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.

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.

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.

The effect of recurrent severe hypoglycemia on cognitive performance in children with type 1 diabetes: a meta-analysis.

The purpose of this study was to investigate the existence and extent of cognitive impairment in type 1 diabetic children with episodes of recurrent severe hypoglycemia, using meta-analysis to synthesize data across studies. The meta-analysis sample included: 441 children with diabetes and recurrent severe hypoglycemia, 560 children with diabetes and without recurrent severe hypoglycemia. Overall, children with type 1 diabetes and recurrent severe hypoglycemia had slightly lower performance than diabetic children without severe hypoglycemia, only in some cognitive domains: intelligence, memory, learning, and verbal fluency/language. Greater impairment was found in memory and learning. No impairment was found for motor speed. Our results seem to confirm the hypothesis that recurrent severe hypoglycemia has a selective negative effect on the children's cognitive functions. However, these results must be considered with caution taking into account factors such as small sample sizes, the different definitions of severe hypoglycemia, and the variety of neuropsychological tests used.

Variables associated with severe hypoglycemia in children and adolescents with type 1 diabetes: a population-based study.

OBJECTIVE: Hypoglycemia remains a central problem in the management of type 1 diabetes mellitus (T1DM) and limits the achievement of good or normal glycemic control. The Diabetes Control and Complication Trial showed that intensive treatment of T1DM increased the risk of severe hypoglycemia (SH) when compared to conventional therapy. The aim of our study was to determine the incidence of SH and associated variables in a population of children and adolescents with T1DM. RESEARCH DESIGN AND METHODS: We performed a 7.5-yr prospective study enrolling 195 patients aged 13.9 ± 6.6 yr. The study was carried out by referring to the T1DM population-based register in the Abruzzo region of Italy. The incidence of SH, defined as blood glucose levels <50 mg/dL (<2.77 mmol/L) associated with altered states of consciousness (including confusional state, seizures, and coma) was recorded. Glycated hemoglobin (HbA1c) percentage, insulin dose, insulin regimen, time since diagnosis, and age at onset were also recorded. RESULTS: One hundred and thirty-three severe hypoglycemic events occurred during the study period; the overall incidence was 9.4 episodes per 100 patient-years. Significant predictors of hypoglycemia were diabetes duration >10 yr (p = 0.01), basal/bolus insulin ratio (ratio of daily basal insulin units to daily bolus insulin units) >0.8 (p = 0.01). No relationship was found between hypoglycemic episodes and HbA1c levels, daily insulin requirements, or insulin regimen. CONCLUSIONS: In these patients, a relatively low incidence of SH was recorded, without pronounced association with lower HbA1c or multiple daily injection insulin therapy. SH seems to be mainly related to management of diabetes. We believe that the main path to SH prevention is through patient and family education in the management of T1DM.