Ioanna Eleftheriadou

Acute Hyperhomocysteinemia Impairs Endothelium Function in Subjects with Type 2 Diabetes Mellitus

The objective of the present study was to examine the effect of acute, methionine-induced hyperhomocysteinemia (HHCY) on endothelial function and indices of arterial stiffness in subjects with type 2 diabetes mellitus (T2DM). A total of 30 subjects with T2DM, free of macrovascular disease were examined in a crossover study. L-methionine (M) (0.1 g/kg) and water (W) load were given in random order with an interval of about 1 week in between. Endothelial function was assessed by flow-mediated vasodilation (FMD). Arterial stiffness was assessed by determination of augmentation index (AI). Measurements were performed in the fasting state, 1, 2 and 3 h after the M or the W load. Total plasma homocysteine (HCY) levels did not change after W administration, while M administration resulted in a significant increase in HCY concentrations at 3 h. FMD throughout the experiment expressed as area under the curve (AUC) was significantly lower after the M than after the W load. Consistent with impairment in endothelial function, the AUC of AI was significantly higher after the M than after the W administration. Acute HHCY impairs endothelial function and increases arterial stiffness in patients with T2DM. This effect is probably mediated by a reduction of nitric oxide bioavailability in endothelium.

Association of plasma fetuin-a levels with peripheral arterial disease and lower extremity arterial calcification in subjects with type 2 diabetes mellitus.

AIMS Fetuin-A is a hepatic glycoprotein that is involved in insulin resistance and atherosclerosis. Herein we examined the association of plasma fetuin-A levels with peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS A total of 71 patients with T2DM and 57 non-diabetic individuals were recruited. Diagnosis of PAD was based on the absence of triphasic waveform at pedal arteries, while ankle-brachial index (ABI) was calculated. Radiographs of both feet and ankles were taken for the assessment of lower extremity arterial calcification (LEAC). Plasma fetuin-A levels were measured using ELISA. RESULTS Patients with T2DM had higher fetuin-A levels than non-diabetic participants. Participants with diabetes and PAD had lower fetuin-A levels than non-PAD diabetic patients. In subjects with T2DM fetuin-A levels were associated with ABI. Multivariate analysis demonstrated that in patients with T2DM the odds of PAD increased with long diabetes duration, smoking, presence of arterial hypertension and dyslipidemia, as well as with lower fetuin-A levels. A trend towards higher fetuin-A levels in subjects with less severe LEAC was found. CONCLUSION Plasma fetuin-A levels are lower in patients with T2DM and PAD and are associated with PAD, irrespective of traditional cardiovascular risk factors. Moreover, fetuin-A may be involved in arterial calcification.

Pulse wave velocity and cardiac autonomic function in type 2 diabetes mellitus

BackgroundIncreased carotid-femoral pulse wave velocity (PWV) has been associated with incident cardiovascular disease, independently of traditional risk factors. Cardiac autonomic dysfunction is a common complication of diabetes and has been associated with reduced aortic distensibility. However, the association of cardiac autonomic dysfunction with PWV is not known. In this study we examined the association between cardiac autonomic function and PWV in subjects with type 2 diabetes mellitus.MethodsA total of 290 patients with type 2 diabetes were examined. PWV was measured at the carotid-femoral segment with applanation tonometry. Central mean arterial blood pressure (MBP) was determined by the same apparatus. Participants were classified as having normal (n = 193) or abnormal (n = 97) PWV values using age-corrected values. Cardiac autonomic nervous system activity was determined by measurement of parameters of heart rate variability (HRV).ResultsSubjects with abnormal PWV were older, had higher arterial blood pressure and higher heart rate than those with normal PWV. Most of the values of HRV were significantly lower in subjects with abnormal than in those with normal PWV. Multivariate analysis, after controlling for various confounding factors, demonstrated that abnormal PWV was associated independently only with peripheral MBP [odds ratio (OR) 1.049, 95% confidence intervals (CI) 1.015–1.085, P = 0.005], central MBP (OR 1.052, 95% CI 1.016–1.088, P = 0.004), log total power (OR 0.490, 95% CI 0.258–0.932, P = 0.030) and log high frequency power (OR 0.546, 95% CI 0.301–0.991, P = 0.047).ConclusionsIn subjects with type 2 diabetes, arterial blood pressure and impaired cardiac autonomic function is associated independently with abnormal PWV.

