Elevated Resistin Linked with Increased Risk of Type 2

The adipose-secreted hormone resistin was "weakly associated" with an increased risk of Type 2 diabetes mellitus, according to results of two case-control studies.

The Women's Health Study involved nearly 40,000 apparently healthy postmenopausal women followed for a median of 10 years. The researchers focused on 359 participants who developed Type 2 diabetes by follow-up. This group was matched with 359 healthy controls.

The Physicians' Health Study II included close to 15,000 men who were apparently healthy at baseline. One hundred seventy men had developed Type 2 diabetes at follow-up. They were matched with 170 healthy controls.
At baseline, resistin levels were significantly higher in women than in men and higher in the men and women diabetics than in the controls.

After adjusting for physical activity, alcohol intake, smoking, and family history of diabetes, the relative risk (RR) of Type 2 diabetes in women in the highest resistin quartile was 2.22 compared with women in the lowest quartile.

When adjusted for body mass index (BMI), the risk of Type 2 diabetes among the women in the highest quartile compared with those in the lowest quartile was somewhat less (RR = 1.51) and after adjusting for C-reactive protein, the RR dropped to 1.18.

"A similar but weaker pattern was observed in men," the investigators report.

"In our prospective study of men and women, elevated resistin levels were weakly associated with increased risk of Type 2 diabetes," Dr. Song commented. "These positive associations appeared to be largely explained by levels of adiposity or inflammatory markers."

"We do not believe that measuring resistin levels could add more predictive value for the identification of individuals at high risk for Type 2 diabetes," because it is such a weak risk factor, the Harvard researcher added.

"There is growing evidence from much basic research...that resistin, as an adipose-secreted hormone, plays a pivotal role in the molecular pathway between adiposity and insulin resistance and thus may be a potentially useful biomarker for risk of developing Type 2 diabetes," Dr. Song commented.

"However, no clear relation has yet been firmly established in humans due to limited data and inconsistent results. Our findings lend support to the hypothesis that resistin may act as the molecular link between obesity and the pathogenesis of Type 2 diabetes."

"Our results are also supportive of the notion that the role of resistin in the development of Type 2 diabetes is mediated through the inflammatory pathway, although specific regulation and effectors of resistin remain to be clarified," Dr. Song concluded.

Dr. YiQing Song of Harvard Medical School in Boston and colleagues conducted the studies with participants from the Women's Health Study and the Physicians' Health Study II.

Diabetes Care Feb. 2009;32:329-334.

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