Due to new genetic insights, etiologic classification of diabetes is under constant scrutiny. Hundreds, or even thousands, of genes are linked with type 2 diabetes. Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to be predisposed to type 2 diabetes mellitus across many large studies. Individually, each of these polymorphisms is o...

AIMS Recessive PDX1 (IPF1) mutations are a rare cause of pancreatic agenesis, with three cases reported worldwide. A recent report described two cousins with a homozygous hypomorphic PDX1 mutation causing permanent neonatal diabetes with subclinical exocrine insufficiency. The aim of our study was to investigate the possibility of hypomorphic PDX1 mutations in a large cohort of patients with pe...

Permanent neonatal diabetes (PND), requiring insulin within the first months of life, is unexplained at the molecular level in most cases. It has very recently been shown that heterozygous activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive K(+) channel involved in the regulation of insulin secretion, cause PND. In the present study, we screened ...

OBJECTIVE Two novel mutations (E1506D, E1506G) in the nucleotide-binding domain 2 (NBD2) of the ATP-sensitive K(+) channel (K(ATP) channel) sulfonylurea receptor 1 (SUR1) subunit were detected heterozygously in patients with neonatal diabetes. A mutation at the same residue (E1506K) was previously shown to cause congenital hyperinsulinemia. We sought to understand why mutations at the same resi...

Since the discovery of the KATP channel in 1983, numerous studies have revealed its physiological functions. The KATP channel is expressed in various organs, including the pancreas, brain and skeletal muscles. It functions as a "metabolic sensor" that converts the metabolic status to electrical activity. In pancreatic beta-cells, the KATP channel regulates the secretion of insulin by sensing a ...

AIMS An early genetic diagnosis of neonatal diabetes guides clinical management and results in improved treatment in ~ 40% of patients. In the offspring of individuals with neonatal diabetes, a prenatal diagnosis allows accurate estimation of the risk of developing diabetes and, eventually, the most appropriate treatment for the baby. In this study, we performed non-invasive prenatal genetic te...

BACKGROUND Neonatal diabetes has not been previously studied in Ukraine. We investigated the genetic etiology in patients with onset of diabetes during the first 9 months of life. METHODS We established a Pediatric Diabetes Register to identify patients diagnosed with diabetes before 9 months of age. Genetic testing was undertaken for 42 patients with permanent or transient diabetes diagnosed ...

BACKGROUND Isolated hyperinsulinaemic hypoglycaemia (HH) commonly results from recessively inherited mutations in the ABCC8 and KCNJ11 genes that are located on chromosome 11p15.1. More rarely, HH can feature in patients with Beckwith-Wiedemann syndrome (BWS), a congenital overgrowth disorder, resulting from defects at a differentially methylated region telomeric to the K-ATP channel genes at c...

It has been proposed that type 1 and 2 diabetes might share common pathophysiological pathways and, to some extent, genetic background. However, to date there has been no convincing data to establish a molecular genetic link between them. We have genotyped three single nucleotide polymorphisms associated with type 2 diabetes in a large type 1 diabetic family collection of European descent: Gly9...

BACKGROUND Children with neonatal diabetes often present with diabetic ketoacidosis and hence are at risk of cerebral oedema and subsequent long-term neurological deficits. These complications are difficult to identify because neurological features can also occur as a result of the specific genetic aetiology causing neonatal diabetes. CASE REPORTS We report two cases of neonatal diabetes wher...