Cuma Bulent Gul

Decreased plasma levels of soluble receptor for advanced glycation endproducts (sRAGE) in patients with nonalcoholic fatty liver disease

OBJECTIVES Levels of soluble receptor for advanced glycation endproducts (sRAGE) have been linked to several components of the metabolic syndrome. We tested the hypothesis that plasma levels of sRAGE may be associated with non-alcoholic fatty liver disease. DESIGN AND METHODS We enrolled subjects with definite nonalcoholic steatohepatitis (NASH, n=40), borderline NASH (n=8), simple fatty liver (n=9) and healthy controls (n=14). Plasma levels of sRAGE were measured by ELISA. RESULTS Concentrations of sRAGE were significantly lower in patients with definite NASH (1080+/-392 pg/mL, P<0.01) and borderline NASH (1050+/-278 pg/mL, P<0.05) compared to controls (1480+/-387 pg/mL). Levels of sRAGE were significantly and inversely correlated with ALT (r=-0.30, P<0.05) and AST (r=-0.23, P<0.05). CONCLUSION Plasma levels of sRAGE are significantly reduced in definite and borderline NASH.

Urinary IL-18: a marker of contrast-induced nephropathy following percutaneous coronary intervention?

OBJECTIVES Contrast-induced nephropathy (CIN) is a complication that is underestimated in clinical practice after cardiac catheterization. Recently, the value of interleukin (IL)-18 as a novel biomarker for the detection of acute renal failure has been highlighted. In the present study, we sought to investigate whether urine IL-18 may be an early diagnostic marker of CIN. DESIGN AND METHODS We performed a nested case-control study using a hospital based cohort of all patients (n=157) admitted for elective PCI for stable angina to the Uludag University School of Medicine between February 2007 and June 2007. We identified 15 patients (9.5%) with CIN. Controls were matched with cases at an attempted 2.5:1 ratio by age and gender. Urinary IL-18 values were measured before as well as 24 and 72 h after the PCI. RESULTS No statistically significant differences in urine IL-18 were detected between cases (n=15) and controls (n=36) or between the patient samples obtained before PCI and after the invasive procedure in both study groups. CONCLUSIONS These findings argue against the hypothesis that urine IL-18 may be clinically useful as a biomarker of CIN after radiological procedures requiring intravascular administration of iodinated contrast media. Further studies with larger sample sizes are needed to validate our findings.

Predictive value of the modified Early Warning Score in a Turkish emergency department.

Objective The modified Early Warning Score (mEWS) is a triage instrument that promises to predict patient disposition and clinical outcome in emergency departments (EDs). We investigated whether mEWS can predict death, hospital admission, intensive care unit (ICU) admission, and in-hospital deaths in a Turkish setting. Methods We conducted an ED-based prospective study of 309 patients who presented to an academic medical center. The mEWS was recorded in all patients on ED admission. A mEWS >4 was used to define patients at high-risk for the study outcomes. Results Patients categorized as being at high-risk either were admitted to ICU (n=23) or to hospital (n=37) 56.6% of the time, or died in ED (n=16) or in hospital (n=29) 42.4% of the time. Patients categorized as being at low-risk either were admitted to ICU (n=25) or to hospital (n=52) 37.4% of the time, or died in ED (n=1) or in hospital (n=4) 2.5% of the time. In multivariate regression analysis, patients with a mEWS of 5 or more were 1.95 times more likely to be admitted to ICU than those with a score less than 5. Patients with high-risk mEWS were 35 times more likely to die in ED and 14 times more likely to die in hospital than those presenting with a low-risk score. Conclusion We conclude that scores on the mEWS predict ICU admission as well as ICU and in-hospital deaths.

Comparative effects of pioglitazone and rosiglitazone on plasma levels of soluble receptor for advanced glycation end products in type 2 diabetes mellitus patients

Low levels of soluble receptor for advanced glycation end products (sRAGE) have been associated with the occurrence of vascular complications in patients with type 2 diabetes mellitus. Preliminary evidence has suggested that thiazolidinediones have the ability to modulate circulating levels of this molecule in the hyperglycemic milieu. The aim of this pilot study was to assess the differential effect of 2 different thiazolidinediones-pioglitazone and rosiglitazone-on plasma levels of sRAGE in type 2 diabetes mellitus patients. Sixty type 2 diabetes mellitus subjects were randomly assigned to receive pioglitazone (30 mg/d, n = 19), rosiglitazone (4 mg/d, n = 20), or placebo (medical nutrition therapy, n = 21) for 12 weeks. Changes in plasma glucose, glycosylated hemoglobin, insulin resistance (homeostasis model assessment), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and sRAGE were evaluated at baseline and after 12 weeks. At 12 weeks, the pioglitazone (P < .001) group had a significant increase from baseline in sRAGE values that was not seen in the medical nutrition therapy and rosiglitazone groups. We conclude that, in type 2 diabetes mellitus patients, pioglitazone-but not rosiglitazone-significantly raised sRAGE, which may contribute to its antiatherogenic effects.

