Insulin resistance relates to DKA severity and affects insulin requirement in children with type 1 diabetes at onset.

BACKGROUND: Fluid and insulin treatments are the cornerstones of DKA management and indications on dosages are available. However, according to possible confounding factors, relevant data are still required to explain the different insulin dosages adopted at diabetes onset, particularly based upon insulin sensitivity. OBJECTIVE: We aimed to explore whether DKA severity is related to different insulin sensitivity states, thus resulting in different insulin requirement at diabetes onset. METHODS: Retrospective data from hospital records of 62 newly diagnosed children with type 1 diabetes with DKA were analyzed. The population was divided into three groups: severe, moderate, and mild DKA. Anthropometric, laboratory test, insulin, and glucose administration data were analyzed. The Glucose Infusion Rate (GIR), Insulin Infusion Rate (IIR), and GIR/IIR were calculated and used as indexes of insulin sensitivity. The area under the curve (AUC) for insulin and glucose infusion was calculated. RESULTS: Moving among the three groups, IIR decreased while GIR and GIR/IIR increased from severe to mild DKA group (all p < 0.01). A similar trend was documented for AUC-insulin and AUC-glucose as well as AUC-glucose/AUC-insulin ratio. The Spearman correlation showed a negative correlation between pH and both IIR and AUC-Insulin as well as a positive correlation between pH and both GIR/IIR and AUC-glucose/AUC-insulin ratio. CONCLUSIONS: Subjects with severe DKA have a higher insulin requirement compared to those with less severe DKA. Significant differences in terms of insulin sensitivity might be documented according to the severity of DKA, which might result in tailored insulin pH requirement in children with new onset type 1 diabetes.

Feeding Twins with Human Milk and Factors Associated with Its Duration: A Qualitative and Quantitative Study in Southern Italy.

BACKGROUND: Over the past year, there has been a rise in twin births. The current scientific consensus recommended breast-feed milk for all newborns for at least 6 months. They stated that it is possible to meet the nutritional needs of two or more newborns with only one mother's milk. More information would be desirable about the factors that influence or lead to the initiation and interruption of breastfeeding. The quality of the evidence available from multiple studies has been inconclusive and therefore led to controversial interpretations and practices. AIMS: The first aim of this study was to analyze the extent of the feeding of multiples with breast milk in the experience of our clinical unit in terms of incidence and duration. The second objective was to evaluate the correlation between maternal, perinatal and neonatal variables with breast milk feeding rates and duration. METHODS: The study was conducted between 2015 and 2020, in a NICU in Southern Italy (San Giovanni Rotondo, Foggia). Sixty-one women who have given birth to multiples were enrolled into the study. Newborn data were retrospectively collected by informatic database and breastfeeding information were collected by a questionnaire. RESULTS: In our centre, the percentage of twins out of the total number of births over the years has almost doubled from 1.28% in 2015 to 2.48% in 2020 and the 88% of twins are premature. 18.1% received breast milk for more than 6 months and 6.3% received it for more than 12 months. Infants of lower gestational age and weight, born to multiparous, more mature and medium-high schooling mothers received breast milk for a longer period. 35% of women explained that the interruption of breastfeeding was due to the insufficient milk production and 41% to the stress and difficulties in managing the twins. Qualitative analysis of maternal narrative revealed, for many of them, the awareness of the importance of breastfeeding and the efforts made to try to give breast milk, but also fears about the quantity of milk and satiety of their children. CONCLUSIONS: It is important to identify the factors both favoring and obstructing maternal milk feeding of multiples and it would be desirable the activation of a network of training and support for mothers after discharge, with particular regard to the categories found to be less inclined.

Hyperglycaemic hyperosmolar state in an obese prepubertal girl with type 2 diabetes: case report and critical approach to diagnosis and therapy.

INTRODUCTION: Isolated Hyperosmolar Hyperglycaemic Syndrome (HHS) is a life-threatening condition characterized by elevated serum glucose concentrations and hyperosmolality without significant ketosis. It is often described in obese adults with unknown Type 2 Diabetes (T2D), rarely in youth. In childhood the most common cause of metabolic glucose related derangement is Diabetic Ketoacidosis (DKA) in Type 1 Diabetes (T1D). Interestingly, both components can be combined with each other, thus the prevalent condition needs to be recognised implying a different therapeutic approach. CASE PRESENTATION: In this case, we report a prepubertal Caucasian obese girl admitted for two episodes of combined HHS/DKA in order to elucidate her clinical course taking into account the current pediatric recommendations based on adult guidelines for HHS. CONCLUSIONS: The treatment of HHS and even more of HHS/DKA in youth is still controversial as no specific guidelines for children are available especially during the prepubertal age. The description of our case might be helpful and offer relevant points for future consensus.

Role of the KCNJ Gene Variants in the Clinical Outcome of Type 1 Diabetes.

