OBJECTIVE: Insulin release from the pancreatic beta-cells is controlled by ATP-sensitive K(+) (K(ATP)) channels, which consist of a hetero-octameric complex of four sulfonylurea receptor 1 (SUR1) and four Kir6.2 proteins. Mutations in the SUR1 gene are the major cause of congenital hyperinsulinemia (CHI). Despite the hereditary nature of CHI, studies of glucose homeostasis in heterozygous relatives of CHI patients are lacking. Theoretically, in the heterozygous state of the SUR1 gene mutation, only 1 of 16 K(ATP) channels consists of entirely normal subunits. The aim of our study was to investigate in vivo the glucose homeostasis of heterozygous SUR1 mutation carriers. RESEARCH DESIGN AND METHODS: We studied 8 parents of CHI patients, all 8 of whom were heterozygous for the inactivating SUR1 mutation V187D, and 10 matched control subjects. We evaluated glucose tolerance and insulin secretory capacity with oral and intravenous glucose tests, rates of whole-body glucose uptake with hyperinsulinemic-euglycemic clamps, C-peptide response to hypoglycemia during hyperinsulinemic-hypoglycemic clamp, and function of the K(ATP) channels with intravenous tolbutamide test. RESULTS: Carriers of the V187D substitution had normal glucose tolerance, normal tissue sensitivity to insulin, and no signs of inappropriate insulin secretion. The normal insulin response to tolbutamide indicated that heterozygosity for the V187D mutation did not impair K(ATP) channel function. CONCLUSIONS: We conclude that the heterozygous carriers of the SUR1 mutation had normal glucose metabolism and insulin secretion, indicating that carriers of recessive K(ATP) channel mutations are unlikely to be at an increased risk of hypoglycemia or other disturbances in glucose metabolism.

ATP-Binding Cassette Transporters↗

PubMedDate not supplied

Continuous subcutaneous insulin infusion in the treatment of children and adolescents with type 1 diabetes mellitus.

Continuous subcutaneous insulin infusion (CSII) with a portable insulin pump has been used for several years in the treatment of adult patients with diabetes mellitus (DM). This treatment, however, has rarely been utilised in children and adolescents. We studied the use of CSII in 16 children and adolescents with type 1 DM at Tampere and Kuopio University Hospitals between 1992 and 1997. The longest treatment periods are more than 4 years. The reasons for switching to CSII treatment and the goals achieved were evaluated. Glycaemic control before and during CSII treatment and the occurrence of hypoglycaemia and ketoacidosis were analysed. Compared with conventional insulin treatment, improved glycaemic control and a reduced frequency of hypoglycaemic events were achieved with CSII in those with particularly poor initial metabolic control (HbA1c >10.0%). The overall satisfaction with pump therapy was high in both patients and their families. According to our experience, CSII may be of benefit, especially in young infants with type 1 DM, but also in affected adolescents with unacceptable glycaemic control.

Adolescent↗