Efficacy and safety of sirolimus therapy in familial hypoinsulinemic hypoglycemia caused by AKT2 mutation inherited from the mosaic father.

Activating mutation in the insulin signal-transducing kinase AKT2 results in severe hypoinsulinemic hypoketotic hypoglycemia and a characteristic phenotype of possible overgrowth and, sometimes, acanthosis nigricans. Herein, we describe a metabolic and hormonal profile before and during treatment with sirolimus in two brothers with AKT2 mutation inherited from the mosaic father, who showed low-level mosaicism in sperm. The boys, aged 1 and 14, who had severe non-insulin-dependent hypoketotic hypoglycemia and a typical dysmorphism, were admitted to endocrinology department for the analysis of their metabolic parameters: lipids, lactate, ammonia, glucose, insulin, c-peptide, and hormones (GH, IGF1, IGFBP3, TSH, fT4, cortisol, ACTH) before and during treatment with sirolimus. Previously, they had been treated with high-carbohydrate diet. The brothers were started on sirolimus with subsequent normalization of glycemia and reduced carbohydrate feedings overnight. The lowest fasting glucose levels improved from 20 mg/dl to 45 mg/dl in both sibs. The BMI of both brothers significantly dropped. After 6 months of sirolimus therapy we did not observe any laboratory or clinical side effects of the treatment.

Nutritional issues in a diabetic patient with Kearns-Sayre syndrome.

SUMMARY: Kearns-Sayre syndrome (KSS) is a multi-system mitochondrial disease with wide clinical presentation. We describe the case of a 16-year-old girl with KSS accompanied by insulin-dependent diabetes, eosinophilic esophagitis (EoE), Fanconi syndrome, insufficiency of parathyroid gland and severe nutritional problems. Based on recent knowledge, ketogenic diet was introduced to improve metabolic and neurological condition, however in our patient we observed its bad consequences. Unresolved nutritional disorders forced us to proceed with esophagogastroduodenoscopy which revealed EoE. PEG procedure was performed and elemental diet with PPI's was introduced leading to general improvement in the patient's health condition. LEARNING POINTS: Nutrition is an important factor in supportive care of patients with KSS. Ketogenic diet in patients affected by mitochondrial diseases and diabetes requires careful selection and monitoring. To the best of our knowledge, this is the first case that shows the coexistence of EoE, insulin-dependent diabetes and KSS.

Increased frequency of severe diabetic ketoacidosis at type 1 diabetes onset among children during COVID-19 pandemic lockdown: an observational cohort study.

INTRODUCTION: On March 11, 2020 the WHO announced a coronavirus disease 2019 (COVID-19) pandemic. Lockdown restrictions, compromised access to medical care and fear of potential exposure to SARS-CoV-2 have forced patients with non-COVID-19 illnesses such as type 1 diabetes (T1D) to stay home. This situation can lead to delay in T1D diagnosis and insulin treatment resulting in rapid progression to diabetic ketoacidosis (DKA) and therefore increased risk of complications and death.  . AIM: The aim of this study was to evaluate the frequency and severity of DKA at the onset of T1D in children diagnosed in our department during COVID-19 pandemic lockdown from March 2020 till May 2020 in comparison to corresponding period of the previous year. . MATERIAL AND METHODS: We collected data of children with newly diagnosed T1D. DKA was defined according to ISPAD guidelines. . RESULTS: The study cohort comprised 34 children in group 2020 and 52 in group 2019 with an average age 9.90 ±4.9 vs. 9.59±4.7 years with mean HbA1c 12.9 ±2.4 vs. 11.5 ±2.2%, respectively. The incidence of DKA was higher by 12% in group 2020 vs. 2019 (52.94% vs 40.38%; p = 0.276).  Regarding the DKA severity (2020 vs. 2019) 32.35% vs. 11.54% were severe (p = 0.026), 17.65 vs. 13% were moderate (p = 0.759), and 2.94 vs. 15.38% were mild (p = 0.081). None of the analyzed patients were COVID-19 positive. CONCLUSIONS: During the COVID-19 pandemic lockdown changes in society and health care system, the DKA rate has increased by 12 percentage points with more severe cases noted in children with newly diagnosed T1D. Regular education of the whole society about the symptoms of diabetes could contribute to faster diagnosis of T1D and reduction of DKA prevalence. .

Assessment of Exercise Capacity in Children with Type 1 Diabetes in the Cooper Running Test.

Regular physical activity increases lifespan for those with type 1 diabetes. However, disease-related barriers may deter children from exercise and affect their fitness. This study examined the safety of the Cooper test concerning diabetes-related acute complications in children with type 1 diabetes and their fitness. Blood glucose was recorded before and 0, 30, 60 min after the test. The covered distances were transformed to z-scores based on the national charts. Body mass index, body fat percentage and glycated hemoglobin were measured. The run was completed by 80 individuals (45% boys, age 13.6±2.1 years; diabetes duration 6.3±3.5 years). During the follow-up 11 children reached glucose alert values (3-3.9 mmol/L), 3 presented clinically significant hypoglycemia (<3 mmol/L), none experienced severe hypoglycemia. The covered distance was 1914±298 m, not significantly different from the reference population (z-score -0.12±0.71 vs 0, p=0.12). The study participants were more overweight than general pediatric population in terms of body mass index (z-score 0.48±0.94 vs 0, p<0.001) and body fat percentage (z-score: 0.37±0.85 vs 0, p<0.001). In conclusion, the Cooper test can be safely used in children with diabetes to assess their physical capacity. Youth with type 1 diabetes present fitness similar to healthy children but exhibit increased body mass index and adiposity.