C-18 Thematic Poster - Reduction of Metabolic Syndrome and Chronic Disease Thursday, May 29, 2014, 8:00 AM - 10:00 AM Room: 110 B
Metformin may blunt exercise-induced increases in peripheral insulin sensitivity, however, it is unclear whether this is a direct metabolic interaction between treatments or the result of phenotypic variability (i.e. inter-subject responsiveness) in VO2peak and/or weight change following exercise training.
PURPOSE: To evaluate phenotypic variability in insulin sensitivity, VO2peak, and weight loss following exercise training, metformin or the combination of exercise training and metformin.
METHODS: Thirty-four overweight, sedentary adults with prediabetes were randomly assigned to one of four 12-week interventions: A combined aerobic and resistance exercise training (EX; 65%VO2peak, 60%1-RM, N=9), Metformin (M; 2000mg/d, N=8), exercise training plus metformin (EX+M, N=9), or placebo (P, N=8). Clamp-derived insulin sensitivity (∼90mg/dl, 80 mU/m2/min), VO2peak (cycle ergometer) and weight responses were characterized as non-responder (NON), moderate responder (MOD) or high responder (HI) based on fold change. Significant within- and between-group differences were determined using chi-squared and linear mixed models with planned contrasts. Data are presented as mean±SEM.
RESULTS: There were no group differences in the proportion of HI responders with respect to clamp-derived insulin sensitivity between the interventions (EX=4/9 vs. EX+M=5/9 vs. M=2/8, p=0.70). VO2peak HI responders were also not different between EX or EX+M (EX=4/9 vs. EX+M=4/9) p=0.84). Weight was significantly lower in EX+M compared to both EX (212±10.5 lbs vs.199.8±10.3 lbs, p=0.01) and M (212±10.5 lbs vs. 209.1±11.0 lbs p=0.03) at week 12, but there were no significant group differences between EX+M, EX or M at intermediate time-points.
Conclusion: Compared to exercise training alone, the addition of metformin did not alter the proportion of high responders with respect to insulin sensitivity or VO2peak. Although weight loss was greater after the combined treatment, this did not result in significantly more high responders. These data suggest that phenotypic variability was consistent between exercise groups, and metformin may act directly on metabolic pathways that regulate glucose homeostasis.
Supported by: NIH 5-R56-DK-081038 (BB)