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1.
Endocrine ; 36(3): 425-32, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19784800

ABSTRACT

Ischemia-modified albumin (IMA) is a novel marker of tissue ischemia. Nowadays, IMA is accepted as a marker of oxidative stress. In this study, we aimed at establishing an association between IMA and hyperglycemia, blood pressure, lipid parameters, microvascular complications, hsCRP, and microalbuminuria in type 2 diabetes patients without overt macrovascular disease and acute ischemia. Fifty type 2 diabetes mellitus patients without a history of macrovascular disease or end-stage renal disease were enrolled into the study. Age-matched 30 healthy individuals were also included in the study as a control group. Plasma IMA (0.329 ± 0.046 and 0.265 ± 0.045 AbsU; P < 0.0001) and hsCRP levels (0.51 ± 0.36 and 0.32 ± 0.17 mg/dl; P < 0.0001) were significantly higher in the diabetic group compared to healthy controls. IMA level was significantly correlated with hsCRP (r = 0.76; P < 0.0001), HbA1c (r = 0.72; P < 0.0001), microalbuminuria (r = 0.40; P = 0.004), systolic blood pressure (r = 0.28; P = 0.049), diastolic blood pressure (r = 0.44; P = 0.005), and HOMA-IR (r = 0.42; P = 0.005) levels in the entire diabetic subjects. In the diabetic patients group, presence of microalbuminuria was associated with a higher plasma IMA level (0.355 ± 0.035 and 0.265 ± 0.0045 AbsU; P < 0.0001, patients with microalbuminuria and control subjects, respectively). In the type 2 diabetes patients with nephropathy, IMA level (0.355 ± 0.035 and 0.311 ± 0.046 AbsU; P = 0.002) was determined higher compared to the diabetes patients without nephropathy. Diabetic patients without an overt cardiovascular disease still have a higher serum IMA level compared to healthy controls. The correlation of high plasma IMA levels with high hsCRP and microalbuminuria levels in diabetic subjects indicates the presence of a chronic ischemic process. Therefore, elevated IMA levels may indicate an underlying subclinical vascular disease in type 2 diabetes mellitus patients.


Subject(s)
Albumins/physiology , Diabetes Mellitus, Type 2/diagnosis , Diabetic Angiopathies/diagnosis , Endothelium, Vascular/pathology , Ischemia/diagnosis , Reperfusion Injury/diagnosis , Serum Albumin/physiology , Adult , Aged , Albumins/analysis , Albumins/metabolism , Biomarkers/analysis , Biomarkers/metabolism , Case-Control Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/etiology , Diabetic Angiopathies/pathology , Diabetic Angiopathies/physiopathology , Diagnostic Techniques, Endocrine , Disease Progression , Endothelium, Vascular/physiopathology , Female , Humans , Ischemia/blood , Ischemia/etiology , Male , Middle Aged , Prognosis , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Reperfusion Injury/physiopathology , Serum Albumin/analysis , Serum Albumin/metabolism
2.
Endocrine ; 36(2): 255-61, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19598005

ABSTRACT

Hyperhomocysteinemia is a well-defined risk factor for endothelial dysfunction and atherosclerosis. A point mutation (677 C-T) of MTHFR gene results in a significant increase at plasma homocysteine levels. In this study we aimed to evaluate the effects of MTHFR gene mutation and consequent hyperhomocysteinemia on the development of diabetic microvascular complications in comparison with the other defined risk factors. Diabetic patients without a history of macrovascular complication or overt nephropathy enrolled into the study. The presence of MTHFR 677 C-T point mutation was evaluated by Real-Time PCR technique by using a LightCycler. MTHFR heterozygous mutation was present in 24 patients over 52. Patients with diabetes were divided into two groups according to the presence of MTHFR gene mutation. Both groups were well matched regarding age and diabetes duration. Metabolic parameters, plasma homocysteine, microalbuminuria, folic acid, and vitamin B12 levels were also studied. Presence of neuropathy and retinopathy were evaluated by specific tests. Duration of diabetes, BMI, systolic and diastolic blood pressure, plasma CRP, HbA1c, and lipid levels were not different between the two groups. Plasma homocysteine (12.89 +/- 1.74 and 8.98 +/- 1.91 micromol/l; P < 0.0001) and microalbuminuria levels (73.40 +/- 98.15 and 29.53 +/- 5.08 mg/day; P = 0.021) were significantly higher in the group with MTHFR gene mutation while creatinine clearance levels (101.1 +/- 42.6 and 136.21 +/- 51.50 ml/min; P = 0.008) were significantly lower. Sixteen over 22 (73%) of the patients with diabetic nephropathy had MTHFR gene mutation, while this was only 27% (8 over 30) in normoalbuminuric patients (P = 0.017). There was a significant correlation of plasma homocysteine level with microalbuminuria (r = 0.54; P = 0.031) in the patients with diabetic nephropathy who had C677T polymorphism. We did not find any specific association of MTHFR gene mutation and hyperhomocysteinemia with retinopathy or neuropathy.


