title: Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes.
abstract: OBJECTIVE
  Physical activity or metformin enhances insulin sensitivity and opposes the progression from prediabetes to type 2 diabetes. The combination may be more effective because each treatment stimulates AMP-activated protein kinase activity in skeletal muscle. We evaluated the effects of exercise training plus metformin on insulin sensitivity in men and women with prediabetes, compared with each treatment alone.
  
  
  METHODS
  For 12 weeks, men and women with prediabetes were assigned to the following groups: placebo (P), 2,000 mg/day metformin (M), exercise training with placebo (EP), or exercise training with metformin (EM) (n = 8 per group). Before and after the intervention, insulin sensitivity was measured by euglycemic hyperinsulinemic (80 mU/m(2)/min) clamp enriched with [6,6-(2)H]glucose. Changes due to intervention were compared across groups by repeated-measures ANOVA.
  
  
  RESULTS
  All three interventions increased insulin sensitivity (P < 0.05) relative to the control group. The mean rise was 25-30% higher after EP than after either EM or M, but this difference was not significant.
  
  
  CONCLUSIONS
  Insulin sensitivity was considerably higher after 12 weeks of exercise training and/or metformin in men and women with prediabetes. Subtle differences among condition means suggest that adding metformin blunted the full effect of exercise training.
authors: Energy Metabolism Laboratory, Department of Kinesiology, University of Massachusetts, Amherst, Massachusetts, USA. bbraun@kin.umass.edu
authors: Steven K
authors: SK
authors: Malin
authors: Robert
authors: R
authors: Gerber
authors: Stuart R
authors: SR
authors: Chipkin
authors: Barry
authors: B
authors: Braun
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance; D008019:Life Style; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011236:Prediabetic State / Q000188:drug therapy*
chemical_list: D001786:Blood Glucose; D008687:Metformin; D055372:AMP-Activated Protein Kinases