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]; Ptrend = 0.002). This association was attenuated after further adjustment for BMI (1.51 [0.86-2.65]; Ptrend = 0.20) or C-reactive protein (1.18 [0.68-2.07]; Ptrend = 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.