Prediabetes: how pathophysiology drives potential intervention on a subclinical disease with feared clinical consequences

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder whose rising incidence suggests the epidemic proportions of the disease. Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT) - alone or combined - represent two intermediate metabolic condition between Normal Glucose Tolerance (NGT) and overt T2DM. Several studies have demonstrated that insulin resistance and beta-cell impairment can be identified even in normoglycemic prediabetic individuals. Worsening of these two conditions may lead to progression of IGT and/or IFG status to overt diabetes. Starting from these assumptions, it seems logical to suppose that interventions aimed at improving metabolic conditions, even in prediabetes, could represent an effective target to halt transition from IGT/IFG to manifest T2DM. Starting from pathophysiological knowledge, in this review we evaluate two possible interventions (lifestyle modifications and pharmacological agents) eligible as prediabetes therapy since they have been demonstrated to improve insulin resistance and beta-cell impairment. Detecting high-risk people and treating them could represent an effective strategy to slow down progression to overt diabetes, normalize glucose tolerance, and even prevent micro- and macrovascular complications.