10 units daily.³⁴ The AACE follows this recommendation for ­patients with baseline A1C < 8%, but it proposes a more aggressive initiation of 0.2 to 0.3 units/kg/d for patients with baseline A1C > 8%.³⁵ Titrate the dose by 2 units every 3 days to reach the target fasting blood glucose level. As hyperglycemia resolves, simplify the regimen and transition to noninsulin options per the previously discussed considerations.

It’s not just about glycemic control

In addition to the direct effects of hyperglycemia, a T2D diagnosis introduces an increased risk for ASCVD, a reduced ability to fight infection, and heightened risk for depression. Order a lipid panel at the time of T2D diagnosis and initiate lipid management as needed (TABLE 3^35,63,64). Both the ADA and the American Heart Association recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.⁶³ The AACE uses specific lipid targets and recommends moderate- to high-intensity statin therapy for patients with T2D.³⁵ All recommendations by professional organizations list high-intensity statins for patients with established ASCVD.

Both the ADA and the AHA recommend starting a moderate-intensity statin as primary prevention for all patients with T2D between 40 and 75 years of age regardless of the 10-year ASCVD risk.

It is also vital to recommend that patients with newly diagnosed T2D remain up to date on all indicated vaccinations. They should promptly receive the hepatitis B and pneumococcal vaccines if they have not already done so for a previous indication. COVID-19 and annual influenza vaccines also should be prioritized for these patients.⁶⁵

Finally, patients with diabetes are twice as likely to develop depression than patients without diabetes.⁶⁶ Individuals with T2D and depression exhibit poorer medication adherence, lifestyle choices, and glycemic control.⁶⁶ Screen for and treat these issues in all patients with T2D across the course of the disease.

Overall, work closely with patients to support them in managing their new diagnosis with evidence-based pharmacologic and nonpharmacologic approaches. The importance of lifestyle changes including high-fiber diets, regular exercise, and weight loss should not be overlooked. Do not delay starting pharmacotherapy after diagnosing T2D and consider medication-specific and patient-specific factors to individualize therapy, improve adherence, and prevent complications.

CORRESPONDENCE
Jennie B. Jarrett, PharmD, MMedEd, 833 South Wood Street (MC 886), Chicago, IL 60612; [email protected]

A low-carbohydrate breakfast was better than a control (low-fat) breakfast to decrease glycemic variability throughout the day in type 2 diabetes, in new research.

These findings from a 3-month randomized study in 121 patients in Canada and Australia were published online recently in the American Journal of Clinical Nutrition.

The researchers aimed to determine whether a low-carbohydrate, high-fat breakfast (focused around eggs), compared with a standard, low-fat control breakfast (designed to have no/minimal eggs), would improve blood glucose control in individuals with type 2 diabetes.

“We’ve determined that if the first meal of the day is low-carb and higher in protein and fat we can limit hyperglycemic swings,” lead author Barbara Oliveira, PhD, School of Health and Exercise Sciences, University of British Columbia, Kelowna, said in a press release from the university.

“Having fewer carbs for breakfast not only aligns better with how people with [type 2 diabetes] handle glucose throughout the day,” she noted, “but it also has incredible potential for people with [type 2 diabetes] who struggle with their glucose levels in the morning.”

“By making a small adjustment to the carb content of a single meal rather than the entire diet,” Dr. Oliveira added, “we have the potential to increase adherence significantly while still obtaining significant benefits.”

The researchers conclude that “this trial provides evidence that advice to consume a low-carbohydrate breakfast could be a simple, feasible, and effective approach to manage postprandial hyperglycemia and lower glycemic variability in people living with type 2 diabetes.”
 

Could breakfast tweak improve glucose control?

People with type 2 diabetes have higher levels of insulin resistance and greater glucose intolerance in the morning, the researchers write.

And consuming a low-fat, high-carbohydrate meal in line with most dietary guidelines appears to incur the highest hyperglycemia spike and leads to higher glycemic variability.

They speculated that eating a low-carb breakfast, compared with a low-fat breakfast, might be an easy way to mitigate this.

They recruited participants from online ads in three provinces in Canada and four states in Australia, and they conducted the study from a site in British Columbia and one in Wollongong, Australia.

The participants were aged 20-79 years and diagnosed with type 2 diabetes. They also had a current hemoglobin A1c < 8.5% and no allergies to eggs, and they were able to follow remote, online guidance.

After screening, the participants had a phone or video conference call with a member of the research team who explained the study.

The researchers randomly assigned 75 participants in Canada and 46 participants in Australia 1:1 to the low-carbohydrate intervention or the control intervention.

The participants had a mean age of 64 and 53% were women. They had a mean weight of 93 kg (204 lb), body mass index of 32 kg/m², and A1c of 7.0%.

Registered dietitians in Canada and Australia each designed 8-10 recipes/menus for low-carb breakfasts and an equal number of recipes/menus for control (low-fat) breakfasts that were specific for those countries.

Each recipe contains about 450 kcal, and they are available in Supplemental Appendix 1A and 1B, with the article.

Each low-carbohydrate breakfast contains about 25 g protein, 8 g carbohydrates, and 37 g fat. For example, one breakfast is a three-egg omelet with spinach.

Each control (low-fat) recipe contains about 20 g protein, 56 g carbohydrates, and 15 g fat. For example, one breakfast is a small blueberry muffin and a small plain Greek yogurt.

The participants were advised to select one of these breakfasts every day and follow it exactly (they were also required to upload a photograph of their breakfast every morning). They were not given any guidance or calorie restriction for the other meals of the day.

The participants also filled in 3-day food records and answered a questionnaire about exercise, hunger, and satiety, at the beginning, middle, and end of the intervention.

They provided self-reported height, weight, and waist circumference, and they were given requisitions for blood tests for A1c to be done at a local laboratory, at the beginning and end of the intervention.

The participants also wore a continuous glucose monitor (CGM) during the first and last 14 days of the intervention.
 

Intervention improved CGM measures

There was no significant difference in the primary outcome, change in A1c, at the end of 12 weeks, in the two groups. The mean A1c decreased by 0.3% in the intervention group vs 0.1% in the control group (P = .06).

Similarly, in secondary outcomes, weight and BMI each decreased about 1% and waist circumference decreased by about 2.5 cm in each group at 12 weeks (no significant difference). There were also no significant differences in hunger, satiety, or physical activity between the two groups.

However, the 24-hour CGM data showed that mean and maximum glucose, glycemic variability, and time above range were all significantly lower in participants in the low-carbohydrate breakfast intervention group vs. those in the control group (all P < .05).

Time in range was significantly higher among participants in the intervention group (P < .05).

In addition, the 2-hour postprandial CGM data showed that mean glucose and maximum glucose after breakfast were lower in participants in the low-carbohydrate breakfast group than in the control group.

This work was supported by investigator-initiated operating grants to senior author Jonathan P. Little, PhD, School of Health and Exercise Sciences, University of British Columbia, from the Egg Nutrition Center, United States, and Egg Farmers of Canada. The authors declare that they have no relevant financial relationships.

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

A low-carbohydrate breakfast was better than a control (low-fat) breakfast to decrease glycemic variability throughout the day in type 2 diabetes, in new research.

These findings from a 3-month randomized study in 121 patients in Canada and Australia were published online recently in the American Journal of Clinical Nutrition.

The researchers aimed to determine whether a low-carbohydrate, high-fat breakfast (focused around eggs), compared with a standard, low-fat control breakfast (designed to have no/minimal eggs), would improve blood glucose control in individuals with type 2 diabetes.

“We’ve determined that if the first meal of the day is low-carb and higher in protein and fat we can limit hyperglycemic swings,” lead author Barbara Oliveira, PhD, School of Health and Exercise Sciences, University of British Columbia, Kelowna, said in a press release from the university.

“Having fewer carbs for breakfast not only aligns better with how people with [type 2 diabetes] handle glucose throughout the day,” she noted, “but it also has incredible potential for people with [type 2 diabetes] who struggle with their glucose levels in the morning.”

“By making a small adjustment to the carb content of a single meal rather than the entire diet,” Dr. Oliveira added, “we have the potential to increase adherence significantly while still obtaining significant benefits.”

The researchers conclude that “this trial provides evidence that advice to consume a low-carbohydrate breakfast could be a simple, feasible, and effective approach to manage postprandial hyperglycemia and lower glycemic variability in people living with type 2 diabetes.”
 

Could breakfast tweak improve glucose control?

People with type 2 diabetes have higher levels of insulin resistance and greater glucose intolerance in the morning, the researchers write.

And consuming a low-fat, high-carbohydrate meal in line with most dietary guidelines appears to incur the highest hyperglycemia spike and leads to higher glycemic variability.

They speculated that eating a low-carb breakfast, compared with a low-fat breakfast, might be an easy way to mitigate this.

They recruited participants from online ads in three provinces in Canada and four states in Australia, and they conducted the study from a site in British Columbia and one in Wollongong, Australia.

The participants were aged 20-79 years and diagnosed with type 2 diabetes. They also had a current hemoglobin A1c < 8.5% and no allergies to eggs, and they were able to follow remote, online guidance.

