TY - JOUR

T1 - Early differential defects of insulin secretion and action in 19-year-old caucasian men who had low birth weight.

AU - Jensen, Christine B

AU - Storgaard, Heidi

AU - Dela, Flemming

AU - Holst, Jens Juul

AU - Madsbad, Sten

AU - Vaag, Allan A

N1 - Keywords: 3-Hydroxybutyric Acid; Alanine; Birth Weight; Blood Glucose; C-Peptide; Denmark; European Continental Ancestry Group; Fatty Acids, Nonesterified; Glucagon; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Glycerol; Humans; Hyperinsulinism; Infant, Low Birth Weight; Infant, Newborn; Insulin; Lactates; Male; Reference Values; Registries

PY - 2002

Y1 - 2002

N2 - 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/m(2) per min), indirect calorimetry, and [3-(3)H]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 x 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.

AB - 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/m(2) per min), indirect calorimetry, and [3-(3)H]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 x 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.

M3 - Journal article

C2 - 11916955

VL - 51

SP - 1271

EP - 1280

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -