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 - Texas Children'S Hospital; 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: N/A
Citation: N/A

Interpretive Summary: Type 2 diabetes (T2D) and prediabetes in youth are growing public health concerns, closely linked to rising childhood obesity rates. These conditions increase the risk of serious complications like heart disease, kidney problems, and early death—often beginning much earlier in life than in adults. In this article, we reviewed the data on how prediabetes and T2D develop in youth, why it’s more aggressive than in adults, and how it can be managed. T2D in young people is not just about high blood sugar—it’s a complex condition involving insulin resistance and a rapid decline in the pancreas’s ability to make insulin (called beta-cell dysfunction). This decline often starts during the prediabetes phase and progresses faster than it does in adults. The disease is heavily influenced by genetics, body weight, lifestyle, social environment, and stress—including childhood trauma and socioeconomic challenges. We emphasized that while lifestyle changes and medications like metformin are the foundation of treatment, they are often not enough for youth, and more advanced therapies and supportive care (including mental health) are needed. New drugs like GLP-1 receptor agonists are promising but have limitations. Early diagnosis and tailored, long-term support—both medical and social—are key to preventing complications and managing this serious, fast-moving disease in young people.

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 adultonset 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 b-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 b-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.