Gretchen Cuda Kroen

New data released today from the Diabetes Prevention Program Outcomes Study (DPPOS) shows that in over 2000 patients followed for an average of 22 years, lifestyle programs and treatment with metformin continues to prevent the development of type 2 diabetes (T2D) in at risk populations.

New Data on Clinical Outcomes from the Diabetes Prevention Program Outcomes Study (DPPOS)

were presented today at the American Diabetes Association’s® (ADA’s) 80th Virtual Scientific Sessions.

 a multicenter trial conducted from 1996 to 2001 that established the success of either an intensive lifestyle program or treatment with metformin to prevent or delay the development of T2D in individuals who were considered at high risk for developing the disease. The DPP demonstrated lifestyle intervention, aimed at achieving weight loss, and metformin treatment reduced the risk of T2D development by 58% and 31%, respectively, compared to placebo after an average of three years. Metformin, one of the most commonly used medications worldwide for the treatment of T2D, is currently not labeled by the FDA for prevention purposes, although it is approved in other countries.

88% of the original 3,234 DPP participants enrolled in the DPPOS, including the DPP participants who had developed T2D and those who still had not developed diabetes. Currently, after an average of 22 years of study, 75% of the participants who enrolled in the DPP who are still alive have continued to be evaluated. The mean age of the participants is now 72 years.

The newest results indicate that prevention effects in the original lifestyle group and metformin treatment group remain 22 years after the start of the study with a 25% and 18% reduced risk of diabetes development, respectively, compared with the original placebo group.

“The DPP/DPPOS is the longest duration and largest prevention study that continues to actively follow its participants,” said DPPOS chair David M. Nathan, MD, director of the Clinical Research Center and Diabetes Center at Massachusetts General Hospital and professor of medicine at Harvard Medical School. “The current results indicate that prevention of type 2 diabetes is possible and has important clinical benefits. The long-term benefits of the two DPP interventions on diabetes development, still present many years after they were started, are a testament to the power of these interventions and reinforce their importance in the reduction of diabetes.”

The participants who did not develop diabetes had a significant (57% and 37%) lower risk of developing early changes of eye and kidney disease, respectively, and a 39% lower risk of major cardiovascular disease endpoints, such as heart attacks and stroke.

There was no significant benefit in heart disease or the development of kidney disease or diabetic retinopathy with either of the individual interventions—metformin or the lifestyle intervention.However, stroke and cardiovascular events were reduced in the subgroup of people who started the study before age 45, and there was a non-significant (12%) lower risk of cancer in the Metformin group compared with the placebo group. The intensive lifestyle intervention group also had a long-term reduction in the development of frailty.

There was a modest increase in kidney disease with metformin, which appeared only in the oldest group of participants.

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New data released today from the Diabetes Prevention Program Outcomes Study (DPPOS) shows that in over 2000 patients followed for an average of 22 years, lifestyle programs and treatment with metformin continues to prevent the development of type 2 diabetes in at risk populations.

Diabetes Study Shows Lifestyle Interventions and Metformin Continue to Prevent Type 2 Diabetes After 2 Decades

Environmental Determinants of Diabetes in the Young (TEDDY) study

 illuminate the environmental triggers that are thought to cause the autoimmune response leading to type 1 diabetes(T1D) and celiac disease. The data was presented in a symposium at the American Diabetes Association meeting.

TEDDY is an international multi-center trial researching the potential causes T1D in children. The study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).It has been collecting prospective data since 2004, researching the link between genetic and environmental factors in the autoimmune destruction of the beta islet cells of the pancreas.

Although many children are genetically predisposed to T1D, not all children develop it, resulting in the conclusion that an environmental trigger is required. The study enrolls infants identified as “at-risk” for developing T1D and follows them for 15 years to look for the appearance of various beta-cell autoantibodies and diabetes. TEDDY has also studied biomarkers that can predict faster or slower progression to diabetes after the autoimmune destruction has begun.

An update of the results presented at the ADA meeting this week showed that the destruction of beta islet cells begins in the first two years of life, and that there are two clearly different genetic subtypes of T1D.

“There appear to be two subtypes of T1D that differ by genetic factors and immune phenotypes,” said study TEDDY co-chair Marian Rewers, MD, PhD, a professor of pediatrics and medicine and executive director of the Barbara Davis Center for Diabetes at the University of Colorado School of Medicine. “Metabolomic biomarkers may offer clues to the subtypes and whether a child develops T1D. Interestingly, HbA1c has very different predictive characteristics for progression to clinical diabetes in children with islet autoantibodies, compared to adults with risk factors for type 1 diabetes.”

Research also showed that the persistent presence of enterovirus B species in a child’s stool predicts development of islet autoimmunity, especially the earlier subtype characterized by the presence of autoantibodies to insulin.

