Ahmed A. Battah

Relationship of BsmI polymorphism of vitamin D receptor gene with left ventricular hypertrophy and atherosclerosis in hemodialysis patients

Abstract Background. Left ventricular hypertrophy (LVH) is a common manifestation of cardiovascular disease and has an important prognostic value in patients with end-stage renal disease (ESRD). Vitamin D receptor (VDR) has been intensively investigated, and one of these (BsmI) already has been associated with survival in the dialysis population. Objective. The aim of this study was to investigate the role of VDR polymorphism (BsmI) on the development of ventricular hypertrophy and atherosclerosis in hemodialysis patients. Subject and methods. The subjects were 80 patients with end-stage renal disease on maintenance hemodialysis, and 40 healthy controls. Clinical and laboratory parameters, including genetic variation in VDR gene (BsmI), were assessed. In addition, echocardiography and intima-media thickness were performed for all subjects. Results. There was no significant difference in the distribution of BsmI genotypes either in patients or in the control group. The frequency of the B allele of BsmI polymorphism (41.6%) in dialysis patients was similar to that of healthy control subjects (39.2%). Patients with BB genotype had significantly lower serum concentrations of 25-hydroxy vitamin D compared to both Bb and bb genotypes. The number of B alleles was positively correlated with left ventricular mass index (LVMI), but not with intima-media thickness. Conclusion. These results suggest that the B alleles of the BsmI polymorphism could be considered as novel markers of altered vitamin D signaling in ESRD patients, and this alteration in BB genotype produces an increase in left ventricle mass.

Apelin: a potential link between inflammation and cardiovascular disease in end stage renal disease patients.

Abstract Background and objectives. Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients. Increasing evidence suggests a role for apelin in the pathology of the cardiovascular system. In the present study, the plasma level of apelin was studied in patients with hemodialysis to assess the effect of renal transplantation and dialysis session on plasma apelin and whether circulating apelin levels reflect cardiovascular homeostasis and inflammation in these patients. Patients and methods. Plasma apelin, high sensitive CRP (hsCRP) and IL-6 levels were investigated in 30 end stage renal disease (ESRD) patients on maintenance hemodialysis (HD), a group of 15 HD patients scheduled for renal transplantation and a group of 15 HD patients on maintenance HD, as well as ten healthy volunteer subjects who served as controls. An echocardiography was performed for all subjects. Results. Plasma apelin levels were significantly lower in hemodialyzed patients compared to controls. Plasma apelin was also found to be positively correlated with left ventricular end systolic dimension (LVESD), left ventricular end diastolic dimension (LVEDD), interventricular septum (IVS), right ventricle (RV), left atrium (LA), Aorta (Ao), while, it was negatively correlated with hsCRP and IL-6 in ESRD patients. Regarding the effect of hemodialysis on plasma apelin levels, no significant effect was found after a single hemodialysis session, while levels increased significantly in the early post-transplant period. Conclusions. Apelin is related to echocardiographic features and inflammatory markers in hemodialyzed patients. Apelin may provide a mechanism for systemic inflammatory monitoring and adaptive regulation of cardiovascular function.

Natural progression of cardiac autonomic neuropathy in patients with type 1 diabetes: a four-year follow-up study

OBJECTIVE To determine the prevalence and clinical characteristics of cardiac autonomic neuropathy in type 1 diabetic patients who were followed up for 4 years to shed further light on the natural progression of cardiac autonomic neuropathy. METHODS It is a prospective cohort observational study, consisted of 57 patients who were originally studied using the standard tests proposed by Ewing and Clarke (1985). At two years follow up, 46 patients were reevaluated, 55 patients from the original study were reevaluated after another 2 years for the 3rd time using the same protocol. The control group comprised 30 age and sex matched healthy volunteers. McNemar test, ANOVA for repeated measurements, paired t test and unpaired t test were used for statistical analyses. RESULTS The prevalence of established cardiac autonomic neuropathy (CAN) at the beginning was 14%. Q-Tc intervals were found to be significantly higher in patients with abnormal cardiovascular reflex (CVRs) in the 2nd examination (0.4±0.04 vs 0.5±0.05 sec, p=0.006). Eighteen patients showed deterioration of their CVRs test between 1st and 3rd examination. There was deterioration of their glycemic control guided by glycosylated hemoglobin (8.5±1.4 vs 9.9±1.5%, p=0.05*) and albumin/creatinine ratio (4.4±4.0 vs 28.2±28.0 mg/g creatinine, p=0.04). On the other hand, 12 patients showed regression of their CVRs test. Only their insulin dose showed significant decrease (1.8±1.3 vs 1.1±0.3 dose/kg, p=0.02). CONCLUSION The prevalence of established CAN in diabetic patients is high at the beginning of the study. Glycosylated hemoglobin, systolic and diastolic blood pressure were significantly increased in diabetics with deterioration of their CAN. However, the dose of insulin was significantly decreased in diabetics with regression of their CAN.

