Neonatal diabetes mellitus (NDM) is a monogenic disorder caused by mutations in genes involved in regulation of insulin secretion from pancreatic β-cells. Mutations in the KCNJ11 and ABCC8 genes, encoding the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel Kir6.2 and SUR1 subunits, respectively, are found in ∼50% of NDM patients. In the pancreatic β-cell, K(ATP) channel activi...

Address correspondence to: Francisco Nieves, MD, PO Box 365067, San Juan, PR 00936-5067. E-mail: [email protected] Neonatal diabetes mellitus (NDM) is a rare disorder. A one-month-old boy presented with vomiting, hyperglycemia (968 mg/dl [53.8 mmol/L]), severe acetonemia, and metabolic acidosis (pH 6.95, HCO34.2 mmol/L). A second child (three months of age) presented with upper respirat...

The prevalence of type 2 diabetes (T2D) is rising rapidly and in Mexicans is ~19%. T2D is affected by both environmental and genetic factors. Although specific genes have been implicated in T2D risk few of these findings are confirmed in studies of Mexican subjects. Our aim was to replicate associations of 39 single nucleotide polymorphisms (SNPs) from 10 genes with T2D-related phenotypes in a ...

OBJECTIVE Activating mutations in the KCNJ11 and ABCC8 genes encoding the Kir6.2 and SUR1 subunits of the pancreatic ATP-sensitive K(+) channel are the most common cause of permanent neonatal diabetes. In contrast to KCNJ11, where only dominant heterozygous mutations have been identified, recessively acting ABCC8 mutations have recently been found in some patients with neonatal diabetes. These ...

The genes ABCC8 and KCNJ11 have received intense focus in type 2 diabetes mellitus (T2DM) research over the past two decades. It has been hypothesized that the p.E23K (KCNJ11) mutation in the 11p15.1 region may play an important role in the development of T2DM. In 2009, Hamming et al. found that the p.1369A (ABCC8) variant may be a causal factor in the disease; therefore, in this study we perfo...

The aim of the present study was to investigate whether genetic markers considered risk factors for metabolic syndromes, including dyslipidemia, obesity and type 2 diabetes mellitus (T2DM), can be applied to a Northeastern Mexican population. A total of 37 families were analyzed for 63 single nucleotide polymorphisms (SNPs), and the age, body mass index (BMI), glucose tolerance values and blood...

OBJECTIVE To characterise the phenotype and genotype of neonates born small-for-gestational age (SGA; birth weight <10th centile) who developed hyperinsulinaemic hypoglycaemia (HH). METHODS Clinical information was prospectively collected on 27 SGA neonates with HH, followed by sequencing of KCNJ11 and ABCC8. RESULTS There was no correlation between the maximum glucose requirement and serum...

BACKGROUND Neonatal diabetes mellitusis a rare disorder with an incidence of 1 in 2,60,000 live births. METHODS Retrospective analysis of clinical and genetic profile of children admitted with neonatal diabetes mellitus in a tertiary-care hospital in Chennai, India over 11 years. RESULTS Ten children were diagnosed with neonatal diabetes of whom 9 had permanent neonatal diabetes mellitus. T...

Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of permanent neonatal diabetes mellitus (PNDM) and several cases have been successfully treated with oral sulfonylureas. We report on the attempted transfer of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND syndrome, bearing a C166Y mutation in KCNJ11. An inpatient transition from subcutane...