Pathophysiology and treatment of prediabetes and type 2 diabetes in youth

Authors: BACHA, FIDA - Children'S Nutrition Research Center (CNRC); HANNON, TAMARA - Indiana University School Of Medicine; TOSUR, MUSTAFA - Children'S Nutrition Research Center (CNRC); PIKE, JULIE - Indiana University School Of Medicine; BUTLER, ASHLEY - Baylor College Of Medicine; TOMMERDAHL, KALIE - University Of Colorado; ZEITLER, PHILIP - University Of Colorado

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/20/2024
Publication Date: 9/9/2024
Citation: Bacha, F., Hannon, T.S., Tosur, M., Pike, J.M., Butler, A., Tommerdahl, K.L., Zeitler, P.S. 2024. Pathophysiology and treatment of prediabetes and type 2 diabetes in youth. Diabetes Care. 47(12):2038-2049. https://doi.org/10.2337/dci24-0029.
DOI: https://doi.org/10.2337/dci24-0029

Interpretive Summary: This study is a review of prediabetes and type 2 diabetes in youth. Researchers in Houston wanted to provide an overview of the current understanding of the risk factors and mechanisms of prediabetes and type 2 diabetes in childhood. They also wanted to give an update for the public and for treating physicians regarding treatment approaches for these conditions. They found that youth-onset type 2 diabetes is different from adult onset disease, with more severe insulin resistance in childhood, and a rapid progression of dysfunction in the cells in the pancreas that make insulin. This leads to more difficulty in treating the disease in childhood. This also is associated with earlier onset of comorbidities compared with adult-onset disease. The defect in making insulin can be detected in the prediabetes stage. There are new therapeutic options. The investigators discuss these newer therapies, the clinical studies available and their limitations. They also discuss the importance of efforts needed in the prevention of the disease and to address social determinants of health. This work is important to review the advances in therapy and highlight knowledge gaps and areas of future research.

Technical Abstract: Youth-onset type 2 diabetes is a heterogeneous disease with increasing prevalence in relation to increased rates of obesity in children. It has genetic, epigenetic, social, and environmental determinants. Youth-onset type 2 diabetes is alarming given a rapidly progressive course compared with the course of adult-onset disease, early-onset vascular complications, and long-term exposure to hyperglycemia and associated complications. It is often preceded by prediabetes, a disease phase where defects in ß-cell function relative to insulin sensitivity emerge. Herein, we review the current understanding of the pathophysiology of prediabetes and type 2 diabetes in youth. We describe the mechanisms underlying insulin resistance, the precipitous decline of ß-cell function, and the role of other hormonal abnormalities in the pathogenesis of the disease. We discuss the critical importance of social determinants of health in the predisposition and progression of these conditions and present current management strategies and the advances in therapeutic approaches. These must adapt to meet the unique needs of the individual patient and family. Significant knowledge gaps remain that need to be addressed in future research.