Diabetes is considered as a disease with a wide and continuous clinical spectrum, ranging from Type 1 (T1D) and Type 2 Diabetes (T2D) with complex multifactorial causes. In the last years, particular attention has been focused on the predictive value and therapeutic potential of single nucleotide polymorphisms (SNPs). SNPs can alter the seed-sequence in miRNA's loci and miRNA target sites causing changes in the structure and influencing the binding function. Only few studies have investigated the clinical influence of SNPs, in particular potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ) gene variants in T1D population. The aim of the study is to investigate the occurrence and the possible metabolic significance of KCNJ polymorphism in a group of pediatric patients with T1D. The study was performed in a cohort of 90 Caucasian children and adolescents with T1D and 93 healthy subjects. Rs5210 polymorphism has been analyzed with a prevalence of the GG genotype in the patient group suggesting its association with T1D. Therefore, a relationship was found between GG genotype and body mass index (BMI) at diagnosis and insulin requirement (IR) after 6 months. The study suggested an action for rs5210 in determining the metabolic features of T1D pediatric patients, by showing some clues of insulin resistance in patients carrying that polymorphism.

Insulin/carbohydrates ratio during the first 6-month therapy with insulin degludec in a paediatric population with type 1 diabetes previously treated with insulin glargine. An observational longitudinal study.

BACKGROUND: No data exist about the changes induced by the transition from first-generation long-acting insulins to second-generation long-acting analogues in the paediatric population. OBJECTIVE: To assess changes in insulin/carbohydrate ratio (I:CHO) after the first 6 months of degludec therapy in a paediatric population with type 1 diabetes previously treated with glargine U100. SUBJECTS: All patients treated with degludec under routine clinical practice conditions were retrospectively analysed. METHODS: Nonprofit observational retrospective study. Changes during the follow-up in mean CHO/I ratio were assessed using longitudinal linear models for repeated measures. Rate of hypoglycaemia, ketoacidosis and adverse events was evaluated. RESULTS: Overall, 51 children (mean age 13.8 ± 4.6 years; mean diabetes duration 5.8 ± 3.9 years) started therapy with degludec in the period between April 2017 and April 2018. I:CHO ratio before starting degludec therapy significantly differed among the three meals, being the lowest at breakfast and the highest at dinner. After introducing degludec, I:CHO ratio at lunch (-1.29 95% CI -2.02;-0.57) and at dinner (-3.08 95% CI -4.35;-1.8) significantly decreased, while it slightly increased at breakfast (+1.37 95% CI 0.47;2.28). No episodes of severe hypoglycaemia, ketoacidosis and adverse event were recorded during 6 months. CONCLUSIONS: Our data show that the use of degludec is associated with a significant change in the I:CHO ratio at the different meals compared to the previous glargine therapy. This could derive from the flat and prolonged pharmacokinetic profile of degludec. This has important clinical implications for daily insulin dose adjustments.

Effectiveness and safety of flexible therapeutic schemes including first- and secondgeneration basal insulins during a pediatric summer diabetes camp.

Outcomes of insulin analogues in pediatric diabetes camps are poorly investigated; no data is available about insulin degludec (IDeg).Our aim was to assess impact of insulin therapy adopted by the participants to a 4-day diabetes camp held in 2017, hypothesizing a possible excess risk of hypoglycemia in patients treated with IDeg. Overall, 40 children with type 1 diabetes (mean age 13.4±3.0 years; 62.5% males) attended the camp (20.0% on continuous subcutaneous insulin infusion and 80.0% on multiple daily injections - MDI). Among children in MDI regimen, 71.9% were treated with IDeg as basal insulin and 28.1% with glargine U100 (IGlar). All patients used Lispro or Aspart as short-acting insulin. Daily plan of the camp included educational sessions, physical exercise, 3 main meals and 2 snacks. At the arrival, IGlar and short-acting insulin doses were revised according to existing guidelines, while IDeg dose was revised based on an empirical individualized approach. At the arrival, insulin doses were reduced in 22 participants (-19.4±10.5%), while doses were increased in 17 children (+17.8±12.7%), based on individual needs. No statistically significant between-group difference emerged in mean blood glucose and glucose variability. No excess risk of hypoglycemia was found in the IDeg group. The study suggests similar effectiveness and safety of different insulin schemes when associated with appropriate diabetes education and management, and flexible dose adjustments. Despite its longer halflife and the lack of a validated algorithm, IDeg was not associated with an excess risk of hypoglycemia.

Anti-Infective, Anti-Inflammatory, and Immunomodulatory Properties of Breast Milk Factors for the Protection of Infants in the Pandemic From COVID-19.

