Understanding and Targeting the Pathophysiology of Youth-onset Type 2 Diabetes

May 2020 Council

Lead Division/Office

DEM

Point(s) of Contact

Barbara Linder, M.D., Ph.D.

Executive Summary

The obesity epidemic has resulted in an increase in type 2 diabetes (T2D) in youth, particularly during puberty and in minority populations. SEARCH, TODAY and other studies have shown that glycemic control is poor in youth with T2D, and there is a high prevalence of risk factors for diabetes complications and evidence of early complications. The TODAY and RISE studies have also shown that youth with T2D cannot maintain reasonable glycemic control on metformin monotherapy (the mainstay of treatment in adults) and that loss of beta cell function occurs at a more rapid rate than in adults with comparable diabetes duration. These data paint a grim picture of youth-onset T2D, creating a compelling argument to better understand any unique pathophysiology that distinguishes youth-onset T2D from the typical disease in adults.

A racially/ethnically diverse cohort of early pubertal youth at risk for developing T2D will be recruited to undergo serial OGTTs. The goal will be to 1) develop more precise prediction of which individuals are truly at risk for developing T2D and identify determinants of progression from prediabetes to T2D so that, ultimately, targeted prevention approaches can be developed and tested; and 2) understand the physiologic drivers of T2D when it develops at a young age to be better able to develop and/or test strategies that could be more effective in achieving glycemic control and preserving beta cell function.