The association between pulse wave velocity and peripheral neuropathy in patients with type 2 diabetes mellitus

AIMS Diabetic peripheral neuropathy (DPN) is the most common diabetic complication, affecting up to half of the patients with type 2 diabetes mellitus (T2DM). Increased aortic stiffness, measured with the carotid-femoral pulse wave velocity (PWV), has been associated with incidence of cardiovascular disease independently of traditional risk factors. Previous data showed associations between risk factors for macroangiopathy and DPN in diabetes. However, the association between PWV and DPN is not well known. In this study we examined the association between PWV and presence as well as severity of DPN in subjects with T2DM. MATERIAL AND METHODS A total of 381 patients with T2DM were recruited. Participants were classified as having DPN and not having DPN. PWV was measured at the carotid-femoral segment with a non-invasive method using applanation tonometry. DPN was assessed by determination of the Neuropathy Symptom Score (NSS) and the Neuropathy Disability Score (NDS). RESULTS A hundred and seven participants (28.1%) had DPN. Patients with DPN were significantly more often male and older, had longer diabetes duration, higher height, larger waist circumference, higher systolic arterial blood pressure (SBP) and higher PWV (all P<0.05). Furthermore, participants with DPN were treated more often with statins and had lower low density lipoprotein cholesterol; in addition, they were treated more often with antiplatelets, b-blockers and insulin than those without DPN. Univariative logistic regression analysis demonstrated that presence of DPN was significantly associated with age, male gender, longer diabetes duration, height, waist circumference, SBP, PWV, dyslipidemia, HbA1c, retinopathy, nephropathy and peripheral arterial disease. Multivariate logistic regression analysis, after adjustment for age, gender, waist circumference, SBP, nephropathy and use of b-blockers, demonstrated that the odds [OR (95% confidence intervals)] of peripheral neuropathy were associated significantly and independently only with diabetes duration [1.044 (1.009-1.081), P=0.013], height [1.075 (1.041-1.110), P<0.001], HbA1c [1.468 (1.164-1.851), P<0.001], PWV [1.174 (1.054-1.309), P=0.004], dyslipidemia [1.941 (1.015-3.713), P=0.045], retinopathy [4.426 (2.217-8.837), P<0.001] and peripheral arterial disease [4.658 (2.264-9.584), P<0.001]. In addition, multivariate linear regression analysis, after controlling for age, gender, diabetes duration, SBP, HbA1c and nephropathy, demonstrated that an increased NDS was significantly and independently associated with height [standardized regression coefficient (beta=0.229, P<0.001)], PWV (beta=0.197, P<0.001), retinopathy (beta=0.268, P<0.001) and peripheral arterial disease (beta=0.374, P<0.001). CONCLUSION Increased PWV is associated strongly and independently not only with the presence but also with the severity of DPN in patients with T2DM, irrespective of known risk factors.

