Intensive lifestyle intervention or metformin on inflammation and coagulation in participants with impaired glucose tolerance

Abstract

Increases in subclinical inflammation (C-reactive protein [CRP]) and impaired coagulation have been associated with increased obesity and insulin resistance. Only a few small studies have examined the effect of lifestyle changes, such as weight loss, increased physical activity, and insulin-sensitizing intervention on inflammation and coagulation. The Diabetes Prevention Program (DPP) clinical trial studied the effect of an intensive lifestyle intervention or metformin on progression to diabetes relative to placebo in 3,234 adults with impaired glucose tolerance. The effects of these interventions on CRP and fibrinogen at 12 months are examined in this report. Metformin reduced CRP in women compared with the placebo group. In men, the median changes in CRP from baseline to 1 year were -33% in the lifestyle group, -7% in the metformin group, and +5% in the placebo group. In women, the changes in CRP from baseline to follow-up were -29% in the lifestyle group, -14% in the metformin group, and 0% in the placebo group. In the lifestyle group weight loss rather than increased physical activity seems to account for most of the changes in CRP. Only modest reductions (although significant) were seen in fibrinogen levels in the lifestyle group relative to the metformin and placebo group. Lifestyle intervention reduced levels of nontraditional cardiovascular risk factors relative to both placebo and to a lesser degree to metformin.

FIG. 1

Median percentage of change in CRP from baseline at month 6 and year 1 by sex. The data are presented as mean (gray dot), median (white line), and 25th (top of the gray box) and 75th percentiles (bottom of the gray box). At 6 months and at year 1 after randomization, the Wilcoxon’s test yielded P < 0.001 for intensive lifestyle vs. metformin and intensive lifestyle vs. placebo in both men and women. After 6 months and 1 year of intervention, the P value from the Wilcoxon’s test between metformin vs. placebo was <0.001 for women. Among men, the Wilcoxon’s test for comparing metformin vs. placebo yielded P = 0.01 at 6 months and 0.006 at year 1.