Total and High-Molecular-Weight Adiponectin and Resistin in Relation to the Risk for Type 2 Diabetes in Women

Abstract

Background Adiponectin, particularly high-molecular weight 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 the future risk for type 2 diabetes, independent of obesity and other known diabetes risk factors. Design Prospective, nested case-control study. Settings United States. Participants 1,038 initially healthy women of the Nurses’ Health Study who developed type 2 diabetes after blood sampling (1989–1990) through 2002 and 1,136 matched control subjects. Measurements Plasma concentrations of adipokines were measured by enzyme-linked immunosorbent assays. Results In multivariate models adjusting for diabetes risk factors including body-mass index (BMI), both higher total and high-molecular weight adiponectin levels were associated with a substantially lower risk for type 2 diabetes. The odds ratios comparing the highest with the lowest quintiles were 0.17 (95% CI, 0.12–0.25) for total adiponectin and 0.10 (CI, 0.06–0.15) for high-molecular weight adiponectin. In addition, a higher high-molecular weight-to-total adiponectin ratio was associated with a significantly lower risk even after adjusting for total adiponectin (odds ratio, 0.45 [CI, 0.31–0.65]). In the multivariate model adjusting for diabetes risk factors except BMI, high resistin levels were significantly associated with an increased diabetes risk for (odds ratio, 1.68 [CI, 1.25–2.25]). However, after additional adjustment for BMI, this association was no longer statistically significant (odds ratio, 1.28 [CI, 0.93–1.76]). Limitations Residual confounding by imperfectly or unmeasured confounders cannot be excluded. Conclusions These results indicate that adiponectin, but not resistin is strongly associated with diabetes risk independent of BMI. The high-molecular weight-to-total adiponectin ratio is related to diabetes risk independent of total adiponectin, suggesting an important role of the relative proportion of high-molecular weight adiponectin in diabetes pathogenesis.

Adiponectin and its association with bone mass accrual in childhood

“…For example, mutations that inhibit the formation of high-molecular-weight adiponectin lead to type 2 diabetes, suggesting that this isoform may be a better predictor of insulin resistance and diabetes than total adiponectin, as reported recently. (32) Since the assay used in this study measured total adiponectin levels, we were unable to determine the relative contribution of different isoforms to the associations with the parameters related to skeletal development that we observed. A further limitation to this study was the use of self-assessment by questionnaire to evaluate pubertal stage as opposed to evaluation by a trained examiner.…”

Relationship between ADIPOQ gene, circulating high molecular weight adiponectin and albuminuria in individuals with normal kidney function: evidence from a family-based study

“…Adiponectin, a hormone exclusively secreted by adipocytes, circulates abundantly in the bloodstream, as low, medium and high molecular weight (LMW, MMW and HMW) multimers [4,5] and has well-recognised antiatherogenic, anti-inflammatory and insulin-sensitising properties [4,6]. Studies in humans have persistently reported that insulin resistance and related clinical outcomes are associated with lower adiponectin concentrations [7][8][9] as well as with increased UAE [10,11]. Based upon these well established associations, one would expect an inverse relationship between circulating adiponectin and albuminuria.…”

Characterisation of adiponectin multimers and the IGF axis in humans with a heterozygote mutation in the tyrosine kinase domain of the insulin receptor gene

“…In the majority of studies, total and HMW adiponectin are reduced in obesity and type 2 diabetes and show stronger association with insulin resistance, risk of type 2 diabetes and coronary artery diseases than MMW and LMW adiponectin (32,33,34,35,36,37,38). In this context, the finding of normal total and HMW adiponectin and the relative increase in the fraction of HMW adiponectin and the decrease in absolute levels and fraction of LMW adiponectin may play a beneficial role for the Arg1174Gln carriers.…”