Effect of α-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy:

Objective To examine the effect of α-lipoic acid on neuropathic symptoms in patients with diabetic neuropathy (DN). Methods Patients with painful DN were treated with 600 mg/day α-lipoic acid, orally, for 40 days. Neuropathy Symptom Score (NSS), Subjective Peripheral Neuropathy Screen Questionnaire (SPNSQ) and douleur neuropathique (DN)4 questionnaire scores were assessed at baseline and day 40. Quality-of-life treatment effects were assessed by Brief Pain Inventory (BPI), Neuropathic Pain Symptom Inventory (NPSI) and Sheehan Disability Scale (SDS). Changes in body weight, arterial blood pressure, fasting serum glucose and lipids were also assessed. Results Out of 72 patients included, significant reductions in neuropathic symptoms were shown by reduced NSS, SPNSQ and DN4 scores at day 40 versus baseline. BPI, NPSI, and SDS in terms of work disability, social life disability, and family life disability scores were also significantly reduced. Moreover, 50% of patients rated their health condition as ‘very much better’ or ‘much better’ following α-lipoic acid administration. Fasting triglyceride levels were reduced, but no difference was found in body weight, blood pressure, fasting glucose, or other lipids at day 40 versus baseline. Conclusions A-lipoic acid administration was associated with reduced neuropathic symptoms and triglycerides, and improved quality of life.

Pulse pressure amplification and cardiac autonomic dysfunction in patients with type 2 diabetes mellitus

The main aim of this cross-sectional study was to investigate the association between pulse pressure amplification (PPA) and cardiac autonomic activity (baroreflex sensitivity (BRS) and heart rate variability (HRV)) in patients with type 2 diabetes mellitus (T2DM). In addition, we examined the association between cardiac autonomic activity and central hemodynamic parameters that may affect PPA such as augmentation index (AIx), aortic stiffness (pulse wave velocity (PWV)), and common carotid artery stiffness distensibility coefficient (DC). A total of 142 patients with T2DM were included in the study. In multivariate linear regression analysis—after controlling for age, diabetes duration, height, waist circumference, aortic PWV, use of β-blockers, and BRS—PPA was associated significantly and independently with male gender (standardized regression coefficient (β) = 0.156, p = 0.007), aortic systolic blood pressure (β = −0.221, p < 0.001), heart rate (β = 0.521, p < 0.001), AΙx (β = −0.443, p < 0.001), and parameters of HRV, such as total power of HRV (β = −0.157, p = 0.005). No significant associations were found between BRS or parameters of HRV with aortic PWV, AIx, or DC. In patients with T2DM, cardiac autonomic dysfunction was associated with enhanced PPA. This association was independent from the well-described effect of resting heart rate, as well as from traditional cardiovascular risk factors or diabetes-related factors. Moreover, it was not mediated by effects of the autonomic dysfunction on arterial stiffness or on pressure wave reflections. These findings suggest that cardiac autonomic dysfunction affects PPA by mechanisms other than resting tachycardia and arterial properties.

Plasma Irisin Levels in Subjects with Type 1 Diabetes: Comparison with Healthy Controls

Irisin is a myokine that increases energy expenditure. In this cross-sectional study, we examined for differences in plasma irisin concentrations between subjects with type 1 diabetes mellitus and healthy individuals and searched for associations between plasma irisin levels and clinical and biochemical characteristics as well as self-reported physical activity. A total of 79 subjects with type 1 diabetes [age 38.2±12.5 years, men/women (n): 27/52], were consecutively recruited. Moreover, 53 healthy controls, matched for age and body mass index with those with diabetes were recruited. Plasma irisin was measured with ELISA. Participants were asked about their physical activity during the last week. We also measured trunk and visceral fat. Circulating irisin levels were lower in subjects with diabetes than in controls [median value (interquartile range): 53.0 (35.2, 106.3) vs. 178.1 (42.6, 641.6) ng/ml, respectively, p<0.001]. In the group of diabetes, univariate analysis showed that irisin levels were associated with waist circumference (beta=-0.283, p=0.023), serum triglycerides (beta=-0.282, p=0.031), and trunk fat (beta=-0.324, p=0.012). In multivariate analysis after adjustment for potential confounders, irisin levels were associated independently only with waist circumference (beta=-0.403, p=0.005). Among controls, multivariate analysis demonstrated that irisin levels were associated with pack-years of smoking (beta=-0.563, p=0.012) and fasting triglycerides (beta=-0.338, p=0.041). Circulating irisin levels were lower in subjects with diabetes in comparison with healthy-matched controls. In conclusion, plasma irisin concentrations in subjects with diabetes were associated with waist circumference, while in controls with serum triglycerides and pack-years of smoking.

