We report a rare case of permanent neonatal diabetes (PND) due to insulin (INS) gene mutation in a 51-month-old girl who presented with hyperglycemia in the neonatal period.
Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood.
In this report we present a family with permanent neonatal diabetes, heterozygous for a novel INS gene missense mutation, p.A24V, manifested with marked hyperglycemia and ketoacidosis, unstable glycemic control, requiring insulin therapy, rapid progression of long-term complications and accompanying physical pathological signs and brain lesions.
We hope to emphasize instead the homogeneity of nephropathy risk in both IDDM and NIDDM and also the idea that a common genetic susceptibility exists for all types of diabetes and is conditional on cumulative exposure to hyperglycemia.
We studied 86 adult offspring (mean age 40 years), 49 born to glucokinase mothers (exposed to hyperglycaemia in utero) and 37 born to glucokinase fathers (controls).
Moreover, an additive effect of GCKR rs1260326(T) and GCK (-30G) alleles conferred lower fasting glycemia (P = 1 x 10(-13)), insulinemia (P = 5 x 10(-6)), and hyperglycemia risk (P = 1 x 10(-6)).
In pregnancies where the mother has hyperglycemia due to a GCK mutation, knowing the fetal GCK genotype guides the management of maternal hyperglycemia.
Functional studies of naturally occurring GCK mutations associated with hyperglycaemia provide further insight into the biochemical basis of glucose sensor regulation.
Mutants of glucokinase cause hypoglycaemia- and hyperglycaemia syndromes and their analysis illuminates fundamental quantitative concepts of glucose homeostasis.
We found that multiple cave populations carry a mutation in the insulin receptor that leads to decreased insulin binding in vitro and contributes to hyperglycaemia.
The principal objective of the current study is to determine the outcomes and clinical management of hyperglycemia in pregnancies complicated by glucokinase gene (GCK) and hepatocyte nuclear factor (HNF)-1α MODY mutations.
Mutations in glucokinase/MODY2 result in mild chronic hyperglycaemia due to reduced pancreatic beta-cell responsiveness to glucose as well as decreased net accumulation of hepatic glycogen and increased hepatic gluconeogenesis following meals.