Glutathione S-transferases (GSTs) are enzymes involved in the metabolism of many disease-causing electrophilic substrates and protect the cells against oxidative stress. In the present study, we investigated the GSTM1, GSTT1 and GSTP1 gene polymorphisms in diabetic patients and healthy individuals and searched whether polymorphisms in GST genes are associated with diabetes mellitus (DM) in the Turkish population. The study population consisted of 98 unrelated healthy individuals and 98 patients with DM. Genotyping of GSTM1, GSTT1 and GSTP1 genes was performed using real time polymerase chain reaction with a Light Cycler instrument. Patients had a higher frequency of the GSTM1 null genotype than the control group (Odds ratios, OR = 3.7; 95% confidence intervals, CI = 2.05-6.70). However, there was no significant difference in the frequencies of the GSTT1 and GSTP1 gene polymorphisms between the patients and control group. The combined analysis of these three GST genotypes showed a further DM risk increase (OR = 5.7, 95% CI = 1.51-31.07). This is the first study to determine the association of diabetes with GST gene polymorphism in the Turkish population. These results show that GSTM1 null genotype may play a significant role in the aetiopathogeneses of DM and the GSTM1 gene may be a useful marker in the prediction of DM susceptibility of the Turkish population.

OBJECTIVE -Orlistat leads to improved glycemic control in obese type 2 diabetic patients, which is attributed to decreased insulin resistance associated with weight loss. Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are gut hormones that are secreted in response to food intake, and they both stimulate insulin secretion. Orlistat decreases fat absorption and increases intestinal fat content, which may lead to increased secretion of these peptides. In this pilot study, we tested the hypothesis that increased levels of these intestinal hormones may be involved in the improvement of postprandial hyperglycemia observed previously with orlistat in type 2 diabetic patients.RESEARCH DESIGN AND METHODS -A total of 29 type 2 diabetic patients, who were not taking insulin or ␣-glucosidase inhibitors, were enrolled in the study. On a crossover and single-blind design, after an overnight fasting, the patients received 120-mg orlistat or placebo capsules, followed by a standard 600-kcal mixed meal that contained 38% fat. At baseline and 60 min after the meal, blood samples were obtained for the measurement of GLP-1, GIP, insulin, C-peptide, triglycerides, free fatty acids, and glucose.RESULTS -All measured parameters increased significantly in response to the mixed meal compared with baseline, both with orlistat or placebo. When compared with the placebo, the orlistat administration resulted in a significantly enhanced postprandial increase in GLP-1 and C-peptide levels and attenuated the postprandial rise in glucose and triglycerides.CONCLUSIONS -The results of this study suggest that apart from decreasing insulin resistance as a result of weight loss, orlistat may increase postprandial GLP-1 levels, thereby enhancing the insulin secretory response to the meal and blunting the postprandial rise in glucose in type 2 diabetic patients. Increased GLP-1 levels, which lead to decreased food intake, may also contribute to the weight loss that is associated with the use of this drug.

The aim of our study was to investigate the effects of ovariectomy on rat femur biomechanical parameters. Bone mineral density (BMD) and histological investigation were also evaluated. Fourteen female Sprague-Dawley rats (seven ovariectomized, seven control) were used. BMD was measured by dual-energy X-ray absorbsiometry. Bone biomechanical parameters were measured in femoral midshaft with tensile test using a biomaterial testing machine and maximum load, stiffness, energy absorption capacity (structural properties), ultimate stress, ultimate strain, and elastic modulus (material properties) were calculated. Diaphyseal cortical bone thickness was measured by using histological method. The ovariectomized (OVX) rat femur's BMD was 14% lower than control rats (p=0.006). Mean maximum load was 55% less than the control group's (p=0.0001). Stiffness was 72% less in OVX rats (p=0.05). Femurs of rats with OVX had 32% less absorbed energy than controls (p=0.09). From the stress-strain curve ultimate stress, ultimate strain and elastic modulus was calculated. Elastic modulus was 53% less than controls (p=0.05). Ultimate stress decreased 21% in OVX rats (p=0.097). Ultimate strain was 25% less than controls in OVX rats. Cortical thickness was significantly decreased in OVX rats than in controls (p<0.05). In conclusion, femur biomechanical parameters are decreased in osteoporosis.

OBJECTIVES:The aim of this study was to examine the frequency of Cushing’s syndrome (CS) in obese patients devoid of specific clinical symptoms of Cushing’s syndrome.METHODS:A total of 150 obese patients (129 female, 21 male; mean age 44.41 ± 13.34 yr; mean BMI 35.76 ± 7.13) were included in the study. As a first screening step, we measured 24-h urinary free cortisol (UFC). An overnight 1-mg dexamethasone suppression test was also performed on all patients. Urinary free cortisol levels above 100 μg/24 h were considered to be abnormal. Suppression of serum cortisol <1.8 μg/dL after administration of 1 mg dexamethasone was the cut-off point for normal suppression. The suppression of the serum cortisol levels failed in all of the patients.RESULTS:Measured laboratory values were as follows: ACTH, median level 28 pg/ml, interquartile range (IQR) 14–59 pg/ml; fasting glucose, 100 (91–113) mg/dL; insulin, 15.7 (7.57–24.45) mU/ml; fT4, 1.17 (1.05–1.4) ng/dL; TSH, 1.70 (0.91–2.90) mIU/L; total cholesterol, 209 (170.5–250) mg/dL; LDL-c, 136 (97.7–163) mg/dL; HDL-c, 44 (37.25–50.75) mg/dL; VLDL-c, 24 (17–36) mg/dL; triglycerides, 120.5 (86–165) mg/dL. The median UFC level of the patients was 30 μg/24 h (IQR 16–103). High levels of UFC (>100 μg/24 h) were recorded in 37 patients (24%). Cushing’s syndrome was diagnosed in 14 of the 150 patients (9.33%). Etiologic reasons for Cushing’s syndrome were pituitary microadenoma (9 patients), adrenocortical adenoma (3 patients), and adrenocortical carcinoma (1 patient).CONCLUSION:A significant proportion (9.33%) of patients with simple obesity were found to have Cushing’s syndrome. These findings argue that obese patients should be routinely screened for Cushing’s syndrome.