After screening, the participants had a phone or video conference call with a member of the research team who explained the study.

The researchers randomly assigned 75 participants in Canada and 46 participants in Australia 1:1 to the low-carbohydrate intervention or the control intervention.

The participants had a mean age of 64 and 53% were women. They had a mean weight of 93 kg (204 lb), body mass index of 32 kg/m², and A1c of 7.0%.

Registered dietitians in Canada and Australia each designed 8-10 recipes/menus for low-carb breakfasts and an equal number of recipes/menus for control (low-fat) breakfasts that were specific for those countries.

Each recipe contains about 450 kcal, and they are available in Supplemental Appendix 1A and 1B, with the article.

Each low-carbohydrate breakfast contains about 25 g protein, 8 g carbohydrates, and 37 g fat. For example, one breakfast is a three-egg omelet with spinach.

Each control (low-fat) recipe contains about 20 g protein, 56 g carbohydrates, and 15 g fat. For example, one breakfast is a small blueberry muffin and a small plain Greek yogurt.

The participants were advised to select one of these breakfasts every day and follow it exactly (they were also required to upload a photograph of their breakfast every morning). They were not given any guidance or calorie restriction for the other meals of the day.

The participants also filled in 3-day food records and answered a questionnaire about exercise, hunger, and satiety, at the beginning, middle, and end of the intervention.

They provided self-reported height, weight, and waist circumference, and they were given requisitions for blood tests for A1c to be done at a local laboratory, at the beginning and end of the intervention.

The participants also wore a continuous glucose monitor (CGM) during the first and last 14 days of the intervention.
 

Intervention improved CGM measures

There was no significant difference in the primary outcome, change in A1c, at the end of 12 weeks, in the two groups. The mean A1c decreased by 0.3% in the intervention group vs 0.1% in the control group (P = .06).

Similarly, in secondary outcomes, weight and BMI each decreased about 1% and waist circumference decreased by about 2.5 cm in each group at 12 weeks (no significant difference). There were also no significant differences in hunger, satiety, or physical activity between the two groups.

However, the 24-hour CGM data showed that mean and maximum glucose, glycemic variability, and time above range were all significantly lower in participants in the low-carbohydrate breakfast intervention group vs. those in the control group (all P < .05).

Time in range was significantly higher among participants in the intervention group (P < .05).

In addition, the 2-hour postprandial CGM data showed that mean glucose and maximum glucose after breakfast were lower in participants in the low-carbohydrate breakfast group than in the control group.

This work was supported by investigator-initiated operating grants to senior author Jonathan P. Little, PhD, School of Health and Exercise Sciences, University of British Columbia, from the Egg Nutrition Center, United States, and Egg Farmers of Canada. The authors declare that they have no relevant financial relationships.

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

A low-carbohydrate breakfast was better than a control (low-fat) breakfast to decrease glycemic variability throughout the day in type 2 diabetes, in new research.

These findings from a 3-month randomized study in 121 patients in Canada and Australia were published online recently in the American Journal of Clinical Nutrition.

The researchers aimed to determine whether a low-carbohydrate, high-fat breakfast (focused around eggs), compared with a standard, low-fat control breakfast (designed to have no/minimal eggs), would improve blood glucose control in individuals with type 2 diabetes.

“We’ve determined that if the first meal of the day is low-carb and higher in protein and fat we can limit hyperglycemic swings,” lead author Barbara Oliveira, PhD, School of Health and Exercise Sciences, University of British Columbia, Kelowna, said in a press release from the university.

“Having fewer carbs for breakfast not only aligns better with how people with [type 2 diabetes] handle glucose throughout the day,” she noted, “but it also has incredible potential for people with [type 2 diabetes] who struggle with their glucose levels in the morning.”

“By making a small adjustment to the carb content of a single meal rather than the entire diet,” Dr. Oliveira added, “we have the potential to increase adherence significantly while still obtaining significant benefits.”

The researchers conclude that “this trial provides evidence that advice to consume a low-carbohydrate breakfast could be a simple, feasible, and effective approach to manage postprandial hyperglycemia and lower glycemic variability in people living with type 2 diabetes.”
 

Could breakfast tweak improve glucose control?

People with type 2 diabetes have higher levels of insulin resistance and greater glucose intolerance in the morning, the researchers write.

And consuming a low-fat, high-carbohydrate meal in line with most dietary guidelines appears to incur the highest hyperglycemia spike and leads to higher glycemic variability.

They speculated that eating a low-carb breakfast, compared with a low-fat breakfast, might be an easy way to mitigate this.

They recruited participants from online ads in three provinces in Canada and four states in Australia, and they conducted the study from a site in British Columbia and one in Wollongong, Australia.

The participants were aged 20-79 years and diagnosed with type 2 diabetes. They also had a current hemoglobin A1c < 8.5% and no allergies to eggs, and they were able to follow remote, online guidance.

After screening, the participants had a phone or video conference call with a member of the research team who explained the study.

The researchers randomly assigned 75 participants in Canada and 46 participants in Australia 1:1 to the low-carbohydrate intervention or the control intervention.

The participants had a mean age of 64 and 53% were women. They had a mean weight of 93 kg (204 lb), body mass index of 32 kg/m², and A1c of 7.0%.

Registered dietitians in Canada and Australia each designed 8-10 recipes/menus for low-carb breakfasts and an equal number of recipes/menus for control (low-fat) breakfasts that were specific for those countries.

Each recipe contains about 450 kcal, and they are available in Supplemental Appendix 1A and 1B, with the article.

Each low-carbohydrate breakfast contains about 25 g protein, 8 g carbohydrates, and 37 g fat. For example, one breakfast is a three-egg omelet with spinach.

Each control (low-fat) recipe contains about 20 g protein, 56 g carbohydrates, and 15 g fat. For example, one breakfast is a small blueberry muffin and a small plain Greek yogurt.

The participants were advised to select one of these breakfasts every day and follow it exactly (they were also required to upload a photograph of their breakfast every morning). They were not given any guidance or calorie restriction for the other meals of the day.

The participants also filled in 3-day food records and answered a questionnaire about exercise, hunger, and satiety, at the beginning, middle, and end of the intervention.

They provided self-reported height, weight, and waist circumference, and they were given requisitions for blood tests for A1c to be done at a local laboratory, at the beginning and end of the intervention.

The participants also wore a continuous glucose monitor (CGM) during the first and last 14 days of the intervention.
 

Intervention improved CGM measures

There was no significant difference in the primary outcome, change in A1c, at the end of 12 weeks, in the two groups. The mean A1c decreased by 0.3% in the intervention group vs 0.1% in the control group (P = .06).

Similarly, in secondary outcomes, weight and BMI each decreased about 1% and waist circumference decreased by about 2.5 cm in each group at 12 weeks (no significant difference). There were also no significant differences in hunger, satiety, or physical activity between the two groups.

However, the 24-hour CGM data showed that mean and maximum glucose, glycemic variability, and time above range were all significantly lower in participants in the low-carbohydrate breakfast intervention group vs. those in the control group (all P < .05).

Time in range was significantly higher among participants in the intervention group (P < .05).

In addition, the 2-hour postprandial CGM data showed that mean glucose and maximum glucose after breakfast were lower in participants in the low-carbohydrate breakfast group than in the control group.

This work was supported by investigator-initiated operating grants to senior author Jonathan P. Little, PhD, School of Health and Exercise Sciences, University of British Columbia, from the Egg Nutrition Center, United States, and Egg Farmers of Canada. The authors declare that they have no relevant financial relationships.

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

Nearly 60% of Medicaid-covered adults with concurrent diabetes and heart failure did not receive guideline-concordant postdischarge care within 7-10 days of leaving the hospital, according to a large Alabama study. Moreover, affected Black and Hispanic/other Alabamians were less likely than were their White counterparts to receive recommended postdischarge care.

In comparison with White participants, Black and Hispanic adults were less likely to have any postdischarge ambulatory care visits after HF hospitalization or had a delayed visit, according to researchers led by Yulia Khodneva, MD, PhD, an internist at the University of Alabama at Birmingham. “This is likely a reflection of a structural racism and implicit bias against racial and ethnic minorities that persists in the U.S. health care system,” she and her colleagues wrote.

The findings point to the need for strategies to improve access to postdischarge care for lower-income HF patients.

Among U.S. states, Alabama is the sixth-poorest, the third in diabetes prevalence (14%), and has the highest rates of heart failure hospitalizations and cardiovascular mortality, the authors noted.

Study details

The cohort included 9,857 adults with diabetes and first hospitalizations for heart failure who were covered by Alabama Medicaid during 2010-2019. The investigators analyzed patients’ claims for ambulatory care (any, primary, cardiology, or endocrinology) within 60 days of discharge.

The mean age of participants was 53.7 years; 47.3% were Black; 41.8% non-Hispanic White; and 10.9% Hispanic/other, with other including those identifying as non-White Hispanic, American Indian, Pacific Islander, and Asian. About two-thirds (65.4%) of participants were women.

Analysis revealed low rates of follow-up care after hospital discharge; 26.7% had an ambulatory visit within 0-7 days, 15.2% within 8-14 days, 31.3% within 15-60 days, and 26.8% had no follow-up visit at all. Of those having a follow-up visit, 71% saw a primary care physician and 12% saw a cardiologist.

