Stavroula Papaoikonomou

The association of the 174G > C polymorphism of interleukin 6 gene with diabetic nephropathy in patients with type 2 diabetes mellitus

AIMS To evaluate the association of 174G>C polymorphism on interleukin-6 (IL-6) gene with diabetic nephropathy in patients with type 2 diabetes. METHODS A total of 393 Greek subjects with type 2 diabetes (mean age 66.5±10.0years, men n=203, women n=190) were examined. Diabetic nephropathy was defined as presence of microalbuminuria and/or proteinuria. The IL-6 174G>C polymorphism was detected by polymerase chain reaction and appropriate restriction enzyme digestion. High sensitivity C-reactive protein was assayed by particle-enhanced immunonephelometry. RESULTS The genotype distribution (%) was GG: 49.1, GC: 26.8 and CC: 24.1, with no gender difference. The CC homozygotes had lower albumin excretion (mg/24h) in comparison with the GC genotype [CC: 8.9 (4.0-20.9) vs GC: 21.95 (9.1-53.35), P=0.004]. Participants with the GC genotype tended to have more frequently nephropathy than those with the GG or the CC genotype [GC: 44.55% vs GG: 35.1% and CC: 28.3%, P=0.07)]. The CC homozygotes in comparison with GC heterozygotes had lower odds to have nephropathy (odds ratio: 0.51, 95% confidence intervals=0.28-0.91, P=0.02), even after adjustment for sex, age, duration of diabetes, body mass index, smoking, hypertension, lipids and glycated hemoglobin, (P=0.01). CONCLUSION In type 2 diabetes states, CC homozygotes have lower albumin excretion and are protected from nephropathy in comparison with GC genotypes.

The impact of diabetes mellitus on coronary artery disease: new therapeutic approaches.

Patients with diabetes mellitus (DM) type 2 have a high prevalence of coronary artery disease (CAD), as diabetes is implicated in the formation of atherosclerotic plaque. Hyperglycemia, elevated free fatty acid, increased amount of circulating end-glucosylated serum products and insulin resistance are the main mechanisms involved in the accelerated atherosclerotic process observed in type 2 DM patients. Novel treatments have been proposed to prevent and treat CAD in patients with diabetes, mainly in those with diabetes type 2. Several clinical trials have been designed in order to examine the effectiveness of these agents, such as angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, glitazones, statins and antioxidants, but the results are still controversial.

Management of type 2 diabetes and its prescription drug cost before and during the economic crisis in Greece: an observational study

BackgroundThe aim of the present study is to examine the clinical indices related to cardiovascular risk management of Greek patients with type 2 diabetes, before and after the major economic crisis that emerged in the country.MethodsIn this retrospective database study, the medical records of patients with type 2 diabetes treated at three diabetes outpatient centers of the national health system during 2006 and 2012 were examined. Only patients with at least six months of follow-up prior to the recorded examination were included. The prescription cost was calculated in Euros per patient-year (€PY).ResultsA total of 1953 medical records (938 from 2006 and 1015 from 2012) were included. There were no significant differences in adjusted HbA1c, systolic blood pressure and HDL-C, while significant reductions were observed in LDL-C and triglycerides. In 2012, a higher proportion of patients were prescribed glucose-lowering, lipid-lowering and antihypertensive medications. Almost 4 out of 10 patients were prescribed the new incretin-based medications, while the use of older drugs, except for metformin, decreased. A significant increase in the adjusted glucose-lowering prescription cost (612.4 [586.5-638.2] €PY vs 390.7 [363.5-418.0]; p < 0.001) and total prescription cost (1306.7 [1264.6-1348.7] €PY vs 1122.3[1078.1-1166.5]; p < 0.001) was observed. The cost of antihypertensive prescriptions declined, while no difference was observed for lipid-lowering and antiplatelet agents.ConclusionsDuring the economic crisis, the cardiovascular risk indices of Greek patients with type 2 diabetes being followed in public outpatient diabetes clinics did not deteriorate and in the case of lipid profile improved. However, the total prescription cost increased, mainly due to the higher cost of glucose-lowering prescriptions.

Effects of the C-344T aldosterone synthase gene variant on preclinical vascular alterations in essential hypertension

regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation. J Am Coll Cardiol 2000;35:1669–77. [43] Kumagai K, Nakashima H, Urata H, et al. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol 2003;41:2197–204. [44] Shimano M, Tsuji Y, Inden Y, et al. Pioglitazone, a peroxisome proliferators-activated receptor-gamma activator, attenuates atrial fibrosis and atrial fibrillation promotion in rabbits with congestive heart failure. Heart Rhythm 2008;5:451–9.

