Juvenile-onset diabetes differs from adult-onset diabetes

Abstract

In the DCCT study, 14% of participants were adolescents aged 13 to 18, demonstrating the benefits of optimized treatment; the subsequent EDIC study gave rise to the concept of "metabolic memory." Achieving metabolic control proved more difficult in adolescents, with HbA1c levels 1 percentage point higher than in adults. A novel finding that altered metabolic control targets in pediatrics was the evidence linking both hypoglycemia and hyperglycemia to cognitive impairment in the developing brain.

With the emergence of pediatric type 2 diabetes (T2D) cases in the 1990s, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) launched multicenter studies: 1) SEARCH for Diabetes in Youth, to describe its epidemiology; 2) Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY), to understand pathophysiology and identify treatment options; and 3) Restoring Insulin Secretion (RISE), to compare treatment responses between juvenile-onset and adult-onset type 2 diabetes.

In the TODAY study, regardless of the therapeutic intervention, low baseline β-cell function—rather than insulin sensitivity—predicted treatment failure and the early onset of microvascular and macrovascular complications. Given the rapid rate of β-cell decline, the NIDDK funded the RISE study, featuring interventions designed to preserve or improve β-cell function in both adults and youth with prediabetes or newly diagnosed type 2 diabetes, and to assess the differences between these groups. In the RISE study, youth exhibited lower insulin sensitivity and insulin clearance, along with significantly higher β-cell secretory responses (acute, steady-state, and maximal C-peptide and insulin responses) compared to adults. Notably, β-cell function in youth declined significantly over 12 months of treatment, in contrast to the findings in adults. The DISCOVERY study (Discovery of Risk Factors for Type 2 Diabetes in Youth) is currently recruiting at-risk young people prior to a type 2 diabetes diagnosis to identify “who, when, and how” they will develop the disease.