In contrast, a much higher proportion of heart failure patients in a Swedish registry – 63% – received ambulatory follow-up in cardiology.
 

Ethnic/gender/age disparities

Black and Hispanic/other adults were less likely to have any postdischarge ambulatory visit (P <.0001) or had the visit delayed by 1.8 days (P = .0006) and 2.8 days (P = .0016), respectively. They were less likely to see a primary care physician than were non-Hispanic White adults: adjusted incidence rate ratio, 0.96 (95% confidence interval [CI], 0.91-1.00) and 0.91 (95% CI, 0.89-0.98), respectively.

Men and those with longer-standing heart failure were less likely to be seen in primary care, while the presence of multiple comorbidities was associated with a higher likelihood of a postdischarge primary care visit. Men were more likely to be seen by a cardiologist, while older discharged patients were less likely to be seen by an endocrinologist within 60 days. There was a U-shaped relationship between the timing of the first postdischarge ambulatory visit and all-cause mortality among adults with diabetes and heart failure. Higher rates of 60-day all-cause mortality were observed both in those who had seen a provider within 0-7 days after discharge and in those who had not seen any provider during the 60-day study period compared with those having an ambulatory care visit within 7-14 or 15-60 days. “The group with early follow-up (0-7 days) likely represents a sicker population of patients with heart failure with more comorbidity burden and higher overall health care use, including readmissions, as was demonstrated in our analysis,” Dr. Khodneva and associates wrote. “Interventions that improve access to postdischarge ambulatory care for low-income patients with diabetes and heart failure and eliminate racial and ethnic disparities may be warranted,” they added.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of Alabama at Birmingham Diabetes Research Center. Dr. Khodneva reported funding from the University of Alabama at Birmingham and the Forge Ahead Center as well as from the NIDDK, the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Alabama Medicaid Agency. Coauthor Emily Levitan, ScD, reported research funding from Amgen and has served on Amgen advisory boards. She has also served as a scientific consultant for a research project funded by Novartis.

Nearly 60% of Medicaid-covered adults with concurrent diabetes and heart failure did not receive guideline-concordant postdischarge care within 7-10 days of leaving the hospital, according to a large Alabama study. Moreover, affected Black and Hispanic/other Alabamians were less likely than were their White counterparts to receive recommended postdischarge care.

In comparison with White participants, Black and Hispanic adults were less likely to have any postdischarge ambulatory care visits after HF hospitalization or had a delayed visit, according to researchers led by Yulia Khodneva, MD, PhD, an internist at the University of Alabama at Birmingham. “This is likely a reflection of a structural racism and implicit bias against racial and ethnic minorities that persists in the U.S. health care system,” she and her colleagues wrote.

The findings point to the need for strategies to improve access to postdischarge care for lower-income HF patients.

Among U.S. states, Alabama is the sixth-poorest, the third in diabetes prevalence (14%), and has the highest rates of heart failure hospitalizations and cardiovascular mortality, the authors noted.

Study details

The cohort included 9,857 adults with diabetes and first hospitalizations for heart failure who were covered by Alabama Medicaid during 2010-2019. The investigators analyzed patients’ claims for ambulatory care (any, primary, cardiology, or endocrinology) within 60 days of discharge.

The mean age of participants was 53.7 years; 47.3% were Black; 41.8% non-Hispanic White; and 10.9% Hispanic/other, with other including those identifying as non-White Hispanic, American Indian, Pacific Islander, and Asian. About two-thirds (65.4%) of participants were women.

Analysis revealed low rates of follow-up care after hospital discharge; 26.7% had an ambulatory visit within 0-7 days, 15.2% within 8-14 days, 31.3% within 15-60 days, and 26.8% had no follow-up visit at all. Of those having a follow-up visit, 71% saw a primary care physician and 12% saw a cardiologist.

In contrast, a much higher proportion of heart failure patients in a Swedish registry – 63% – received ambulatory follow-up in cardiology.
 

Ethnic/gender/age disparities

Black and Hispanic/other adults were less likely to have any postdischarge ambulatory visit (P <.0001) or had the visit delayed by 1.8 days (P = .0006) and 2.8 days (P = .0016), respectively. They were less likely to see a primary care physician than were non-Hispanic White adults: adjusted incidence rate ratio, 0.96 (95% confidence interval [CI], 0.91-1.00) and 0.91 (95% CI, 0.89-0.98), respectively.

Men and those with longer-standing heart failure were less likely to be seen in primary care, while the presence of multiple comorbidities was associated with a higher likelihood of a postdischarge primary care visit. Men were more likely to be seen by a cardiologist, while older discharged patients were less likely to be seen by an endocrinologist within 60 days. There was a U-shaped relationship between the timing of the first postdischarge ambulatory visit and all-cause mortality among adults with diabetes and heart failure. Higher rates of 60-day all-cause mortality were observed both in those who had seen a provider within 0-7 days after discharge and in those who had not seen any provider during the 60-day study period compared with those having an ambulatory care visit within 7-14 or 15-60 days. “The group with early follow-up (0-7 days) likely represents a sicker population of patients with heart failure with more comorbidity burden and higher overall health care use, including readmissions, as was demonstrated in our analysis,” Dr. Khodneva and associates wrote. “Interventions that improve access to postdischarge ambulatory care for low-income patients with diabetes and heart failure and eliminate racial and ethnic disparities may be warranted,” they added.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of Alabama at Birmingham Diabetes Research Center. Dr. Khodneva reported funding from the University of Alabama at Birmingham and the Forge Ahead Center as well as from the NIDDK, the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Alabama Medicaid Agency. Coauthor Emily Levitan, ScD, reported research funding from Amgen and has served on Amgen advisory boards. She has also served as a scientific consultant for a research project funded by Novartis.

Nearly 60% of Medicaid-covered adults with concurrent diabetes and heart failure did not receive guideline-concordant postdischarge care within 7-10 days of leaving the hospital, according to a large Alabama study. Moreover, affected Black and Hispanic/other Alabamians were less likely than were their White counterparts to receive recommended postdischarge care.

In comparison with White participants, Black and Hispanic adults were less likely to have any postdischarge ambulatory care visits after HF hospitalization or had a delayed visit, according to researchers led by Yulia Khodneva, MD, PhD, an internist at the University of Alabama at Birmingham. “This is likely a reflection of a structural racism and implicit bias against racial and ethnic minorities that persists in the U.S. health care system,” she and her colleagues wrote.

The findings point to the need for strategies to improve access to postdischarge care for lower-income HF patients.

Among U.S. states, Alabama is the sixth-poorest, the third in diabetes prevalence (14%), and has the highest rates of heart failure hospitalizations and cardiovascular mortality, the authors noted.

Study details

The cohort included 9,857 adults with diabetes and first hospitalizations for heart failure who were covered by Alabama Medicaid during 2010-2019. The investigators analyzed patients’ claims for ambulatory care (any, primary, cardiology, or endocrinology) within 60 days of discharge.

The mean age of participants was 53.7 years; 47.3% were Black; 41.8% non-Hispanic White; and 10.9% Hispanic/other, with other including those identifying as non-White Hispanic, American Indian, Pacific Islander, and Asian. About two-thirds (65.4%) of participants were women.

Analysis revealed low rates of follow-up care after hospital discharge; 26.7% had an ambulatory visit within 0-7 days, 15.2% within 8-14 days, 31.3% within 15-60 days, and 26.8% had no follow-up visit at all. Of those having a follow-up visit, 71% saw a primary care physician and 12% saw a cardiologist.

In contrast, a much higher proportion of heart failure patients in a Swedish registry – 63% – received ambulatory follow-up in cardiology.
 

Ethnic/gender/age disparities

Black and Hispanic/other adults were less likely to have any postdischarge ambulatory visit (P <.0001) or had the visit delayed by 1.8 days (P = .0006) and 2.8 days (P = .0016), respectively. They were less likely to see a primary care physician than were non-Hispanic White adults: adjusted incidence rate ratio, 0.96 (95% confidence interval [CI], 0.91-1.00) and 0.91 (95% CI, 0.89-0.98), respectively.

Men and those with longer-standing heart failure were less likely to be seen in primary care, while the presence of multiple comorbidities was associated with a higher likelihood of a postdischarge primary care visit. Men were more likely to be seen by a cardiologist, while older discharged patients were less likely to be seen by an endocrinologist within 60 days. There was a U-shaped relationship between the timing of the first postdischarge ambulatory visit and all-cause mortality among adults with diabetes and heart failure. Higher rates of 60-day all-cause mortality were observed both in those who had seen a provider within 0-7 days after discharge and in those who had not seen any provider during the 60-day study period compared with those having an ambulatory care visit within 7-14 or 15-60 days. “The group with early follow-up (0-7 days) likely represents a sicker population of patients with heart failure with more comorbidity burden and higher overall health care use, including readmissions, as was demonstrated in our analysis,” Dr. Khodneva and associates wrote. “Interventions that improve access to postdischarge ambulatory care for low-income patients with diabetes and heart failure and eliminate racial and ethnic disparities may be warranted,” they added.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of Alabama at Birmingham Diabetes Research Center. Dr. Khodneva reported funding from the University of Alabama at Birmingham and the Forge Ahead Center as well as from the NIDDK, the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Alabama Medicaid Agency. Coauthor Emily Levitan, ScD, reported research funding from Amgen and has served on Amgen advisory boards. She has also served as a scientific consultant for a research project funded by Novartis.

