Can We RISE to the Challenge of Youth-Onset Type 2 Diabetes?

Abstract

Over the past three decades, type 2 diabetes (T2D) in adolescents has become steadily more prevalent (1), raising the specter of increasing rates of premature micro- and macrovascular disease as affected youth move into adulthood. While T2D in adolescents is clearly linked to obesity, there is otherwise no explanation for the sudden appearance of what had previously been an adult condition in young people. Despite a steadily growing body of evidence descriptive of T2D in youth (2,3), there is a paucity of information comparing diabetic phenotypes in adults and teenagers. This issue of Diabetes Care contains three papers from the Restoring Insulin Secretion (RISE) Consortium (4–6) that provide the most direct examination of this question yet, with the potential for new understanding of T2D. Present understanding of the pathophysiology of T2D holds that insulin resistance, generally a consequence related to increased adiposity, requires hyperfunction of pancreatic β-cells to maintain glucose tolerance. People whose β-cells cannot make this compensation progress to steadily worsening states of dysglycemia over time (7). Moreover, although insulin resistance does not necessarily cause β-cell failure, hyperglycemia and its associated metabolic disturbances do, such that insufficiently treated diabetes begets more severe diabetes (8). There is evidence in adults with prediabetes that interventions to alleviate insulin resistance (9) or minimize hyperglycemia (10) reduce progression to worse glucose tolerance. Similarly, intensive glucose lowering in adults with T2D can improve hyperglycemia and mitigate the typical course of disease (11). These findings provide the rationale for the RISE Consortium’s efforts (12). The RISE design paper, published in 2014, provides details of this project (12). Three intervention protocols were established, two in adults and one in children, all testing whether β-cell function and metabolic control could be effectively altered by specific interventions. All three studies recruited and randomized …