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The Independent Effect of Plasminogen Activator Inhibitor 1

Alka M. Kanaya, MD; Christina Wassel Fyr, MS; Eric Vittinghoff, PhD; Tamara B. Harris, MD; Seok Won Park, PhD; Bret H. Goodpaster, PhD; Fran Tylavsky, PhD; Steven R. Cummings, MD

Arch Intern Med. 2006;166:350-356.

Background  Adipose tissue produces "adipocytokines" of uncertain clinical significance.

Methods  We analyzed the relationships among adiposity, adipocytokines, glycemia, and incident diabetes mellitus in 2356 white and black adults aged 70 to 79 years in the Health, Aging, and Body Composition Study who did not have diabetes at baseline. We measured the levels of adipocytokines adiponectin, leptin, interleukin 6, tumor necrosis factor , and plasminogen activator inhibitor 1. Regional fat area was determined by means of computed tomography. New diabetes was defined as a self-reported diagnosis of diabetes or as a fasting plasma glucose level of 126 mg/dL or greater (7.0 mmol/L) at the second, fourth, or sixth annual examination.

Results  A total of 143 participants (14.1 cases per 1000 person-years) developed diabetes across 5 years. Visceral fat area (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.10-1.60 per standard deviation increase) and body mass index (white individuals: OR, 1.65; 95% CI, 1.26-2.15 per standard deviation increase; black individuals: OR, 1.22; 95% CI, 0.99-1.51 per standard deviation increase) independently predicted incident diabetes. Adiponectin, leptin, and plasminogen activator inhibitor 1 attenuated the relationship between adiposity and diabetes. After controlling for body mass index, visceral fat, fasting glucose, fasting insulin, high-density lipoprotein cholesterol, triglycerides, and hypertension at baseline, plasminogen activator inhibitor 1 was the only adipocytokine independently associated with increased odds of diabetes (OR, 1.35; 95% CI, 1.01-1.81). Fasting glucose level at baseline remained a strong predictor of incident diabetes, whereas associations with body mass index and visceral fat were attenuated.

Conclusions  Adipocytokines and glycemia partially account for the relationship between adiposity and risk of type 2 diabetes due to adiposity. Plasminogen activator inhibitor 1 may be a useful predictor of diabetes in addition to measurements of body fat.

Author Affiliations: Division of General Internal Medicine, Department of Medicine (Dr Kanaya), Women's Health Clinical Research Center (Drs Kanaya, Vittinghoff, and Cummings and Ms Wassel Fyr), and Department of Epidemiology and Biostatistics (Drs Kanaya, Vittinghoff, and Cummings), University of California, San Francisco; Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institutes of Health, Bethesda, Md (Dr Harris); Division of Endocrinology and Metabolism, Department of Medicine (Dr Goodpaster), and Department of Epidemiology (Dr Park), University of Pittsburgh, Pittsburgh, Pa (Drs Park and Goodpaster); and Department of Preventive Medicine, University of Tennessee, Memphis (Dr Tylavsky).

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