Correlation of circulating full-length visfatin (PBEF/NAMPT) with metabolic parameters in subjects with and without diabetes: a cross-sectional study.

OBJECTIVE: Here we use a novel ELISA that is specific for full-length visfatin (PBEF/NAMPT), compare it with the existing C-terminal based assay and use it to investigate associations of visfatin with metabolic parameters. DESIGN, PATIENTS AND MEASUREMENTS: We established the specificity and effectiveness of the new ELISA and evaluated the associations of full-length visfatin with clinical, anthropometric and metabolic parameters in a cross-sectional study of 129 Thai subjects, consisting of 50 outpatients with type 2 diabetes and 79 healthy volunteers. RESULTS: The new ELISA accurately recovered full-length recombinant visfatin and detected visfatin secreted by primary human and rat adipocytes. We found serum full-length visfatin was significantly higher in subjects with diabetes compared to their nondiabetic peers (median 2.75 vs. 2.22 ng/ml, P = 0.0142). After adjustment for age, gender and traditional metabolic risk factors, adjusted mean visfatin remained significantly higher in the diabetes group (3.80 vs. 2.10 ng/ml, P = 0.0021). On Spearman univariate correlation analysis, visfatin was significantly associated with resistin (r = 0.30, P = 0.0011), but not with any other anthropometric or metabolic variables, including adiponectin multimers. On multiple linear regression analysis, the only covariates independently associated with visfatin were diabetes (t = 3.11, P = 0.0024) and log resistin (t = 2.68, P = 0.0086). CONCLUSIONS: Circulating visfatin is independently associated with diabetes and resistin concentration, but is not related to adiponectin multimers or other metabolic covariates. These data are suggestive of a potential role of visfatin in subclinical inflammatory states.

Total and high molecular weight but not trimeric or hexameric forms of adiponectin correlate with markers of the metabolic syndrome and liver injury in Thai subjects.

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: A total of 53 diabetic and 68 nondiabetic 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, fasting glucose, homeostasis model of assessment of insulin resistance, triglycerides, and alanine aminotransferase (ALT) (all |r| >or= 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 body mass index (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, whereas 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.