Continuous glucose monitors (CGMs) could enhance care of hospitalized people with diabetes, supplementing or possibly even replacing the use of finger sticks to draw blood to measure a patient’s glucose level. But that technological future will require ensuring that the monitoring devices are as accurate as the conventional method, experts told this news organization.

In 2020, the U.S. Food and Drug Administration enabled in-hospital use of CGMs to reduce contact between patients and health care providers during the COVID-19 pandemic. Diabetes is a risk factor for more severe COVID, meaning that many patients with the infection also required ongoing care for their blood sugar problems. 

Prior to the pandemic, in-person finger-stick tests were the primary means of measuring glucose for hospitalized patients with diabetes.

The trouble is that finger-stick measurements quickly become inaccurate.

“Glucose is a measurement that changes pretty rapidly,” said Eileen Faulds, RN, PhD, an endocrinology nurse and health services researcher at the Ohio State University, Columbus. Finger sticks might occur only four or five times per day, Dr. Faulds noted, or as often as every hour for people who receive insulin intravenously. But even that more frequent pace is far from continuous.

“With CGM we can get the glucose level in real time,” Dr. Faulds said. 

Dr. Faulds is lead author of a new study in the Journal of Diabetes Science and Technology, which shows that nurses in the ICU believe that using continuous monitors, subcutaneous filaments connected to sensors that regularly report glucose levels, enables better patient care than does relying on periodic glucose tests alone. Nurses still used traditional finger sticks, which Dr. Faulds notes are highly accurate at the time of the reading.

In a 2022 study, glucose levels generated by CGM and those measured by finger sticks varied by up to 14%. A hybrid care model combining CGMs and finger stick tests may emerge, Dr. Faulds said.
 

A gusher of glucose data

People with diabetes have long been able to use CGMs in their daily lives, which typically report the glucose value to a smartphone or watch. The devices are now part of hospital care as well. In 2022, the Food and Drug Administration granted a breakthrough therapy designation to the company Dexcom for use of its CGMs to manage care of people with diabetes in hospitals.

One open question is how often CGMs should report glucose readings for optimum patient health. Dexcom’s G6 CGM reports glucose levels every five minutes, for example, whereas Abbott’s FreeStyle Libre 2 delivers glucose values every minute. 

“We wouldn’t look at each value, we would look at the big picture,” to determine if a patient is at risk of becoming hyper- or hypoglycemic, said Lizda Guerrero-Arroyo, MD, a postdoctoral fellow in endocrinology at the Emory University School of Medicine, Atlanta. Dr. Guerrero-Arroyo recently reported that clinicians in multiple ICUs began to use CGMs in conjunction with finger sticks during the pandemic and felt the devices could reduce patient discomfort. 

“A finger stick is very painful,” Dr. Guerrero-Arroyo said, and a bottleneck for nursing staff who administer these tests. In contrast, Dr. Faulds said, CGM placement is essentially painless and requires less labor on the ward to manage.

Beyond use in the ICU, clinicians are also experimenting with use of CGMs to monitor blood sugar levels in people with diabetes who are undergoing general surgery. And other researchers are describing how to integrate data from CGMs into patient care tools such as the electronic health record, although a standard way to do this does not yet exist.

Assuming CGMs remain part of the mix for in-hospital care of people with diabetes, clinicians may mainly need trend summaries of how glucose levels rise and fall over time, said data scientist Samantha Spierling Bagsic, PhD, of the Scripps Whittier Diabetes Institute, San Diego. Dr. Guerrero-Arroyo said that she shares that vision. But a minute-by-minute analysis of glucose levels also may be necessary to get a granular sense of how changing a patient’s insulin level affects their blood sugar, Dr. Spierling Bagsic said.

“We need to figure out what data different audiences need, how often we need to measure glucose, and how to present that information to different audiences in different ways,” said Dr. Spierling Bagsic, a co-author of the study about integrating CGM data into patient care tools.

The wider use of CGMs in hospitals may be one silver lining of the COVID-19 pandemic. As an inpatient endocrinology nurse, Dr. Faulds said that she wanted to use CGMs prior to the outbreak, but at that point, a critical mass of studies about their benefits was missing.

“We all know the terrible things that happened during the pandemic,” Dr. Faulds said. “But it gave us the allowance to use CGMs, and we saw that nurses loved them.”

Dr. Faulds reports relationships with Dexcom and Insulet and has received an honorarium from Medscape. Dr. Guerrero-Arroyo and Dr. Spierling Bagsic reported no financial conflicts of interest.

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

Continuous glucose monitors (CGMs) could enhance care of hospitalized people with diabetes, supplementing or possibly even replacing the use of finger sticks to draw blood to measure a patient’s glucose level. But that technological future will require ensuring that the monitoring devices are as accurate as the conventional method, experts told this news organization.

In 2020, the U.S. Food and Drug Administration enabled in-hospital use of CGMs to reduce contact between patients and health care providers during the COVID-19 pandemic. Diabetes is a risk factor for more severe COVID, meaning that many patients with the infection also required ongoing care for their blood sugar problems. 

Prior to the pandemic, in-person finger-stick tests were the primary means of measuring glucose for hospitalized patients with diabetes.

The trouble is that finger-stick measurements quickly become inaccurate.

“Glucose is a measurement that changes pretty rapidly,” said Eileen Faulds, RN, PhD, an endocrinology nurse and health services researcher at the Ohio State University, Columbus. Finger sticks might occur only four or five times per day, Dr. Faulds noted, or as often as every hour for people who receive insulin intravenously. But even that more frequent pace is far from continuous.

“With CGM we can get the glucose level in real time,” Dr. Faulds said. 

Dr. Faulds is lead author of a new study in the Journal of Diabetes Science and Technology, which shows that nurses in the ICU believe that using continuous monitors, subcutaneous filaments connected to sensors that regularly report glucose levels, enables better patient care than does relying on periodic glucose tests alone. Nurses still used traditional finger sticks, which Dr. Faulds notes are highly accurate at the time of the reading.

In a 2022 study, glucose levels generated by CGM and those measured by finger sticks varied by up to 14%. A hybrid care model combining CGMs and finger stick tests may emerge, Dr. Faulds said.
 

A gusher of glucose data

People with diabetes have long been able to use CGMs in their daily lives, which typically report the glucose value to a smartphone or watch. The devices are now part of hospital care as well. In 2022, the Food and Drug Administration granted a breakthrough therapy designation to the company Dexcom for use of its CGMs to manage care of people with diabetes in hospitals.

One open question is how often CGMs should report glucose readings for optimum patient health. Dexcom’s G6 CGM reports glucose levels every five minutes, for example, whereas Abbott’s FreeStyle Libre 2 delivers glucose values every minute. 

“We wouldn’t look at each value, we would look at the big picture,” to determine if a patient is at risk of becoming hyper- or hypoglycemic, said Lizda Guerrero-Arroyo, MD, a postdoctoral fellow in endocrinology at the Emory University School of Medicine, Atlanta. Dr. Guerrero-Arroyo recently reported that clinicians in multiple ICUs began to use CGMs in conjunction with finger sticks during the pandemic and felt the devices could reduce patient discomfort. 

“A finger stick is very painful,” Dr. Guerrero-Arroyo said, and a bottleneck for nursing staff who administer these tests. In contrast, Dr. Faulds said, CGM placement is essentially painless and requires less labor on the ward to manage.

Beyond use in the ICU, clinicians are also experimenting with use of CGMs to monitor blood sugar levels in people with diabetes who are undergoing general surgery. And other researchers are describing how to integrate data from CGMs into patient care tools such as the electronic health record, although a standard way to do this does not yet exist.

Assuming CGMs remain part of the mix for in-hospital care of people with diabetes, clinicians may mainly need trend summaries of how glucose levels rise and fall over time, said data scientist Samantha Spierling Bagsic, PhD, of the Scripps Whittier Diabetes Institute, San Diego. Dr. Guerrero-Arroyo said that she shares that vision. But a minute-by-minute analysis of glucose levels also may be necessary to get a granular sense of how changing a patient’s insulin level affects their blood sugar, Dr. Spierling Bagsic said.

“We need to figure out what data different audiences need, how often we need to measure glucose, and how to present that information to different audiences in different ways,” said Dr. Spierling Bagsic, a co-author of the study about integrating CGM data into patient care tools.

The wider use of CGMs in hospitals may be one silver lining of the COVID-19 pandemic. As an inpatient endocrinology nurse, Dr. Faulds said that she wanted to use CGMs prior to the outbreak, but at that point, a critical mass of studies about their benefits was missing.

“We all know the terrible things that happened during the pandemic,” Dr. Faulds said. “But it gave us the allowance to use CGMs, and we saw that nurses loved them.”

