Dilated Cardiomyopathy as the First Early Complication in a 14 Year-Old Girl with Diabetes Mellitus Type 1

Diabetic cardiomyopathy (DC) has been reported in type 2 diabetics with short duration of clinically overt diabetes, Impaired left ventricular function has been reported in young patients with diabetes mellitus type 1 (IDDM), but severe cardiomyopathy as the first early major complication of IDDM is very rare. We report a 14 year-old girl with a 5-year history of IDDM and very poor compliance with treatment and follow-up. She was referred to our clinic upon the development of congestive heart failure and dilated cardiomyopathy was diagnosed based on clinical findings, electrocardiogram, chest X-ray and echocardiography, She had no evidence of other major complications of IDDM such as retinopathy, nephropathy or neuropathy

Inhibition of the formation or action of angiotensin II reverses attenuated K+ currents in type 1 and type 2 diabetes

Transient and sustained calcium-independent outward K+ currents (It and ISS) as well as action potentials were recorded in cardiac ventricular myocytes isolated from two models of diabetes mellitus.Rats injected (i.v.) with streptozotocin (STZ, 100 mg kg−1) 6–10 days before cell isolation developed insulin-dependent (type 1) diabetes. It and ISS were attenuated and the action potential prolonged. Incubation of myocytes (6–9 h) with the angiotensin II (ATII) receptor blockers saralasin or valsartan (1 μm) significantly augmented these currents. Inclusion of valsartan (1 g l−1) in the drinking water for 5–10 days prior to and following STZ injection partially prevented current attenuation.Incubation of myocytes from STZ-treated rats (6–9 h) with 1 μm quinapril, an angiotensin-converting enzyme (ACE) inhibitor, significantly augmented It and ISS and shortened the ventricular action potential. It augmentation was not due to changes in steady-state inactivation or in recovery from inactivation. No acute effects of quinapril were observed.The effects of quinapril and valsartan were abolished by 2 μm cycloheximide.Myocytes were isolated from the db/db mouse, a leptin receptor mutant that develops symptoms of non-insulin-dependent (type 2) diabetes. K+ currents in these cells were also attenuated, and the action potentials prolonged. Incubation of these cells (> 6 h) with valsartan (1 μm) significantly enhanced the transient and sustained outward currents.These results confirm recent suggestions that cardiac myocytes contain a renin-angiotensin system, which is activated in diabetes. It is proposed that chronic release of ATII leads to changes in ionic currents and action potentials, which can be reversed by blocking the formation or action of ATII. This may underlie the proven benefits of ATII receptor blockade or ACE inhibition in diabetes, by providing protection against cardiac arrhythmias

Pre-clinical diabetic cardiomyopathy: prevalence, screening, and outcome

AIMS: Diabetic cardiomyopathy, characterized by left ventricular (LV) dysfunction and LV hypertrophy independent of myocardial ischaemia and hypertension, could contribute to the increased life-time risk of congestive heart failure seen in patients with diabetes. We assessed prospectively the prevalence, effectiveness of screening methods [brain natriuretic peptide (BNP) and C-reactive protein in combination with clinical parameters], and outcome of pre-clinical diabetic cardiomyopathy. METHODS AND RESULTS: We studied 100 adults (mean age 57.4 +/- 10.2 years, 44% females) with diabetes and no previous evidence of structural heart disease. By echocardiography, diabetic cardiomyopathy was present in 48% of patients. Screening with combinations of clinical parameters (gender, systolic blood pressure, and body mass index), but not BNP, resulted in high negative predictive values for diabetic cardiomyopathy. During a mean follow-up of 48.5 +/- 9.0 months, in the groups with and without diabetic cardiomyopathy, 12.5 vs. 3.9% (P < 0.2) patients died or experienced cardiovascular events and 37.5 vs. 9.6% (P < 0.002) had a deterioration in NYHA functional class. Overall event-free survival was 54 vs. 87% (P = 0.001) in the groups with and without diabetic cardiomyopathy, respectively. Brain natriuretic peptide was an independent predictor of events [odds ratio 3.5 (1.1-10.9), P = 0.02]. CONCLUSION: Pre-clinical diabetic cardiomyopathy is common. Screening with combinations of simple clinical parameters, but not BNP, can be useful to identify those patients needing further evaluation. Patients with pre-clinical diabetic cardiomyopathy are at increased risk for functional deterioration and possibly cardiovascular events during follow-up. Brain natriuretic peptide was shown to be an independent predictor of future events

Endothelial dysfunction relates to folate status in children and adolescents with type 1 diabetes

Copyright © 2002 by the American Diabetes Association.Endothelial dysfunction occurs early in the development of vascular disease in diabetes. Total plasma homocyst(e)ine (tHcy) is associated with endothelial dysfunction. We therefore aimed to assess endothelial function in children with type 1 diabetes in relation to tHcy and its determinants. Endothelial function was assessed in 36 children with type 1 diabetes aged 13.7 +/- 2.2 years and 20 age- and sex-matched control subjects using ultrasound assessment of flow-mediated dilatation (FMD) and glyceryl trinitrate (GTN)-dependent brachial artery responses. von Willebrand factor (vWF) and thrombomodulin, markers of endothelial activation, were measured in 64 children with type 1 diabetes and 52 control subjects. Fasting glucose, tHcy, serum and red cell folate, vitamin B12, HbA(1c), creatinine, and lipids were also measured. FMD (5.2 +/- 4.7 vs. 9.1 +/- 4.0%, P = 0.002) and the ratio of FMD:GTN-induced dilatation (0.22 +/- 0.39 vs. 0.41 +/- 0.29%, P = 0.008) were significantly lower in diabetic subjects, indicating endothelial dysfunction. In diabetic subjects, red cell folate correlated independently with FMD (beta = 0.42, P = 0.028) and the ratio of FMD:GTN-induced dilatation (beta = 0.59, P < 0.001). Resting vessel diameter correlated independently with tHcy (beta = -0.51, P < 0.001) and height (beta = 0.65, P < 0.001). vWF correlated independently with HbA(1c) (beta = 0.38, P = 0.003), and thrombomodulin correlated independently with red cell folate (beta = -0.38, P = 0.005), tHcy (beta = -0.37, P = 0.004), diastolic blood pressure (beta = -0.28, P = 0.025), and creatinine clearance (beta = 0.26, P = 0.033). Children with type 1 diabetes have early endothelial dysfunction. Better folate status is associated with better endothelial function, as measured by higher FMD, higher FMD:GTN ratio, and lower thrombomodulin. Folate may therefore protect against endothelial dysfunction in children with diabetes.Esko J. Wiltshire, Roger Gent, Craig Hirte, Alexia Pena, David W. Thomas, and Jennifer J. Coupe