Oguzhan Deyneli

Effects of ACE inhibition and AT1-receptor antagonism on endothelial function and insulin sensitivity in essential hypertensive patients

Objective Disturbed endothelial function is closely associated with hyperinsulinaemia and insulin resistance in essential hypertension. The aims of this study were: 1) to evaluate whether the two alternative drugs, angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II (Ang II) antagonists, had comparable effects on glucose metabolism and endothelial function. 2) to determine whether they improve endothelial dysfunction through modulating insulin resistance and oxidative stress. Study design and methods Study design and methods Essential hypertensive patients were randomised into two groups: Twelve (nine patients in final analysis) patients were given enalapril (enalapril group), and twelve (nine patients in final analysis) were given losartan (losartan group). Twelve sex- and age-matched normotensive volunteers were included as controls. Before and after six months of treatment, endothelial function, insulin sensitivity and lipid peroxidation (TBARs) and NO metabolites (NOx) were evaluated. Results Endothelial function, measured as flow mediated dilatation (FMD), was improved in both of the treatment groups (p=0.0001). Calculated insulin sensitivity index also improved in the enalapril-treated group (p=0.05) but not in the losartan-treated group, compared with baseline levels. TBARS values decreased significantly in the enalapril group compared with baseline levels (p<0.001). FMD was positively correlated with insulin sensitivity index (r=0.32, p<0.05) and NOx levels (r=0.39, p=0.01) and negatively correlated with TBARS levels (r=-0.53, p=0.0002) in hypertensive patients. Conclusion Inhibition of the renin-angiotensin system, either with ACE inhibitors or AT1-receptor blockers improves endothelial dysfunction. ACE inhibition has prominent effects on improving insulin sensitivity and decreasing oxidative stress in essential hypertensive patients.

Epicardial Fat Tissue Thickness Correlates with Endothelial Dysfunction and Other Cardiovascular Risk Factors in Patients with Metabolic Syndrome

BACKGROUND Epicardial adipose tissue has shown to be related to cardiovascular risk. The aim of this study is to investigate the relationship between epicardial adiposity and endothelial function in metabolic syndrome. METHODS Fifty patients with metabolic syndrome were recruited. Anthropometric measurements, fasting blood glucose, insulin, lipid profile, high-sensitivity C-reactive protein (hsCRP), fibrinogen, apolipoprotein A (Apo A), Apo B1, and lipoprotein (a) [Lp(a)] were determined. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Epicardial fat thickness was measured via two-dimensional M-mode echocardiography. Endothelial function was assessed as flow-mediated dilatation at the brachial artery. RESULTS Epicardial fat tissue thickness was shown to be correlated negatively with FMD and positively with age, diastolic blood pressure, hsCRP, fibrinogen, HOMA-IR, and lipid parameters. Multiple regression analysis showed epicardial fat tissue thickness to be an independent factor influencing the endothelial function. CONCLUSIONS Epicardial fat tissue may be a useful parameter in the assessment of patients with metabolic syndrome.

Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goitre patients

objective  Low serum paraoxonase (PON) activity is thought to be a risk factor for the development of atherosclerosis. The present study was designed to evaluate PON1 activity and its relationship with preatherosclerotic markers such as lipid peroxidation and insulin resistance in hyperthyroid patients before and after propylthiouracil (PTU) treatment and in subjects with iatrogenic subclinical hyperthyroidism.

Effect of low- and high-dose levothyroxine on thyroid nodule volume: a crossover placebo-controlled trial.

objective The efficacy and the effective dose of levothyroxine suppressive therapy in the treatment of benign thyroid nodules are controversial. In this study, we aimed to determine the response of solitary thyroid nodules to low‐ or high‐level TSH suppression in a placebo‐controlled, randomized crossover trial.

Circulating endothelial cells are elevated in patients with type 1 diabetes mellitus

OBJECTIVE Circulating endothelial cells (CECs) have emerged as vascular damage markers and are increased in type 2 diabetic patients. Since type 1 diabetes is associated with vascular damage, we hypothesized high CEC numbers in this patient population. METHODS Thirty-nine patients with type 1 diabetes and 39 controls were included. CECs were isolated using anti-CD146-coated Dynabeads, stained with Ulex lectin-1, and counted by fluorescence microscopy. Endothelial function was measured as flow-mediated dilation (FMD). Thiobarbituric acid reactive substances (TBARS), total glutathione levels (GSH), and paraoxonase (PON) activity levels were measured as oxidative stress markers. RESULTS Patients with type 1 diabetes mellitus had higher number of CECs (7.46+/-5.37 vs 2.13+/-1.13 cells/ml, P<0.001), lower FMD (7.87+/-2.19 vs 12.06+/-2.34%, P<0.001), higher TBARS (4.94+/-1.20 vs 3.07+/-0.75 nmol/MDA, P<0.001), lower GSH (206.12+/-98.06 vs 353.61+/-68.45 microM, P<0.001), and lower PON activity levels (89.10+/-17.82 vs 127.65+/-29.01 U/l, P<0.001) as compared to controls. There was positive correlation between CEC numbers and HbAlc levels (r=0.49, P=0.002). CECs and fasting glucose levels were not correlated. There was no correlation between the number of CECs and FMD. Furthermore, there were no correlations between the number of CECs and TBARS, GSH and PON activity levels. Multiple regression analysis showed that HbAlc levels (r(2)=0.40, P<0.009) were associated with CEC numbers. CONCLUSION CECs are elevated in patients with type 1 diabetes mellitus reflecting endothelial damage. This increase is dependent on long-term glucose control.

