Non-obese diabetic (NOD) mice are well-established models of independently developing spontaneous autoimmune diseases, Sjögren’s syndrome (SS) and type 1 diabetes (T1D). The key determining factor for T1D is the strong association with particular MHCII molecule and recognition by diabetogenic T cell receptor (TCR) of an insulin peptide presented in the context of I-Ag7 molecule. For SS the association with MHCII polymorphism is weaker and TCR diversity involved in the onset of the autoimmune phase of SS remains poorly understood. To compare the impact of TCR diversity reduction on the development of both diseases we generated two lines of TCR transgenic NOD mice. One line expresses transgenic TCRβ chain originated from a pathogenically irrelevant TCR, and the second line additionally expresses transgenic TCRαmini locus. Analysis of TCR sequences on NOD background reveals lower TCR diversity on Treg cells not only in the thymus, but also in the periphery. This reduction in diversity does not affect conventional CD4+ T cells, as compared to the TCRmini repertoire on B6 background. Interestingly, neither transgenic TCRβ nor TCRmini mice develop diabetes, which we show is due to lack of insulin B:9–23 specific T cells in the periphery. Conversely SS develops in both lines, with full glandular infiltration, production of autoantibodies and hyposalivation. It shows that SS development is not as sensitive to limited availability of TCR specificities as T1D, which suggests wider range of possible TCR/peptide/MHC interactions driving autoimmunity in SS.

This study aims to determine the prevalence of hypertension among children with diabetes mellitus, and describe adherence to the standard of practice regarding early diagnosis and treatment of hypertension in this population. Diabetes renders higher susceptibility to cardiovascular disease in affected patients and thus early detection of hypertension can be beneficial for future quality of life. We hypothesize that a number of diabetic children with hypertension are not promptly diagnosed and treated due to the difficult process preceding diagnosis. This cross-sectional study in an out-patient clinic of a university hospital was based on a group of 263 children (both females and males, age range between 3-18) diagnosed with type 2 diabetes. At the visit, the child's weight and height were recorded, BMI was calculated, systolic and diastolic blood pressure (BP) was taken, and blood sample drawn for hemoglobin A1C (HbA1C) readings. Within the study population we have identified a group of 73 children with hypertension. Comparing the two groups: the normotensive with the hypertensive, we have observed that the normotensive patients have significantly lower average BMI (26.7), p=0.000012 and slightly reduced HbA1C (8.9%), p=0.28 levels compared to the hypertensive group: BMI (32.5) and HbA1C (9.3%), respectively. We investigated the same parameters within every age group starting from age 10, and recorded that HbA1C was only significantly different for the group of 14 year-olds (8.7%; 11.7%, p=0.039). We also found that a significantly higher BMI is linked with hypertension for groups: age 13: BMI (29.2; 33.9, p=0.047), age 14: BMI (24.1; 35.6, p=0.00007) and age 18: BMI (31.8; 45.6, p=0.045). Within the different age groups there were differences between normotensive and hypertensive patients in BMI and HbA1C measurements, but they were not statistically significant and we assume that an increased sample size would be needed to confirm the data. We are currently working on identifying other risk factors including sex, race, height, urine creatinine, urine microalbumin, serum creatinine, lipid profile and thyroid function, that might be responsible for hypertension in pediatric patients with type 2 diabetes.

Objective The aim of our study was to assess the impact of psychiatric medications and concomitant risk factors on the prevalence of QTc prolongation and torsades de pointes (TdP) in hospitalized subjects. We examined the association between individual risk scores and QTc prolongation and proposed an evidence-based protocol for electrocardiogram monitoring on psychotropic medications. Method Electrocardiograms (ECGs) of subjects hospitalized over a 1-year period were analyzed for QTc prolongation, associated risk factors, and use of medications. Analysis was performed using logistic regression to identify independent predictors of QTc prolongation, and the Pearson χ2 test was used for risk score assessment. Results A total of 1249 ECGs of 517 subjects were included in this study. Eighty-seven subjects had QTcB intervals greater than 470 milliseconds for females and greater than 450 milliseconds for males. Twelve (2.3%) subjects had QTcB of 500 milliseconds or greater, or greater than 60 milliseconds of change from baseline. Of these subjects, only 1 case of QTc interval change was related to routine use of psychiatric medications. There were no incidents of TdP. Age, diabetes, hypokalemia, overdose, diphenhydramine, and haloperidol were significant independent predictors of QTc prolongation. Risk scores were significantly correlated with QTc prolongation (P = 0.001). Conclusion Our retrospective review study found that the occurrence of TdP and QTc prolongation was low in this subject population. QT abnormalities were associated with known risk factors, and risk scores correlated well with QTc prolongation. Providers can use the protocol proposed in this study, which incorporates risk scores and the CredibleMeds classification system to determine the need for ECG monitoring and to guide treatment.

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