Candeger Yilmaz

Effect of Weight Loss on Bone Metabolism: Comparison of Vertical Banded Gastroplasty and Medical Intervention

Background: We studied the effects of weight loss on bone metabolism. Methods: 16 consecutive surgically-treated (14 female, 2 male) morbidly obese patients and 65 obese (53 male, 12 female) medically-treated patients were enrolled in an observational study. Surgical treatment for morbidly obese patients was vertical banded gastroplasty (VBG). Studies were performed prior to and 12 months after the start of treatment. Bone mineral density (BMD), bone turnover markers, sex steroids, calcium excretion and parathyroid hormone measurements were done at each visit. Results: Weight loss was more prominent with surgical than with medical treatments. Bone loss was also pronounced in the surgical treatment group, and occurred at the hip level only (P<0.05). Compared to previously reported studies, where the effects of malabsorptive treatments for obesity on bone metabolism were studied, calcium excretion and parathyroid hormone levels did not change after VBG or medical therapy. For both groups, bone markers indicated an increased bone turnover, evidenced by increased urinary excretion of deoxypyridinoline and serum levels of osteocalcin (P<0.05). Sex steroid measurements revealed a decrease in estradiol levels in the surgical treatment group, but not in medical treatment group. This finding was thought to be secondary to less weight loss in the medical group. Conclusion: Our data indicate that weight loss causes bone loss. The bone loss is independent of the method of weight reduction. However, the mechanism of the bone loss is not clear. It may be explained partly by reduced estradiol levels in female patients. Because the mechanisms of bone disease after weight loss remain unclear, it is difficult to determine the most effective treatment. It is important to detect osteopenia early, before fractures occur. Measuring BMD appears to be the only reliable method for screening.

Efficacy of insulin-sensitizing agents in nonalcoholic fatty liver disease.

Aim To investigate the efficacy of insulin-sensitizing agents in nonalcoholic fatty liver disease (NAFLD) patients. Methods This is an open-label, randomized, a single-center study. Sixty-four patients, with impaired glucose metabolism and elevated alanine aminotransferase for at least 6 months before enrollment and NAFLD activity score at least 5 in liver biopsy, were randomized as group 1 and received metformin 1700 mg/day, group 2 received rosiglitazone 4 mg/day, and group 3 received a combination of metformin 1700 mg/day and rosiglitazone 4 mg/day for 12 months. Results Baseline demographic and laboratory findings were similar in all the three groups, except baseline insulin level that was significantly higher in group 1 and group 3 versus group 2 (P<0.05). Serum transaminase levels showed a significant decrease after treatment in both group 2 and group 3. Serum &ggr;-glutamyl transpeptidase levels decreased significantly only in the group 3. However, there was no significant change in liver tests of group 1. Postprandial glucose levels showed significant decrease in all of the three groups. Homeostasis model assessment-insulin resistance was reduced significantly in only group 2. NAFLD score was significantly decreased on follow-up biopsy of the patients in group 2 and group 3. Fibrosis did not change significantly after the treatment. Conclusion Rosiglitazone therapy seems to be more effective in metabolic control and histological improvement in NAFLD patients with impaired glucose metabolism.

Metabolic syndrome, insulin resistance, fibrinogen, homocysteine, leptin, and C-reactive protein in obese patients with obstructive sleep apnea syndrome

OBJECTIVE: The prevalence of obstructive sleep apnea syndrome (OSAS) and metabolic syndrome is increasing worldwide, in part linked to epidemic of obesity. The purposes of this study were to establish the rate of metabolic syndrome and to compare fibrinogen, homocysteine, high-sensitivity C-reactive protein (hsCRP), leptin levels, and homeostasis model assessment insulin resistance (HOMA-IR) in the obese patients with and without OSAS. METHODS: The study population included 36 consecutive obese patients with OSAS (23 males; mean age, 50.0 ±19.7 years), and 34 obese patients without OSAS (17 males; mean age, 49.7±11.1 years) were enrolled as control group. Metabolic syndrome was investigated; fibrinogen, homocysteine, CRP, and leptin levels were measured, and IR was assessed. RESULTS: Metabolic syndrome was found in 17 (47.2%) obese OSAS patients, whereas only 29.4% of obese subjects had metabolic syndrome (P > 0.05). Obese patients with OSAS had significantly higher mean levels of triglyceride (P < 0.001), total-cholesterol (P = 0.003), low-density lipoprotein-cholesterol (P = 0.001), fasting glucose (P = 0.01), HOMA-IR (P <0.001), thyroid-stimulating hormone (P = 0.03), fibrinogen (P < 0.003), hsCRP (P <0.001), and leptin (P = 0.03) than control group . Besides, leptin level was positively correlated with waist (r = 0.512, P = 0.03) and neck circumferences (r = 0.547, P = 0.03), and fasting glucose (r = 0.471, P = 0.04) in OSAS patients, but not in obese subjects. CONCLUSION: This study demonstrated that obese OSAS patients may have an increased rate of metabolic syndrome and higher levels of serum lipids, fasting glucose, IR, leptin, fibrinogen, and hsCRP than obese subjects without sleep apnea. Thus, clinicians should be encouraged to systematically evaluate the presence of metabolic abnormalities in OSAS and vice versa.