Effect of glycemic control on the progress of left ventricular hypertrophy and diastolic dysfunction in children with type I diabetes mellitus

OBJECTIVE To evaluate progression of left ventricular (LV) structural and functional changes in patients with type 1 diabetes and effect of glycemic control on these changes. METHODS A prospective, longitudinal study consisted of 48 patients who were originally studied. At two years follow-up, 44 patients were reevaluated, 35 patients from the original study were reevaluated after another 2 years for the 3rd time using the same protocol. The control group comprised 30 age-and sex-matched healthy volunteers. All studied patients were subjected to full history taking, clinical and cardiac examination. M-mode echocardiography was done, blood samples were taken and examined for HbA1c and urine samples were tested for the presence of albuminuria. ANOVA for repeated measurements, t-test for dependent and independent variables, and Mann-Whitney U test were used for statistical analyses. RESULTS Seven (14.6%) of our patients had LV hypertrophy, 23 (47.9%) patients had diastolic dysfunction and ten patients only achieve improvement in glycemic control. Duration of diabetes was significantly higher in patients with LV hypertrophy (LVH) (p<0.05). Patients with no improvement in glycemic control had a significant increase in interventricular septum (IVS) and left ventricular posterior wall (LVPW) in the third examination (p<0.05 for both). CONCLUSION Prevalence of LVH and diastolic dysfunction among diabetic patients is high. Glycemic control in diabetic patients could not improve LVH or diastolic dysfunction. On the other hand, failure to achieve glycemic control leads to deterioration in structural parameters.

Evaluation of fetuin-A and carotid intima-media thickness in adolescent type 1 diabetic patients.

Abstract Objective: To evaluate fetuin-A level and carotid intima-media thickness (CIMT) in adolescent type 1 diabetics. Patients and methods: The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood sample was taken for assessment of glycosylated hemoglobin (HbA1), lipid profile, and fetuin-A. Urine sample was also taken for assessment of albumin/creatinine ratio. Anthropometric measurements were taken, including weight, height, and waist and hip circumference. CIMT was assessed for all patients and controls. Results: Serum fetuin-A, Rt., Lt. and both CIMT were significantly higher in diabetics. Fetuin-A had a significant positive correlation with duration of disease, waist and hip circumference, BMI, BMI SDS, waist/height ratio, Rt., Lt. and both CIMT. Stepwise multiple regression analysis revealed that the duration of disease, waist/height ratio, and HDL-c were the factors related to fetuin-A. Conclusion: Adolescent type 1 diabetic patients have high fetuin-A levels and increased CIMT, with the latter representing the development of early atherosclerosis. In this light, adolescents with type 1 diabetes require frequent follow up for early detection of atherosclerosis.

Assessment of human cartilage glycoprotein 39 (YKL-40), preptin, and nitric oxide in adolescent patients with type 1 diabetes and its relation to cardiorenal affection.

Abstract Aim: To evaluate new biomarkers such as YKL-40, preptin, and nitric oxide (NO) in patients with diabetes and to assess its relation to cardiorenal injury. Patients and methods: The study included 62 patients with type 1 diabetes and 30 healthy volunteers. Blood sample was taken for assessment of glycosylated hemoglobin, lipid profile, YKL-40, preptin, and NO. Also, urine sample was taken for analysis of albumin/creatinine ratio. Echocardiography was also done. Results: NO was lower, whereas YKL-40, preptin, and albumin/creatinine ratio were significantly higher in patients with diabetes. NO had a significant negative correlation with LVEDD, LVESD, PWT, LV mass, YKL-40, preptin, and albumin/creatinine ratio. YKL-40 had a significant positive correlation with waist/height ratio, preptin and negative correlation with E/A ratio. Stepwise multiple regression revealed that E/A ratio is the only parameter related to YKL-40. On the contrary, NO and systolic blood pressure are related to preptin. Conclusion: A significant reduction of NO and elevation of YKL-40 and preptin was found in patients with diabetes. A decrease in NO is associated with diastolic dysfunction, LV hypertrophy, and renal impairment, whereas YKL-40 is associated with diastolic dysfunction. An increase in preptin level was associated with hypertension.

