INSULIN-RESISTANCE WITH RESPECT TO LIPOLYSIS IN NONDIABETIC RELATIVESOF EUROPEAN PATIENTS WITH TYPE-2 DIABETES

Type 2 diabetes is characterized by resistance to insulin action of gl ucose metabolism and lipolysis. First-degree relatives of diabetic pat ients are at increased risk of developing diabetes themselves and earl y metabolic abnormalities in these relatives may represent primary def ects in the pathogenesis of diabetes. Our previous work has demonstrat ed impaired suppression of lipolysis after an oral glucose load in glu cose-tolerant relatives of Asian origin, but not in European relatives . To investigate whether a more subtle defect exists in the European p opulation we studied 8 first-degree relatives of European patients and 9 matched control subjects. All had normal glucose tolerance. Glycero l and glucose turnovers were measured using a primed constant infusion of the stable isotopic tracers [1,1,1,2,3(2)H(5)] glycerol and [6,6(2 )H] glucose, basally and in response to a very low dose insulin infusi on (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 tur novers and plasma concentrations of glycerol, glucose, and non-esterif ed fatty acids (NEFA) were similar. Following insulin, the suppression of glycerol appearance in the circulation measured isotopically was s ignificantly less complete in the relatives compared with controls (me an change +/- SEM: + 0.06 +/- 0.21 vs -0.51 +/- 0.16 mu mol kg(-1) min (-1) p<0.05). Plasma glycerol concentration decreased to a similar ext ent in relatives and controls, as did glucose and NEFA levels (mean ch ange +/- SEM: glycerol -12 +/- 3 vs -8 +/- 4 mu mol 1(-1); glucose -0. 37 +/- 0.06 vs -0.30 +/- 0.10 mmol.l(-1); NEFA -152 +/- 48 vs -130 +/- 32 mu mol.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.