Dr. Faulds reports relationships with Dexcom and Insulet and has received an honorarium from Medscape. Dr. Guerrero-Arroyo and Dr. Spierling Bagsic reported no financial conflicts of interest.

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

Continuous glucose monitors (CGMs) could enhance care of hospitalized people with diabetes, supplementing or possibly even replacing the use of finger sticks to draw blood to measure a patient’s glucose level. But that technological future will require ensuring that the monitoring devices are as accurate as the conventional method, experts told this news organization.

In 2020, the U.S. Food and Drug Administration enabled in-hospital use of CGMs to reduce contact between patients and health care providers during the COVID-19 pandemic. Diabetes is a risk factor for more severe COVID, meaning that many patients with the infection also required ongoing care for their blood sugar problems. 

Prior to the pandemic, in-person finger-stick tests were the primary means of measuring glucose for hospitalized patients with diabetes.

The trouble is that finger-stick measurements quickly become inaccurate.

“Glucose is a measurement that changes pretty rapidly,” said Eileen Faulds, RN, PhD, an endocrinology nurse and health services researcher at the Ohio State University, Columbus. Finger sticks might occur only four or five times per day, Dr. Faulds noted, or as often as every hour for people who receive insulin intravenously. But even that more frequent pace is far from continuous.

“With CGM we can get the glucose level in real time,” Dr. Faulds said. 

Dr. Faulds is lead author of a new study in the Journal of Diabetes Science and Technology, which shows that nurses in the ICU believe that using continuous monitors, subcutaneous filaments connected to sensors that regularly report glucose levels, enables better patient care than does relying on periodic glucose tests alone. Nurses still used traditional finger sticks, which Dr. Faulds notes are highly accurate at the time of the reading.

In a 2022 study, glucose levels generated by CGM and those measured by finger sticks varied by up to 14%. A hybrid care model combining CGMs and finger stick tests may emerge, Dr. Faulds said.
 

A gusher of glucose data

People with diabetes have long been able to use CGMs in their daily lives, which typically report the glucose value to a smartphone or watch. The devices are now part of hospital care as well. In 2022, the Food and Drug Administration granted a breakthrough therapy designation to the company Dexcom for use of its CGMs to manage care of people with diabetes in hospitals.

One open question is how often CGMs should report glucose readings for optimum patient health. Dexcom’s G6 CGM reports glucose levels every five minutes, for example, whereas Abbott’s FreeStyle Libre 2 delivers glucose values every minute. 

“We wouldn’t look at each value, we would look at the big picture,” to determine if a patient is at risk of becoming hyper- or hypoglycemic, said Lizda Guerrero-Arroyo, MD, a postdoctoral fellow in endocrinology at the Emory University School of Medicine, Atlanta. Dr. Guerrero-Arroyo recently reported that clinicians in multiple ICUs began to use CGMs in conjunction with finger sticks during the pandemic and felt the devices could reduce patient discomfort. 

“A finger stick is very painful,” Dr. Guerrero-Arroyo said, and a bottleneck for nursing staff who administer these tests. In contrast, Dr. Faulds said, CGM placement is essentially painless and requires less labor on the ward to manage.

Beyond use in the ICU, clinicians are also experimenting with use of CGMs to monitor blood sugar levels in people with diabetes who are undergoing general surgery. And other researchers are describing how to integrate data from CGMs into patient care tools such as the electronic health record, although a standard way to do this does not yet exist.

Assuming CGMs remain part of the mix for in-hospital care of people with diabetes, clinicians may mainly need trend summaries of how glucose levels rise and fall over time, said data scientist Samantha Spierling Bagsic, PhD, of the Scripps Whittier Diabetes Institute, San Diego. Dr. Guerrero-Arroyo said that she shares that vision. But a minute-by-minute analysis of glucose levels also may be necessary to get a granular sense of how changing a patient’s insulin level affects their blood sugar, Dr. Spierling Bagsic said.

“We need to figure out what data different audiences need, how often we need to measure glucose, and how to present that information to different audiences in different ways,” said Dr. Spierling Bagsic, a co-author of the study about integrating CGM data into patient care tools.

The wider use of CGMs in hospitals may be one silver lining of the COVID-19 pandemic. As an inpatient endocrinology nurse, Dr. Faulds said that she wanted to use CGMs prior to the outbreak, but at that point, a critical mass of studies about their benefits was missing.

“We all know the terrible things that happened during the pandemic,” Dr. Faulds said. “But it gave us the allowance to use CGMs, and we saw that nurses loved them.”

Dr. Faulds reports relationships with Dexcom and Insulet and has received an honorarium from Medscape. Dr. Guerrero-Arroyo and Dr. Spierling Bagsic reported no financial conflicts of interest.

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

The Food and Drug Administration is warning people to avoid using compounded medicines as substitutes for the popular weight loss and diabetes drugs Ozempic, Rybelsus, and Wegovy.

Compounded medicines are not FDA approved but are allowed to be made during an official drug shortage. Ozempic and Wegovy are currently on the FDA’s shortage list, but the federal agency warned that it has received reports of people experiencing “adverse events” after using compounded versions of the drugs. (The FDA did not provide details of those events or where the drugs involved were compounded.)

Agency officials are concerned that the compounded versions may contain ingredients that sound like the brand name drugs’ active ingredient, semaglutide, but are different because the ingredients are in salt form.

“Patients should be aware that some products sold as ‘semaglutide’ may not contain the same active ingredient as FDA-approved semaglutide products and may be the salt formulations,” the FDA warning stated. “Products containing these salts, such as semaglutide sodium and semaglutide acetate, have not been shown to be safe and effective.”

The agency said salt forms don’t meet the criteria for compounding during a shortage and sent a letter to the National Association of Boards of Pharmacy expressing “concerns with use of the salt forms in compounded products.”

Patients and health care providers should be aware that “compounded drugs are not FDA approved, and the agency does not verify the safety or effectiveness of compounded drugs,” the FDA explained in its statement.

The Alliance for Pharmacy Compounding’s board of directors said in a statement that some compounders’ arguments for the suitability of semaglutide sodium are “worthy of discussion,” but the board did not endorse those arguments.

For people who use an online pharmacy, the FDA recommends checking the FDA’s website BeSafeRx to check its credentials.

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

The Food and Drug Administration is warning people to avoid using compounded medicines as substitutes for the popular weight loss and diabetes drugs Ozempic, Rybelsus, and Wegovy.

Compounded medicines are not FDA approved but are allowed to be made during an official drug shortage. Ozempic and Wegovy are currently on the FDA’s shortage list, but the federal agency warned that it has received reports of people experiencing “adverse events” after using compounded versions of the drugs. (The FDA did not provide details of those events or where the drugs involved were compounded.)

Agency officials are concerned that the compounded versions may contain ingredients that sound like the brand name drugs’ active ingredient, semaglutide, but are different because the ingredients are in salt form.

“Patients should be aware that some products sold as ‘semaglutide’ may not contain the same active ingredient as FDA-approved semaglutide products and may be the salt formulations,” the FDA warning stated. “Products containing these salts, such as semaglutide sodium and semaglutide acetate, have not been shown to be safe and effective.”

The agency said salt forms don’t meet the criteria for compounding during a shortage and sent a letter to the National Association of Boards of Pharmacy expressing “concerns with use of the salt forms in compounded products.”

Patients and health care providers should be aware that “compounded drugs are not FDA approved, and the agency does not verify the safety or effectiveness of compounded drugs,” the FDA explained in its statement.

The Alliance for Pharmacy Compounding’s board of directors said in a statement that some compounders’ arguments for the suitability of semaglutide sodium are “worthy of discussion,” but the board did not endorse those arguments.

For people who use an online pharmacy, the FDA recommends checking the FDA’s website BeSafeRx to check its credentials.

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

The Food and Drug Administration is warning people to avoid using compounded medicines as substitutes for the popular weight loss and diabetes drugs Ozempic, Rybelsus, and Wegovy.

Compounded medicines are not FDA approved but are allowed to be made during an official drug shortage. Ozempic and Wegovy are currently on the FDA’s shortage list, but the federal agency warned that it has received reports of people experiencing “adverse events” after using compounded versions of the drugs. (The FDA did not provide details of those events or where the drugs involved were compounded.)

Agency officials are concerned that the compounded versions may contain ingredients that sound like the brand name drugs’ active ingredient, semaglutide, but are different because the ingredients are in salt form.

“Patients should be aware that some products sold as ‘semaglutide’ may not contain the same active ingredient as FDA-approved semaglutide products and may be the salt formulations,” the FDA warning stated. “Products containing these salts, such as semaglutide sodium and semaglutide acetate, have not been shown to be safe and effective.”

The agency said salt forms don’t meet the criteria for compounding during a shortage and sent a letter to the National Association of Boards of Pharmacy expressing “concerns with use of the salt forms in compounded products.”

Patients and health care providers should be aware that “compounded drugs are not FDA approved, and the agency does not verify the safety or effectiveness of compounded drugs,” the FDA explained in its statement.

The Alliance for Pharmacy Compounding’s board of directors said in a statement that some compounders’ arguments for the suitability of semaglutide sodium are “worthy of discussion,” but the board did not endorse those arguments.

