Circulating Adiponectin Levels Are Reduced in Nonobese but Insulin-Resistant First-Degree Relatives of Type 2 Diabetic Patients

Publisher Website
Google Scholar
Abstract
Adiponectin, one of the most abundant gene transcript proteins in human fat cells, has been shown to improve insulin action and is also suggested to exert antiatherogenic effects. We measured circulating adiponectin levels and risk factors for atherosclerosis in 45 healthy first-degree relatives of type 2 diabetic subjects (FDR) as well as 40 healthy control subjects (CON) without a known family history of diabetes. Insulin sensitivity (Si) was studied with the minimal model, and measurements of adiponectin, metabolic variables, inflammatory markers, and endothelial injury markers, as well as lipoprotein concentrations, were performed. FDR were insulin resistant (3.3 ± 2.4 vs. 4.5 ± 2.6 × 10−4 × min−1 per μU/ml [mean ± SD], P < 0.01), and their circulating plasma adiponectin levels (6.6 ± 1.8 vs. 8.1 ± 3.0 μg/ml, P < 0.03) were decreased. After adjustments for age in FDR, adiponectin levels were negatively correlated with fasting proinsulin (r −0.64, P < 0.001), plasminogen activator inhibitor (PAI)-1 activity (r −0.56, P < 0.001), fasting insulin (r −0.55, P < 0.001), and acute insulin response (r −0.40, P < 0.05); they were positively related to HDL cholesterol (r 0.48, P < 0.01) and Si (r 0.41, P < 0.01). Furthermore, when adjusted for age, waist, and Si, adiponectin was associated with HDL cholesterol and proinsulin, which explained 51% of the variation in adiponectin in multiple regression analyses in that group. In conclusion, circulating plasma adiponectin levels were decreased in nonobese but insulin-resistant FDR and, in addition, related to several facets of the insulin resistance syndrome (IRS). Thus, hypoadiponectinemia may be an important component of the association between cardiovascular disease and IRS.