Early Differential Defects of Insulin Secretion and Action in 19-Year-Old Caucasian Men Who Had Low Birth Weight
- Christine B. Jensen1,
- Heidi Storgaard1,
- Flemming Dela23,
- Jens Juul Holst4,
- Sten Madsbad1 and
- Allan A. Vaag15
- 1Department of Endocrinology and Clinical Research Unit, Hvidovre University Hospital, Hvidovre, Denmark
- 2Copenhagen Muscle Research Center, Rigshospitalet, Copenhagen, Denmark
- 3Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, Herlev, Denmark
- 4Department of Medical Physiology, the Panum Institute, Copenhagen, Denmark
- 5Steno Diabetes Center, Gentofte, Denmark
Abstract
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.
Footnotes
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Address correspondence and reprint requests to Christine B. Jensen, Department of Endocrinology, Hvidovre University Hospital, 2650 Hvidovre, Denmark. E-mail: cbjensen{at}dadlnet.dk.
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.
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