Decreased high-molecular-weight adiponectin in gestational diabetes: implications for the pathophysiology of Type 2 diabetes

Aims Low serum concentrations of the insulin-sensitizing protein adiponectin predict the development of incident Type 2 diabetes (T2DM). It has recently emerged that the anti-diabetic activity of adiponectin may be mediated by its high-molecular-weight (HMW) isoform, circulating levels of which are decreased in T2DM. The relevance of decreased HMW adiponectin to incident T2DM, however, has not been assessed. Since gestational diabetes (GDM) identifies a population of young women at high risk of future T2DM (i.e. representing an early stage in the natural history of the disease), we sought to determine if decreased HMW adiponectin is a feature of GDM. Methods HMW and total adiponectin were measured in 121 women at the time of oral glucose tolerance testing (OGTT) in late pregnancy, following an abnormal glucose challenge test. Based on the OGTT, there were 41 women with and 80 without GDM. Results Median HMW adiponectin concentration was lower in women with GDM (3.5 mu g/ml) than in those without GDM (5.5 mu g/ml) (P < 0.0001). After full adjustment for covariates, mean HMW adiponectin remained significantly lower in women with GDM compared with their peers (3.6 vs. 5.3 mu g/ml, P = 0.0035). HMW adiponectin was positively associated with insulin sensitivity (ISOGTT) (r = 0.38, P < 0.0001) and pancreatic B-cell function [insulin secretion-sensitivity index (ISSI)] (r = 0.33, P = 0.0002) and inversely related to blood glucose levels, including area-under-the-glucose-curve during the OGTT (AUC(glucose)) (r = -0.31, P = 0.0007). On separate multiple linear regression analyses, HMW adiponectin emerged as an independent determinant of AUC(glucose), ISOGTT and ISSI, respectively, mirroring the relationships of total adiponectin. Conclusions HMW adiponectin is significantly decreased in women with GDM. Deficiency of HMW adiponectin may be an early event in the natural history of T2DM.