Prevalence of cardiovascular risk factors in children and adolescents with type 1 diabetes in Austria.

Mortality of cardiovascular diseases in patients with type 1 diabetes is increased 2- to 20-fold compared to non-diabetic individuals. In young adults with type 1 diabetes, cardiovascular events are more often the cause of premature death than nephropathy. The aim of this study was to evaluate the prevalence and extent of cardiovascular risk factors in children and adolescents with type 1 diabetes in Austria. In a cross sectional study data of children with type 1 diabetes <18 years of age treated at the Children's department of the University Hospitals of Vienna and Graz were collected. We recorded body mass index, waist circumference, blood pressure, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol according to age, sex, age at manifestation, diabetes duration, and insulin requirement. From 264 patients (49.4% male) complete data were available. Of all patients, 76.1% had one or more risk factors, 20.8% had two or more, 10.2% had three or more, and 4.9% had four or more risk factors. Insufficient glycemic control was the most frequent risk factor, present in 60.6% of our patients, followed by elevated triglycerides (22.7%) and increased body mass index (20.1%). Higher prevalence of risk factors was correlated with increasing age, diabetes duration, HbA1c, and insulin requirement. In conclusion, children and adolescents with type 1 diabetes have a much higher prevalence of cardiovascular risk factors compared to non-diabetic individuals. To prevent future cardiovascular events, achieving the best possible glycemic control, early detection of further risk factors, and adequate intervention are highly important.

Regulatory T cells ameliorate angiotensin II-induced cardiac damage.

BACKGROUND: Hypertensive target organ damage, especially cardiac hypertrophy with heart failure and arrhythmia, is a major source of morbidity and mortality. Angiotensin II, a major mediator of hypertension and cardiac damage, has proinflammatory properties. Inflammation and activation of the immune system play a pivotal role in pathogenesis of hypertensive target organ damage. However, the role of immunosuppressive CD4+CD25+ regulatory T (Treg) cells in the pathogenesis of hypertensive target organ damage is unexplored. METHODS AND RESULTS: We conducted adoptive transfer of Treg cells into angiotensin II-infused hypertensive mice. Treg cell recipients exhibited improved cardiac hypertrophy and less cardiac fibrosis despite sustained hypertension. Amelioration of cardiac morphology was accompanied by an improvement in arrhythmogenic electric remodeling, indicating the functional significance of the enhanced cardiac morphology. Delocalization of the connexin 43 gap junction protein is one of the major pathomechanisms in electric remodeling. Pronounced connexin 43 immunoreactivity was found at the lateral borders of cardiomyocytes in angiotensin II-treated mice. In contrast, connexin 43 was restricted to the intercalated disk regions in sham controls. Surprisingly, angiotensin II+Treg-treated mice showed normal connexin 43 gap junction protein localization. Adoptive Treg cell transfer resulted in a marked reduction in cardiac CD4+, CD8+, and CD69+ cell and macrophage infiltration. CONCLUSIONS: Immunosuppressive effects of transferred Treg cells ameliorated cardiac damage and accounted for the improved electric remodeling independently of blood pressure-lowering effects. Our results provide new insights into the pathogenesis of hypertensive cardiac damage and could therefore lead to new therapeutic approaches that involve manipulation of the immune system.

Dietary n-3 polyunsaturated fatty acids and direct renin inhibition improve electrical remodeling in a model of high human renin hypertension.

We compared the effect n-3 polyunsaturated fatty acids (PUFAs) with direct renin inhibition on electrophysiological remodeling in angiotensin II-induced cardiac injury. We treated double-transgenic rats expressing the human renin and angiotensinogen genes (dTGRs) from week 4 to 7 with n-3 PUFA ethyl-esters (Omacor; 25-g/kg diet) or a direct renin inhibitor (aliskiren; 3 mg/kg per day). Sprague-Dawley rats were controls. We performed electrocardiographic, magnetocardiographic, and programmed electrical stimulation. Dietary n-3 PUFAs increased the cardiac content of eicosapentaenoic and docosahexaenoic acid. At week 7, mortality in dTGRs was 31%, whereas none of the n-3 PUFA- or aliskiren-treated dTGRs died. Systolic blood pressure was modestly reduced in n-3 PUFA-treated (180+/-3 mm Hg) compared with dTGRs (208+/-5 mm Hg). Aliskiren-treated dTGRs and Sprague-Dawley rats were normotensive (110+/-3 and 119+/-6 mm Hg, respectively). Both n-3 PUFA-treated and untreated dTGRs showed cardiac hypertrophy and increased atrial natriuretic peptide levels. Prolonged QRS and QT(c) intervals and increased T-wave dispersion in dTGRs were reduced by n-3 PUFAs or aliskiren. Both treatments reduced arrhythmia induction from 75% in dTGRs to 17% versus 0% in Sprague-Dawley rats. Macrophage infiltration and fibrosis were reduced by n-3 PUFAs and aliskiren. Connexin 43, a mediator of intermyocyte conduction, was redistributed to the lateral cell membranes in dTGRs. n-3 PUFAs and aliskiren restored normal localization to the intercalated disks. Thus, n-3 PUFAs and aliskiren improved electrical remodeling, arrhythmia induction, and connexin 43 expression, despite a 70-mm Hg difference in blood pressure and the development of cardiac hypertrophy.