title: Preservation of β-cell function: the key to diabetes prevention.
abstract: BACKGROUND
  The Centers for Disease Control and Prevention estimates that there are approximately 79,000,000 individuals in the United States with prediabetes [impaired glucose tolerance (IGT) and/or impaired fasting glucose] and that approximately 40-50% will progress to type 2 diabetes mellitus (T2DM) during their lifetime. Therefore, treatment of high-risk IGT individuals to prevent T2DM has important medical, economic, social, and human implications. Individuals in the upper tertile of IGT are maximally/near-maximally insulin resistant, have lost 70-80% of their β-cell function, and have approximately a 10% incidence of diabetic retinopathy. Therefore, preservation of the remaining 20-30% of β-cell function is critical to prevent future development of T2DM.
  
  
  METHODS
  We searched MEDLINE from 2000 to the present to identify placebo-controlled trials in which individuals with IGT received pharmacological therapy to prevent progression to diabetes.
  
  
  RESULTS
  Lifestyle modification reduces IGT conversion to T2DM, but it is difficult to implement and maintain. Moreover, 40-50% of IGT subjects progress to T2DM despite weight loss. In contrast, pharmacological intervention with medications that reverse known pathophysiological abnormalities (β-cell dysfunction and insulin resistance) uniformly prevents IGT progression to T2DM. Thiazolidinediones reduce IGT conversion to diabetes by approximately 50-70%. Metformin in the U.S. Diabetes Prevention Program reduced the development of T2DM by 31% and has been recommended by the American Diabetes Association. Because glucagon-like peptide-1 analogs augment insulin secretion, preserve β-cell function, and promote weight loss, they may be efficacious in preventing IGT progression to T2DM.
  
  
  CONCLUSIONS
  Pharmacological intervention with a variety of agents (thiazolidinediones, metformin, acarbose, glucagon-like peptide-1 analogs) consistently reduces the rate of conversion of IGT to T2DM.
authors.affiliation: University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA. albarado@uthscsa.edu
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Abdul-Ghani
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology*; D011236:Prediabetic State / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D007004:Hypoglycemic Agents