In HNF4A-MODY and HNF1A-MODY patients, normal or even increased insulin sensitivity together with glucose-independent mechanism of action of the first-line therapy - sulphonylurea derivatives - often leads to hypoglycemia, even at the much lower dose used in type 2 diabetes.
Neonatal hypoglycemia is generally observed in MODY 1 infants, but it is possible to hypothesize that some HNF-1α mutations could lead to a functionally impaired protein that might dysregulate HNF-4α expression determining hypoglycemia.
Of note, 40% of people with HNF1A-MODY and medical treatment were receiving insulin alone and thus were not being treated in line with up-to-date International Society for Pediatric and Adolescent Diabetes/International Diabetes Federation guidelines, despite insulin treatment being associated with worse metabolic control and the risk of hypoglycaemia.
The observation of fetal macrosomia and hypoglycemia in childhood is suggestive of a biphasic impact of the HNF1A mutation on beta-cell function over the lifespan, leading from inappropriate insulin oversecretion to final clinical diabetes.
The observation of fetal macrosomia and hypoglycemia in childhood is indicative of a biphasic impact of the HNF1A mutation on p-cell function over the lifespan, leading from inappropriate insulin oversecretion to final clinical diabetes.
Diabetic subjects with mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha (MODY3) are prone to develop hypoglycaemia at low doses of glibenclamide, interpreted as sulphonylurea hypersensitivity.
Diabetic subjects with mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha (MODY3) are prone to develop hypoglycaemia at low doses of glibenclamide, interpreted as sulphonylurea hypersensitivity.
These data indicate that mutations of HNF-1alpha in MODY3 do not result in a decreased glucagon secretion or alterations of glucose production during hypoglycemia.