Adiponectin A Marker for Type 2 Diabetes

Adiponectin is inversely linked with the risk for type 2 diabetes in women, but resistin is not, according to the results of a prospective, nested case-control study. The study authors suggest that adiponectin may be a marker for type 2 diabetes. “Adiponectin and resistin are recently discovered adipokines that may provide a molecular link between adiposity and type 2 diabetes,” write Christin Heidemann, DrPH, MSc, from Harvard School of Public Health, Massachusetts General Hospital in Boston.

The goal of this study was to determine whether total adiponectin and resistin and high-molecular-weight adiponectin and resistin are linked to a subsequent risk for type 2 diabetes, independent of obesity and other known risk factors for diabetes.
The study cohort consisted of 1038 women enrolled in the Nurses’ Health Study who were initially healthy at baseline but who went on to have type 2 diabetes after blood sampling (1989-1990) through 2002. Plasma concentrations of total adiponectin and resistin and high-molecular weight adiponectin and resistin in these case participants were compared with those in 1136 matched-control participants.

Adiponectin levels were associated with a significantly lower risk for type 2 diabetes in multivariate models that adjusted for body mass index (BMI). For the highest quintiles vs the lowest quintiles, odds ratio (OR) was 0.17 for total adiponectin and 0.10 for high-molecular-weight adiponectin. Even after adjustment for total adiponectin, a higher ratio of high-molecular-weight adiponectin to total adiponectin was associated with a statistically significantly lower risk for type 2 diabetes (OR, 0.45; 95% CI, 0.31 – 0.65).

Higher resistin levels were associated with a higher risk for diabetes in the multivariate model without BMI. However, this association was no longer statistically significant after adjustment for BMI.

Limitations of this study include study sample composed mainly of white women; possible residual confounding from imperfectly measured or unmeasured variables; and results based on single measurements of the adipokines, which therefore may not reflect long-term exposure to these hormones.

“Adiponectin is strongly and inversely associated with risk for diabetes, independent of body mass index, whereas resistin is not,” the study authors write. “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….In contrast, the positive association between resistin and type 2 diabetes was largely explained by BMI.”

Adipose tissue secretes various hormones and cytokines, known as adipokines, which may be a connecting molecular link between adiposity and type 2 diabetes. Adiponectin and resistin are adipokines that may be especially important in the relationship of excess adiposity to type 2 diabetes.

In contrast to other adipokines, adiponectin concentrations are paradoxically decreased in obese persons vs lean persons. Prospective studies have shown a decreased risk for type 2 diabetes with increasing concentrations of total adiponectin. Although high-molecular-weight adiponectin is the most biologically active form, few epidemiologic studies have evaluated high-molecular-weight adiponectin separately from total adiponectin.

Practice Pearls

Adiponectin is strongly and inversely associated with the risk for diabetes, independent of BMI and markers of insulin resistance or inflammation, whereas resistin is not. The inverse association with the risk for diabetes was particularly marked in the lower ranges of total adiponectin and high-molecular-weight adiponectin distributions

The ratio of high-molecular-weight adiponectin to total adiponectin is related to the risk for diabetes independent of total adiponectin, suggesting an important role of the relative proportion of high-molecular-weight adiponectin in diabetes pathogenesis

Ann Intern Med. 2008;149:307-316