ESPE Abstracts (2016) 86 RFC5.4

[ldquo]Transient[rdquo] Neonatal Diabetes In Adulthood: Metabolic Outcomes

Kanetee Busiaha, Baz Bazb, Fleur Lebourgeoisc, Malek Ait Djoudid, Nadege Bacheree, Olivier Bourronf, Hubert Ythierg, Nathalie Pouvreauh, Christine Bellanne-Chanteloti, Bernard Vialettesj, Pierre Gourdyk, Agnes Hartemannl, Jean-Jacques Robertm, Hélène Cavén, Michel Polako & Jean-François Gautierp


aService endocrinologie, gynécologie et diabétologie pédiatrique, Hôpital universitaire Necker Enfants Malades Assistance Publique Hôpitaux de Paris, Faculté de médecine Paris Descartes et Institut Ima, Paris, France; bCentre Universitaire du Diabète et ses Complications, Hôpital Lariboisière, Clinical Investigation Center, INSERM-CIC 9504, Faculté de médecine Paris Diderot - Université Paris 7, Inserm U1138, Centre, Paris, France; cService endocrinologie, gynécologie et diabétologie pédiatrique, Hôpital universitaire Necker Enfants Malades, Assitance Publique Hôpitaux de Paris, Paris, France; dCentre Universitaire du Diabète et ses Complications, Hôpital Lariboisière, Clinical Investigation Center, INSERM-CIC 9504, Paris, France; eCentre Hospitalier de Mont de Marsan, Mont de Marsan, France; fDiabétologie de l’Institut E3M, Hôpital Universitaire de la Pitié Salpétrière, Assistance Publique Hôpitaux de Paris, Faculté de médecine Pierre et Marie Curie - Université Paris 6, Inserm U1138, Cent, Paris, France; gCentre Hospitalier de Roubaix, Roubaix, France; hService de génétique, Hôpital Universitaire Robert Debré, Université Denis7 Diderot, Paris, France; iGénétique des Maladies Métaboliques et des Neutropénies Congénitales, Hôpital Universitaire de la Pitié Salpétrière, Assistance Publique Hôpitaux de Paris, Faculté de médecine Pierre et Marie Curie -, Paris, France; jEndocrinologie, nutrition et maladies métaboliques - Hôpital Nord, Hôpital universitaire de Marseille, Assistance Publique Hôpitaux de Marseilles, Marseilles, France; kDiabétologie, maladies métaboliques et nutrition, Hôpital universitaire de Toulouse, Inserm/Université Paul Sabatier UMR 1048 - I2MC, Equipe 9, Toulouse, France; lDiabétologie de l’Institut E3M, Hôpital Universitaire de la Pitié Salpétrière, Assistance Publique Hôpitaux de Paris, Faculté de médecine Pierre et Marie Curie - Université Paris 6, Inserm U1138, Cent, Paris, France; mService endocrinologie, gynécologie et diabétologie pédiatrique, Hôpital universitaire Necker Enfants Malades, Assitance Publique Hôpitaux de Paris, Paris, France; nService de génétique, Hôpital Universitaire Robert Debré, Université Denis7 Diderot, Paris, France; oService endocrinologie, gynécologie et diabétologie pédiatrique, Hôpital universitaire Necker Enfants Malades Assistance Publique Hôpitaux de Paris, Faculté de médecine Paris Descartes et Institut Ima, Paris, France; pCentre Universitaire du Diabète et ses Complications, Hôpital Lariboisière, Clinical Investigation Center, INSERM-CIC 9504, Faculté de médecine Paris Diderot - Université Paris 7, Inserm U1138, Centre, Paris, France


Background: “Transient” Neonatal Diabetes Mellitus (TNDM) is a rare genetic beta cells dysfunction leading to hyperglycaemia that resolves in early childhood. About 80% of patients relapse during adolescence or adulthood. Glucose homeostasis had not been investigated in adulthood.

Objective and hypotheses: To investigate insulin secretion and insulin sensitivity in adults affected with TNDM or in their 1st degree mutated relatives.

Method: The patients originated from the French Neonatal Diabetes Study Group cohort. We selected those with TNDM and aged 18 years or more in September 2013, and their 1st degree adult mutated relatives. We measured insulin sensitivity using a two-step hyperinsulinemic euglycemic clamp and maximal insulin secretion in response to a graded intra-venous glucose infusion followed by a bolus of arginine. Body composition was assessed using dual energy X-ray absorptiometry.

Results: We included 15 individuals (6 males, 9 females). Median age was 36 (18–55) years. Median BMI was 21 (17.5–30.9)kg/m2. We identified abnormalities in 6q24 (n=2, 13.3%), and mutations in ABCC8 (n=9, 60.1%) and KCNJ11 (n=2, 13.3%) genes. 2 (13.3%) patients had no identified molecular defect. 8 (53%) patients had a TNDM. Among them 6 (40%) had a recurrence of diabetes. 7 (47%) patients were 1st degree relatives. Among them, 4 (27%) had a diabetes. Mean insulin secretion rate in the last 40 minutes of the glucose ramp was as follow: 4.9 pmol/kg per min in 10 (67%) diabetic patients, and 12.5 pmol/kg per min in 5 (33%) non-diabetic patients, There was no significant disturbance in insulin sensitivity and the mean M-value was 12.8 mg/kg per min.

Conclusion: Our study suggests that monogenic diabetes in adulthood is due to a partial insulin secretion defect, not associated with insulin resistance. These results underscore the importance of genetic evaluation in order to personalize the treatment in adulthood.