Several studies have linked low birth weight (LBW) and type 2 diabetes. We investigated hepatic and peripheral insulin action including intracellular glucose metabolism in 40 19-year-old men (20 LBW, 20 matched control subjects), using the hyperinsulinemic-euglycemic clamp technique at two physiological insulin levels (10 and 40 mU/m2 per min), indirect calorimetry, and [3-3H]glucose. Insulin secretion was examined during an oral and intravenous glucose tolerance test. Fasting p-glucose was higher in the LBW group (5.6 ± 0.1 vs. 5.4 ± 0.1; P < 0.05). Basal plasma glycerol concentrations were significantly lower in the LBW group. Insulin-stimulated glycolytic flux was significantly reduced, and suppression of endogenous glucose production was enhanced in the LBW group. Nevertheless, basal and insulin-stimulated rates of whole-body peripheral glucose disposal, glucose oxidation, lipid oxidation, exogenous glucose storage, and nonoxidative glucose metabolism were similar in the two groups. Insulin secretion was reduced by 30% in the LBW group, when expressed relative to insulin sensitivity (disposition index = insulin secretion × insulin action). We propose that reduced insulin-stimulated glycolysis precedes overt insulin resistance in LBW men. A lower insulin secretion may contribute to impaired glucose tolerance and ultimately lead to diabetes.
Address correspondence and reprint requests to Christine B. Jensen, Department of Endocrinology, Hvidovre University Hospital, 2650 Hvidovre, Denmark. E-mail:.
Received for publication 30 May 2001 and accepted in revised form 17 December 2001.
AUC, area under the curve; Di, disposition index; EGP, endogenous glucose production; EGS, exogenous glucose storage; FFA, free fatty acids; FFM, fat-free mass; GF, glycolytic flux; GIP, gastric inhibitory polypeptide; GLP-1, glucagon-like peptide-1; IA, insulin action; IGT, impaired glucose tolerance; IVGTT, intravenous glucose tolerance test; LBW, low birth weight; NOGM, nonoxidative glucose metabolism; OGTT, oral glucose tolerance test; Ra, appearance rate; Rd, disposal rate; Si, sensitivity index; TCA, tricarboxylic acid; Vo2max, maximal aerobic capacity.