The diagnostic and prognostic power of the IDAA1c measure is kept but due to the higher Boost stimulation in the Danish cohort, the specificity of the formula is lower with the chosen limits for SCP (300 pmol/L) and IDAA1c ≤9, respectively.

We present the first clinical report of sibs with the multiple maternal hypomethylation syndrome. Both sisters presented with transient neonatal diabetes mellitus (TNDM). By methylation-specific PCR of bisulphite-treated DNA, we found a mosaic spectrum of hypomethylation at the following maternally methylated loci in both sibs:, and NESPAS (20q13). While the older sister has a milder phenotype, the younger one was severely ill and died at 11 months of age. Despite phenotypic differences, the sisters had several manifestations of both TNDM and BWS in common. The family is highly consanguineous, and the parents are first cousins. We suggest that the genetic defect in this family is a novel, most likely autosomal recessive defect of methylation mechanisms, either in the sisters or in their mother, affecting her oocyte imprinting. The recurrence with affected sibs as reported in this family has implications for genetic counselling.

Our study supports the recent in vitro data showing a stimulation of glucagon secretion by high glucose levels. Postprandial glucagon levels were not associated with HbA(1c), adjusted for insulin dose, during the first year after onset of childhood type 1 diabetes.

Objective: The ATP-dependent K C -channel (K ATP ) is critical for glucose sensing and normal glucagon and insulin secretion from pancreatic endocrine a-and b-cells. Gastrointestinal endocrine L-and Kcells are also glucose-sensing cells secreting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) respectively. The aims of this study were to 1) investigate the expression and co-localisation of the K ATP channel subunits, Kir6.2 and SUR1, in human L-and K-cells and 2) investigate if a common hyperactive variant of the Kir6.2 subunit, Glu23Lys, exerts a functional impact on glucose-sensing tissues in vivo that may affect the overall glycaemic control in children with new-onset type 1 diabetes. Design and methods: Western blot and immunohistochemical analyses were performed for expression and co-localisation studies. Meal-stimulated C-peptide test was carried out in 257 children at 1, 6 and 12 months after diagnosis. Genotyping for the Glu23Lys variant was by PCR-restriction fragment length polymorphism. Results: Kir6.2 and SUR1 co-localise with GLP-1 in L-cells and with GIP in K-cells in human ileum tissue. Children with type 1 diabetes carrying the hyperactive Glu23Lys variant had higher HbA 1C at diagnosis (coefficientZ0.61%, PZ0.02) and 1 month after initial insulin therapy (coefficientZ0.30%, PZ0.05), but later disappeared. However, when adjusting HbA 1C for the given dose of exogenous insulin, the dose-adjusted HbA 1C remained higher throughout the 12 month study period (coefficientZ0.42%, PZ0.03). Conclusions: Kir6.2 and SUR1 co-localise in the gastrointestinal endocrine L-and K-cells. The hyperactive Glu23Lys variant of the K ATP channel subunit Kir6.2 may cause defective glucose sensing in several tissues and impaired glycaemic control in children with type 1 diabetes.