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EPM Tools - Progression to Diabetes - Beta Cell Rest
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The following is from Dr. Thomas A. Buchanan's presentation at the Ist International Congress on Prediabetes and the Metabolic Syndrome.  April, 2005, Berlin, Germany

What is Pre-Diabetes?  His definition: 

  1. "Rising glucose levels and
  2. falling B-cell function
  3. Occurring on a background of insulin resistance."

General concepts:

  • IGT and IFG are not synonymous with Prediabetes.
  • People with normal glucose tolerance can have pre-diabetes.
  • Rising glucose is the important clinical phenotype.

What are the effects of thiazolidinediones (TZD) on progression to Diabetes?

  • TRIPOD (TRoglitazone in Prevention of Diabetes) used Rezulin (has been withdrawn from the market).
  • PIPOD used Pioglitazone (Actos)

PIPOD:  Main Messages

  • Actos treatment was associated with a relatively low incidence rate of diabetes
  • Actos stabilized falling B-cell function in women who had been losing function on placebo and maintained relatively stable b-cell function in women who had already been stabilized on Rezulin.
  • B-cell rest (for definition see below) was associated with protection from diabetes inn PIPOD, as it was in TRIPOD.
  • Beta Cell Rest -- reduction in secretory demands imposed on B-cells by chronic insulin resistance

    Did Pioglitazone (Actos) alter the course of b-cell function compared to the pattern observed in TRIPOD (Rezulin)?  Yes

    TRIPOD:  Main Messages

    • Rezulin treatment reduced the incidence of type 2 diabetes by 55% in high-risk Hispanic women.
    • The mechanism for protection appeared to be a reduction in secretory demands imposed on B-cells by chronic insulin resistance (B-cell "rest")
    • It is impossible to stop progression toward and to type 2 diabetes (true prevention)

    Role of Pharmacology in Diabetes Prevention

    Step OneScreening
    Step TwoInsulin Resistance
    Step ThreeMeasure Glucose
    DiabeticTreat Diabetes
    ImpairedHigher Risk
    Diet and Exercise Intervention
    Rising Glycemia -- Pharmacological treatment with TZD
    Stable Glycemia -- Continue Diet and Exercise
    NormalLower Risk
    Diet and Exercise Advice -- Annual follow-up

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