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Permanent neonatal diabetes mellitus (PNDM) is a rare condition characterized by severe hyperglycemia constantly requiring insulin treatment from its onset. Complete deficiency of glucokinase (GCK) can cause PNDM; however, the genetic etiology is unknown in most PNDM patients. Recently, heterozygous activating mutations of KCNJ11, encoding Kir6.2, the pore forming subunit of the ATP-dependent potassium (KATP) channel of the pancreatic b-cell, were found in patients with PNDM. Closure of the KATP channel exerts a pivotal role in insulin secretion by modifying the resting membrane potential that leads to insulin exocytosis. We screened the KCNJ11 gene in 12 Italian patients with PNDM (onset within 3 months from birth) and in six patients with non-autoimmune, insulin-requiring diabetes diagnosed during the first year of life. Five different heterozygous mutations were identified: c.149G>C (p.R50P), c.175G>A (p.V59M), c.509A>G (p.K170R), c.510G>C (p.K170N), and c.601C>T (p.R201C) in eight patients with diabetes diagnosed between day 3 and 182. Mutations at Arg50 and Lys170 residues are novel. Four patients also presented with motor and/or developmental delay as previously reported. We conclude that KCNJ11 mutations are a common cause of PNDM either in isolation or associated with developmental delay. Permanent diabetes of non autoimmune origin can present up to 6 months from birth in individuals with KCNJ11 and EIF2AK3 mutations. Therefore, we suggest that the acronym PNDM be replaced with the more comprehensive permanent diabetes mellitus of infancy (PDMI), linking it to the gene product (e.g., GCK-PDMI, KCNJ11-PDMI) to avoid confusion between patients with early-onset, autoimmune type 1 diabetes. Hum Mutat 25:22–27, 2005. r 2004 Wiley-Liss, Inc.

OBJECTIVE: Excessive GH secretion may lead to secondary diabetes mellitus, while prolonged GH treatment may accelerate the onset of type 2 diabetes mellitus in predisposed individuals. Turner's syndrome (TS) patients are a population at risk since they have reduced glucose tolerance (GT) spontaneously and because they are usually treated with high doses of GH. DESIGN AND METHODS: The aim of the study was to evaluate insulin sensitivity (IS) and glucose tolerance (GT) in a group of TS patients treated with GH for a period of 6 years. Forty-seven TS girls were included in the study. GH was administered at a mean weekly dosage of 0.35 mg/kg, injected subcutaneously over 6-7 days. GT was assessed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. IS was evaluated with the quantitative insulin sensitivity check index (QUICK-I). RESULTS: No significant increase of impaired GT was observed in the patients during the follow-up period, while a reduced IS was detected. IS in TS patients was already lower than in prepubertal controls (P

SummaryObjective It is still not known whether fat mass excess could exert a positive effect on bone. The aim of our study was to evaluate bone strength and quality in a group of overweight and obese children and adolescents by assessing bone geometry at metacarpal bones and ultrasound at phalangeal level. Design and patients This is a cross sectional observational study performed in 123 subjects, aged 11·2 ± 2·9 years. Measurements Digitalized X-rays were evaluated at the level of the 2nd metacarpal bone for the determination of the outer (D) and inner (d) diameter, cortical area (CA), medullary endocortical area (EA), metacarpal index (MI) and bone strength (Bending Breaking Resistance Index; BBRI). A total of 98 subjects underwent amplitude dependent speed of sound (Ad-SOS) and bone transmission time (BTT) assessment by phalangeal ultrasonography. Results SDs for each measured parameter were as follows: Males: D = −0·71 ± 0·95, d = −0·29 ± 0·86, CA = −0·69 ± 0·69, EA = −0·32 ± 0·79, Ad-SOS = −1·14 ± 0·91, BTT = −1·17 ± 1·11 and BBRI (417 ± 151 vs 495 ± 174 mm3) were all significantly lower than in controls (P

Summary objective In adults, excessive GH secretion may lead to secondary diabetes mellitus, while prolonged GH treatment may accelerate the onset of type 2 diabetes mellitus in predisposed children. The aim of the study was to evaluate insulin sensitivity (IS) and glucose tolerance (GT) in a group of GH-deficient children treated with GH for a period of 6 years. patients and design One hundred and twenty-eight children (40 females, 88 males) were included in the study. At the beginning of treatment chronological age was 8·9 ± 3·2 years, height standard deviation score (SDS) −2·43 ± 0·90 and body mass index (BMI) SDS 0·18 ± 1·60. At the end of the study chronological age was 13·0 ± 2·9 years, height SDS −1·24 ± 1·27 and BMI SDS 0·23 ± 1·54. GH was administered at a mean weekly dosage of 0·3 mg/kg, injected subcutaneously over 6–7 days. GT was assessed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. IS was evaluated with the quantitative insulin sensitivity check index (QUICKI). results No cases of impaired GT or diabetes were recorded during the follow-up period. IS, already lower than in controls before starting treatment with GH, decreased significantly during the first year of therapy (QUICKI: 0·346 ± 0·033 vs. 0·355 ± 0·044, P