COVID-19 pandemic since the end of 2019 spreads worldwide, counting millions of victims. The viral invasion, systemic inflammation, and consequent organ failure are the gravest features of coronavirus disease 2019 (COVID-19), and they are associated with a high mortality rate. The aim of this study is to evaluate the role of breast milk in the COVID-19 pandemic, analyzing its antiviral, anti-inflammatory, and immunoregulatory effects due to its bioactive components, so numerous and important for the protection of infants. The study tried to demonstrate that all the components of human milk are capable of performing functions on all the pathogenic events recognized and described in COVID-19 disease. Those human milk factors are well-tolerated and practically free of side effects, so breast milk should become a research topic to discover therapies even in this epidemic. In the first part, the mechanisms of protection and defense of the breast milk elements will be delineated; in the second section, it will describe the human milk effects in viral infections and it will be hypothesized how the known mechanisms could act in COVID infection.

C1858T Polymorphism of Protein Tyrosine Phosphatase Non-receptor Type 22 (PTPN22): an eligible target for prevention of type 1 diabetes?

INTRODUCTION: In type 1 diabetes (T1D), several genetic factors are associated to ß-cell autoimmunity onset and clinical progression. HLA-genes play a major role in susceptibility and initiation of ß-cell autoimmunity, whereas non-HLA genes may influence the destruction rate. Areas covered: Our review focuses on the possible role of the PTPN22 C1858 T variant as a prognostic factor, given its influence on disease variability. Moreover, we present the potential role of C1858 T as a target for tertiary prevention trials and new therapeutic strategies, such as the LYP inhibitors. We used PubMed for literature research; key words were 'PTPN22', 'C1858 T polymorphism', 'lymphoid-specific tyrosine phosphatase' and 'type 1 diabetes'. We selected publications between 2000 and 2016. Expert commentary: Current data suggest that PTPN22 can be a promising target for therapeutic interventions and identification of at-risk subjects in autoimmune diseases such as T1D.

Pyomyositis is not only a tropical pathology: a case series.

BACKGROUND: Pyomyositis is an acute bacterial infection of skeletal muscle that results in localized abscess formation. This infection was thought to be endemic to tropical countries, and is also known as "tropical pyomyositis". However, pyomyositis is increasingly recognized in temperate climates and is frequently associated with an immunosuppressive condition, such as human immunodeficiency virus, malignancy, and diabetes mellitus. It is also found in healthy and athletic people after strenuous or vigorous exercise or following localized and possibly unnoticed trauma. It can be primary or secondary to neighboring or remote infection. Primary pyomyositis is a rare condition that can affect children and adolescents. Diagnosis can be delayed because the affected muscle is deeply situated and local signs are not apparent. This delay in diagnosis can result in increased morbidity and a significant mortality rate. The pediatric population, which comprises 35% of the reported pyomyositis cases, is an especially difficult subset of patients to diagnose. CASE PRESENTATION: In our series, we describe the cases of four previously healthy Caucasian children who were admitted to our Pediatric Department with different clinical presentations. Pyomyositis in our patients was related to factors affecting the muscle itself, including strenuous exercise and direct muscle trauma. Therapy was started with a cephalosporin antibiotic and teicoplanin was subsequently added. The minimum length of therapy was 3 weeks. CONCLUSIONS: The diagnosis of pyomyositis in our patients, none of whom were immune-compromised, is confirmation that this disease is not an exclusive pathology of tropical countries and demonstrates that there is an increasing prevalence of pyomyositis in temperate climates.

Role of nutrition in preventing insulin resistance in children.

Nutrition during prenatal, early postnatal and pubertal period is crucial for the development of insulin resistance and its consequences. During prenatal period fetal environment and nutrition seems to interfere with metabolism programming later in life. The type of dietary carbohydrates, glycemic index, protein, fat and micronutrient content in maternal nutrition could influence insulin sensitivity in the newborn. The effects of lactation on metabolism and nutritional behavior later in life have been studied. Dietary habits and quality of diet during puberty could prevent the onset of a pathological insulin resistance through an adequate distribution of macro- and micronutrients, a diet rich in fibers and vegetables and poor in saturated fats, proteins and sugars. We want to overview the latest evidences on the risk of insulin resistance later in life due to both nutritional behaviors and components during the aforementioned periods of life, following a chronological outline from fetal development to adolescence.

Bartonella henselae infection associated with autoimmune thyroiditis in a child.

BACKGROUND: Bartonella henselae was discovered a quarter of a century ago as the causative agent of cat-scratch disease. More recently, Bartonella has been found to be responsible for a broad range of clinical syndromes (prolonged fever, hepatosplenic disease, encephalopathies, ocular disease) and associated with autoimmune conditions. CASE: This is the first report of autoimmune thyroiditis related to B. henselae infection. We describe an 11-year-old boy who presented with goiter and weight loss. At the time of admission a 2 × 1 cm mildly tender right supraclavicular lymph node was noted in association with an erythematous papule at the same side of the neck. We describe an association of autoimmune hyperthyroidism (Hashitoxicosis) with B. henselae infection (cat-scratch disease) in a pediatric patient. CONCLUSION: Different types of infections are implicated in the pathogenesis of autoimmune thyroid disease through molecular mimicry or other mechanisms, despite their role is disputed. We speculated that autoimmune thyroiditis should be added to the spectrum of clinical syndromes that can be triggered by B. henselae.