title: Adiponectin and its response to thiazolidinediones are associated with insulin-mediated glucose metabolism in type 2 diabetic patients and their first-degree relatives.
abstract: Patients with type 2 diabetes (T2D) and their first-degree relatives (FDRs) are characterized by hypoadiponectinaema and insulin resistance. In T2D patients, plasma adiponectin and insulin sensitivity (SI) increase in response to thiazolidinediones (TZDs). These findings suggest a role for adiponectin in the regulation of SI. We studied the relationship between plasma adiponectin and glucose and lipid metabolism and the effect of troglitazone (200 mg/day) for 12 weeks in 19 normoglycaemic, obese FDR and 20 obese T2D patients, using euglycaemic-hyperinsulinaemic clamps, glycolytic flux calculations and indirect calorimetry. Plasma adiponectin was similar in both groups, despite higher glucose disposal (Rd), glucose oxidation and glycolytic flux and lower lipid oxidation during insulin stimulation in FDR compared with T2D patients. Plasma adiponectin correlated with insulin-stimulated Rd, non-oxidative glucose disposal (NOGD), glucose storage and SI in both groups after adjustment for sex and body fat. The troglitazone-mediated upregulation of plasma adiponectin was associated with increased insulin-stimulated Rd, NOGD and glucose storage in both groups. No effect on endogenous glucose production was observed. In FDR, plasma adiponectin correlated with insulin-stimulated glycogen synthase activity and the troglitazone-induced increase in plasma adiponectin correlated with the improvement in insulin-stimulated Rd and SI after adjustment for sex and body fat. In conclusion, plasma adiponectin in weight-matched FDR and T2D patients is comparably low and correlates with insulin-mediated glucose uptake and storage. Moreover, these data provide evidence for an adiponectin-dependent insulin-sensitizing effect of TZDs at an early stage before development of T2D and that this effect is exerted mainly on insulin-mediated glucose metabolism.
authors.affiliation: Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: V
authors.initials: V
authors.lastname: Hulstrøm
authors.forename: K
authors.initials: K
authors.lastname: Højlund
authors.forename: J
authors.initials: J
authors.lastname: Vinten
authors.forename: H
authors.initials: H
authors.lastname: Beck-Nielsen
authors.forename: K
authors.initials: K
authors.lastname: Levin
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D032721:Adult Children; D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis; D002839:Chromans / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D015309:Glucose Clamp Technique; D006006:Glycogen Synthase / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000737:chemistry; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D000077288:Troglitazone
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D014280:Triglycerides; D006006:Glycogen Synthase; D000077288:Troglitazone