OBJECTIVE—The purpose of this study was to investigate the role of circulating resistin levels in the development of type 2 diabetes using two prospective cohorts of well-characterized men and women.

RESEARCH DESIGN AND METHODS—We conducted two prospective case-control studies nested in the Women's Health Study (WHS) and Physicians’ Health Study II (PHS II). In the WHS, during a median of 10-years of follow-up, 359 postmenopausal women, who were apparently healthy at baseline and later developed type 2 diabetes, were prospectively matched with 359 healthy control subjects. In the PHS II, with 8 years of total follow-up, 170 men, who were apparently healthy at baseline and later developed type 2 diabetes, were matched with 170 healthy control subjects. Control subjects were matched by age, race, and time of blood draw.

RESULTS—Resistin levels at baseline were significantly higher in women than in men (P = 0.003) and in case patients than in control subjects for both women (P < 0.001) and men (P = 0.07). After adjustment for matching factors, physical activity, alcohol intake, smoking, and family history of diabetes, the relative risk of type 2 diabetes comparing the highest to the lowest quartile of resistin in women was 2.22 ([95% CI 1.32–3.73]; P_trend = 0.002). This association was attenuated after further adjustment for BMI (1.51 [0.86–2.65]; P_trend = 0.20) or C-reactive protein (1.18 [0.68–2.07]; P_trend = 0.60). A similar but weaker pattern was observed in men.

CONCLUSIONS—Elevated levels of circulating resistin were significantly related to increased risk of type 2 diabetes, which appears to be partially accounted for by adiposity and the inflammatory process.