Impaired insulin secretion and increased insulin sensitivity in familial maturity-onset diabetes of the young 4 (insulin promoter factor 1 gene).

Diabetes resulting from heterozygosity for an inactivating mutation of the homeodomain transcription factor insulin promoter factor 1 (IPF-1) is due to a genetic defect of beta-cell function referred to as maturity-onset diabetes of the young 4. IPF-1 is required for the development of the pancreas and mediates glucose-responsive stimulation of insulin gene transcription. To quantitate islet cell responses in a family harboring a Pro63fsdelC mutation in IPF-1, we performed a five-step (1-h intervals) hyperglycemic clamp on seven heterozygous members (NM) and eight normal genotype members (NN). During the last 30 min of the fifth glucose step, glucagon-like peptide 1 (GLP-1) was also infused (1.5 pmol x kg(-1) x min(-1)). Fasting plasma glucose levels were greater in the NM group than in the NN group (9.2 vs. 5.9 mmol/l, respectively; P < 0.05). Fasting insulin levels were similar in both groups (72 vs. 105 pmol/l for NN vs. NM, respectively). First-phase insulin and C-peptide responses were absent in individuals in the NM group, who had markedly attenuated insulin responses to glucose alone compared with the NN group. At a glucose level of 16.8 mmol/l above fasting level, GLP-1 augmented insulin secretion equivalently (fold increase) in both groups, but the insulin and C-peptide responses to GLP-1 were sevenfold less in the NM subjects than in the NN subjects. In both groups, glucagon levels fell during each glycemic plateau, and a further reduction occurred during the GLP-1 infusion. Sigmoidal dose-response curves of glucose clearance versus insulin levels during the hyperglycemic clamp in the two small groups showed both a left shift and a lower maximal response in the NM group compared with the NN group, which is consistent with an increased insulin sensitivity in the NM subjects. A sharp decline occurred in the dose-response curve for suppression of nonesterified fatty acids versus insulin levels in the NM group. We conclude that the Pro63fsdelC IPF-1 mutation is associated with a severe impairment of beta-cell sensitivity to glucose and an apparent increase in peripheral tissue sensitivity to insulin and is a genetically determined cause of beta-cell dysfunction.

Ingestion of a unilateral removable partial denture causing serious complications.

A case of ingestion of a unilateral removable partial denture is presented. Routine endoscopic retrieval was unsuccessful, and the patient required surgical removal of the prosthesis. Subsequent hospitalization, complications, and recovery from an apparently simple accident are discussed.