OBJECTIVETo determine the prevalence of residual β-cell function (RBF) in children after 3–6 years of type 1 diabetes, and to examine the association between RBF and incidence of severe hypoglycemia, glycemic control, and insulin requirements.RESEARCH DESIGN AND METHODSA total of 342 children (173 boys) 4.8–18.9 years of age with type 1 diabetes for 3–6 years were included. RBF was assessed by testing meal-stimulated C-peptide concentrations. Information regarding severe hypoglycemia within the past year, current HbA1c, and daily insulin requirements was retrieved from the medical records and through patient interviews.RESULTSNinety-two children (27%) had RBF >0.04 nmol/L. Patients with RBF <0.04 nmol/L were significantly more likely to have severe hypoglycemia than patients with RBF >0.04 nmol/L (odds ratio, 2.59; 95% CI, 1.10–7.08; P < 0.03). HbA1c was significantly higher in patients with RBF <0.04 nmol/L compared with patients with RBF >0.04 nmol/L (mean, 8.49 ± 0.08% [69.3 ± 0.9 mmol/mol] vs. 7.92 ± 0.13% [63.1 ± 1.4 mmol/mol]; P < 0.01), and insulin requirements were significantly lower in patients with RBF >0.2 nmol/L (mean ± SE: 1.07 ± 0.02 vs. 0.93 ± 0.07 units/kg/day; P < 0.04).CONCLUSIONSWe demonstrated considerable phenotypic diversity in RBF among children after 3–6 years of type 1 diabetes. Children with RBF are at lower risk for severe hypoglycemia, have better diabetes regulation, and have lower insulin requirements compared with children without RBF. There appears to be a lower limit for stimulated RBF of ∼0.04 nmol/L that confers a beneficial effect on hypoglycemia and metabolic control.

Objective: To describe three cases of Cushing's disease in children with multiple endocrine neoplasia type 1 (MEN1), as clinical manifestations of MEN1 are very rare in childhood. Design and methods: A retrospective review of three cases of Cushing's disease diagnosed between 1997 and 1999. Genetic screening for MEN1 gene mutation was performed in each patient. Results: An ACTH-secreting microadenoma was diagnosed in three children, aged 11 -13 years, presenting with growth retardation and weight gain over a period of 3-4 years. All patients had successful transsphenoidal adenomectomies. Primary hyperparathyroidism was subsequently diagnosed in two of the patients, and in the monozygotic twin of one of the patients. A new mutation in the MEN1 gene (Tyr351His) was identified in two of the patients and the affected members of their families. In the third patient a de novo MEN1 gene mutation (Leu444Pro) was found. Conclusions: MEN1 has to be considered in all children with tumours of the pituitary gland, and in those presenting with primary hyperparathyroidism. The children and their families should be advised to seek genetic counselling. We suggest that careful growth records be kept for children at risk of developing inherited MEN1 and, in the event of a decelerating growth rate, further diagnostic evaluation be undertaken with regards to ACTH-secreting pituitary tumours.European Journal of Endocrinology 151 709-715

Individuals with hypochondroplasia heterozygous for the Asn540Lys substitution are significantly more disproportionate than individuals without this mutation. Our study further confirms the clinical and genetic heterogeneity of hypochondroplasia.

Non-compliance in children receiving growth hormone (GH) treatment is often caused by pain on injection and difficulties in administration of GH. It has been suggested that automatic needle insertion diminishes pain perception. We quantitatively measured pain intensity on injection with two prototype pens for GH administration, providing either manual or automatic sc needle insertion, using a combined visual analogue/facial scale and a five-item scale in 18 children. With the automatic pen there was a significantly lower maximum pain score compared with the manual pen (median 28.5 versus 52.0 mm) as well as a lower mean pain score (mean 13.7 versus 23.5 mm). The five-item scale revealed that automatic needle insertion was significantly less painful than manual insertion and 13 patients chose to continue treatment with the automatic pen. In conclusion, pain during GH injection can be significantly diminished by automatic needle insertion, which may improve compliance in long-term GH treatment.

Intensifying treatment alone does not lead to improved metabolic control in the overall population despite the appearance of lower HbA1c in individuals with a greater number of self-monitored blood glucose measurements and injections/boluses. The contradictory results reflect difficulties in using observational studies to predict results of intervention in the individual. Data collected from population-based registries need to be adjusted continuously to reflect changes in care.