For people who use an online pharmacy, the FDA recommends checking the FDA’s website BeSafeRx to check its credentials.

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

An experimental, proprietary cannabinoid-based drug in development for diabetic neuropathy outperformed pregabalin (Lyrica) in a clinical trial, achieving significant reduction in pain severity, new top-line results released by Zelira Therapeutics suggest.

“The implications of these results for patients are incredibly promising,” principal investigator Bryan Doner, DO, medical director of HealthyWays Integrated Wellness Solutions, Gibsonia, Pa., said in a news release.

“Through this rigorously designed study, we have demonstrated that ZLT-L-007 is a safe, effective, and well-tolerated alternative for patients who would typically seek a Lyrica-level of pain relief,” he added.

The observational, nonblinded trial tested the efficacy, safety, and tolerability of ZLT-L-007 against pregabalin in 60 adults with diabetic nerve pain.

The study had three groups with 20 patients each (pregabalin alone, pregabalin plus ZLT-L-007, and ZLT-L-007 alone).

Top-line results show the study met its primary endpoint for change in daily pain severity as measured by the percent change from baseline at 30, 60, and 90 days on the Numerical Rating Scale.

For the pregabalin-only group, there was a reduction in symptom severity at all follow-up points, ranging from 20% to 35% (median percent change from baseline), the company said.

For the ZLT-L-007 only group, there was about a 33% reduction in symptom severity at 30 days, and 71% and 78% reduction, respectively, at 60 and 90 days, suggesting a larger improvement in symptom severity than with pregabalin alone, the company said.

For the pregabalin plus ZLT-L-007 group, there was a moderate 20% reduction in symptom severity at 30 days, but a larger reduction at 60 and 90 days (50% and 72%, respectively), which indicates substantially greater improvement in symptom severity than with pregabalin alone, the company said.

The study also met secondary endpoints, including significant decreases in daily pain severity as measured by the Visual Analog Scale and measurable changes in the short-form McGill Pain Questionnaire and Neuropathic Pain Symptom Inventory.

Dr. Doner noted that the top-line data showed “no serious adverse events, and participants’ blood pressure and other safety vitals remained unaffected throughout. This confirms that ZLT-L-007 is a well-tolerated product that delivers statistically significant pain relief, surpassing the levels achieved by Lyrica.”

The company plans to report additional insights from the full study, as they become available, during fiscal year 2023-2024.

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

An experimental, proprietary cannabinoid-based drug in development for diabetic neuropathy outperformed pregabalin (Lyrica) in a clinical trial, achieving significant reduction in pain severity, new top-line results released by Zelira Therapeutics suggest.

“The implications of these results for patients are incredibly promising,” principal investigator Bryan Doner, DO, medical director of HealthyWays Integrated Wellness Solutions, Gibsonia, Pa., said in a news release.

“Through this rigorously designed study, we have demonstrated that ZLT-L-007 is a safe, effective, and well-tolerated alternative for patients who would typically seek a Lyrica-level of pain relief,” he added.

The observational, nonblinded trial tested the efficacy, safety, and tolerability of ZLT-L-007 against pregabalin in 60 adults with diabetic nerve pain.

The study had three groups with 20 patients each (pregabalin alone, pregabalin plus ZLT-L-007, and ZLT-L-007 alone).

Top-line results show the study met its primary endpoint for change in daily pain severity as measured by the percent change from baseline at 30, 60, and 90 days on the Numerical Rating Scale.

For the pregabalin-only group, there was a reduction in symptom severity at all follow-up points, ranging from 20% to 35% (median percent change from baseline), the company said.

For the ZLT-L-007 only group, there was about a 33% reduction in symptom severity at 30 days, and 71% and 78% reduction, respectively, at 60 and 90 days, suggesting a larger improvement in symptom severity than with pregabalin alone, the company said.

For the pregabalin plus ZLT-L-007 group, there was a moderate 20% reduction in symptom severity at 30 days, but a larger reduction at 60 and 90 days (50% and 72%, respectively), which indicates substantially greater improvement in symptom severity than with pregabalin alone, the company said.

The study also met secondary endpoints, including significant decreases in daily pain severity as measured by the Visual Analog Scale and measurable changes in the short-form McGill Pain Questionnaire and Neuropathic Pain Symptom Inventory.

Dr. Doner noted that the top-line data showed “no serious adverse events, and participants’ blood pressure and other safety vitals remained unaffected throughout. This confirms that ZLT-L-007 is a well-tolerated product that delivers statistically significant pain relief, surpassing the levels achieved by Lyrica.”

The company plans to report additional insights from the full study, as they become available, during fiscal year 2023-2024.

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

An experimental, proprietary cannabinoid-based drug in development for diabetic neuropathy outperformed pregabalin (Lyrica) in a clinical trial, achieving significant reduction in pain severity, new top-line results released by Zelira Therapeutics suggest.

“The implications of these results for patients are incredibly promising,” principal investigator Bryan Doner, DO, medical director of HealthyWays Integrated Wellness Solutions, Gibsonia, Pa., said in a news release.

“Through this rigorously designed study, we have demonstrated that ZLT-L-007 is a safe, effective, and well-tolerated alternative for patients who would typically seek a Lyrica-level of pain relief,” he added.

The observational, nonblinded trial tested the efficacy, safety, and tolerability of ZLT-L-007 against pregabalin in 60 adults with diabetic nerve pain.

The study had three groups with 20 patients each (pregabalin alone, pregabalin plus ZLT-L-007, and ZLT-L-007 alone).

Top-line results show the study met its primary endpoint for change in daily pain severity as measured by the percent change from baseline at 30, 60, and 90 days on the Numerical Rating Scale.

For the pregabalin-only group, there was a reduction in symptom severity at all follow-up points, ranging from 20% to 35% (median percent change from baseline), the company said.

For the ZLT-L-007 only group, there was about a 33% reduction in symptom severity at 30 days, and 71% and 78% reduction, respectively, at 60 and 90 days, suggesting a larger improvement in symptom severity than with pregabalin alone, the company said.

For the pregabalin plus ZLT-L-007 group, there was a moderate 20% reduction in symptom severity at 30 days, but a larger reduction at 60 and 90 days (50% and 72%, respectively), which indicates substantially greater improvement in symptom severity than with pregabalin alone, the company said.

The study also met secondary endpoints, including significant decreases in daily pain severity as measured by the Visual Analog Scale and measurable changes in the short-form McGill Pain Questionnaire and Neuropathic Pain Symptom Inventory.

Dr. Doner noted that the top-line data showed “no serious adverse events, and participants’ blood pressure and other safety vitals remained unaffected throughout. This confirms that ZLT-L-007 is a well-tolerated product that delivers statistically significant pain relief, surpassing the levels achieved by Lyrica.”

The company plans to report additional insights from the full study, as they become available, during fiscal year 2023-2024.

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

Nearly one in five U.S. adults with type 2 diabetes but without symptoms of cardiovascular disease (CVD) have a clinically meaningful elevation of a marker of cardiac damage – namely, high-sensitivity cardiac troponin T (hs-cTnT) – based on data from a representative sample of more than 10,000 U.S. adults.

The finding suggests hs-cTnT maybe a useful marker for adults with diabetes who could benefit from more aggressive CVD risk reduction despite having no clinical indications of CVD.

The results “highlight the substantial burden of subclinical CVD in persons with diabetes and emphasize the importance of early detection and treatment of CVD for this high-risk population,” say the authors of the research, published in the Journal of the American Heart Association.

Johns Hopkins University

“This is the first study to examine subclinical CVD, defined by elevated cardiac biomarkers, in a nationally representative population of adults with or without diabetes. It provides novel information on the high burden of subclinical CVD [in American adults with diabetes] and the potential utility of hs-cTnT for monitoring this risk in people with diabetes,” said Elizabeth Selvin, PhD, senior author and a professor of epidemiology at Johns Hopkins University, Baltimore.

“What we are seeing is that many people with type 2 diabetes who have not had a heart attack or a history of cardiovascular disease are at high risk for cardiovascular complications,” added Dr. Selvin in an AHA press release. “When we look at the whole population of people diagnosed with type 2 diabetes, about 27 million adults in the U.S., according to the [Centers for Disease Control and Prevention], some are at low risk and some are at high risk for cardiovascular disease, so the open question is: ‘Who is most at risk?’ These cardiac biomarkers give us a window into cardiovascular risk in people who otherwise might not be recognized as highest risk.”

“Our results provide evidence to support use of cardiac biomarkers for routine risk monitoring in high-risk populations such as people with diabetes,” Dr. Selvin noted in an interview.
 

Need for aggressive CVD risk reduction

The findings also indicate that people with diabetes and an elevated hs-cTnT “should be targeted for aggressive cardiovascular risk reduction, including lifestyle interventions, weight loss, and treatment with statins, blood pressure medications, and cardioprotective therapies such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagonlike peptide-1 (GLP-1) receptor agonists,” Dr. Selvin added.