Researchers say there are also subtle differences in the composition and function of gut microbiome in children who develop islet autoantibodies, compared to controls, and data show that the early use of probiotics may decrease the risk, while use of antibiotics was not related to islet or celiac autoimmunity.

The study has also found potentially beneficial effects of vitamin D, vitamin C, or a diet rich in polyunsaturated fatty acids, though these observations need to be confirmed in randomized clinical trials.

Celiac disease shares many genetic factors with T1D, noted Dr. Rewers. For this reason, TEDDY investigators follow study participants for both T1D and celiac disease in an attempt to determine why some children with high-risk genes develop T1D or celiac disease, while most remain disease-free. Recently reported TEDDY 

showed an association between gluten consumption in the early years of childhood and an increased risk of celiac disease among genetically predisposed children.

“While T1D and celiac disease share a lot of genetic characteristics, there are intriguing differences in the ways these diseases develop and progress,” added Dr. Rewers. “TEDDY is contributing exciting clues for design of future trials to prevent both T1D and celiac disease.”

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Andrén Aronsson C, Lee HS, Hård Af Segerstad EM, et al. Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk. 

. 2019;322(6):514-523. doi:10.1001/jama.2019.10329

New data from the Environmental Determinants of Diabetes in the Young (TEDDY) study illuminate the environmental triggers that are thought to cause the autoimmune response leading to type 1 diabetes(T1D) and celiac disease. The data was presented in a symposium at the American Diabetes Association meeting.

Research Illuminates Origins of Type 1 Diabetes and Celiac Disease

 published in the Endocrine Society’s J

ournal of Clinical Endocrinology & Metabolism

 has found that eating a late may be a contributing factor to weight gain and hyperglycemia.

The researchers studied how subjects metabolized dinner eaten at 10 p.m. compared to 6 p.m. in 20 healthy volunteers (10 men and 10 women). The volunteers all went to bed at 11 p.m. The researchers found that for the same meal,  blood sugar levels were higher, and the amount of ingested fat burned was lower if it was eaten later.

“On average, the peak glucose level after late dinner was about 18 percent higher, and the amount of fat burned overnight decreased by about 10 percent compared to eating an earlier dinner. The effects we have seen in healthy volunteers might be more pronounced in people with obesity or diabetes, who already have a compromised metabolism,” said the study’s first author Chenjuan Gu, M.D., Ph.D., of the Johns Hopkins University.

To gather the data, participants wore activity trackers, had blood sampling every hour while staying in a lab, underwent sleep studies and body fat scans, and ate food that contained non-radioactive labels so that the rate of fat burning (oxidation) could be determined.

“We still need to do more experiments to see if these effects continue over time, and if they are caused more by behavior (such as sleeping soon after a meal) or by the body’s circadian rhythms,” said the study’s corresponding author Jonathan C. Jun, M.D., of the Johns Hopkins University School of Medicine in Baltimore, M.d.

Gu C, Brereton N, Schweitzer A, et al. Metabolic Effects of Late Dinner in Healthy Volunteers - A Randomized Crossover Clinical Trial [published online ahead of print, 2020 Jun 11]. J Clin Endocrinol Metab. 2020;dgaa354. 

A study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism has found that eating a late may be a contributing factor to weight gain and hyperglycemia.

For Weight loss, Don’t Eat Late in Day Says Study

The outcomes of clinical trials are often affected by the diversity of the patient population studied.  Things like race and gender can make a real difference in the way drugs work– and yet women, minorities and older adults continue to be underrepresented in pivotal trials for new medications .  Two recent studies demonstrate that fact over the last several decades.  And although the proportion of these populations enrolled in clinical trials has increased, it is still well out of step with the number of patients affected by the diseases in question. Sr. Editor Gretchen Cuda Kroen spoke with Dr. Erin Michos,  co-author  on those studies about the origins of the disparity, and what what we can do about it.

Khan MS, Shahid I, Siddiqi TJ, et al. Ten-Year Trends in Enrollment of Women and Minorities in Pivotal Trials Supporting Recent US Food and Drug Administration Approval of Novel Cardiometabolic Drugs. J Am Heart Assoc. 2020;9(11):e015594. 

Khan SU, Khan MZ, Raghu Subramanian C, et al. Participation of Women and Older Participants in Randomized Clinical Trials of Lipid-Lowering Therapies: A Systematic Review. JAMA Netw Open. 2020;3(5):e205202. Published 2020 May 1. 

Women, Minorities and Older Adults Still Underrepresented in Clinical Trials: Conversation with Erin Michos MD

New guidelines for glucose management in diabetic COVID patients were 

 in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.  

According to the report, more than 20 percent of COVID patients in the ICU are patients with diabetes, presenting challenges for the clinicians managing their care.  Diabetic patients with COVID-19 in the ICU need both complex medical management of their COVID disease, along with blood sugar control to minimize complications and mortality risk- and that can require multiple patient interactions that put the provider at risk.

