Prediabetes as a toxic environment for the initiation of microvascular and macrovascular complications

Prediabetes is a state characterized by impaired fasting glucose or impaired glucose tolerance. Evidence is increasingly demonstrating that prediabetes is a toxic state, in addition to being a harbinger of future development of diabetes mellitus. This minireview discusses the pathophysiology and clinical significance of prediabetes, and approach to its management, in the context of the worldwide diabetes epidemic. The pathophysiologic defects underlying prediabetes include insulin resistance, beta cell dysfunction, increased lipolysis, inflammation, suboptimal incretin effect, and possibly hepatic glucose overproduction. Recent studies have revealed that the long-term complications of diabetes may manifest in some people with prediabetes; these complications include classical microvascular and macrovascular disorders, and our discussion explores the role of glycemia in their development. Finally, landmark intervention studies in prediabetes, including lifestyle modification and pharmacologic treatment, are reviewed.