Preserving insulin secretion in Type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a complex disease characterized by insulin resistance and a progressive decline in β-cell function and mass. Current evidence suggests that β-cell dysfunction is present early in the course of the disease and that this dysfunction, rather than insulin resistance, is primarily responsible for the progression of T2DM. β-cell dysfunction can be accelerated by glucose toxicity, lipotoxicity, oxidative stress, chronic increases in inflammatory mediators and, potentially, the use of sulfonylureas. This review suggests that future efforts to limit the impact of T2DM must focus on strategies to preserve β-cell function. Several interventions have shown promise in this regard, including lifestyle modifications, thiazolidinediones, potassium channel openers, incretin mimetics, cytokine antagonists, bariatric surgery and dipeptidyl peptidase IV inhibitors, although therapeutic insulin remains the most robust and physiological approach.