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.

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.

Identification of the genetic defect underlying early-onset diabetes is important for determining the specific diabetes subtype, which would then permit appropriate treatment and accurate assessment of recurrence risk in offspring. Given the extensive genetic and clinical heterogeneity of the disease, high-throughput sequencing might provide additional diagnostic potential when Sanger sequencing is ineffective. Our aim was to develop a targeted next-generation assay able to detect mutations in several genes involved in glucose metabolism. All 13 known MODY genes, genes identified from a genome-wide linkage study or genome-wide association studies as increasing the risk of type 2 diabetes and genes causing diabetes in animal models, were included in the custom panel. We selected a total of 102 genes by performing a targeting re-sequencing in 30 patients negative for mutations in the GCK, HNF1α, HNF4α, HNF1β and IPF1 genes at the Sanger sequencing analysis. Previously unidentified variants in the RFX6 gene were found in three patients and in two of them we also detected rare variants in WFS1 and ABCC8 genes. All patients showed a good therapeutic response to dipeptidyl peptidase-4 (DPP4) inhibitors. Our study reveals that next-generation sequencing provides a highly sensitive method for identification of variants in new causative genes of diabetes. This approach may help in understanding the molecular etiology of diabetes and in providing more personalized treatment for each genetic subtype.

In recent years, increasing interest has been devoted to the susceptibility gene polymorphisms in type 1 diabetes (T1D) as well as in other autoimmune diseases. Among these, a nucleotide polymorphism of the gene encoding for the protein tyrosine phosphatase non-receptor type 22 (PTPN22) has been associated with T1D in several studies. The aim of this study is to define the frequency of the C1858T polymorphism in the PTPN22 gene in a cohort of 113 Caucasian patients (58 males and 55 females) with T1D, and to assess a possible correlation with a group of clinically relevant variables: age at onset, gender, diabetes-related autoantibodies, residual β-cell function and daily insulin requirement (IR) 6 months after diagnosis. Using a PCR-RFLP approach, we evidenced a 17.7% frequency of the PTPN22 C1858T polymorphism in diabetic patients, higher than the frequency showed in the general population. A statistically significant correlation between this polymorphism and higher levels of C-peptide at diagnosis and lower IR at 6 months from diagnosis was observed (P=0.001 and P=0.04). Moreover, 1858T variant carriers were more frequently positive for glutamic acid decarboxylase (GAD) autoantibodies at diagnosis than wild-type subjects (P=0.19). On the other hand, no significant difference regarding age at onset, gender distribution, insulinoma-associated 2 molecule (IA2) and islet cell antibodies (ICA) positivity was found. These findings, if adequately confirmed in the future and extended to larger samples, may characterize a subset of T1D patients with a defined genetic pattern, who may be eligible for trials aimed to preserve residual β-cell function in the coming years.

We report a rare case of monozygotic (MZ) twins who developed simultaneous onset of type 1 diabetes mellitus (T1DM). Laboratory fi nding showed similar values of blood sugar, pH, glycosylated hemoglobin, and C-peptide. Urinary sugar and ketones were detected in both. Endocrine and immunological assessment showed similar results. No evidence (clinical or serological) of recent viral or bacterial infection was found. In the 4 years of follow-up, the twins also showed a similar course of disease. Concordance rates for T1DM are high in MZ twins; nevertheless, a simultaneous onset and a similar course of disease are unusual, as well as the HLA allelic variants of our patients. This extraordinary concordance in a pair of MZ twins could be the consequence of a greater environmental similarity or the role of genetic factors other than HLA genes in our twins.