“Cholesterol is often the factor that we target to reduce the risk of cardiovascular disease in people with type 2 diabetes,” she observed. “However, type 2 diabetes may have a direct effect on the heart not related to cholesterol levels. If type 2 diabetes is directly causing damage to the small vessels in the heart unrelated to cholesterol plaque buildup, then cholesterol-lowering medications are not going to prevent cardiac damage,” Dr. Selvin explained. “Our research suggests that additional non–statin-related therapies are needed to lower the cardiovascular disease risk in people with type 2 diabetes.”

However, she noted that a necessary step prior to formally recommending such a strategy is to run clinical trials to assess the efficacy of specific treatments, such as SGLT-2 inhibitors and GLP-1 agonists, in people with diabetes and elevated hs-cTnT.

“Randomized controlled trials would be best to test the relevance of measuring these biomarkers to assess risk in asymptomatic people with diabetes,” as well as prospective study of the value of hs-cTnT to guide treatment, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado at Denver, Aurora.

“I doubt measurements [of hs-cTnT] would be reimbursed [by third-party payers] if carried out without such outcome data,” he added.

Dr. Eckel also highlights the need to further validate in additional cohorts the link between elevations in hs-cTnT and CVD events in adults with diabetes, and to confirm that elevated levels of another cardiac biomarker – N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) – do not work as well as troponin as a risk marker for people with diabetes, another finding of the study.
 

ADA report already recommends testing these biomarkers for HF

However, a consensus report published in 2022 by the American Diabetes Association laid out the case for routinely and regularly measuring levels of both high sensitivity cardiac troponin and natriuretic peptides in people with diabetes for early identification of incident heart failure.

“Among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure,” noted the ADA consensus report on heart failure.

The new study run by Dr. Selvin and coauthors used data collected by the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 from U.S. adults who were at least 20 years old and had no history of CVD: myocardial infarction, stroke, coronary heart disease, or heart failure. This included 9,273 people without diabetes and 1,031 with diabetes, defined as a prior diagnosis or hemoglobin A1c of at least 6.5%.

“Cardiovascular risk varies substantially in adults with type 2 diabetes, highlighting the need for accurate risk stratification,” the authors observed.

All study participants had recorded measures of hs-cTnT and NT-proBNP.

The researchers considered an hs-cTnT level of greater than 14 ng/L and an NT-proBNP level of greater than 125 pg/mL as indicators of subclinical CVD.

The crude prevalence of elevated NT-proBNP was 33.4% among those with diabetes and 16.1% in those without diabetes. Elevated hs-cTnT occurred in 19% of those with diabetes and in 5% of those without diabetes. Elevated levels of both markers existed in 9% of those with diabetes and in 3% of those without diabetes.

“Approximately one in three adults with diabetes had subclinical CVD, with 19% having elevated levels of hs-cTnT, 23% having elevated NT-proBNP, and 9% having elevations in both cardiac biomarkers,” the researchers noted.
 

Diabetes linked with a doubled prevalence of elevated hs-cTnT 

After adjustment for several demographic variables as well as traditional CVD risk factors, people with diabetes had a significant 98% higher rate of elevated hs-cTnT, compared with those without diabetes. But after similar adjustments, the rate of elevated NT-proBNP was significantly lower among people with diabetes, compared with controls, by a relative reduction of 24%.

“Our findings suggest that, in people with diabetes, hs-cTnT may be more useful [than NT-proBNP] for general risk monitoring, as its interpretation is less complicated,” said Dr. Selvin, who explained that “NT-proBNP is affected by overweight and obesity.”

In people with diabetes, the age-adjusted prevalence of elevated hs-cTnT ran higher in those with longer duration diabetes, and in those with less well-controlled diabetes based on a higher level of A1c. Neither of these factors showed any significant relationship with measured levels of NT-proBNP.

Further analysis linked the NHANES findings during 1999-2004 with U.S. national death records through the end of 2019. This showed that elevated levels of both hs-cTnT and NT-proBNP significantly linked with subsequently higher rates of all-cause mortality among people with diabetes. Elevated hs-cTnT linked with a 77% increased mortality and NT-proBNP linked with a 78% increased rate, compared with people with diabetes and no elevations in these markers, after adjustment for demographic variables and CVD risk factors.

However, for the outcome of cardiovascular death, elevated hs-cTnT linked with a nonsignificant 54% relative increase, while elevated NT-proBNP linked with a significant 2.46-fold relative increase.

The study “adds new data on biomarkers that are not routinely measured in asymptomatic people with or without diabetes” and the relationships of these markers to CVD mortality and all-cause mortality, Dr. Eckel concluded.

The study received no commercial funding, but used reagents donated by Abbott Laboratories, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics. Dr. Selvin and Dr. Eckel had no disclosures.

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

Nearly one in five U.S. adults with type 2 diabetes but without symptoms of cardiovascular disease (CVD) have a clinically meaningful elevation of a marker of cardiac damage – namely, high-sensitivity cardiac troponin T (hs-cTnT) – based on data from a representative sample of more than 10,000 U.S. adults.

The finding suggests hs-cTnT maybe a useful marker for adults with diabetes who could benefit from more aggressive CVD risk reduction despite having no clinical indications of CVD.

The results “highlight the substantial burden of subclinical CVD in persons with diabetes and emphasize the importance of early detection and treatment of CVD for this high-risk population,” say the authors of the research, published in the Journal of the American Heart Association.

Johns Hopkins University

“This is the first study to examine subclinical CVD, defined by elevated cardiac biomarkers, in a nationally representative population of adults with or without diabetes. It provides novel information on the high burden of subclinical CVD [in American adults with diabetes] and the potential utility of hs-cTnT for monitoring this risk in people with diabetes,” said Elizabeth Selvin, PhD, senior author and a professor of epidemiology at Johns Hopkins University, Baltimore.

“What we are seeing is that many people with type 2 diabetes who have not had a heart attack or a history of cardiovascular disease are at high risk for cardiovascular complications,” added Dr. Selvin in an AHA press release. “When we look at the whole population of people diagnosed with type 2 diabetes, about 27 million adults in the U.S., according to the [Centers for Disease Control and Prevention], some are at low risk and some are at high risk for cardiovascular disease, so the open question is: ‘Who is most at risk?’ These cardiac biomarkers give us a window into cardiovascular risk in people who otherwise might not be recognized as highest risk.”

“Our results provide evidence to support use of cardiac biomarkers for routine risk monitoring in high-risk populations such as people with diabetes,” Dr. Selvin noted in an interview.
 

Need for aggressive CVD risk reduction

The findings also indicate that people with diabetes and an elevated hs-cTnT “should be targeted for aggressive cardiovascular risk reduction, including lifestyle interventions, weight loss, and treatment with statins, blood pressure medications, and cardioprotective therapies such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagonlike peptide-1 (GLP-1) receptor agonists,” Dr. Selvin added.

“Cholesterol is often the factor that we target to reduce the risk of cardiovascular disease in people with type 2 diabetes,” she observed. “However, type 2 diabetes may have a direct effect on the heart not related to cholesterol levels. If type 2 diabetes is directly causing damage to the small vessels in the heart unrelated to cholesterol plaque buildup, then cholesterol-lowering medications are not going to prevent cardiac damage,” Dr. Selvin explained. “Our research suggests that additional non–statin-related therapies are needed to lower the cardiovascular disease risk in people with type 2 diabetes.”

However, she noted that a necessary step prior to formally recommending such a strategy is to run clinical trials to assess the efficacy of specific treatments, such as SGLT-2 inhibitors and GLP-1 agonists, in people with diabetes and elevated hs-cTnT.

“Randomized controlled trials would be best to test the relevance of measuring these biomarkers to assess risk in asymptomatic people with diabetes,” as well as prospective study of the value of hs-cTnT to guide treatment, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado at Denver, Aurora.

“I doubt measurements [of hs-cTnT] would be reimbursed [by third-party payers] if carried out without such outcome data,” he added.

Dr. Eckel also highlights the need to further validate in additional cohorts the link between elevations in hs-cTnT and CVD events in adults with diabetes, and to confirm that elevated levels of another cardiac biomarker – N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) – do not work as well as troponin as a risk marker for people with diabetes, another finding of the study.
 

ADA report already recommends testing these biomarkers for HF

However, a consensus report published in 2022 by the American Diabetes Association laid out the case for routinely and regularly measuring levels of both high sensitivity cardiac troponin and natriuretic peptides in people with diabetes for early identification of incident heart failure.

“Among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure,” noted the ADA consensus report on heart failure.

The new study run by Dr. Selvin and coauthors used data collected by the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 from U.S. adults who were at least 20 years old and had no history of CVD: myocardial infarction, stroke, coronary heart disease, or heart failure. This included 9,273 people without diabetes and 1,031 with diabetes, defined as a prior diagnosis or hemoglobin A1c of at least 6.5%.

“Cardiovascular risk varies substantially in adults with type 2 diabetes, highlighting the need for accurate risk stratification,” the authors observed.

All study participants had recorded measures of hs-cTnT and NT-proBNP.

The researchers considered an hs-cTnT level of greater than 14 ng/L and an NT-proBNP level of greater than 125 pg/mL as indicators of subclinical CVD.

