Taylan Kabalak

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.

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.

Demographic and clinical features of patients with subacute thyroiditis: Results of 169 patients from a single University Center in Turkey

Background: Turkey is an endemic area for thyroid diseases. The Aegean region is well documented for increased prevalence of thyroid disorders. In this study we investigated the demographic and clinical features of subacute thyroiditis (SAT) patients who had been diagnosed and treated in Ege University. Methods: The hospital files of patients admitted to the endocrinology clinic of Ege University between January 1987 and December 2001 were retrospectively evaluated. Patients who had been diagnosed as having any thyroid disorder were determined. Results: 176 fulfilled diagnostic criteria for SAT. The majority of patients with SAT were diagnosed as having subacute granulomatous thyroiditis (169/176) (134 females, 35 males, mean age 34.0±17.8 yr); 69% of the patients were between 30–50 yr of age. Thyroid pain was present in 97.1% of female patients, and in 100% of male patients. High fever was evident in 78 patients (46.2%). Mean erythrocyte sedimentation rate (ESR) was 43.42±39.68 mm/h. Anti-thyroglobulin antibody was positive in 20%, and anti-thyroid peroxydase antibody was positive in 4% of patients. Among patients who were treated with non-steroidal anti-inflammatory drugs (NSAD) 10 female patients (10.6%), and 3 male patients (12%) developed recurrence of the disease. Among patients who were treated with prednisolone 7 female patients (17.5%), and one male patient (10%) developed recurrence. There was no significant difference regarding the recurrence rates between patients who were treated with NSAD and patients who were treated with prednisolone. Conclusion: With the exception of ESR, demographic, clinical, laboratory, and imaging findings and prognoses of our patients were comparable to the previous reports.

Effect of hypo- and hyperthyroidism on gastric myoelectrical activity.

Although hypo- and hyperthyroid patients have different symptoms in the gastrointestinal tract, the mechanism of thyroid action on the gut remains poorly understood. Thus the aim of this study was to investigate the effect of hypo- and hyperthyroidism on gastric myoelectrical activity, gastric emptying, dyspeptic symptoms. Twenty-two hyperthyroid (median age 45, 15 females) and 11 hypothyroid (median age 42, 10 females) patients were included into the study. Dyspepsia score, hypo- and hyperthyroid symptom scale, abdominal ultrasonography and upper gastrointestinal endoscopy were performed. Gastric myoelectrical activity was measured by electrogastrograpy (EGG) before and after therapy both preprandially and postprandially and compared with age, gender, and body-matched controls (12 for hypothyroid, 15 for hyperthyroid patients). Radionuclide gastric emptying studies were performed with a solid meal. Hypothyroid patients revealed a significant increase in preprandial tachygastria as compared with controls (12.3% vs 4.8%). The percentage of preprandial normal slow waves (2.4–3.7 cpm) was below 70% (dysmotility) in 7 of 11 hypothyroid patients versus 2 of 12 controls (P < 0.05). Hyperthyroid patients revealed a significantly higher preprandial (3.1 vs 2.8) and postprandial (3.4 vs 3) DF when compared with the controls (P < 0.05). A higher percentage of postprandial taschygastria (7.9 vs 0) was present in hyperthyroid patients than in the controls (P < 0.05). The decrease on postprandial EGG power (power ratio < 1) was observed in 7 patients the in hyperthyroid group and 1 in controls (P < 0.05). The percentage of postprandial normal slow waves was below 70% in 10 of 20 hyperthyroid patients vs 1 of 15 controls (P < 0.05). After therapy these differences disappeared in the euthyroid state. The hypo- and hyperthyroid symptom scale correlated to dyspepsia score. Dyspepsia score in hyperthyroidism correlated to power ratios in hyperthyroid patients. We detected some correlations between serum levels of fT3 or fT4 and some EGG parameters in hypo- and hyperthyroidism. Dyspepsia score and hypo- and hyperthyroid symptom scale were improved significantly after therapy in the euthyroid state. In conclusions, we showed gastric dysrhythmia by EGG in both hypo- and hyperthyroid patients. Dyspeptic symptoms correlated to the activity of thyroid disease. After therapy, these findings and dyspeptic symptoms improved in the euthyroid state. Abnormalities of power ratios may be responsible of dyspeptic symptoms in hyperthyroid patients. EGG may be a useful and noninvasive tool for detecting gastric disturbances during hypo- and hyperthyroidism.

Fas/Fas ligand gene polymorphism in patients with papillary thyroid cancer in the Turkish population.

