RESUMO
OBJECTIVE: Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. DESIGN: Retrospective analysis of the Italian data set of patients with TNDM. METHODS: Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. RESULTS: Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; -2.27 SD) than those with KATP mutations (4.0 weeks; -1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. CONCLUSIONS: If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.
Assuntos
Diabetes Mellitus , Doenças do Recém-Nascido , Conjuntos de Dados como Assunto , Diabetes Mellitus/classificação , Diabetes Mellitus/congênito , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino/normas , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/classificação , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/genética , Doenças do Recém-Nascido/terapia , Itália , Masculino , Mutação , Canais de Potássio Corretores do Fluxo de Internalização/genética , Indução de Remissão/métodos , Estudos Retrospectivos , Receptores de Sulfonilureias/genéticaRESUMO
CONTEXT: Growth hormone (GH) influences glucose homeostasis mainly by negatively affecting insulin sensitivity. OBJECTIVE: To longitudinally study insulin sensitivity [via homeostasis model assessment of insulin sensitivity (HOMA-S)], insulin secretion [insulinogenic index (IGI)], and capacity of ß cells to adapt to changes in insulin sensitivity [oral disposition index (ODI)] in girls with Turner syndrome (TS) undergoing GH treatment. DESIGN AND SETTING: Longitudinal, retrospective, 7-year study conducted in a tertiary pediatric endocrine unit and university pediatric clinic. PATIENTS AND METHODS: We studied 104 patients with TS (mean age ± standard deviation, 9.1 ± 3.4 years) for a median of 7.2 years. INTERVENTION: Every year, the children underwent an oral glucose tolerance test, which was used to calculate HOMA-S, IGI, and ODI. RESULTS: HOMA-S, IGI, and ODI did not significantly change. CONCLUSION: The results are reassuring, showing no negative influence of GH treatment on insulin sensitivity and on ß-cell secretory capacity in girls with TS.
Assuntos
Glicemia/metabolismo , Hormônio do Crescimento/uso terapêutico , Resistência à Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Síndrome de Turner/tratamento farmacológico , Adolescente , Criança , Feminino , Teste de Tolerância a Glucose , Homeostase , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Estudos Longitudinais , Estudos Retrospectivos , Síndrome de Turner/metabolismoRESUMO
BACKGROUND: Growth hormone (GH) influences glucose homeostasis by negatively affecting insulin sensitivity, leading to a compensatory increase in insulin secretion. It has recently been reported, in animals and humans, that GH might also stimulate insulin secretion by directly affecting the growth and function of pancreatic ß-cells. The aim of this work was to longitudinally study the insulin sensitivity (HOMA-S), insulin secretion [insulinogenic index (IGI)] and capacity of ß-cells to adapt to changes in insulin sensitivity [oral disposition index (ODI)] in GH-deficient (GHD) children under GH treatment. METHODS: We studied 99 GHD (62 male, 37 female; age 8.9 ± 3.5 years) children for a median period of 6 years (range 1.5-16.2). Every year, our patients underwent an oral glucose tolerance test, which was used to calculate the HOMA-S, IGI and ODI. RESULTS: Although HOMA-S remained unchanged, an increase in IGI and ODI was observed, becoming significant after 6 years of treatment (1.25 ± 1.28 vs. 2.35 ± 2.38, p < 0.05 and 0.57 ± 0.68 vs. 1.50 ± 1.92, p < 0.01, respectively). CONCLUSION: Our results suggest a positive influence of GH treatment on the ß-cell secretory capacity in children with GH deficiency. © 2016 S. Karger AG, Basel.