Pancreatic beta-cell loss and preservation in type 2 diabetes

Background: In most individuals, the need to respond to progressive states of insulin resistance is met by increasing insulin production. For insulin-resistant patients, however, the balance between insulin supply and demand may fail from the progressive loss of pancreatic beta-cell function, eventually leading to type 2 diabetes mellitus. Objective: The aim of this review was to discuss the current concepts underlying potential pancreatic beta-cell failure in the progression toward type 2 diabetes and therapies that may alter the process. Methods: Data included in this review were identified through a MEDLINE search for articles published from 1966 to April 2003. Search terms used were beta cell, diabetes, insulin resistance, obesity, cardiovascular disease, thiazolidinediones, and metformin. Results: Evidence of the progressive loss of beta-cell function may include altered conversion of proinsulin to insulin, changes in pulsed and oscillatory insulin secretion, and quantitative reductions in insulin release. Potential underlying mechanisms are glucose toxicity, lipotoxicity, poor tolerance of increased secretory demand, and a reduction in beta-cell mass. Conclusion: Current clinical management of type 2 diabetes is focused on treatment of the signs and symptoms of late-stage disease rather than addressing potential underlying causes, which may be amenable to currently available therapies, based on a broad understanding of existing data, practice experience, and rational speculation.