title: Effects of prolonged administration of ultralente insulin on fasting and postbreakfast beta-cell function in normal adults.
abstract: Treatment with small doses of subcutaneous insulin is being investigated as a possible approach to prevent type 1 diabetes in humans. The mechanism of prophylactic insulin therapy could involve the inhibition of beta-cell secretory activity and/or the initiation of an active immunoregulatory process. To evaluate the pure metabolic effect of exogenous insulin, the present study assessed whether daily subcutaneous administration of ultralente insulin alters beta-cell function in normal adults. Fourteen healthy adults were randomized to receive 0.2 U/kg x d ultralente insulin (Ultratard; Novo Nordisk, Bagsvaerd, Denmark) or placebo subcutaneously once daily for 30 days. Plasma glucose, C-peptide, and insulin concentrations were measured in the fasting state and 1 hour after a standardized breakfast, during treatment and during a recovery period of 10 days. Insulin administration induced a 15% to 40% decrease of fasting plasma C-peptide. In contrast, postbreakfast plasma C-peptide increased by 40% to 90% in subjects receiving insulin. Fasting and postbreakfast C-peptide concentrations were significantly different between groups during the injection period after adjustment for baseline concentrations (P < .05, ANOVA with repeated measures). These alterations disappeared 3 days after cessation of insulin treatment. The present regimen of exogenous insulin alters endogenous insulin secretion in normal subjects. Instead of the expected beta-cell rest, the effect appeared to be dual, with insulin secretion decreasing in the basal state and increasing after meals.
authors.affiliation: Department of Pediatric Endocrinology and Institut National de la Santé et Recherche Médicale U-342, Hôpital Saint Vincent de Paul, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Coutant
authors.forename: J C
authors.initials: JC
authors.lastname: Carel
authors.forename: V
authors.initials: V
authors.lastname: Aubry
authors.forename: N
authors.initials: N
authors.lastname: Lahlou
authors.forename: M
authors.initials: M
authors.lastname: Krokowski
authors.forename: C
authors.initials: C
authors.lastname: Boitard
authors.forename: P F
authors.initials: PF
authors.lastname: Bougnères
mesh_terms: D000328:Adult; D002096:C-Peptide / Q000032:analysis; D005215:Fasting; D005260:Female; D006801:Humans; D049528:Insulin, Long-Acting / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019518:Postprandial Period / Q000502:physiology*; D015430:Weight Gain
chemical_list: D002096:C-Peptide; D049528:Insulin, Long-Acting