Hyperinsulinemia and Insulin Insensitivity in Women with Nonclassical Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: The Relationship between Serum Leptin Levels and Chronic Hyperinsulinemia

Background/Aim: Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (NC-CAH) is associated with hyperandrogenemia, chronic anovulation, hirsutism, acne and adrenal hyperplasia. A few studies have shown hyperinsulinemia and insulin insensitivity in NC-CAH. Hyperinsulinemia can stimulate leptin secretion, and androgens can inhibit leptin secretion. Thus, we designed a study to investigate the insulin levels and insulin sensitivity and the effect of chronic endogenous hyperinsulinemia and androgens on leptin in patients with NC-CAH. Methods: Eighteen women with untreated NC-CAH and 26 normally cycling control women with a similar body mass index (BMI) were studied. Basal hormones, fasted and fed insulin levels, leptin and stimulated 17-hydroxyprogesterone (17-OHP) concentrations were studied. Homeostasis model assessment was used to assess insulin sensitivity. Results: The basal 17-OHP, the free testosterone (fT) and dehydroepiandrosterone sulfate (DHEA-S) were significantly different in the 2 groups (p < 0.05). Fasting and fed insulin levels of the NC-CAH group were higher than those of the control group (p < 0.05) and insulin sensitivity was lower in NC-CAH than in controls (p < 0.05). Insulin levels were correlated with fT and 17-OHP (p < 0.05). Serum leptin levels for NC-CAH (25.9 ± 12.5 µg/l) did not differ from the controls (25.4 ± 12.06 µg/l) and were positively correlated with BMI (r = 0.725) and percent body fat (r = 0.710) for both groups (both p < 0.001). Leptin levels were not correlated with estrogen or androgens, gonadotropins or insulin levels. Conclusion: Hyperinsulinemia and insulin insensitivity associated with hyperandrogenism were detected in untreated NC-CAH patients as in previous reports, whereas serum leptin levels did not differ from those of controls.

Oxidative Stress Markers in Young Patients with Polycystic Ovary Syndrome, The Relationship between Insulin Resistances

OBJECTIVE Polycystic ovary syndrome is a syndrome of ovarian dysfunction. Oxidative stress, inflammation and endothelial cell activation are thought to play concomitant roles in the pathogenesis of the above diseases particularly in the development of atherosclerotic lesions. RESEARCH DESIGN AND METHODS We studied 58 polycystic ovary syndrome patients and age-matched 25 healthy controls consisting of women that have regular, ovulatory cycles and normal androgen levels. Homeostasis Model Assessment-Insulin Resistance for this study was taken as 1.75 that is the upper level of confidence interval of %95 of the mean of the healthy group. PCOS patients were divided into two groups as for below the cut-off level (<1.75) and above the cut-off level (> or =1.75). hs-CRP, fibrinogen, malondialdehyde, nitric oxide and disulfide level results were compared both in PCOS and control groups. RESULTS In this study, sensitive CRP was found to be statical significantly higher in polycystic ovary syndrome groups whose Homeostasis Model Assessment-Insulin Resistance were > or =1.75 and <1.75 when compared to the control group. But, no significantly correlation was determined between malondialdehyde, nitric oxide and disulfide levels and CRP elevation. CONCLUSIONS In our study, because those participants were young and non- obese patients with PCOS, malondialdehyde, nitric oxide and disulfide levels and Carotid Artery Intima-Media Thickness measurements as a pre-indicator of cardiovascular disease were not found to be different from those of the controls.

Effect of surgical weight loss on free radical and antioxidant balance: a preliminary report.