Genetic Variant of the C-reactive Protein Gene and Prevalence of Peripheral Arterial Disease in Patients with Type 2 Diabetes Mellitus

Objective: Diabetes mellitus is strongly associated with inflammatory procedures, obesity and macrovascular complications, while genetic factors are involved in the disease pathogenesis and its complications. The aim of this study was to examine the impact of A3872G polymorphism on C-reactive protein (CRP) gene on the prevalence of peripheral arterial disease (PAD) in Greek Caucasian subjects with type 2 diabetes mellitus (T2DM). Methods: The study population consisted of 423 patients with T2DM. The A3872G polymorphism was detected by polymerase chain reaction and appropriate restriction enzyme digestion (HpyCH4III). High sensitivity CRP was assayed by particle-enhanced immunonephelometry. PAD was diagnosed using clinical or ultrasonography criteria and/or ankle brachial index <0.9. Results: The genotype distribution (%) in PAD patients (GG: 48.1, AG: 29.1, AA: 22.8) did not differ significantly compared to non-PAD disease subjects (GG: 53.8, AG: 26.7, AA: 19.5), (P=0.258). After adjustment for classical risk factors, carriers of “A” allele (AG+AA) compared with GG homozygotes had higher odds (OR) for PAD, (AG+AA): 82 (40.0) vs. GG: 76 (34.2), (OR 1.622, 95% confidence intervals 1.029-2.536, P=0.037). Conclusions: In Caucasian subjects with T2DM, the GG homozygotes of the A3872G genetic polymorphism on the C-reactive protein gene may be protected from the risk of peripheral arterial disease compared to carriers of the “A” allele. These results indicate a potential genetic role of inflammation in atherosclerosis in patients with type 2 diabetes mellitus.

The role of C-reactive protein genetic variability in the onset of carotid artery disease and renal function impairment in patients with diabetes mellitus type 2.

The role of diabetes mellitus (DM) in cardiovascular disease is well established and currently is considered as an equivalent of coronary artery disease. Studies have also reported that DM is associated with the prevalence of occlusive carotid artery disease (AD) [1] as well as the grade carotid artery stenosis [2]. In addition, DM is related to impaired renal function via several mechanisms [3]. During the last years novel data have arisen for the role of genetics in the initiation and progression of carotid AD [4–8] as well as for impaired renal function [9,10]. However, scarce data exist regarding genetic polymorphisms in patients with diabetes mellitus and their role in carotid artery disease and renal function. Thus, in the present study we examined the potential role of a single nucleotide polymorphism (SNP) on C-reactive protein (CRP) gene in the onset of carotid AD and impaired renal function in patients with diabetes mellitus type 2. Our study population consisted of 430 patients with DM2 (documented for carotid AD or not). Subjects were characterized as patients with DM2 if fasting plasma glucose levels were ≥126 mg/dl, or 2-hour post glucose loading plasma levels were ≥200 mg/d according to the American Diabetes Association [11]. Carotid artery disease was evaluated based on history of transient ischemic attack or stroke, important degree of carotid stenosis in Doppler ultrasonography or blowing existence or interventional procedure of carotid revascularization. Subjects were considered to have systemic hypertension if their systolic and/or diastolic blood pressure was ≥140 and/or ≥90 mmHg on two different occasions. Moreover subjects were considered to have systemic hypertension if they were currently being treated with anti-hypertensive drugs or when a significant history of hypertension was present [12]. Subjects were considered to have dyslipidemia if total cholesterol levels ≥200 mg/dl were revealed in biochemical tests or if they were already treated with antihyperlipidemic agents [13]. Current smokers were regarded as subjects smoking 1–10 cigarettes/day for at least the last year [14]. In the exclusion criteriawe included any acute or chronic inflammatory disease, malignancies, and renal or liver failure. Glomerular filtration rate (GFR) was measured by the appropriate formula. The studywas approvedby the institutional ethics committees, and an informed consent was given by all the participants. Venous blood samples were centrifuged at 3500 rpm at 4 °C for 15 min, and plasma or serum was collected and stored at −80 °C until assayed. Serum concentrations of lipids were determined by using colorimetric enzymatic method in a Technicon automatic analyzer RA-

THE ASSOCIATION OF A3872G POLYMORPHISM ON C-REACTIVE PROTEIN WITH PERIPHERAL ARTERIAL DISEASE AND WAIST HIP RATIO INDEX IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Recent data consider inflammatory biomarkers and waist hip ratio (WHR) index prognostic agents of advanced atherosclerosis. C- reactive protein (CRP) contributes to the pathogenesis of type 2 diabetes mellitus (T2DM). However, the impact of common polymorphisms of inflammatory genes on the