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There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using “smart pumps” or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose

Many people with diabetes insipidus may have a brain abnormality or a pituitary hormone deficiency, according to a study of 79 patients. Diabetes insipidus is a form of diabetes caused by a deficiency of arginine vasopressin.

Aim: To test the hypothesis that intensive insulin treatment and optimal glycaemic control are not fully protective against reduction of insulin sensitivity in children with type 1 diabetes. Material and methods: Cohort study of 78 normal‐weight patients with prepubertal onset (T0) and follow‐up waves at 1 (T1), 5 (T5), 10 (T10), and 12 (T12) years; matched for age and sex to 30 controls at T12. Estimated insulin sensitivity (eIS) by three formulae; ultrasound evaluation of para and perirenal fat thickness; hepatic steatosis (HS); carotid intima media thickness (cIMT) at T12. Results: At T12, the 36 patients (46%) who had constantly or prevalently haemoglobin A1c (HbA1c) < 58 mmol/l during follow‐up showed better eIS indexes (p = 0.049 to <0.0001); lipid profile (p = 0.042 to <0.0001), reduced fat mass (p = 0.012) and required lower insulin dose (p = 0.032) than the 42 patients (54%) with HbA1c ≥ 58 at T12. Patients (N = 25) with eISEDC < 8.77 mg kg−1 min−1 showed higher cIMT (p < 0.0001). HS was found in 6 patients (∼8%). In patients and normal‐weight controls, fat mass (p = 0.03), age (p = 0.03), cIMT (p = 0.05) predicted HS; eIS indexes (p from 0.04 to <0.0001) predicted cIMT. Body mass index, perirenal fat, fat mass, and triglycerides to high density lipoprotein cholesterol ratio were associated with eIS indexes (p from 0.03 to <0.0001). Conclusions: Young T1D patients have reduced insulin sensitivity and higher cIMT. Adiposity, glucose, and lipid control over follow‐up are likely to influence both. Enhanced adiposity seems of paramount relevance for the onset of HS in T1D patients alike in healthy youths. [ABSTRACT FROM AUTHOR]

We investigated whether the PTPN22 C1858T polymorphism is associated with the autoimmune conditions present in the family of a child affected by type 1 diabetes ( T1D) carrying the TT genotype (index patient) and the potential immunological effect of the variant. We found that nine family members carried the CT genotype and five suffered from autoimmunity. Interestingly, anti- ZnT8 antibodies were detected in T1D patients and in three healthy relatives. In the TT patient, we showed diminished T-cell proliferation and reduced interleukin-2 ( IL-2) and interferon-gamma (IFN-γ) production. A marked reduction of IL-2 was also observed for all CT relatives with autoimmunity and a lack of IFN-γ production was observed for the younger brother of the index patient, heterozygous for the polymorphism. In this family, the C1858T variant might confer a high risk of autoimmunity. Moreover, our data confirm that impaired IL-2 production upon T-cell receptor stimulation is associated with autoimmunity in the carriers of the polymorphism. This study might prompt to extend the panel of risk markers in relatives of subjects affected by T1D. [ABSTRACT FROM AUTHOR]

Aim: To investigate the role of protein tyrosin phosphatase 22 (PTPN22), maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes (T1D) in Continental Italy and Sardinian populations., Methods: Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032 healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia. PTPN22 genotype was determined by DNA analysis. Maternal age at conception and age at onset of disease were obtained from clinical records. χ(2) test of independence, student t test for differences between means and odds ratio analysis were carried out by SPSS programs. Three way contingency table analysis was carried out according to Sokal and Rohlf., Results: The pattern of association between PTPN22 and T1D is similar in Continental Italy and Sardinia: the proportion of *T allele carriers is 13.6% in T1D vs 6.7% in controls in Continental Italy while in Sardinia is 7.3% in T1D vs 4.4% in controls. The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy: the proportion of newborn from mother aging more than 32 years is 89.3% in T1D vs 32.7% in consecutive newborn in Sardinia (P < 10(-6)) while in Continental Italy is 32.2% in T1D vs 19.1% in consecutive newborns (P = 0.005). This points to an important role of ethnicity. A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia. PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia. Maternal age does not influence significantly age at onset in Italy (8.2 years in T1D infants from mothers aging 32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years: P = 0.824) while in Sardinia a border line effect is observed (5.75 years in T1D infants from mothers aging 32 years or less vs 7.54 years in T1D infants from mothers aging more than 32 years: P = 0.062). No effect of sex on age at onset is observed in Continental Italy while in Sardinia female show a lower age at onset of T1D as compared to males (8.07 years in males vs 6.3 years in females: P = 0.002)., Conclusion: The present data confirm the importance of ethnicity on susceptibility and on the age at onset of T1D.

