Genetics and Natural History of Non-pancreatectomized Patients With Congenital Hyperinsulinism Due to Variants in ABCC8.

CONTEXT: Patients with congenital hyperinsulinism due to ABCC8 variants generally present severe hypoglycemia and those who do not respond to medical treatment typically undergo pancreatectomy. Few data exist on the natural history of non-pancreatectomized patients. OBJECTIVE: This work aims to describe the genetic characteristics and natural history in a cohort of non-pancreatectomized patients with congenital hyperinsulinism due to variants in the ABCC8 gene. METHODS: Ambispective study of patients with congenital hyperinsulinism with pathogenic or likely pathogenic variants in ABCC8 treated in the last 48 years and who were not pancreatectomized. Continuous glucose monitoring (CGM) has been periodically performed in all patients since 2003. An oral glucose tolerance test was performed if hyperglycemia was detected in the CGM. RESULTS: Eighteen non-pancreatectomized patients with ABCC8 variants were included. Seven (38.9%) patients were heterozygous, 8 (44.4%) compound heterozygous, 2 (11.1%) homozygous, and 1 patient carried 2 variants with incomplete familial segregation studies. Seventeen patients were followed up and 12 (70.6%) of them evolved to spontaneous resolution (median age 6.0 ± 4 years; range, 1-14). Five of these 12 patients (41.7%) subsequently progressed to diabetes with insufficient insulin secretion. Evolution to diabetes was more frequent in patients with biallelic variants in the ABCC8 gene. CONCLUSION: The high remission rate observed in our cohort makes conservative medical treatment a reliable strategy for the management of patients with congenital hyperinsulinism due to ABCC8 variants. In addition, a periodic follow-up of glucose metabolism after remission is recommended, as a significant proportion of patients evolved to impaired glucose tolerance or diabetes (biphasic phenotype).

Precisión diagnóstica del índice de masa triponderal (kg/m3) para identificar el fenotipo de riesgo metabólico en pacientes obesos / Diagnostic accuracy of the tri-ponderal mass index in identifying the unhealthy metabolic obese phenotype in obese patients

INTRODUCCIÓN: El fenotipo obeso metabólicamente sano (FOMS) define a los pacientes obesos que tienen preservada la sensibilidad a la insulina y que no presentan complicaciones metabólicas. Este fenotipo se asocia a menor riesgo de padecer enfermedad cardiovascular y diabetes tipo2 en la edad adulta. OBJETIVOS: Determinar la prevalencia del FOMS y del fenotipo obeso con riesgo metabólico (FORM) en una cohorte de niños y adolescentes obesos y establecer la capacidad predictiva del índice de masa triponderal (IMT) y de otros parámetros antropométricos para identificar a estos pacientes. PACIENTES Y MÉTODOS: Estudio transversal de 239 pacientes (125varones) obesos de 8 a 18años de edad. El 45,9% presentan obesidad grado3. Se utilizan las curvas ROC para buscar el mejor punto de corte para: IMT, índice de masa corporal (IMC), valor z-score del IMC (zsIMC) e índice cintura/talla (ICT). Componentes FOMS: glucemia plasmática, triglicéridos plasmáticos, colesterol HDL y presión arterial. RESULTADOS: La prevalencia del FORM en nuestra cohorte es del 62,4%, sin que se observen diferencias entre sexos, incrementándose con la edad y con el grado de obesidad. El IMT tiene una sensibilidad de 75,8 y una especificidad de 42,2 para identificar los pacientes FORM. El mejor punto de corte para el IMT es 18,7kg/m3, para el IMC 30,4kg/m2, para el zsIMC +3,5DE y para el ICT 0,62. CONCLUSIONES: La precisión diagnóstica del IMT para identificar niños y adolescentes con riesgo metabólico es similar al IMC y al ICT. No obstante, su cálculo es más sencillo y además facilita y simplifica la categorización del grado de obesidad en ambos sexos

