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Objectives We aimed to characterize the effects of COVID-19 Pandemic on 2-h glucose values after an OGTT postulating a correlation between 2-h glucose spectrum and the decline of β-cell function. Particularly, we tried to evaluate the effects on the risk of showing 2-h glucose values in the highest range of normal values in obese children and adolescent during COVID-19 Pandemic compared to those evaluated during the 13 years before. Subjects/Methods Data from 532 obese and overweight children and adolescents (before COVID-19 Pandemic, 209M/262F, 2008–2019; during COVID-19 Pandemic, 40M/21F, 2020–2021) who had undergone a complete evaluation and had performed an OGTT after their first visit were analyzed. The two groups were further divided into three sub-groups based on the 2-h glucose values, group 1 (Results A significant difference (P = 0.01) in terms of distribution of the prevalence of 2-h glucose values was documented between the group before COVID-19 (35.6%, 45.9% and 18.5%) and the group during COVID-19 Pandemic period (31.1%, 31.1% and 37.8%). A roughly doble higher prevalence of subjects with pre-IGT was documented in the COVID-19 group. In addition, group 3 of COVID-19 time showed significantly higher values for waist circumference (WC), Waist/Height ratio (WtHR), fasting glucose, HOMA-IR, and AUC Insulin, compared to the group 3 of the period before COVID-19 Pandemic (all P Conclusions During COVID-19 time a higher percentage of children are in the highest range of normal 2-h glucose values which is known to be associated with a significant impairment of β-cell function relative to insulin sensitivity and at higher risk of developing IGT.

Objective Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design Retrospective analysis of the Italian data set of patients with TNDM. Methods Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.

Objective: To investigate whether center differences in glycemic control are present in prepubertal children Research Design and Methods: This cross-sectional study involved 18 pediatric centers worldwide. All children, Results: A total of 1133 children participated (mean age: 8.0 +/- 2.1 y; females: 47.5%, mean diabetes duration: 3.8 +/- 2.1 y). HbA1c (overall mean: 8.0 +/- 1.0%; range: 7.3-8.9%) and severe hypoglycemia frequency (mean 21.7 events per 100 patient-years), but not DKA, differed significantly between centers (p Conclusions: Center differences in metabolic outcomes are present in children

Context: The steroidogenic acute regulatory protein (StAR) has been shown to be essential for steroidogenesis by mediating cholesterol transfer into mitochondria. Inactivating StAR mutations cause the typical clinical picture of congenital lipoid adrenal hyperplasia.Objective: The objective of the investigation was to study the functional and structural consequences of three novel StAR mutations (p.N148K in an Italian patient; p.P129fs and p.Q128R in a Turkish patient).Methods and Results: Transient in vitro expression of the mutant proteins together with P450 side-chain cleavage enzyme, adrenodoxin, and adrenodoxin reductase yielded severely diminished cholesterol conversion of the p.N148K mutant, the combined p.P129fs and p.Q128R mutant, and the p.P129fs mutant by itself. The p.Q128R mutant led to a higher cholesterol conversion than the wild-type StAR protein. As derived from three-dimensional protein modeling, the residue N148 is lining the ligand cavity of StAR. A positively charged lysine residue at position 148 disturbs the hydrophobic cluster formed by the α4-helix and the sterol binding pocket. The frame shift mutation p.P129fs truncates the StAR protein. Residue p.Q128 is situated at the surface of the molecule and is not part of any functionally characterized region of the protein.Conclusion: The mutations p.N148K and p.P129fs cause adrenal insufficiency in both cases and lead to a disorder of sex development with complete sex reversal in the 46, XY case. The mutation p.Q128R, which is not relevant for the patient’s phenotype, is the first reported variant showing a gain of function. We speculate that the substitution of hydrophilic glutamine with basic arginine at the surface of the molecule may accelerate cholesterol transfer.

To investigate whether center differences in glycemic control are present in prepubertal children11 yr with type 1 diabetes mellitus.This cross-sectional study involved 18 pediatric centers worldwide. All children,11 y with a diabetes duration ≥12 months were invited to participate. Case Record Forms included information on clinical characteristics, insulin regimens, diabetic ketoacidosis (DKA), severe hypoglycemia, language difficulties, and comorbidities. Hemoglobin A1c (HbA1c) was measured centrally by liquid chromatography (DCCT aligned, range: 4.4-6.3%; IFFC: 25-45 mmol/mol).A total of 1133 children participated (mean age: 8.0 ± 2.1 y; females: 47.5%, mean diabetes duration: 3.8 ± 2.1 y). HbA1c (overall mean: 8.0 ± 1.0%; range: 7.3-8.9%) and severe hypoglycemia frequency (mean 21.7 events per 100 patient-years), but not DKA, differed significantly between centers (p 0.001 resp. p = 0.179). Language difficulties showed a negative relationship with HbA1c (8.3 ± 1.2% vs. 8.0 ± 1.0%; p = 0.036). Frequency of blood glucose monitoring demonstrated a significant but weak association with HbA1c (r = -0.17; p 0.0001). Although significant different HbA1c levels were obtained with diverse insulin regimens (range: 7.3-8.5%; p 0.001), center differences remained after adjusting for insulin regimen (p 0.001). Differences between insulin regimens were no longer significant after adjusting for center effect (p = 0.199).Center differences in metabolic outcomes are present in children11 yr, irrespective of diabetes duration, age, or gender. The incidence of severe hypoglycemia is lower than in adolescents despite achieving better glycemic control. Insulin regimens show a significant relationship with HbA1c but do not explain center differences. Each center's effectiveness in using specific treatment strategies remains the key factor for outcome.