Background: ACP1 (acid phosphatase locus 1, a cytosolic low-molecular-weight phosphotyrosin phosphatase) and ADA1 (adenosine deaminase locus 1) are two polymorphic systems involved in immune reactions. Observed interactions at the biochemical and clinical levels between the two systems prompted this investigation of a possible interaction concerning susceptibility to type 1 diabetes., Material/methods: Two hundred eighty-seven children admitted consecutively to the hospital for type 1 diabetes and 727 healthy newborn infants were studied. All were from the Caucasian Italian population living in the central area of Italy. ACP1 and ADA1 genotypes were determined by DNA analysis., Results: In the type 1 diabetics the distribution of ACP1 genotypes was dependent on the ADA1 genotypes, showing an excess of the low-activity *A/*A and *A/*B genotypes in the ADA1*2 carriers compared with the ADA1*1/*1 subjects (OR: 2.200, 95%CI: 1.133-4.298). Such an association was not present in the healthy newborn infants., Conclusions: This investigation based on the biological effects of ACP1 and ADA1 on the immune system and on the known biochemical interaction between the two systems showed a significant interaction between the two system concerning susceptibility to type 1 diabetes. The low-activity ACP1 genotypes *A/*A and *A/*B carrying the low-activity ADA1*2 allele were more common in type 1 diabetic than in healthy newborns (OR: 1.699 95%CI: 1.066-2.702).

Introduction: Prevention of childhood obesity and of its complications is an increasingly important public health priority. During 2002-2003 a network of family paediatricians working in the territory of a local health organisation in Rome (Italy) was created, in order to evaluate the health status of obese children. A preferential diagnostic and therapeutic management workup procedure was then developed for these patients at the Paediatrics department of the "Policlinico Tor Vergata" (PTV) university teaching hospital in Rome (Italy)., Methods: Family paediatricians invited children aged 6-14 years with a body mass index (BMI) above the 95th percentile, to a clinical consultation at PTV where each child then underwent a clinical evaluation (including blood pressure measurement and evaluation of family history of cardiovascular disease and type 2 diabetes mellitus) and laboratory testing (including oral glucose tolerance testing-OGTT, measurement of cholesterol and trygliceride levels). The BMI z score and insulin resistance index (HOMA-IR) were also calculated and pubertal stage was assessed., Results: Overall, 168 children, with a mean age of 11 years, were evaluated; 53% were males. The mean BMI z score was 2.43+/-0.45. Forty-four percent of children were found to be hypertensive and 28.3% had a positive family history for type 2 diabetes mellitus. Fifteen children (9%) were found to have Impaired Glucose Tolerance (IGT) while one child was frankly diabetic. Thirty-six children (23.4%) were diagnosed with a metabolic syndrome (MS). Systolic blood pressure was significantly correlated with BMI z score and with 2 hour glucose levels. Obese children with either hypertension or a family history of diabetes were significantly more likely to have glucose intolerance or metabolic syndrome (GI, OR= 4.7 ; MS, OR= 6.8), Conclusions: A high percentage of obese children and adolescents develop metabolic complications. The percentage of children with such complications is greater when other risk factors such as hypertension and family history of type 2 diabetes are present. Family paediatricians play a fundamental role in the prevention, evaluation and treatment of child obesity. This study underscores the importance of performing routine evaluations of BMI and blood pressure in children aged 6-14 years, eventually by extending well-child visits to this age group.