Objective: Fas ligand (FasL) is an apoptotic agent and a member of tumor necrosis factor (TNF) family. FasL exists in cytotoxic T lymphocyte (CTL) and natural killer (NK) cells, and it is increased in tumor cell membrane. On the contrary, CTL and NK are bound to Fas on the surfaces of cell membrane; this triggers apoptosis in cytotoxic cells and leads to their death. This system plays an important role in eliminating viral infections and cancer cells. Malfunction of this system results in the development and spread of the malignancy. This study aims at evaluating the influence of Fas and FasL gene polymorphism in papillary thyroid cancer (PTC) in the Turkish population. Research design and methods: Forty-five patients with PTC and 100 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for Fas 670 A/G and FasL 843 C/T gene polymorphism was performed using the PCR-restriction fragment length polymorphism (RFLP) method. Results: The evaluation of Fas/FasL genotype and gene allele frequency did not show statistically significant differences between the patient and control group (p>0.05). In addition, the univariate analysis did not reveal a statistically significant relationship between the size of the nodule and the Fas/FasL gene polymorphism in patients with PTC. Conclusions: As in other types of malignancy, genetic factors in the pathogenesis of PTC may also show changes in different populations. Fas/FasL gene polymorphysms are possible that different mechanisms function in apoptosis balance in PTC development.

Long-term treatment with acarbose for the treatment of reactive hypoglycemia

Objective: Acarbose, a potent alpha-glucosidase inhibitor, provides a new concept for the treatment of metabolic disorders, and particularly diabetes mellitus. It reduces the postprandial blood glucose increment and insulin response. For this reason the drug has been successfully used not only in the treatment of type 1 and type 2 diabetes, but also in the management of reactive hypoglycemia and dumping syndrome. The primary aim of the present study is to evaluate the long-term effect of acarbose in reducing hypoglycemic symptoms and influencing laboratory measurements in patients with the diagnosis of reactive hypoglycemia. Design and Methods: 21 non-obese (BMI <27 kg/m2) patients (6 males, 15 females) complaining of postprandial symptoms suggesting hypoglycemia and who showed blood glucose values of <54 mg/dI on one or more occasions during a 5 h oral glucose tolerance test (OGTT) were selected. Results: Before treatment, ingestion of glucose decreased plasma glucose levels at the 3rd and 4th hours, the lowest levels being 39 mg/dl and 45 mg/dl respectively. Eighteen patients had hypoglycemic symptoms during OGTT. Following 3 months of acarbose treatment, the lowest plasma glucose levels at the 3rd and 4th hours increased to 67 mg/dI and 75 mg/dI respectively. Plasma insulin and c-peptide levels were reduced between the 1st and 5th hours, but only the 1st and 2nd hour decrements were statistically significant. The area under the curve (AUC) between 0–300 minutes for insulin was not significant. Plasma glucose levels were significantly increased during the last 3 hours The AUC for glucose was not significantly changed. Frequency of hypoglycemic attacks was reduced from 4 times a week to 1. C-peptide levels in 24-hour urine collection did not change significantly: 45 μg/I and 56 μg/I respectively before and after treatment. Conclusions: These results confirm that acarbose may be of value in preventing reactive hypoglycemia by reducing the early hyperglycemic stimulus to insulin secretion, and in the treatment of reactive hypoglycemia.

Increasing severity of cardiac autonomic neuropathy is associated with increasing prevalence of nephropathy, retinopathy, and peripheral neuropathy in Turkish type 2 diabetics.

BACKGROUND Cardiac autonomic neuropathy (CAN) is the most frequent and clinically important form of diabetic autonomic neuropathy. CAN is associated with increased frequency of other microvascular complications of diabetes mellitus (DM). In this study, we evaluated the prevalence diabetic nephropathy, retinopathy, and peripheral neuropathy, and measured gastric emptying time and bladder emptying time in type 2 diabetic patients with varying degrees of CAN. PATIENTS AND METHODS Fifty-three patients with DM complicated by CAN (30 women and 23 men; mean age, 58.8+/-9.15 years; duration of diabetes, 13.9+/-7.7 years) were included in this study. The patients were grouped according to the degree of CAN as early, definite, and severe CAN. RESULTS There were significant differences regarding the prevalence of nephropathy, retinopathy, and peripheral neuropathy diagnosed by EMG among those groups (P<.05). However, there was no significant difference regarding the prevalence of peripheral neuropathy diagnosed by neurological examination (P>.05), and scintigraphic measurements of gastric and bladder emptying time were comparable among the groups (P>.05). CONCLUSION The prevalence of other diabetic microvascular complications increase as the severity of CAN increases in patients with type 2 DM. This study emphasizes the need for an early screening for peripheral neuropathy, retinopathy, and nephropathy in type 2 diabetic patients with CAN, especially with severe involvement.