“This manuscript provides guidance for healthcare providers caring for patients hospitalized for COVID-19 who also have a prior history of diabetes or who have high blood sugar levels at the time of hospitalization,” said lead author Mary T. Korytkowski, M.D., of the University of Pittsburgh School of Medicine in Pittsburgh, Pa. “These healthcare providers are at risk for contracting COVID-19, and while glycemic management in the hospital improves patient outcomes, it also intensifies the amount of time with direct patient contact.”

Clinicians may limit their risk of exposure by minimizing the use of IV insulin infusions and using remote glucose monitoring devices and non-insulin therapies when possible. Diabetes self-management by selected patients who are knowledgeable and capable of this in the hospital also can be considered as a way of limiting direct patient interactions. Clinicians should be aware that some medications used in treating COVID-19 patients, including glucocorticoids and hydroxychloroquine, can affect blood glucose levels.

Korytkowski M, Antinori-Lent K, Drincic A, et al. A Pragmatic Approach to Inpatient Diabetes Management during the COVID-19 Pandemic [published online ahead of print, 2020 Jun 4]. J Clin Endocrinol Metab. 2020;dgaa342. 

New Guidance for Treating Diabetic COVID-19 Patients in the ICU

Hypertensive patients have a two-fold increased risk of dying from the coronavirus COVID-19 compared to patients without high blood pressure, according to 

.  In addition, if the hypertension is untreated, the risk is greater.

But perhaps more significantly, the researchers found that those patients whose hypertension was treated with renin-angiotensin-aldosterone system inhibiting drugs ( which  includes  ACE2 inhibitors and ARB’s ) had lower mortality than those who were not, suggesting that these drugs may be protective in COVID-19 patients instead of detrimental as previously suggested.

The study examined data from 2866 patients with COVID-19 who were admitted to Huo Shen Shan hospital in Wuhan, China, between 5 February and 15 March 2020.  Of these patients, 29.5% (850) had a medical history of high blood pressure (hypertension).

Out of 850 hypertensive patients, 710 were being treated with medication and 140 were not.

In total, 34 of the 850 patients with hypertension (4%)  died of cornonavirus compared to 22 out of 2027 patients without hypertension (1.1%) - a 2.12-fold increased risk after adjustment for factors that could affect the results, such as age, sex and other medical conditions.

Among the patients with hypertension who were not taking medication for the condition, 11 out 140 (7.9%) died from coronavirus compared to 23 out of 710 (3.2%) of those who were taking medication - 2.17-fold increased risk after adjusting for confounding factors.

In a further meta-analysis, the researchers pooled the data from the Huo Shen Wan patients with data from nearly 2,300 patients in three other studies to investigate the death rates in patients being treated with drugs to control blood pressure levels by targeting the renin-angiotensin-aldosterone system (RAAS). These drugs include angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Other, non-RAAS inhibiting drugs used for treating high blood pressure include beta blockers, calcium channel blockers (CCBs) or diuretics.

They found a lower risk of death among the 183 patients treated with RAAS inhibitors than in 527 patients treated with other drugs. However, the researchers say this result should be treated with caution as the number of patients in this analysis was small and so it could be due to chance.

Researchers emphasize the importance that hypertensive patients understand that they are at increased risk of COVID-19, and that they continue to take their medications as prescribed.

"Soon after we started to treat COVID-19 patients in early February in Wuhan, we noticed that nearly half of the patients who died had high blood pressure, which was a much higher percentage compared to those with only mild COVID-19 symptoms. At the same time, some researchers were raising concerns that RAAS inhibitors might be facilitating the entry of the coronavirus into cells and making people more susceptible to the disease,” said Professor Ling Tao of Xijing Hospital and one the paper’s authors.

"We were quite surprised that these results did not support our initial hypothesis; in fact, the results were in the opposite direction, with a trend in favour of ACE inhibitors and ARBs. We think this is exactly why practice based on clinical evidence is more vital than ever," Tao said.

The authors point out that this is a retrospective study with a relatively small sample size and so the results should be interpreted with caution.  However, it does support the initial recommendations of many societies that patient’s should not discontinue ACE’s and ARBs, and, a 


	has also suggested that antihypertensive medications, such as ACE inhibitors and ARBs are not associated with an increased risk of testing positive for COVID-19.

"Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study", by Chao Gao et al. European Heart Journal. 

"Renin-angiotensin-aldosterone system blockers and the risk of COVID-19", by Giuseppe Mancia et al. New England Journal of Medicine, 1 May 2020. 

"Renin-angiotensin system inhibitors in the COVID-19 pandemic: consequences of antihypertensive drugs", by Luis M. Ruilope et al. European Heart Journal. 

Hypertensive patients have a two-fold increased risk of dying from the coronavirus COVID-19 compared to patients without high blood pressure, according to new research published in the European Heart Journal.  In addition, if the hypertension is untreated, the risk is greater.