Effect of sitagliptin monotherapy on serum total ghrelin levels in people with type 2 diabetes.

AIM Sitagliptin is not associated with weight gain and has neutral effects on body weight. It is unclear whether sitagliptin treatment alters serum ghrelin levels in people with type 2 diabetes. METHODS Forty-four subjects with type 2 diabetes were randomly assigned to receive sitagliptin or medical nutrition therapy (MNT) for 12 weeks. Changes in anthropometric variables, glycemic control, insulin resistance, lipid parameters, and total ghrelin levels were evaluated at baseline and following 12 weeks of treatment. RESULTS Significant decreases in body weight and body mass index were observed over the entire study period in both treatment groups. Glycosylated hemoglobin and postprandial plasma glucose levels were statistically significant decreased in the groups receiving sitagliptin compared with baseline values (p=0.021 and p=0.021, respectively), while they were unchanged in the groups receiving MNT. There was a significant decrease in total ghrelin in the groups receiving sitagliptin (p=0.04) compared with baseline values but not in the groups receiving MNT (p=0.46) at the end of the 12 weeks. CONCLUSIONS In this study of patients with type 2 diabetes, treatment with sitagliptin was associated with a significant decrease in serum ghrelin levels. These results suggest that the neutral effect of sitagliptin on weight might be associated with the suppression of fasting serum ghrelin levels.

Evaluation of serum Spondin 2 levels in the different stages of Type 2 diabetic nephropathy

We aimed to determine whether serum SPON2 is a useful biomarker in the detection of Diabetic Nephropathy (DN) and to compare serum SPON2 levels with 24‐hour urinary albumin excretion rate (UAER) in patients with DN at different stages.

Comparative genotoxic and cytotoxic effects of the oral antidiabetic drugs sitagliptin, rosiglitazone, and pioglitazone in patients with type-2 diabetes: A cross-sectional, observational pilot study

This cross-sectional, observational pilot study was designed to investigate the frequency of different endpoints of genotoxicity (sister-chromatid exchange, total chromosome aberrations, and micronucleus formation) and cytotoxicity (mitotic index, replication index, and nuclear division index) in the peripheral lymphocytes of patients with type-2 diabetes treated with different oral anti-diabetic agents for 6 months. A total of 104 patients who met the American Diabetes Association criteria for type-2 diabetes were enrolled in the study. Of the 104 patients, 33 were being treated with sitagliptin (100mg/day), 25 with pioglitazone (30mg/day), 22 with rosiglitazone (4mg/day), and 24 with medical nutrition therapy (control group). The results for all the genotoxicity endpoints were significantly different across the four study groups. Post hoc analysis revealed that the genotoxicity observed in the sitagliptin group was significantly higher than that observed in the medical nutrition therapy group, but lower than that occurring in subjects who received thiazolidinediones. All of the three cytotoxicity endpoints were significantly lower in patients treated by oral anti-diabetic agents compared with those who received medical nutrition therapy. However, the three indexes did not differ significantly in the sitagliptin, rosiglitazone, and pioglitazone groups. Taken together, these pilot data indicate that sitagliptin and thiazolidinediones may exert genotoxic and cytotoxic effects in patients with type-2 diabetes. Further investigations are necessary to clarify the possible long-term differences between oral anti-diabetic drugs in terms of genotoxicity and cytotoxicity, and how these can modulate the risk of developing diabetic complications in general and cancer in particular.

