× Key messages Background From RISE… Conclusions Expert commentary

Expert commentary

by Dana M. Dabelea, MD, PhD

The Restoring Insulin Secretion (RISE) Adult Medication Study measured the function of beta cells (beta-cell) in adults with impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetes (T2D). Researchers found that beta-cell function had improved through active treatment, but a lasting effect was not seen after treatment was stopped. Data presented at during this symposium included 91 youth and 267 adults with prediabetes or newly diagnosed T2D who received insulin and oral medications and 88 adults who received surgery (laparoscopic banding). RISE found that youth with IGT or recently diagnosed T2D, were more insulin resistant and secreted more insulin than adults, for the same BMI levels. Moreover, in youth, neither insulin resistance nor beta-cell function responded to interventions. In adults, the initial benefits did not persist after medication withdrawal.

The analysis further assessed both alpha- and beta-cell function, as well as insulin sensitivity. The main findings were that youth with IGT/T2D were more insulin resistant, with more insulin secretion and less insulin clearance. Compared to adults, they also had more rapid deterioration of beta-cell function. Predictors of glycemic deterioration were also identified. In youth, these included beta-cell responses, while in adults these included insulin sensitivity and first phase beta-cell responses. Moreover, differences in alpha cell function, and specifically glucagon, did not explain the differences between adults and youth. In adults, gastric banding resulted in increased insulin sensitivity, preserved beta-cell function, and improved glycemia over 2 years

Ongoing data analyses from the RISE Study continue to reveal important differences between adults and youth in the onset and progression of T2D. The RISE Study has previously reported that prediabetes and type 2 diabetes in youth is characterized by an inability of insulin to act normally in the tissues, and an inability of the beta-cell to secrete sufficient insulin to maintain normal glucose levels. These abnormalities are similar to those in adults, but despite interventions that would be anticipated to reduce or even reverse these defects as observed in adults, they have no effect in youth. Thus, the beta-cell defect becomes even more severe during 12 months of active treatment.

Additional work is still needed to better understand the mechanisms responsible for the more aggressive nature of T2D in youth. Such improved knowledge is necessary for the  development of new and better approaches to prevent and treat T2D in youth.

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