| Abstract: | ![]()
Type 2 diabetes is characterized by resistance to insulin action of glucose metabolism and lipolysis. First-degree relatives of diabetic patients are at increased risk of developing diabetes themselves and early metabolic abnormalities in these relatives may represent primary defects in the pathogenesis of diabetes. Our previous work has demonstrated impaired suppression of lipolysis after an oral glucose load in glucose-tolerant relatives of Asian origin, but not in European relatives. To investigate whether a more subtle defect exists in the European population we studied 8 first-degree relatives of European patients and 9 matched control subjects. All had normal glucose tolerance. Glycerol and glucose turnovers were measured using a primed constant infusion of the stable isotopic tracers [1, 1, 1, 2, 32H5] glycerol and [6, 62H] glucose, basally and in response to a very low dose insulin infusion (0.005 units kg-1 h-1). The relatives had higher basal insulin concentrations (median (range): 49 (30 to 113) vs 28 (18 to 66) pmol 1-1, p < 0.05) compared to controls, but basal glycerol and glucose turnovers and plasma concentrations of glycerol, glucose, and non-esterifed fatty acids (NEFA) were similar. Following insulin, the suppression of glycerol appearance in the circulation measured isotopically was significantly less complete in the relatives compared with controls (mean change ± SEM: + 0.06 ± 0.21 vs -0.51 ± 0.16 μmol kg-1 min-1, p < 0.05). Plasma glycerol concentration decreased to a similar extent in relatives and controls, as did glucose and NEFA levels (mean change ± SEM: glycerol -12 ± 3 vs -8 ± 4 μmol 1-1; glucose -0.37 ± 0.06 vs -0.30 ± 0.10 mmol.l-1; NEFA -152 ± 48 vs -130 ± 32 μmol.1-1). The change in glucose turnover was not different in relatives and controls (change -0.10 ± 0.03 vs -0.07 ± 0.06 mg kg-1 min-1). We conclude that glucose-tolerant relatives of European origin exhibit subtle defects in insulin sensitivity with respect to lipolysis. |
