Early differential defects of insulin secretion and action in 19-year-old caucasian men who had low birth weight.
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.
Jensen
Christine B
CB
Department of Endocrinology and Clinical Research Unit, Hvidovre University Hospital, Hvidovre, Denmark. cbjensen@dadlnet.dk
Storgaard
Heidi
H
Dela
Flemming
F
Holst
Jens Juul
JJ
Madsbad
Sten
S
Vaag
Allan A
AA
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000409:Alanine / Q000097:blood; D001724:Birth Weight; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003718:Denmark; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D005990:Glycerol / Q000097:blood; D006801:Humans; D006946:Hyperinsulinism; D007230:Infant, Low Birth Weight / Q000502:physiology*; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007773:Lactates / Q000097:blood; D008297:Male; D012016:Reference Values; D012042:Registries; D044465:White People
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D005934:Glucagon; D005947:Glucose; D000409:Alanine; D005990:Glycerol; D020155:3-Hydroxybutyric Acid