Subject(s)
Diabetic Nephropathies/etiology , Hyperhomocysteinemia/complications , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Adult , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Diabetic Nephropathies/blood , Diabetic Nephropathies/genetics , Diabetic Neuropathies/blood , Diabetic Neuropathies/genetics , Disease Susceptibility/etiology , Female , Gene Frequency , Genotype , Homocysteine/blood , Humans , Hyperhomocysteinemia/genetics , Male , Middle Aged , Point Mutation/physiology , Polymorphism, Single Nucleotide/physiology , Risk Factors
3.
Anadolu Kardiyol Derg ; 6(1): 3-8, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16524792

ABSTRACT

OBJECTIVE: The study investigated whether preinfarction angina influences left ventricular functions assessed using Tei index, which is an independent predictor for left ventricular dysfunction in acute myocardial infarction. METHODS: We studied 96 patients with acute myocardial infarction with ST segment elevation (80 men, 16 women; mean age 57.5+/-9.9 years) who were assigned into 2 groups: with and without preinfarction angina. All patients were serially evaluated by 2-dimensional and Doppler echocardiography on the days 1, 6, and 30, and were followed up for 30 days for incidence of complications. RESULTS: We observed that Tei index was lower on the days 1, 6 and 30 (0.49+/-0.20 vs. 0.59+/-0.20, p=0.003, 0.46+/-0.20 vs. 0.56+/-0.20, p=0.001, 0.44+/-0.20 vs. 0.53+/-0.10, p=0.01) in patients with preinfarction angina as compared with those without angina. Tei index significantly decreased during follow-up (0.49+/-0.20, 0.46+/-0.20, 0.44+/-0.20; p=0.02) in patients with preinfarction angina, while it did not change significantly in patients without preinfarction angina (p=0.2). Echocardiographically significant improvements were observed in E deceleration time, isovolumic relaxation time and ejection time in all patients, whereas significant improvements in ejection fraction, wall motion score index and isovolumic contraction time were observed only in patients with preinfarction angina during follow-up. Mortality, Killip class >or=2, pericarditis, atrial fibrillation, and left ventricular thrombus were lower in patients with preinfarction angina. CONCLUSION: These data indicated that the patients with preinfarction angina had better preserved systolic left ventricular function and Tei index values. Also, it was observed that preinfarction angina may cause earlier and more prominent myocardial functional recovery and confer protection against complications on short-term after first acute myocardial infarction.


Subject(s)
Angina, Unstable/physiopathology , Echocardiography, Doppler/methods , Myocardial Infarction/physiopathology , Ventricular Function, Left/physiology , Angina, Unstable/diagnostic imaging , Female , Follow-Up Studies , Heart Function Tests , Humans , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology
4.
Acta Obstet Gynecol Scand ; 84(10): 987-91, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16167916

