Context/Objective: Decreased total adiponectin has been associated with metabolic disorders, including obesity, diabetes, fatty liver and the metabolic syndrome. Although circulating adiponectin is composed of trimers, hexamers and high molecular weight (HMW) multimers, there has been limited study of the specific metabolic correlates of these isoforms in humans. Thus, our objective was to evaluate the associations of these adiponectin isoforms with metabolic and anthropometric parameters.

Design/Participants/Setting: 53 diabetic and 68 non-diabetic subjects attending outpatient clinics underwent cross-sectional metabolic characterization. Circulating levels of HMW, hexameric and trimeric adiponectin were measured using a multimeric adiponectin ELISA based upon selective protease-mediated digestion.

Results: On Spearman univariate analysis, both total and HMW adiponectin levels were inversely associated with body mass index (BMI), fasting glucose, HOMA-IR, triglycerides and ALT (all r 0.22, p<0.05), with the HMW isoform also positively correlated with high-density-lipoprotein cholesterol (r=0.19, p=0.036). In contrast, hexameric and trimeric adiponectin were significantly associated with only BMI (r=-0.23, p=0.0102) and mid-upper arm circumference (r=0.21, p=0.039), respectively. On separate forward stepwise multiple linear regression analyses, fasting glucose and ALT emerged as independent, negative covariates of both total and HMW adiponectin, while no independent covariates of hexameric and trimeric adiponectin were identified. Furthermore, after adjustment for age, gender and diabetes, mean ALT was highest in subjects in the lowest tertile of HMW adiponectin, followed in turn by the middle and highest tertiles, respectively (trend p=0.028).

Conclusions: HMW adiponectin (but not hexameric or trimeric) tracks with the metabolic correlates of total adiponectin. Furthermore, an independent inverse association exists between ALT and HMW adiponectin.