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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^sub trend^ = 0.002). This association was attenuated after further adjustment for BMI (1.51 [0.86-2.65]; P^sub trend^ = 0.20) or C-reactive protein (1.18 [0.68-2.07]; P^sub 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.
Diabetes Care 32:329-334, 2009
Resistin (also known as adipocyte- secreted factor), an adipocyte- derived hormone, may serve as a critical molecular link between obesity and insulin resistance (1-3). Obese and diabetic mice exhibit high levels of resis- tin. In murine models, functional reduc- tions in resistin protein (e.g., anti-resistin antibodies, resistin gene knockouts) have been demonstrated to improve insulin sensitivity as well as to decrease blood glucose (2-4), free fatty acid (2), and tri- glyceride levels (2). A reduction in the amount of functional resistin also increases adipocyte differentiation and adipose mass (2), which can be reversed upon administration of...