Effects of ACE inhibition and angiotensin II receptor blockade on glomerular basement membrane protein excretion and charge selectivity in type 2 diabetic patients.

Angiotensin-converting enzyme (ACE) inhibitors may reduce urinary albumin excretion (UAE) by decreasing glomerular pressure and increasing glomerular charge selectivity through preservation of glycosaminoglycans. The effect of Angiotensin II antagonism on glomerular charge selectivity remains to be determined. The aim of this study was to compare the effects of an AT1 blocker losartan and an ACE inhibitor (ACE-I) enalapril on UAE, extracellular matrix proteins, glycosaminoglycan excretion (UGAG) and red blood cell anionic charge (RBCCh) which are the indirect markers of glomerular basement membrane anionic content in hypertensive Type 2 diabetic patients. Twenty-four patients were randomised into two groups and received either enalapril (5—20 mg/d) or losartan (50—100 mg/d). All parameters were measured at baseline and after six months of treatment. At the end of six months, systolic and diastolic blood pressures (BP), UAE rates, UGAG excretion and RBCCh were significantly and equally reduced in both treatment groups compared with baseline. RBCCh was negatively correlated with UAE (r=-0. O 57, p<0.0001) and UGAG excretion (r=-0.57, Rp<0.0001); UAE was correlated with UGAG excretion (r=0.58, p<0.0001). In conclusion, enalapril and losartan treatment were equally effective in reducing BP, UAE as well as UGAG excretion and preserving RBCCh in hypertensive Type 2 diabetic patients. ACE inhibition and AT1-receptor blockade may have favourable effects on preserving glomerular anionic content in hypertensive diabetic patients.

Translation, Cultural Adaptation, Initial Reliability, and Validation of Turkish 15D’s Version A Generic Health-Related Quality of Life (HRQoL) Instrument

This article describes the adaptation of the Finnish 15D standardized measure of health-related quality of life (HRQoL) instrument for use in Turkey and assesses its psychometric properties. The HRQoL is measured in a sample of 75 patients with Type 2 diabetes using both 15D and Nottingham Health Profile (NHP) instruments. The internal consistency within the domains of 15D was high, with Cronbach’s alpha values 0.89 for 15D scale and 0.89 for NHP. Significant correlations were observed between the scores of similar domains of 15D and the NHP in general health perception supporting the construct validity of the new 15D Turkish version. Overall, the results indicated that the adaptation of the 15D for use in Turkey was successful. The Turkish version was found to be a reliable and valid instrument. It is suitable and applicable to both clinical and population-based studies for the measurement of HRQoL in Turkey.

Exogenous subclinical hyperthyroidism impairs endothelial function in nodular goiter patients.

BACKGROUND Exogenous subclinical hyperthyroidism is associated with cardiovascular and metabolic changes. The aim of this study was to evaluate the effect of levothyroxine (LT4) suppression on endothelial function and insulin sensitivity in euthyroid nodular goiter patients. METHODS Twenty-two euthyroid patients with multinodular goiter (MNG) and 22 matched healthy controls were studied. LT4 was administered in doses ranging from 50 to 150 microg/day to reach target serum thyroid-stimulating hormone (TSH) levels <0.5 mIU/L. Patients were studied before and after 8 weeks after the target TSH level <0.5 mIU/L. The control group was studied twice, 16 weeks apart. Flow mediated vasodilatation (FMD), insulin sensitivity index (ISI), lipid peroxidation, and high-sensitivity C-reactive protein (hsCRP) were the outcome measures. RESULTS LT4 treatment significantly suppressed TSH levels to 0.2 +/- 0.1 mIU/L (minimum and maximum range was 0.05-0.3 mIU/L). FMD decreased from 10.7 +/- 2.7% to 5.4 +/- 1.7% (p < 0.001) and mean ISI decreased from 2.56 +/- 1.10 to 1.41 +/- 0.50 (p < 0.001) with LT4 treatment in the MNG group. Lipid peroxidation measured as thiobarbituric acid reactive substances (Tbars) (p < 0.05), and hsCRP (p < 0.001) levels significantly increased compared to the baseline in the MNG group. FMD measurement inversely correlated with free T4 (p = 0.008) and Tbars (p = 0.004), and positively correlated with ISI (p = 0.004). Serum Tbars and hsCRP were independent predictors of FMD (p = 0.004) in multivariate analysis. All results expressed as mean +/- SD. CONCLUSIONS TSH suppression therapy with LT4 leading to subclinical hyperthyroidism may cause impaired endothelial function, increased oxidative stress, and decreased insulin sensitivity in euthyroid nodular goiter patients.

