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Characterization of Insulin Secretion and Resistance in Type 2 Diabetes of Adolescents

Institut National de la Santé et de la Recherche Médicale, Unité 690, Hôpital Robert Debré (C.D., C.L.-M.), 75019 Paris, France; Pediatric Endocrinology and Diabetes Unit (N.T.-R.) and Service de Biochimie Hormonologie (D.C., O.R.), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, 75019 Paris, France; and Department of Pediatric Endocrinology, Diabetic Unit, Hôpital des Enfants-Malades (M.P.), 75015 Paris, France

Address all correspondence and requests for reprints to: Dr. Céline Druet, Institut National de la Santé et de la Recherche Médicale, Unité 690, Hôpital Robert Debré, 48 boulevard Sérurier, 75019 Paris, France. E-mail: drucel{at}yahoo.fr.

Abstract

Context: Type 2 diabetes (T2D) in obese children is an emerging problem, including in Europe. Its presentation at diagnosis very often differs from that in adults.

Objective: The objective of this study was to investigate the relative contributions of the two components of T2D, insulin resistance and insulin secretion, early in the history of the disease in adolescents.

Patients and Methods: Six obese adolescents with T2D were included 2 months to 4.3 yr after diagnosis (five girls and one boy; median age, 15.4 yr; median body mass index, 4.4 SD). Peripheral and hepatic insulin sensitivity was evaluated with euglycemic hyperinsulinemic (40 mU/m²·min) clamp. First-phase insulin release was evaluated after iv glucose stimulation. A graded iv glucose infusion and an arginine test were performed to measure insulin secretion.

Results: All patients showed decreased peripheral glucose uptake to the same extent. Five patients showed hepatic insulin resistance. First-phase insulin release was very low in two patients. Three patients showed an exaggerated insulin response under graded glucose infusion and preserved secretion under arginine stimulation. Three other patients, with elevated fasting plasma glucose levels, demonstrated a very low insulin response under glucose stimulation and a low insulin response under arginine stimulation.

Conclusions: These data emphasize that together with marked insulin resistance, the failure of ß-cell function is a major component in the course of T2D in childhood.

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