The effects of atorvastatin 30 mg compared with atorvastatin 40 mg in patients with primary hyperlipidemia: a multicenter study

C.V. Rizos1, E.N. Liberopoulos1, E. Mpilianou2, V. Kotsis3, N. Tentolouris4, C. Antza3, I. Eleftheriadou4, V. Tsimihodimos1, M.S. Elisaf1* 1Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. 2Department of Cardiology, Tzaneio Hospital, Piraeus, Greece 3Department of Internal Medicine, Aristotle University of Thessaloniki Medical School, Papageorgiou Hospital, Thessaloniki, Greece 4First Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece

Prevalence of diabetes mellitus as well as cardiac and other main comorbidities in a representative sample of the adult Greek population in comparison with the general population

BACKGROUND Diabetes mellitus (DM) is the most common metabolic disorder that increases the risk of cardiovascular disease by two to four times compared with the general population. There are limited data on the prevalence of heart diseases in subjects with DM in Greece. In this study, we examined the prevalence of self-reported DM as well as cardiac and other main comorbidities in a representative sample of the adult Greek population. METHODS The target study population included 30,843 participants stratified by gender, age, and district, and this was a representative sample of the adult Greek population in 2010. A structured questionnaire was built to report the prevalence of self-reported DM and the main comorbidities in participants with and without DM. Collection of data was performed through telephone interviews. RESULTS The prevalence of self-reported DM was 6.6%. The prevalence of the main comorbidities in participants with DM vs. those without DM was as follows: heart diseases 24.0% vs. 8.9%, p<0.001; lung diseases 11.3% vs. 5.3%, p<0.001; kidney diseases 3.4% vs. 1.2%, p=0.001; liver diseases 1.4% vs. 0.7%, p=0.001; benign blood diseases 1.6% vs. 0.9%, p=0.005; and solid organ and/or blood malignancies 2.9% vs. 1.5%, p<0.001. CONCLUSIONS The prevalence of self-reported DM in a representative sample of the adult Greek population in 2010 was 6.6%. The prevalence of heart diseases in subjects with DM was 2.7-fold higher than the prevalence in those without DM. Diseases of the lung, kidney, liver, and blood as well as malignancies were significantly more common among participants with DM.

The Effect of the Oral Administration of Leucine on Endothelial Function, Glucose and Insulin Concentrations in Healthy Subjects

OBJECTIVE The aim of our study was to investigate the potential differential effect of hyperglycaemia and hyperinsulinaemia induced by glucose infusion alone and in combination with leucine consumption on endothelial function in healthy individuals. METHODS Ten male volunteers were examined in random order twice. In one visit, they consumed 250 ml water (baseline) and 30 min later glucose was infused iv. In the other visit, they consumed 250 ml water with 25 g of leucine and 30 min later the same amount of glucose was infused. Serum glucose and insulin were measured at baseline and every 10 min after glucose infusion for 1 h. Endothelial function was evaluated by measurement of flow mediated vasodilatation (FMD) at baseline, 10 and 60 min after glucose infusion. RESULTS In both visits, glucose levels increased to the same degree, whereas insulin response was significantly higher after leucine administration. FMD values declined significantly compared to baseline 10 min after glucose infusion in the control visit (6.9±2.7 vs. 3.2±3.5%, respectively, p=0.006), while no significant change was observed when glucose infusion was followed by leucine consumption. CONCLUSIONS Acute hyperglycaemia impairs endothelial function in healthy male individuals. Leucine administration prevents hyperglycaemia-mediated endothelial dysfunction probably due to enhanced insulin secretion.