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Normal Secretion and Action of the Gut Incretin Hormones Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide in Young Men with Low Birth Weight

Steno Diabetes Center (J.H.S., K.P., C.B.J., A.A.V.), 2820 Gentofte, Denmark; Department of Internal Medicine F (T.V.), Gentofte Hospital, DK 2820 Hellerup, Denmark; Department of Medical Physiology (C.F.D., J.J.H.), Panum Institute, University of Copenhagen, DK 2200 Copenhagen, Denmark; Novo Nordisk (A.V.), DK-2880 Bagsværd, Denmark; and Department of Endocrinology (S.M.), Hvidovre University Hospital, DK 2650 Hvidovre, Denmark

Address all correspondence and requests for reprints to: Jakob Hagen Schou or Kasper Pilgaard, Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark. E-mail: oranje{at}tiscali.dk or kasperpilgaard{at}hotmail.com.

Context: Low birth weight (LBW) is associated with increased risk of type 2 diabetes mellitus. An impaired incretin effect was reported previously in type 2 diabetic patients.

Objective: We studied the secretion and action of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in young LBW men (n = 24) and matched normal birth weight controls (NBW) (n = 25).

Results: LBW subjects were 5 cm shorter but had a body mass index similar to NBW. LBW subjects had significantly elevated fasting and postprandial plasma glucose, as well as postprandial (standard meal test) plasma insulin and C-peptide concentrations, suggestive of insulin resistance. Insulin secretion in response to changes in glucose concentration ("ß-cell responsiveness") during the meal test was similar in LBW and NBW but inappropriate in LBW relative to insulin sensitivity. Fasting and postprandial plasma GLP-1 and GIP levels were similar in the groups. First- and second-phase insulin responses were similar in LBW and NBW during a hyperglycemic clamp (7 mM) with infusion of GLP-1 or GIP, respectively, demonstrating normal action of these hormones on insulin secretion.

Conclusion: Reduced secretion or action of GLP-1 or GIP does not explain a relative reduced ß-cell responsiveness to glucose or the slightly elevated plasma glucose concentrations observed in young LBW men.

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