Background:This study observes the effect of surgical weight loss on free radical and antioxidant vitamin balance. Patients and Methods: 22 consecutive morbidly obese patients undergoing vertical banded gastroplasty (VBG) were chosen for the study. Postoperative studies were done at 12 and 24 weeks. Plasma antioxidant and vitamin determinations were performed by HPLC method. Results: Subjects lost a significant amount of weight (P<0.01). Compared to preoperative measurements, postoperative measurements of plasma betacarotene were not statististically different both at 12 and 24 weeks (13.86±1.26 μg/dl, 12.35±1.2, P=0.44; 14.33±2.03, P=0.77; preoperatively, 12 and 24 weeks respectively). Alpha-tocopherol increased slightly at the 12th week; the difference was not significant (8.50±0.77; 9.56±0.82, P=0.37; preoperatively and 12th week respectively). The levels of alpha-tocopherol rose at 24th week significantly (10.89±0.55, P=0.028). The indicator of lipid peroxidation (malondialdehyde) decreased with weight loss (1.505±0.11 μmol/L preoperatively; 0.75±0.062 at 12th week, P=0.01; 0.712±0.05 at 24th week, P<0.01). Conclusion: Our data show that free radical generation falls markedly in association with weight loss after VBG. Surgical weight loss leads to significant decrease in oxidant production and also leads to increase in some antioxidant vitamins. The demon stration of decreased free radical generation and correction of balance between free radicals and antioxidant vitamins has important implications for oxidative mechanisms underlying obesity-associated disorders.

Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat

This study investigates the contribution of vitamin supplementation to the efficacy of oral antidiabetic therapy on the reversal of endothelial dysfunction in a model of type‐2 diabetes in rat.

The relationship of the interleukin-6 -174 G>C gene polymorphism with oxidative stress markers in Turkish polycystic ovary syndrome patients.

Objective: Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular (CD) diseases. Cardiovascular risk factors that have been reported include oxydative stress markers [nitric oxide (NO), malondialdehyde (MDA), disulphite (SH)]. We aimed to evaluate the relation between the IL-6 G/C gene polymorphism and oxidative stress markers in polycystic ovary syndrome (PCOS) patients. Design and patients: We studied 85 PCOS patients and 115 healthy controls. PCOS was defined by the Rotterdam PCOS consensus criteria. Results: The genotype IL-6 distribution did differ between the control group (CC 9.6%, GC 63.4%, GG 27.0%) and the PCOS patients (CC 4.7%, GC 29.4%, GG 65.9%) (p<0.001). The frequency of the polymorphic G allele was also not similar for the group with PCOS as for the control group with 80.6% and 58.7%, respectively (p<0.001). No statistically significant difference was determined for MDA and NO levels in PCOS patients and control group (p>0.05). Only SH levels were found to be high in favor of patient group (p<0.05). No statistically significant difference was determined between IL-6 G/C gene polymorphism and oxidative stress markers in PCOS patients and in the control group. Conclusion: Gene polymorphism of IL-6 −174 G>C is a risk factor for PCOS in Turkish patients. IL-6 gene polymorphisms are not related to NO, MDA, and SH levels in PCOS. Our negative results in risks factors of CV disorders can probably be explained by the fact that metabolic parameters and endothelial systems of patients may not yet be affected in this short period of time.

The relationship of the methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy

Poor glycaemic control, hypertension and duration of diabetes are risk factors for the development of diabetic nephropathy, but there may be genetic factors. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677C > T) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. We aim to investigate Turkish type 2 diabetic patients with/without diabetic nephropathy and healthy group and examine the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy.

Effect of I-deprenyl and gliclazide on oxidant stress/antioxidant status and dna damage in a diabetic rat model.

Background: This study investigates the possible effect of monoamine oxidase inhibitor (MAOI), selegyline (l-deprenyl), in combination with oral antidiabetic-gliclazide (OAD), in preventing oxidative stress in streptozotocin-induced diabetes model in male Swiss Albino rats by measuring oxidant stress/DNA damage and antioxidant levels. Methods: Diabetic rats were divided into four groups (n = 10) as [1] diabetic untreated (DM), [2] deprenyl treated (DM + D), [3] gliclazide treated (DM + O), and [4] gliclazide and deprenyl treated (DM + O + D). Controls were divided into two groups (n = 8) [1] untreated (C), and [2] deprenyl treated (C + D). Gliclazide 5 mg/kg and/or MAOI 0.25 mg/kg daily were given orally by gavage for 4 weeks. At the end of the 12th week, catalase and superoxide dismutase (SOD) levels in erythrocyte lysates (EL); total antioxidant status (TAS), 8-hydroxy-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and vitamin A and E levels in plasma, MDA, and MAO in liver homogenates were determined. Results: Diabetic rats showed a decrease in EL-SOD, plasma TAS, and vitamin E, and an increase in plasma 8-OHdG, plasma, and liver MDA levels (p < 0.05). Gliclazide and/or deprenyl decreased 8OHdG levels and increased antioxidant levels and survival when compared with untreated diabetic rats (p < 0.05). The lowest 8-OHdG levels were determined in the DM + O + D group. Conclusions: The combined treatment of deprenyl and gliclazide may contribute to the control of the physiopathological mechanisms underlying both the process of aging and type 2 diabetes by reducing oxidant stress and DNA damage, improving antioxidant status, and increasing survival, and may have implications for further clinical studies.