INTRODUCTION: The metabolically healthy obese (MHO) phenotype defines obese patients who have preserved insulin sensitivity and absence of metabolic complications. This phenotype is associated with a lower risk of cardiovascular disease and type2 diabetes in adulthood. OBJECTIVES: To determine the prevalence of MHO and the metabolically unhealthy obesity (MUO) phenotype in a cohort of obese children and adolescents and to establish the predictive capacity of the tri-ponderal mass index (TMI) and other anthropometric parameters in order to identify these patients. PATIENTS AND METHODS: A cross-sectional study was conducted on 239 obese patients (125 males) from 8 to 18 years of age. Grade3 obesity was present in 45.9% of the patients. ROC curves were used to find the best cut-off point for: TMI, body mass index (BMI), BMI z-score (BMIzs), and waist/height index (WHI). MHO components: plasma blood glucose, plasma triglycerides, HDL-cholesterol, and blood pressure. RESULTS: The prevalence of MUO in the study cohort was 62.4%. No differences between genders were observed, and it was increasing with the age and obesity degree. The TMI has a sensitivity of 75.8 and a specificity of 42.2 to identify the MUO patients. The best cut-off point for TMI is 18.7 kg/m3, for BMI it was 30.4 kg/m2, for BMIzs + 3.5SD, and 0.62 for WHI. CONCLUSIONS: The diagnostic accuracy of TMI in identifying obese adolescents with metabolic risk was similar to BMI and WHI. However, the TMI is much simpler to use and simplifies the categorization of the obesity in both genders

[Diagnostic accuracy of the tri-ponderal mass index in identifying the unhealthy metabolic obese phenotype in obese patients]. / Precisión diagnóstica del índice de masa triponderal (kg/m3) para identificar el fenotipo de riesgo metabólico en pacientes obesos.

INTRODUCTION: The metabolically healthy obese (MHO) phenotype defines obese patients who have preserved insulin sensitivity and absence of metabolic complications. This phenotype is associated with a lower risk of cardiovascular disease and type2 diabetes in adulthood. OBJECTIVES: To determine the prevalence of MHO and the metabolically unhealthy obesity (MUO) phenotype in a cohort of obese children and adolescents and to establish the predictive capacity of the tri-ponderal mass index (TMI) and other anthropometric parameters in order to identify these patients. PATIENTS AND METHODS: A cross-sectional study was conducted on 239 obese patients (125males) from 8 to 18years of age. Grade3 obesity was present in 45.9% of the patients. ROC curves were used to find the best cut-off point for: TMI, body mass index (BMI), BMI z-score (BMIzs), and waist/height index (WHI). MHO components: plasma blood glucose, plasma triglycerides, HDL-cholesterol, and blood pressure. RESULTS: The prevalence of MUO in the study cohort was 62.4%. No differences between genders were observed, and it was increasing with the age and obesity degree. The TMI has a sensitivity of 75.8 and a specificity of 42.2 to identify the MUO patients. The best cut-off point for TMI is 18.7kg/m3, for BMI it was 30.4kg/m2, for BMIzs +3.5SD, and 0.62 for WHI. CONCLUSIONS: The diagnostic accuracy of TMI in identifying obese adolescents with metabolic risk was similar to BMI and WHI. However, the TMI is much simpler to use and simplifies the categorization of the obesity in both genders.

Hyperinsulinaemic hypoglycaemia, renal Fanconi syndrome and liver disease due to a mutation in the HNF4A gene.

SUMMARY: HNF4A gene mutations have been reported in cases of transient and persistent hyperinsulinaemic hypoglycaemia of infancy (HHI), particularly in families with adulthood diabetes. The case of a patient with HHI, liver impairment and renal tubulopathy due to a mutation in HNF4A is reported. LEARNING POINTS: Urine specimen study in cases of HHI with diazoxide response is necessary to rule out specific metabolic conditions (l-3-hydroxyacyl-coenzyme A dehydrogenase deficiency) or tubular renal involvement.Hyperinsulinaemic hypoglycaemia due to the heterozygous mutation (p.Arg63Trp, c. 187C > T) in the HNF4A gene is associated with renal tubulopathy and liver involvement.Follow-up of patients diagnosed of HHI is mandatory to detect associated conditions.