Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males

Aims/hypothesis: It is well established that total systemic adiponectin is reduced in type 2 diabetic subjects. To date most studies have been concerned with the singular full-length protein or proteolytically cleaved globular domain. It is, however, apparent that the native protein circulates in serum as a lower molecular weight hexamer and as larger multimeric structures of high molecular weight (HMW). In this study we address the clinical significance of each form of the protein with respect to glucose tolerance. Methods: Serum was obtained from 34 Indo-Asian male subjects (BMI 26.5±3.1; age 52.15±10.14 years) who had undertaken a 2-h oral glucose tolerance test. An aliquot of serum was fractionated using velocity sedimentation followed by reducing SDS-PAGE. Western blots were probed for adiponectin, and HMW adiponectin as a percentage of total adiponectin (percentage of higher molecular weight adiponectin [S _A] index) was calculated from densitometry readings. Total adiponectin was measured using ELISA; leptin, insulin and IL-6 were determined using ELISA. Results: Analysis of the cohort demonstrated that total adiponectin (r=0.625, p=0.0001), fasting insulin (r=-0.354, p=0.040) and age (r=0.567, p=0.0001) correlated with S _A. S _A showed a tighter, inverse correlation with 2-h glucose levels (r=-0.58, p=0.0003) than total adiponectin (r=-0.38, p=0.0001). Conclusions/interpretation: This study demonstrates the importance of the S _A index as a better determinant of glucose intolerance than measurements of total adiponectin. Our findings suggest that HMW adiponectin is the active form of the protein.