Progression to Diabetes

  • Weir G
  • Bonner-weir S
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This article proposes five stages in the progression of diabetes, each of which is characterized by different changes in -cell mass, phenotype, and function. Stage 1 is compensation: insulin secretion increases to maintain normoglycemia in the face of insulin resistance and/or decreasing -cell mass. This stage is characterized by maintenance of differentiated function with intact acute glucose-stimulated insulin secretion (GSIS). Stage 2 occurs when glucose levels start to rise, reach- ing 5.0–6.5 mmol/l; this is a stable state of -cell adaptation with loss of -cell mass and disruption of function as evidenced by diminished GSIS and -cell dedifferentiation. Stage 3 is a transient unstable period of early decompensation in which glucose levels rise relatively rapidly to the frank diabetes of stage 4, which is characterized as stable decompensation with more severe -cell dedifferentiation. Finally, stage 5 is char- acterized by severe decompensation representing a pro- found reduction in -cell mass with progression to ketosis. Movement across stages 1–4 can be in either direction. For example, individuals with treated type 2 diabetes can move from stage 4 to stage 1 or stage 2. For type 1 diabetes, as remission develops, progression from stage 4 to stage 2 is typically found. Delineation of these stages provides insight into the pathophysiology of both progression and remission of diabetes. Diabetes

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  • Gordon C Weir

  • Susan Bonner-weir

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