In 25 of 28 patients with this type of hypoglycemia we found 1.5-8-fold elevated serum levels of immunoreactive big (15-25 kD), but decreased levels of normal IGF II.
There is now convincing evidence that some tumors secrete sufficient IGF-II to have systemic endocrine effects as recognized as nonislet cell tumor hypoglycemia.
Here, we report a family carrying the dominant heterozygous germ line E1506K mutation in ABCC8 associated with persistent hypoglycemia in the newborn period and diabetes in adulthood.
We postulated that the pathogenesis of her hypoglycemia involved production of IGF-II by her neuroblastoma, leading to GH suppression and an abnormally elevated ratio of IGF to IGF binding protein.
Mutations in both the Kir6.2 and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a disorder of pancreatic beta-cell function characterized by excess insulin secretion and hypoglycemia.
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.
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.
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.
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.
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.
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.
Covariate-adjusted indirect comparison using meta-regression analyses revealed that SGLT2i/INS achieved greater reduction in HbA<sub>1c</sub> [weighted mean difference (WMD) -0.24%, 95% confidence interval (CI) -0.43 to -0.05%], fasting plasma glucose (WMD -18.0 mg/dL, 95% CI -28.5 to -7.6 mg/dL) and body weight (WMD -2.38 kg, 95% CI -3.18 to -1.58 kg) from baseline than DPP4i/INS without increasing the risk of hypoglycaemia (relative risks 1.19, 95% CI 0.78 to 1.82).
Proinsulin levels remained within the normal range (suppressed with hypoglycemia) despite simultaneous almost unmeasurable C-peptide levels during hyperglycemia.
Inhibition of hepatic gluconeogenesis and enhanced glucose uptake contribute to the development of hypoglycemia in mice bearing interleukin-1beta- secreting tumor.
Tumor necrosis factor α (TNFα) expression oscillates across the host circadian cycle, and increased TNFα correlates with hypoglycemia and a higher frequency of non-replicative ring forms of trophozoites.
The ACTH responses to human corticotropin-releasing factor (CRF) or insulin-induced hypoglycemia were greater in G rats and tended to be smaller in R rats compared with those in the control rats, whereas the corticosterone response was similar.
Impaired blockade of insulin-like growth factor I (IGF-I)-induced hypoglycemia by IGF binding protein-3 analog with reduced ternary complex-forming ability.