Asymmetric dimethyl L-arginine, nitric oxide and cardiovascular disease in adolescent type 1 diabetics

Abstract Objective: To evaluate asymmetric dimethyl L-arginine (ADMA), nitric oxide (NO) and cardiovascular disease in adolescent type 1 diabetics. Methods: The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood samples were taken for assessment of ADMA, NO, oxidized low density lipoprotein (OxLDL), glycosylated hemoglobin, and lipid profile. Urine samples were taken for assessment of albumin/creatinine ratio. M mode echocardiography and flow mediated dilatation (FMD) via ultrasound were completed; t-test for independent variables, Pearson’s correlation, and stepwise multiple regression analysis were used. Results: The mean age of patients was 16.3±1.5 years and mean duration of diabetes was 9.4±2.9 years. Nitric oxide, ADMA and FMD were significantly lower, while OxLDL and the albumin/creatinine ratio were significantly higher in diabetics. Nitric oxide had a significant negative correlation with left ventricular end-diastolic dimension, left ventricular end-systolic dimension, posterior wall thickness, left ventricular mass, albumin/creatinine ratio, and OxLDL, as well as a positive correlation with ADMA. Albumin/creatinine ratio had a significant positive correlation with OxLDL and negative correlation with ADMA. Stepwise multiple regression analysis revealed that ADMA is the only parameter related to NO, however, albumin/creatinine ratio and OxLDL are related to ADMA. Conclusions: Type 1 diabetic patients had endothelial and diastolic dysfunction. The reduction in NO, ADMA, and elevation of OxLDL, and its relation to echocardiographic data and albumin/creatinine ratio, may reflect their role in cardiac and renal affection.

Cardiovascular Autonomic Neuropathy and Early Atherosclerosis in Adolescent Type 1 Diabetic Patient

AIM: To evaluate cardiovascular autonomic neuropathy (CAN) in type 1 Diabetics and to detect its relation to coronary artery calcification. PATIENTS AND METHODS: It is a cross sectional study included 62 diabetics and 30 controls. Clinical, laboratory assessment and 24 Hr holter were done for all patients and controls and coronary artery calcium (CAC) scoring by multisclice CT was done for all patients only. T-test, Mann Whitney U test, and stepwise multiple regression were used for statistical analyses. RESULTS: CAC score was positive in 8.1 % of patients. Heart rate variability (HRV) was significantly lower in diabetics. All parameters of HRV were insignificantly lower in diabetics with positive CAC score. Patients with microalbuminuria had a significantly lower HRV. HRV had a significant correlation with age of patients, duration of disease, HbA1, and Qtc in diabetics. CONCLUSION: Percentage of arrhythmia and early atherosclerosis is high in adolescent type 1 diabetic patients. CAN is associated with early atherosclerosis. Cardiac autonomic neuropathy is associated with older age, longer duration, and poor glycemic control and microalbuminuria.

Cardiac Affection in Type 1 Diabetic Patients in Relation to Omentin

AIM: To evaluate cardiac affection in type 1 diabetes in relation to Omentin. PATIENTS AND METHODS: Sixty two diabetics and 30 volunteer of the same age and sex were included as a control group. Blood sample was taken for assessment of omentin and oxidized low density lipoprotein (OxLDL), glycosylated hemoglobin (HbA1) and lipid profile. Urine sample was taken for assessment of albumin/creatinine ratio. 24 hour holter was also done. T-test, simple correlation followed by stepwise multiple regression analysis was used for analysis of data. RESULTS: Parameters of 24 hour holter were significantly lower in diabetics. Omentin was significantly lower, while OxLDL were significantly higher than controls. RMSSD, ST deviation and OxLDL were the parameters related to omentin by stepwise multiple regression analysis in diabetics. CONCLUSION: Diabetic patients had a cardiac autonomic neuropathy. A significant reduction of omentin and elevation OxLDL imply that they influence glucose metabolism in type 1 diabetes. Omentin had a significant relation to 24 hr holter which may reflect its role in cardiac affection. Omentin and OxLDL had a role in renal affection.

Assessment of Increase in Aortic and Carotid Intimal Medial Thickness in Type 1 Diabetic Patients

AIM: To assess aortic and carotid intima-media thickness (aIMT and cIMT) in diabetic patients. PATIENTS AND METHODS: The study included 75 type 1 diabetic patients and 30 age and sex matched healthy volunteer. A blood sample was taken for analysis of HbA1 and lipid profile and the urine sample was taken for analysis of albumin/creatinine ratio. aIMT and cIMT via ultrasound were also done. RESULTS: cIMT & aIMT were significantly higher in diabetics. aIMT was found to be significantly higher than cIMT in diabetic patients (0.72 ± 0.11 vs. 0.52 ± 0.06, P = 0.0001). Ten of our patients (14%) with normal cIMT revealed significantly increased aIMT. aIMT had a significant positive correlation with age of patients, waist/hip ratio & cIMT. CONCLUSION: Diabetic patients had increased aIMT and cIMT with a relatively greater increase in the aIMT than in the cIMT. Because atherosclerosis begins first in the intima of the aorta, these data suggest that the aIMT might provide the best currently available noninvasive marker of preclinical atherosclerosis in children. We recommend frequent follow up of diabetic patients for early detection of diabetic complication.