title: [Neonatal diabetes: a disease linked to multiple mechanisms].
abstract: Transient (TNDM) and Permanent (PNDM) Neonatal Diabetes Mellitus are rare conditions occurring in about 1: 300,000 live births. In TNDM growth retarded infants develop diabetes in the first few weeks of life only to go into remission in a few months with possible relapse to a permanent diabetes state usually around adolescence or as adults. We believe that pancreatic dysfunction in this condition is maintained throughout life with relapse initiated at times of metabolic stress such as puberty or pregnancy. In PNDM, insulin secretory failure occurs in the late fetal or early postnatal period. A number of conditions are associated with PNDM, some of which have been elucidated at the molecular levels. Among those, the very recently elucidated mutations in KCNJ11 and ABCC8 gene, encoding the Kir6.2 and SUR1 subunit of the pancreatic K(ATP) channel involved in regulation of insulin secretion accounts for one third to a half of the PNDM cases. Patients with TNDM are more likely to have intrauterine growth retardation and less likely to develop ketoacidosis than patients with PNDM. In TNDM, patients are younger at the diagnosis of diabetes and have lower initial insulin requirements. Considerable overlap occurs between the two groups, so that TNDM cannot be distinguished from PNDM based on clinical features. Very early onset diabetes mellitus seems to be unrelated to autoimmunity in most instances. Recurrent diabetes is common in patients with "transient" neonatal diabetes mellitus and, consequently, prolonged follow-up is imperative. Molecular analysis of chromosome 6 anomalies, the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1 provide a tool to identify transient from permanent neonatal diabetes mellitus in the neonatal period. This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 from insulin therapy to sulfonylureas. Realizing how difficult it is to take care of a child of this age with diabetes mellitus should prompt clinicians to transfer these children to specialized centers. Insulin therapy and high caloric intake are the basis of the treatment. Insulin pump may offer an interesting therapeutic tool in this age group in experienced hands.
authors.affiliation: Service d'endocrinologie pédiatrique, hôpital Necker-Enfants-Malades, 149, rue de Sèvres, 75015 Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Flechtner
authors.forename: M
authors.initials: M
authors.lastname: Vaxillaire
authors.forename: H
authors.initials: H
authors.lastname: Cavé
authors.forename: P
authors.initials: P
authors.lastname: Froguel
authors.forename: M
authors.initials: M
authors.lastname: Polak
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D005317:Fetal Growth Retardation; D005817:Genetic Counseling; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007231:Infant, Newborn; D007328:Insulin / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011379:Prognosis; D011955:Receptors, Drug / Q000235:genetics; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human