We evaluated the long-term glycemic control in children with type 1 diabetes, using continuous subcutaneous insulin infusion (CSII) for at least 5 years in three diabetes centers from three different countries: Canada, Italy and Spain. This was an observational retrospective multicenter cohort study. Subjects were included if they were followed at one of the participating centers, had type 1 diabetes, age 5-20 years at time of data collection and used CSII for more than 5 years. Data collected included gender, age, disease duration, age at CSII initiation, body mass index (BMI), hemoglobin A1c (HbA1c), insulin requirement and serious adverse events (SAE) at baseline and every 12 months during follow-up. One hundred fifteen patients were included in the study (55% males), aged 5-20 years (mean: 13.5 ± 3.8 years), with mean diabetes duration of 6.3 ± 3.4 years, using CSII for mean of 6.9 ± 1.2 years (range 5-12 years.). HbA1c significantly improved after 1 year of CSII treatment and during follow-up (p = 0.02). When HbA1c was compared between countries, a difference was observed, with slightly lower values in Italy than in Canada and Spain (p = 0.04). When evaluated by gender, HbA1c was similar at baseline, but significantly improved only in males during all follow-up (p = 0.004). No significant differences were observed for BMI, insulin requirement or SAE. Insulin pump therapy is safe and effective in the pediatric population, although in this study, the major benefit in HbA1c was seen in males. The use of advanced pump features was associated with greater improvement in HbA1c.

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Context Heterozygous variants in the Indian hedgehog gene (IHH) have been reported to cause brachydactyly type A1 and mild hand and feet skeletal anomalies with short stature. Genetic screening in individuals with short stature and mild skeletal anomalies has been increasing over recent years, allowing us to broaden the clinical spectrum of skeletal dysplasias. Objective The objective of this article is to describe the genotype and phenotype of 16 probands with heterozygous variants in IHH. Patients and Methods Targeted next-generation sequencing or Sanger sequencing was performed in patients with short stature and/or brachydactyly for which the genetic cause was unknown. Results Fifteen different heterozygous IHH variants were detected, one of which is the first reported complete deletion of IHH. None of the patients showed the classical phenotype of brachydactyly type A1. The most frequently observed clinical characteristics were mild to moderate short stature as well as shortening of the middle phalanx on the fifth finger. The identified IHH variants were demonstrated to cosegregate with the short stature and/or brachydactyly in the 13 probands whose family members were available. However, clinical heterogeneity was observed: Two short-statured probands showed no hand radiological anomalies, whereas another 5 were of normal height but had brachydactyly. Conclusions Short stature and/or mild skeletal hand defects can be caused by IHH variants. Defects in this gene should be considered in individuals with these findings, especially when there is an autosomal dominant pattern of inheritance. Although no genotype-phenotype correlation was observed, cosegregation studies should be performed and where possible functional characterization before concluding that a variant is causative.

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Generalized congenital lipodystrophy or Berardinelli-Seip Syndrome is a rare autosomal recessive condition characterized by the absence of adipose tissue and eventually a defect in leptin synthesis. Affected subjects tend to show a classical phenotype with acromegaloid appearance, generalized atrophy of subcutaneous adipose tissue with muscular hypertrophy, acanthosis nigricans, hepatomegaly and prominent abdomen. From metabolic point of view and as a consequence of leptin absence, hypertriglyceridemia leading to hepatic steatosis and insulin resistance may appear. Two cases of unrelated subjects affected of generalized congenital lipodystrophy are presented. Both developed difficult-to-manage diabetes mellitus and were treated with high doses of insulin. In both cases early microvascular complications were present. A mutation for LMNA gene was found in one of the subjects.

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