Abstract
BACKGROUND: Adiponectin and resistin are recently discovered adipokines that may provide a molecular link between adiposity and type 2 diabetes. OBJECTIVE: To evaluate whether total and high-molecular-weight adiponectin and resistin are associated with future risk for type 2 diabetes, independent of obesity and other known diabetes risk factors. DESIGN: Prospective, nested, case-control study. SETTING: United States. PARTICIPANTS: 1038 initially healthy women of the Nurses' Health Study who developed type 2 diabetes after blood sampling (1989 to 1990) through 2002 and 1136 matched control participants. MEASUREMENTS: Plasma concentrations of total and high-molecular-weight adiponectin and resistin. RESULTS: In multivariate models including body mass index, higher total and high-molecular-weight adiponectin levels were associated with a substantially lower risk for type 2 diabetes (odds ratio [OR] comparing the highest with the lowest quintiles, 0.17 [95% CI, 0.12 to 0.25] for total adiponectin and 0.10 [CI, 0.06 to 0.15] for high-molecular-weight adiponectin). A higher ratio of high-molecular-weight to total adiponectin was associated with a statistically significantly lower risk even after adjustment for total adiponectin (OR, 0.45 [CI, 0.31 to 0.65]). In the multivariate model without body mass index, higher resistin levels were associated with a higher risk for diabetes (OR, 1.68 [CI, 1.25 to 2.25]), but the association was no longer statistically significant after adjustment for body mass index (OR, 1.28 [CI, 0.93 to 1.76]). LIMITATION: The findings apply mainly to white women and could be partly explained by residual confounding from imperfectly measured or unmeasured variables. CONCLUSION: Adiponectin is strongly and inversely associated with risk for diabetes, independent of body mass index, whereas resistin is not. The ratio of high-molecular-weight to total adiponectin is related to risk for diabetes independent of total adiponectin, suggesting an important role of the relative proportion of high-molecular-weight adiponectin in diabetes pathogenesis.