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OBJECTIVETo describe the diabetes phenotype in Wolfram syndrome compared with type 1 diabetes, to investigate the effect of glycemic control on the neurodegenerative process, and to assess the genotype-phenotype correlation.RESEARCH DESIGN AND METHODSThe clinical data of 50 patients with Wolfram syndrome-related diabetes (WSD) were reviewed and compared with the data of 24,164 patients with type 1 diabetes. Patients with a mean HbA1c during childhood and adolescence of ≤7.5 and >7.5% were compared with respect to the occurrence of additional Wolfram syndrome symptoms. The wolframin (WFS1) gene was screened for mutations in 39 patients. WFS1 genotypes were examined for correlation with age at onset of diabetes.RESULTSWSD was diagnosed earlier than type 1 diabetes (5.4 ± 3.8 vs. 7.9 ± 4.2 years; P < 0.001) with a lower prevalence of ketoacidosis (7 vs. 20%; P = 0.049). Mean duration of remission in WSD was 2.3 ± 2.4 vs. 1.6 ± 2.1 in type 1 diabetes (NS). Severe hypoglycemia occurred in 37 vs. 7.9% (P < 0.001). Neurologic disease progression was faster in the WSD group with a mean HbA1c >7.5% (P = 0.031). Thirteen novel WSF1 mutations were identified. Predicted functional consequence of WFS1 mutations correlated with age at WSD onset (P = 0.028).CONCLUSIONSEndoplasmic reticulum stress–mediated decline of β-cells in WSD occurs earlier in life than autoimmune-mediated β-cell destruction in type 1 diabetes. This study establishes a role for WFS1 in determining the age at onset of diabetes in Wolfram syndrome and identifies glucose toxicity as an accelerating feature in the progression of disease.

Monogenic diabetes is highly prevalent in patients referred to Italian pediatric diabetes centers. A genetic diagnosis guided the therapeutic decisions, allowed the formulation of a prognosis regarding chronic diabetic complications for a relevant number of patients (i.e.,GCK/MODY), and helped to provide genetic counseling.

OBJECTIVE -We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes.RESEARCH DESIGN AND METHODS -Women in two unselected birth cohorts, one retrospective (n ϭ 3,158) and one prospective (n ϭ 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months.RESULTS -In the retrospective study, within the nondiabetic range (2.1-7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean Ϯ SEM) 2.1 Ϯ 0.8% (P ϭ 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 Ϯ 0.8% (P Ͻ 0.0001) rise in emergency cesarean delivery, a 3.1 Ϯ 0.7% (P Ͻ 0.0001) rise in elective cesarean delivery, and a 46 Ϯ 8 g (P Ͻ 0.0001) increase in offspring birth weight. In the prospective study, fetal macrosomia (birth weight Ͼ90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per ϩ1 mmol/l [95% CI 1.15-5.93]) and prepregnancy BMI (1.10 per ϩ1 kg/m 2 [1.04 -1.18]). The mother's higher fasting glycemia (P ϭ 0.004), lower insulin sensitivity (P ϭ 0.01), and lower insulin secretion (P ϭ 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P Ͻ 0.05).CONCLUSIONS -Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health.

Aim: To analyze the factors that might allow an early discrimination between permanent (P) and transient (T) congenital hypothyroidism (CH). Methods: Clinical, biochemical and imaging data of 64 children with eutopic gland, who were positively screened and treated for CH during the period 1998-2011, were retrospectively analyzed. Results: During a 3-year treatment period, the mean doses of L-thyroxine (L-T4) per kilogram of body weight at various times were significantly lower in the 46 children with T CH than in the remaining 18 with P CH. No patients with T CH had required any increment of the doses of L-T4 per kilogram of body weight to maintain normal thyroid-stimulating hormone levels over time, whereas 16/18 children with P CH during the same period had needed some dose increments (p < 0.0001). Conclusions: (a) L-T4 requirements >4.9 µg/kg/day at 12 months or >4.27 µg/kg/day at 24 months are highly suggestive of P CH, irrespective of gland ultrasonography; (b) L-T4 requirements <1.7 µg/kg/day at 12 months or <1.45 µg/kg/day at 24 months are highly suggestive of T CH, at least in the cases with eutopic gland, and (c) the analysis of L-T4 requirements during the first years of treatment might allow an early discrimination between T and P CH in the cases with eutopic gland.

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Aim of this commentary is to summarize the salient literature news on the relationships between autoimmune thyroid diseases (ATDs) and either Down syndrome (DS) or Turner syndrome (TS).According to literature reports both Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are more frequent in children with DS or TS than in those without these chromosomopathies.An up-regulation of proinflammatory cytokines might be responsible for the enhanced susceptibility of TS children to ATDs, whereas a dysregulation of immune system may favor the development of ATDs in DS.In TS children biochemical presentation of HT is less severe than in peer controls. In both DS and TS GD picture at the time of diagnosis is not significantly different than in the pediatric general population.The evolution over time of GD in DS and TS does not differ from that observed in the pediatric general population, whereas the evolution of HT in both TS and DS is more severe than in girls without these chromosomopathies.Conclusions: The association with TS or DS is able to affect both epidemiology and course of ATDs by conditioning: a) an increased susceptibility to these disorders; b) a less severe biochemical presentation and a more severe evolutive pattern of HT in TS girls; c) a more severe biochemical presentation and evolution of HT in DS patients.

Background: A crucial aspect of the 2019 coronavirus disease (COVID-19) pandemic was the psychological impact on the population. Most countries issued restrictive laws to reduce community-based viral spread. Children and adolescents were forced to experience physical and social distancing. Subjects with chronic diseases, such as type 1 diabetes, were more vulnerable and at higher risk of developing psychological disorders. Methods: We conducted a web-based survey to investigate the behavioral responses during quarantine due to the COVID-19 outbreak in a cohort of pediatric patients with type 1 diabetes. Data were collected on demographic and clinical characteristics, lifestyle changes, and the impact of COVID-19 on the management of diabetes. Results: Two hundred four pediatric patients (aged 5-18 years) with type 1 diabetes completed the questionnaire. Interestingly, patients ≤12 years were significantly more influenced by the quarantine period in their approach to the disease than older patients. Conclusion: Although quarantine was a stressful psychological condition, our results showed that most children and adolescents with type 1 diabetes developed high levels of resilience and excellent coping skills by using technology in a proper way.