Total and high-molecular-weight adiponectin and resistin in relation to the risk for type 2 diabetes in women

Abstract

Background: Adiponectin and resistin are recently discovered adipokines that may provide a molecular link between adiposity and type 2 diabetes.

Objective: To evaluate whether total and high-molecular-weight adiponectin and resistin are associated with future risk for type 2 diabetes, independent of obesity and other known diabetes risk factors.

Design: Prospective, nested, case-control study.

Setting: United States.

Participants: 1038 initially healthy women of the Nurses' Health Study who developed type 2 diabetes after blood sampling (1989 to 1990) through 2002 and 1136 matched control participants.

Measurements: Plasma concentrations of total and high-molecular-weight adiponectin and resistin.

Results: In multivariate models including body mass index, higher total and high-molecular-weight adiponectin levels were associated with a substantially lower risk for type 2 diabetes (odds ratio [OR] comparing the highest with the lowest quintiles, 0.17 [95% CI, 0.12 to 0.25] for total adiponectin and 0.10 [CI, 0.06 to 0.15] for high-molecular-weight adiponectin). A higher ratio of high-molecular-weight to total adiponectin was associated with a statistically significantly lower risk even after adjustment for total adiponectin (OR, 0.45 [CI, 0.31 to 0.65]). In the multivariate model without body mass index, higher resistin levels were associated with a higher risk for diabetes (OR, 1.68 [CI, 1.25 to 2.25]), but the association was no longer statistically significant after adjustment for body mass index (OR, 1.28 [CI, 0.93 to 1.76]).

Limitation: The findings apply mainly to white women and could be partly explained by residual confounding from imperfectly measured or unmeasured variables.

Conclusion: Adiponectin is strongly and inversely associated with risk for diabetes, independent of body mass index, whereas resistin is not. 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.

Figure 1. Multivariate-adjusted odds ratio (95% CI) of type 2 diabetes according to the joint classification of adipokines

Joint analysis of total adiponectin and resistin (A), high-molecular weight adiponectin and resistin (B), and total adiponectin and the high-molecular weight-to-total adiponectin ratio (C). Odds ratios are adjusted for the same variables as in the multivariate model including BMI of table 3. Tertiles were calculated among control subjects and defined as ≤12.55, 12.56–18.36, and >18.36 ng/mL for resistin, ≤14.67, 14.68–21.19, and >21.19 μg/mL for total adiponectin, ≤4.97, 4.98–8.58, and >8.58 μg/mL for high-molecular weight adiponectin, and ≤0.342, 0.343–0.442, and >0.442 for the high-molecular weight-to-total adiponectin ratio. HMW = high-molecular weight.

Figure 1. Multivariate-adjusted odds ratio (95% CI) of type 2 diabetes according to the joint classification of adipokines

Joint analysis of total adiponectin and resistin (A), high-molecular weight adiponectin and resistin (B), and total adiponectin and the high-molecular weight-to-total adiponectin ratio (C). Odds ratios are adjusted for the same variables as in the multivariate model including BMI of table 3. Tertiles were calculated among control subjects and defined as ≤12.55, 12.56–18.36, and >18.36 ng/mL for resistin, ≤14.67, 14.68–21.19, and >21.19 μg/mL for total adiponectin, ≤4.97, 4.98–8.58, and >8.58 μg/mL for high-molecular weight adiponectin, and ≤0.342, 0.343–0.442, and >0.442 for the high-molecular weight-to-total adiponectin ratio. HMW = high-molecular weight.

Figure 2. Multivariate-adjusted odds ratio (95% CI) of type 2 diabetes according to continuous adipokine concentrations

Spline regression models to examine the possible non-linear relation of total adiponectin (A), high-molecular weight adiponectin (B), the high-molecular weight-to-total adiponectin ratio (C), and resistin (D) to type 2 diabetes (adjusted for same variables as in the multivariate model including BMI of table 3). The solid black line represents odds ratios and the dotted lines represent 95% CIs. Women with extreme low or high adipokine concentrations (<1st or >99th percentile) were excluded from these analyses (n=41 for total adiponectin, n=42 for high-molecular weight adiponectin, n=43 for the high-molecular weight-to-total adiponectin ratio, and n=42 for resistin). HMW = high-molecular weight.