ABSTRACT

BACKGROUND: Markers of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were studied for the evaluation of short-term effects of raloxifene administration in postmenopausal women. METHODS: Thirty-nine postmenopausal women with osteopenia or osteoporosis were included in this prospective, controlled clinical study. Twenty-five women were given raloxifene hydrochloride (60 mg/day) plus calcium (500 mg/day). Age-matched controls (n = 14) were given only calcium. Plasma TAFI, tPA, and PAI-1 antigen levels were measured at baseline and after 3 months of treatment by commercially available ELISA kits. Variations of individuals were assessed by Wilcoxon's test. Relationship between those markers and demographic characteristics were investigated. RESULTS: Three months of raloxifene treatment was associated with a significant decrease in the plasma TAFI antigen concentrations (16% change, P < 0.01), and a significant increase in tPA antigen concentrations (25% change, P < 0.05). A significant correlation was found between baseline TAFI antigen concentrations and the duration of amenorrhea (P < 0.05; r = 0.33). CONCLUSION: We suggest that the increased risk of venous thromboembolism due to raloxifene treatment may be related to increased tPA levels, but not TAFI levels.


Subject(s)
Carboxypeptidase B2/blood , Osteoporosis, Postmenopausal/drug therapy , Raloxifene Hydrochloride/administration & dosage , Selective Estrogen Receptor Modulators/administration & dosage , Administration, Oral , Antigens/analysis , Calcium, Dietary , Drug Administration Schedule , Enzyme-Linked Immunosorbent Assay , Female , Humans , Middle Aged , Osteoporosis, Postmenopausal/blood , Plasminogen Activator Inhibitor 1/blood , Prospective Studies , Raloxifene Hydrochloride/adverse effects , Selective Estrogen Receptor Modulators/adverse effects , Thromboembolism/blood , Thromboembolism/chemically induced , Tissue Plasminogen Activator/blood
5.
Jpn Heart J ; 45(6): 977-87, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15655273

ABSTRACT

Statins have pleiotrophic effects related to the pathogenesis of atherosclerosis and thrombogenicity of the vessel wall beyond lipid lowering. The aim of the present study was to examine the effect of atorvastatin treatment on the fibrinolytic system in patients with dyslipidemia. The investigation was carried out on 41 dyslipidemic patients (21 males and 20 females) with a mean age of 53.8 years (range, 30-76). The patients were divided into subgroups according to their cholesterol and triglyceride levels as hypercholesterolemic (n = 26) and mixed-type hyperlipidemic (n = 15) and their risk factors for coronary heart disease including age, sex, hypertension, obesity, smoking, and family history. The patients were started on atorvastatin 10 mg/day, and evaluated within 6-12 weeks to assess the changes in fibrinolytic parameters including global fibrinolytic capacity, plasminogen activator inhibitor type-1 and tissue plasminogen activator, and lipids. After successful lipid-lowering therapy, global fibrinolytic capacity (P = 0.003) and tissue plasminogen activator levels (P = 0.04) were found to be increased and plasminogen activator inhibitor type-1 levels (P = 0.02) decreased in dyslipidemic patients. Global fibrinolytic capacity levels increased (P < 0.001) and plasminogen activator inhibitor type-1 levels decreased (P = 0.01) in patients with hypercholesterolemia (n = 26). However, no significant changes were observed in fibrinolytic parameters in patients with mixed-type hyperlipidemia (n = 15). When the patients were separately evaluated according to risk factors, significant beneficial effects on the fibrinolytic system were observed, especially in patients without obesity and hypertension as well as in older patients and males. These findings suggest that atorvastatin treatment has a beneficial effect on the fibrinolytic system in patients with hypercholesterolemia, but not in patients with mixed-type hyperlipidemia. Further studies are needed to show whether higher doses and longer periods of lipid lowering treatment have beneficial effects in patients with mixed type hyperlipidemia and some risk factors.


Subject(s)
Fibrinolysis , Heptanoic Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipidemias/drug therapy , Pyrroles/therapeutic use , Adult , Aged , Atorvastatin , Cholesterol/blood , Diet, Fat-Restricted , Drug Administration Schedule , Female , Humans , Hyperlipidemias/blood , Male , Middle Aged , Obesity/blood , Plasminogen Activator Inhibitor 1/blood , Risk Factors , Smoking/blood , Tissue Plasminogen Activator/blood , Triglycerides/blood
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