Effect of angiotensin-converting enzyme inhibition on endothelial function and insulin sensitivity in hypertensive patients

Introduction Evidence suggests an association between insulin resistance, hypertension and impaired endothelial function. Studies have shown that insulin resistance precedes the development of hypertension. By improving insulin sensitivity, it may be possible to improve hypertension and the subsequent damage to vessel walls. Some data indicates beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on insulin sensitivity and endothelial function. We aimed to investigate these effects of ACE inhibition in the same group of patients with essential hypertension. Materials and methods Nine non-smoking, untreated hypertensive patients (38.3 9 years, 4/5 male/female) and 12 age-matched healthy subjects (35.2 6.7 years, 5/7 male/female) were included in the study. Hypertensive patients were given enalapril maleate (5—40 mg/day) for six months. The following parameters were studied at baseline and at the end of treatment period. Whole body insulin sensitivity was measured by a formula derived from an oral glucose tolerance test and named I as the insulin sensitivity index (ISI). Insulin was measured by chemiluminescence and glucose by a glucose oxidase method. Endothelial function was evaluated as flow-mediated dilatation (FMD) of the brachial artery by ultrasonography and expressed as a percentage change relative to baseline diameter. Endothelialindependent vasodilatation was measured after sublingual nitroglycerine. Results FMD was impaired in the hypertensive group compared with healthy subjects (7.3 3.1% vs. 15.3 4.8%, p<0.0005), and ISI values were 1.18 0.6 vs. 4.4 0.9 (p<0.0001) respectively. Both insulin sensitivity and FMD improved after the treatment period compared with baseline values, FMD increased from 7.3 3.1% to 16.0 2.9% (p<0.0005) and ISI from 1.18 0.6 to 4.2 1.0 (p<0.0001). FMD and ISI showed a significant positive correlation (r=0.67, p<0.001) in the hypertensive group. Conclusions Patients with essential hypertension have impaired endothelial function and decreased whole body insulin sensitivity compared with healthy subjects. Treatment for six months with enalapril maleate seems to improve both FMD and ISI. This study confirms the beneficial effects of ACE inhibition on both endothelial function and insulin sensitivity tested in the same group of essential hypertensive patients. The mechanism of these favourable effects of ACE inhibition needs to be clarified.

Serum Adipokine Levels in Type 1 Diabetic Patients: Association with Carotid Intima Media Thickness

BACKGROUND Adipokines are markers of insulin resistance and play a role in the atherosclerotic process. The association of adipokines with the macrovascular complications of type 1 diabetes mellitus (DM) needs to be determined. The aim of this study was to measure serum adiponectin, leptin, and resistin levels in type 1 DM patients and investigate their relationship with carotid intima media thickness (CIMT), a clinical marker of atherosclerosis. METHODS Seventy-five type 1 DM patients and 115 sex and age-matched healthy controls were included in the study. Serum adiponectin, leptin, and resistin levels were measured by the enzyme-linked immunosorbent assay (ELISA method). CIMT was assessed by Doppler ultrasonography. RESULTS Adiponectin levels in diabetics were higher (25.8±14.8 μg/mL vs. 5.5±7.3 μg/mL; P<0.0001) and leptin levels were lower than controls (9.4±6.2 ng/mL vs. 12.8±8.6 ng/mL; P=0.01). Resistin levels were also higher in the diabetic group compared to controls (2.1±1.4 ng/mL vs. 1.6±0.8 ng/mL; P=0.04). Adiponectin was correlated negatively with CIMT (r=-0.24, P=0.03), age (r=-0.30, P=0.02), BMI (r=-0.33, P=0.02), waist-to-hip ratio (WHR) (r=-0.38, P=0.01) and positively with creatinine (r=0.44, P=0.004). Leptin levels were correlated with total cholesterol (r=0.53, P=0.01) and high-density lipoprotein (HDL) (r=0.67, P=0.001). Resistin was correlated with CIMT (r=0.24, P=0.03) and systolic blood pressure (r=0.48, P=0.009). Multivariate analysis revealed resistin and creatinine to be independent predictors of CIMT among adiponectin, leptin, resistin, WHR, glycosylated hemoglobin (HbA1c), and creatinine. CONCLUSIONS Increased adiponectin correlates negatively and resistin positively with CIMT in type 1 diabetic patients, but adjusting for other known predictors reveals only resistin to be associated with subclinical atherosclerosis in this group of patients.