Pathobiology of Prediabetes: Understanding and Interrupting Progressive Dysglycemia and Associated Complications

Prediabetes, an intermediate stage in the pathogenesis of type 2 diabetes (T2D), affects ∼98 million U.S. adults and >800 million people worldwide. Prediabetes shares common pathophysiological mechanisms with T2D and progresses to T2D at variable rates based on risk factor burden. Less well studied is the initial transition from normoglycemia to prediabetes. Discussed herein are behavioral, clinical, biochemical, and molecular factors associated with development of prediabetes. Current approaches to prediabetes management are discussed, with an interpretive focus on their limitations and the need for novel interventions for durable reversal of prediabetes and avoidance of related complications.