The crude prevalence of elevated NT-proBNP was 33.4% among those with diabetes and 16.1% in those without diabetes. Elevated hs-cTnT occurred in 19% of those with diabetes and in 5% of those without diabetes. Elevated levels of both markers existed in 9% of those with diabetes and in 3% of those without diabetes.

“Approximately one in three adults with diabetes had subclinical CVD, with 19% having elevated levels of hs-cTnT, 23% having elevated NT-proBNP, and 9% having elevations in both cardiac biomarkers,” the researchers noted.
 

Diabetes linked with a doubled prevalence of elevated hs-cTnT 

After adjustment for several demographic variables as well as traditional CVD risk factors, people with diabetes had a significant 98% higher rate of elevated hs-cTnT, compared with those without diabetes. But after similar adjustments, the rate of elevated NT-proBNP was significantly lower among people with diabetes, compared with controls, by a relative reduction of 24%.

“Our findings suggest that, in people with diabetes, hs-cTnT may be more useful [than NT-proBNP] for general risk monitoring, as its interpretation is less complicated,” said Dr. Selvin, who explained that “NT-proBNP is affected by overweight and obesity.”

In people with diabetes, the age-adjusted prevalence of elevated hs-cTnT ran higher in those with longer duration diabetes, and in those with less well-controlled diabetes based on a higher level of A1c. Neither of these factors showed any significant relationship with measured levels of NT-proBNP.

Further analysis linked the NHANES findings during 1999-2004 with U.S. national death records through the end of 2019. This showed that elevated levels of both hs-cTnT and NT-proBNP significantly linked with subsequently higher rates of all-cause mortality among people with diabetes. Elevated hs-cTnT linked with a 77% increased mortality and NT-proBNP linked with a 78% increased rate, compared with people with diabetes and no elevations in these markers, after adjustment for demographic variables and CVD risk factors.

However, for the outcome of cardiovascular death, elevated hs-cTnT linked with a nonsignificant 54% relative increase, while elevated NT-proBNP linked with a significant 2.46-fold relative increase.

The study “adds new data on biomarkers that are not routinely measured in asymptomatic people with or without diabetes” and the relationships of these markers to CVD mortality and all-cause mortality, Dr. Eckel concluded.

The study received no commercial funding, but used reagents donated by Abbott Laboratories, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics. Dr. Selvin and Dr. Eckel had no disclosures.

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

Nearly one in five U.S. adults with type 2 diabetes but without symptoms of cardiovascular disease (CVD) have a clinically meaningful elevation of a marker of cardiac damage – namely, high-sensitivity cardiac troponin T (hs-cTnT) – based on data from a representative sample of more than 10,000 U.S. adults.

The finding suggests hs-cTnT maybe a useful marker for adults with diabetes who could benefit from more aggressive CVD risk reduction despite having no clinical indications of CVD.

The results “highlight the substantial burden of subclinical CVD in persons with diabetes and emphasize the importance of early detection and treatment of CVD for this high-risk population,” say the authors of the research, published in the Journal of the American Heart Association.

Johns Hopkins University

“This is the first study to examine subclinical CVD, defined by elevated cardiac biomarkers, in a nationally representative population of adults with or without diabetes. It provides novel information on the high burden of subclinical CVD [in American adults with diabetes] and the potential utility of hs-cTnT for monitoring this risk in people with diabetes,” said Elizabeth Selvin, PhD, senior author and a professor of epidemiology at Johns Hopkins University, Baltimore.

“What we are seeing is that many people with type 2 diabetes who have not had a heart attack or a history of cardiovascular disease are at high risk for cardiovascular complications,” added Dr. Selvin in an AHA press release. “When we look at the whole population of people diagnosed with type 2 diabetes, about 27 million adults in the U.S., according to the [Centers for Disease Control and Prevention], some are at low risk and some are at high risk for cardiovascular disease, so the open question is: ‘Who is most at risk?’ These cardiac biomarkers give us a window into cardiovascular risk in people who otherwise might not be recognized as highest risk.”

“Our results provide evidence to support use of cardiac biomarkers for routine risk monitoring in high-risk populations such as people with diabetes,” Dr. Selvin noted in an interview.
 

Need for aggressive CVD risk reduction

The findings also indicate that people with diabetes and an elevated hs-cTnT “should be targeted for aggressive cardiovascular risk reduction, including lifestyle interventions, weight loss, and treatment with statins, blood pressure medications, and cardioprotective therapies such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagonlike peptide-1 (GLP-1) receptor agonists,” Dr. Selvin added.

“Cholesterol is often the factor that we target to reduce the risk of cardiovascular disease in people with type 2 diabetes,” she observed. “However, type 2 diabetes may have a direct effect on the heart not related to cholesterol levels. If type 2 diabetes is directly causing damage to the small vessels in the heart unrelated to cholesterol plaque buildup, then cholesterol-lowering medications are not going to prevent cardiac damage,” Dr. Selvin explained. “Our research suggests that additional non–statin-related therapies are needed to lower the cardiovascular disease risk in people with type 2 diabetes.”

However, she noted that a necessary step prior to formally recommending such a strategy is to run clinical trials to assess the efficacy of specific treatments, such as SGLT-2 inhibitors and GLP-1 agonists, in people with diabetes and elevated hs-cTnT.

“Randomized controlled trials would be best to test the relevance of measuring these biomarkers to assess risk in asymptomatic people with diabetes,” as well as prospective study of the value of hs-cTnT to guide treatment, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado at Denver, Aurora.

“I doubt measurements [of hs-cTnT] would be reimbursed [by third-party payers] if carried out without such outcome data,” he added.

Dr. Eckel also highlights the need to further validate in additional cohorts the link between elevations in hs-cTnT and CVD events in adults with diabetes, and to confirm that elevated levels of another cardiac biomarker – N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) – do not work as well as troponin as a risk marker for people with diabetes, another finding of the study.
 

ADA report already recommends testing these biomarkers for HF

However, a consensus report published in 2022 by the American Diabetes Association laid out the case for routinely and regularly measuring levels of both high sensitivity cardiac troponin and natriuretic peptides in people with diabetes for early identification of incident heart failure.

“Among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure,” noted the ADA consensus report on heart failure.

The new study run by Dr. Selvin and coauthors used data collected by the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 from U.S. adults who were at least 20 years old and had no history of CVD: myocardial infarction, stroke, coronary heart disease, or heart failure. This included 9,273 people without diabetes and 1,031 with diabetes, defined as a prior diagnosis or hemoglobin A1c of at least 6.5%.

“Cardiovascular risk varies substantially in adults with type 2 diabetes, highlighting the need for accurate risk stratification,” the authors observed.

All study participants had recorded measures of hs-cTnT and NT-proBNP.

The researchers considered an hs-cTnT level of greater than 14 ng/L and an NT-proBNP level of greater than 125 pg/mL as indicators of subclinical CVD.

The crude prevalence of elevated NT-proBNP was 33.4% among those with diabetes and 16.1% in those without diabetes. Elevated hs-cTnT occurred in 19% of those with diabetes and in 5% of those without diabetes. Elevated levels of both markers existed in 9% of those with diabetes and in 3% of those without diabetes.

“Approximately one in three adults with diabetes had subclinical CVD, with 19% having elevated levels of hs-cTnT, 23% having elevated NT-proBNP, and 9% having elevations in both cardiac biomarkers,” the researchers noted.
 

Diabetes linked with a doubled prevalence of elevated hs-cTnT 

After adjustment for several demographic variables as well as traditional CVD risk factors, people with diabetes had a significant 98% higher rate of elevated hs-cTnT, compared with those without diabetes. But after similar adjustments, the rate of elevated NT-proBNP was significantly lower among people with diabetes, compared with controls, by a relative reduction of 24%.

“Our findings suggest that, in people with diabetes, hs-cTnT may be more useful [than NT-proBNP] for general risk monitoring, as its interpretation is less complicated,” said Dr. Selvin, who explained that “NT-proBNP is affected by overweight and obesity.”

In people with diabetes, the age-adjusted prevalence of elevated hs-cTnT ran higher in those with longer duration diabetes, and in those with less well-controlled diabetes based on a higher level of A1c. Neither of these factors showed any significant relationship with measured levels of NT-proBNP.

Further analysis linked the NHANES findings during 1999-2004 with U.S. national death records through the end of 2019. This showed that elevated levels of both hs-cTnT and NT-proBNP significantly linked with subsequently higher rates of all-cause mortality among people with diabetes. Elevated hs-cTnT linked with a 77% increased mortality and NT-proBNP linked with a 78% increased rate, compared with people with diabetes and no elevations in these markers, after adjustment for demographic variables and CVD risk factors.

However, for the outcome of cardiovascular death, elevated hs-cTnT linked with a nonsignificant 54% relative increase, while elevated NT-proBNP linked with a significant 2.46-fold relative increase.

The study “adds new data on biomarkers that are not routinely measured in asymptomatic people with or without diabetes” and the relationships of these markers to CVD mortality and all-cause mortality, Dr. Eckel concluded.

The study received no commercial funding, but used reagents donated by Abbott Laboratories, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics. Dr. Selvin and Dr. Eckel had no disclosures.

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