Further RISE'ing to the Challenge of Type 2 Diabetes in Youth.

Abstract

Despite three decades of increasing prevalence of type 2 diabetes (T2D) in adolescents (1), the diabetes community continues to grapple with the pathophysiology of youth-onset T2D. Accumulating evidence indicates that when compared with T2D in adults, T2D in youth follows a more aggressive course (2–4). Adolescents are therefore entering adulthood with an advanced and perhaps misunderstood disease that puts them at risk for morbidity from micro- and macrovascular complications. Moreover, as the susceptibility of individuals with diabetes to poor outcomes during the coronavirus pandemic became increasingly apparent (5), the urgency to address the health crisis of T2D in youth has been amplified. The Restoring Insulin Secretion (RISE) study, designed in 2014, tested interventions in both adolescents and adults to determine whether β-cell decline could be halted in people with prediabetes or early T2D (6). The primary analyses were overall disheartening regarding slowing the progression of T2D in youth (7–12). However, the RISE study provides the most direct opportunity yet to examine differences between T2D in youth and adults. In this issue of Diabetes Care , the RISE Consortium delivers three articles that offer mechanistic insights into the pathogenesis of T2D and potentially a path forward for the treatment of T2D in youth (13–15). A summary of these articles is presented in Table 1 and discussed in subsequent paragraphs. View this table: Table 1 Summary of RISE papers in this issue RISE was predicated on the critical role of progressive β-cell decline in the pathogenesis of T2D, where β-cell dysfunction results in excessive glucose and fatty acid exposure, termed glucolipotoxicity (6). Glucolipotoxicity coupled with insulin resistance compounds β-cell stress and contributes to β-cell failure. Previous data in adults suggest that early intensive intervention may delay β-cell dysfunction and slow the course of T2D (16–18). Prior to RISE, no …