Relationship between glycemic control, microalbuminuria and cognitive functions in elderly type 2 diabetic patients

Abstract Aim: The prevalence of diabetes is increasing in elderly populations, and is thought to be an important risk factor for cognitive dysfunction in this age group. Methods: The study included 104 patients aged over 60 years who were followed-up for type 2 diabetes for at least 6 months, in addition to 44 controls. Glycemic parameters, microangiopathic complications, microalbumin elimination, and the Standardized Mini Mental State Examination (SMMSE) scores were used as indicators of cognitive function. Results: The SMMSE scores of diabetic patients were significantly lower than the control group (p < 0.05). The average SMMSE score for normoalbuminuric diabetic patients was 22.36 ± 4.66, compared with 22.61 ± 4.90 for the microalbuminuria patients (p = 0.84). A positive correlation was found between SMMSE scores and patients’ hemoglobin values and education levels, whereas a negative correlation was noted between SMMSE scores and systolic and diastolic blood pressures and hemoglobin A1c levels (p < 0.05). Patients with diabetic neuropathy, a microvascular complication of diabetes, were found to have significantly lower SMMSE scores (p = 0.011). Conclusion: Elderly diabetic patients showed decreased cognitive function compared to volunteers. No relationship was established between microalbuminuria and cognitive functions, although diabetic neuropathy was found to be related to decreased cognitive function.

The Impact of Patient Education on Anthropometric, Lipidemic, and Glycemic Parameters Among Patients With Poorly Controlled Type II Diabetes Mellitus: A 3-Month Prospective Single-Center Turkish Study.

This study evaluated the impact of patient education on adherence to a diabetes care plan (e.g., anthropometric, lipidemic, and glycemic parameters) among adults with type II diabetes mellitus without adequate glycemic control. A total of 61 ambulatory adults with type II diabetes mellitus (mean age: 53.6 ± 8.2 years, 70.5% female) were evaluated for anthropometrics, duration of diabetes mellitus, type of anti-diabetic treatment, blood biochemistry, and glycemic parameters in this 3-month prospective observational single-center study. During the course of the study, participants demonstrated a significant decrease in body weight and fat percentage and HbA1c (p < .001 for each). None of the factors evaluated was a significant determinant for glycemic parameters. These findings revealed that adults with type II diabetes mellitus who received education on adherence to routine self-monitoring of blood glucose, standard diabetic diet, and an exercise program delivered by certified diabetes educators had better glycemic control and significant decrease in body weight and fat percentage over a 3-month monitoring period.

Cytokine signal suppressor (SOCS) 1-1478 CA/del gene polymorphism in Turkish patients with polycystic ovary syndrome

Abstract Eighty-four subjects, premenopausal female patients (n = 42, mean (SD) age: 26.4 (4.2) years) diagnosed with polycystic ovary syndrome (PCOS) and age-matched healthy volunteers (n = 42, mean (SD) age: 27.6(3.4) years), were included in this study. Data on physical examination, anthropometric measurements and blood biochemistry analysis were recorded for each subject along with analysis for SOCS1-1478 CA/del polymorphism by polymerase chain reaction-restriction fragment length polymorphism. The relation of SOCS1-1478 CA/del polymorphism to PCOS status and insulin resistance was analysed via logistic regression analysis. Mean (SD) levels for BMI (28.5(6.5) vs.22.5 (4.9) kg/m2, p < .001), HOMA-IR (3.1(1.8) vs.1.5 (1.0), p < .001), LDL-cholesterol (115.9(32.7) vs.100.7 (27.3)mg/dL, p = .03) and triglyceride (113.8(64.9) vs.83.3(36.3)mg/dL, p = .017) were significantly higher in patients. Groups were similar in terms of SOCS1-1478 CA/del polymorphism. No significant relation of this polymorphism was noted to PCOS and HOMA-IR. Our findings revealed no difference between groups in terms of the rate of SOCS1-1478 CA/del polymorphism, and no significant relation of this polymorphism to insulin resistance and PCOS status. Impact statement Polycystic ovary syndrome (PCOS), the most common cause of anovulation and the most commonly encountered form of female endocrine disease. SOCS proteins have been suggested to play a fundamental role in the negative feedback regulation of the JAK-STAT pathway, which is the major signalling pathway involved in a wide range of physiologic and pathologic processes, including inflammatory diseases, malignancies and immune disorders. Pathways involving the induction of suppression of SOCS proteins were also shown likely to be involved in mediating cytokine-induced insulin resistance. The present study was designed to determine the frequency of SOCS1-1478 CA/del gene polymorphism in patients with PCOS in relation to healthy controls and insulin resistance. Our findings revealed significantly higher rates of insulin resistance, obesity and dyslipidaemia in Turkish patients with PCOS compared with age-matched healthy controls, while no difference between study groups in terms of the rate of SOCS1-1478 CA/del polymorphism along with no significant relation of SOCS1-1478 CA/del polymorphism to insulin resistance and PCOS status. Future larger scale studies with the application of standardised diagnostic methods and criteria, and of state-of-the-art modern techniques including genomics, proteomics and pharmacogenetics would provide better understanding of the association between PCOS and genomic variants.