Assessment of Insulin Resistance in the Idiopathic Hirsutism

Background: Idiopathic hirsutism (IH) is the second most common cause of hirsutism, after polycystic ovary syndrome and occurs in about 15% of hirsute women. There are not many studies showing whether patients with IH also have insulin resistance. In the present study, we aimed to investigate the insulin sensivity in IH with non-obese and changing hormone levels during the hyperinsulinemic-euglycemic clamp. Methods: Twenty (20) non-obese women with IH (Group I) ranging in age from 20 to 30 (mean 25 ± 5) years were studied. Hirsutism in women with normal testosterone (T) levels and regular menstrual cycles is as defined IH. Twenty (20) healthy women (mean age 23 ± 2 years) (Group II) were included in this study as the control group. Insulin sensitivity was assessed with modified euglycemic insulin clamp technique. Samples of prolactin, luteinizing hormone (LH), follicle-stimulating hormone, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate, cortisol, estradiol, progesterone, 17-OH progesterone (17-OHP), total T, and free T (FT) were obtained at baseline and at 2nd hour during clamp. Results: Steady-state (120 min) glucose disposal rates were higher in Group II than Group I (7.51 ± 0.83 vs. 5.76 ± 1.89 mg/kg/min). Mean FT, ACTH, cortisol, LH, prolactin and 17-OHP levels were found to have decreased statistically significantly (p < 0.05) in Group I. Mean FT, ACTH, and prolactin levels were found to have decreased statistically significantly (p < 0.05) in Group II during the clamp. Mean baseline levels of FT, LH and prolactin were greater in women with hirsutism than in the control subjects (p < 0.05). Insulin mediated glucose disposal was lower in the normal weight women with IH than in those without hirsutism. Conclusions: Mean FT, 17-OHP and dehydroepiandrosterone sulfate levels decreased during euglcemic-hyperinsulinemic clamp in IH.

Effects of sibutramine on thermogenesis in obese patients assessed via immersion calorimetry

Glucose utilization studies show that sibutramine-induced thermogenesis is mediated via selective sympathetic activation of brown adipose tissue. The goal of the present study was to use a new calorimetry method in which resting metabolic rate is enhanced to evaluate the effects of sibutramine treatment on thermogenesis. Sixty obese women were included in the study. Subjects were divided into 2 equal groups-the placebo and sibutramine treatment groups. The sibutramine group was given sibutramine 10 mg daily for 12 wk. At baseline and at the end of the 12-wk treatment period, thermogenic measurements were taken with the use of water immersion calorimetry. Subjects were examined at weeks 4, 8, and 12 of treatment to identify adverse effects. Body mass index, measured at 31.5±2.05 kg/m2 in the placebo group, decreased to 30.4±2.94 kg/m2 after 12 wk (P=.07). In the sibutramine group, it decreased from 33.5±4.1 kg/m2 to 30.9±4.8 kg/m2 (P < .05). In the sibutramine group, mean thermogenic response changed from a baseline value of 1.27±0.29 kcal/kg/h to 1.44±0.13 kcal/kg/h after 12 wk of treatment. In the placebo group, the baseline value was 1.56±0.27 kcal/kg/h; it changed to 1.33±0.36 kcal/kg/h at the end of 12 wk. The findings of this study suggest that sibutramine treatment promotes thermogenesis, thus facilitating weight loss. Calorimetry enhances resting metabolism through more efficient heat transfer from the body.

Ret proto-oncogene mutations in apparently sporadic Turkish medullary thyroid carcinoma patients: Turkmen study.

Objective: Medullary thyroid carcinoma (MTC) frequently occurs in a sporadic form, but a substantial number of cases are hereditary and appear as part of the multiple endocrine neoplasia type 2 (MEN2) syndromes. Germline mutations in ret proto-oncogene have been shown to be the underlying cause of MEN2 syndromes. Design: We carried out a multi-center study that aimed to perform mutational analysis of so called sporadic MTC patients. Methods: Fifty-six MTC patients verified by histopathologic examination were subjected to genetic analysis. Exon 10, 11, 13, 14, 15 and 16 of the ret gene were analyzed by DNA sequencing and restriction enzyme digestion method. Results: Among 56 apparently sporadic MTC patients, we identified 6 (10.7%) ret germline mutation carriers. Three individuals carried mutations at codon 634 in exon 11, one at codon 618 in exon 10, and two at codon 804 in exon 14. Identification of the predisposition gene mutation has allowed DNA-based strategy for direct mutation detection in patients with apparently sporadic MTCs. A substantial number of patients with apparently sporadic MTC carried germline mutations and 50% of their first degree relatives are expected to have or to develop MTC and/or other endocrine tumors. Conclusions: These results indicate the importance of careful genetic surveillance of any patient with apparently sporadic MTCs.