The Progression of Prediabetes to Type 2 Diabetes in Children and Adolescents in the United States: Current Challenges and Solutions

Prediabetes, the precursor of type 2 diabetes (T2D), is on the rise among children and adolescents in the United States. The natural history of prediabetes is poorly characterized in children compared to adults. The available data indicate a phenotype of an accelerated β-cell failure in youth with prediabetes. Data from randomized controlled trials showed no benefit on β-cell preservation or A1c in youth with prediabetes from therapeutic agents such as metformin and insulin. As a result, the American Diabetes Association recommends only lifestyle intervention, but not therapeutic agents, for the management of prediabetes in children and adolescents. These recommendations for lifestyle modification in youth, largely derived from data in adults, lack the precision necessary for efficacy in youth. However, a recent 4-year real-world study on youth reported that adherence to nutrition visits was associated with a 4-fold reduction in the likelihood of progressing from prediabetes to T2D. The finding that this reversal is associated with reduced insulin resistance (IR) and not with decreased body weight is novel and provides the foundation for trialing investigational products that may protect β-cells and reduce IR and/or body weight. This study provides the much-needed foundation for further exploration of the impact of lifestyle modification in conjunction with other approaches for the reversal of prediabetes in youth. The systematization of the protocol for medical nutrition therapy for the reversal of prediabetes in youth will ensure optimal and consistent results from adherent patients. This communication provides updates on the pathobiology of prediabetes in youth and a clear direction for efficacious studies in the field.