Type 2 Diabetes More Aggressive in Youth Interview with:
Dr. Ellen Leschek MD
Program Director: Division of Diabetes, Endocrinology, and Metabolic Diseases
The National Institute of Diabetes and Digestive and Kidney Diseases
Health Information Center What is the background for this study? What are the main findings? 

Response: Type 2 diabetes (T2D) is thought to be characterized by a progressive loss of pancreatic beta cell (insulin producing/releasing cell) function. For this reason, T2D medications eventually stop working and individuals with T2D require treatment with insulin.

The Restoring Insulin Secretion (RISE) Consortium was established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to evaluate the effects of treatment and treatment withdrawal on the loss of pancreatic beta cell function. In the RISE Study, progression of disease was assessed by the measurement of pancreatic beta cell function in youth and adults who had either impaired glucose tolerance (IGT; prediabetes) or recently diagnosed Type 2 diabetes before, during and after treatment with study medications. Importantly, the RISE Pediatric Medication Study and the RISE Adult Medication Study were designed in tandem to allow direct comparison of the effects of two pharmacologic treatment regimens (the only two FDA-approved medications for Type 2 diabetes in youth) on disease progression in youth and adults. For more information about the RISE Study, please visit What is the background for this study? What are the main findings? 

  • In adults, Type 2 diabetes progression slowed during treatment with RISE medications (those on liraglutide plus metformin showed the most improvement), but once treatment was stopped, these improvements did not persist, and disease progression continued. Specifically, preservation of the pancreatic beta cells was observed during treatment with all three adult study drug regimens (metformin, glargine insulin followed by metformin, and liraglutide plus metformin), but once the study medications were discontinued, pancreatic beta cell function declined.
  • In youth, Type 2 diabetes progression did not slow during treatment with study medications. Pancreatic beta cell function declined during treatment, and continued to worsen after treatment withdrawal. There were no differences between the treatment groups (metformin and glargine insulin followed by metformin). In addition, at baseline (prior to treatment), youth had more insulin resistance and other signs of disease progression compared to their adult counterparts at the same stage in the disease. There were only two medications assessed in the youth study because insulin and metformin are the only U.S. Food and Drug Administration-approved medications for youth with type 2 diabetes.
  • In summary, youth with IGT and recently diagnosed Type 2 diabetes experience more deterioration in beta cell function compared to adults before and during treatment, and both youth and adults demonstrate a decline in beta cell function following medication withdrawal. What should readers take away from your report?

  • Type 2 diabetes disease progression is more aggressive in youth compared to adults, both before and during treatment.
  • To prevent disease progression, adults with IGT and Type 2 diabetes must stay on an effective therapeutic regimen, as withdrawal of effective drug regimens leads to progressive loss of beta cell function.
  • In youth, beta cell function declines during treatment with all medications that are currently approved by the FDA for use in Type 2 diabetes. This strongly reinforces the critical need for additional studies to address the insulin resistance and progressive loss of beta cell function in youth with IGT and T2D to better understand the disease process and to identify effective therapies. What recommendations do you have for future research as a result of this work?

Response: Additional studies are needed to better understand the mechanisms underlying the more aggressive disease process observed in youth. In addition, studies evaluating additional therapies for youth with IGT and T2D are critical, as the only FDA-approved drugs for youth with T2D, insulin and metformin, do not effectively prevent disease progression. 

I have no conflicts to disclose.


Effects of Treatment of Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes With Metformin Alone or in Combination With Insulin Glargine on β-Cell Function: Comparison of Responses In Youth And Adults

The RISE Consortium*

Diabetes 2019 Jun; db190299. 

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Last Updated on June 18, 2019 by Marie Benz MD FAAD