Association of Adiponectin Level and Variants in the Adiponectin Gene with Glucose Metabolism, Energy Expenditure, and Cytokines in Offspring of Type 2 Diabetic Patients

Abstract

Adiponectin is an adipose-specific secretory protein abundantly present in the circulation. The role of adiponectin in the control of energy expenditure and substrate utilization has not yet been established. We performed detailed metabolic studies in a large cohort (n = 158) of offspring of patients with type 2 diabetes (T2DM) to determine the association of adiponectin level with glucose and lipid oxidation, energy expenditure, insulin sensitivity, and visceral obesity by applying the euglycemic clamp technique and indirect calorimetry. The adiponectin level was lower in offspring of T2DM patients than in control subjects. When the data were analyzed by adiponectin tertiles, an elevated adiponectin level was associated with high total, oxidative, and nonoxidative glucose disposal and high energy expenditure during hyperinsulinemia; low levels of free fatty acids and low rates of lipid oxidation during hyperinsulinemia; as well as low levels of inflammatory cytokines; and a low amount of intraabdominal fat evaluated by computed tomography. No association of single nucleotide polymorphism 45 or single nucleotide polymorphism 276 with adiponectin level was found. We conclude that adiponectin has multiple effects on glucose, lipid and free fatty acid metabolism, and cytokines in offspring of T2DM subjects.