Mustafa Kemal Balci

The effect of body weight and weight loss on thyroid volume and function in obese women

objective Thyroid volume and thyroid function may vary in obese and nonobese women. It is not known whether weight loss could affect thyroid volume and function in obese subjects.

Musculoskeletal manifestations in patients with thyroid disease

objective Thyroid dysfunction may cause musculoskeletal symptoms. We have evaluated the prevalence of adhesive capsulitis, Dupuytrens contracture, trigger finger, limited joint mobility and carpal tunnel syndrome in a series of patients with various thyroid diseases and differing levels of function.

Incretins: their physiology and application in the treatment of diabetes mellitus.

Therapies targeting the action of incretin hormones have been under close scrutiny in recent years. The incretin effect has been defined as postprandial enhancement of insulin secretion by gut‐derived factors. Likewise, incretin mimetics and incretin effect amplifiers are the two different incretin‐based treatment strategies developed for the treatment of diabetes. Although, incretin mimetics produce effects very similar to those of natural incretin hormones, incretin effect amplifiers act by inhibiting dipeptidyl peptidase‐4 (DPP‐4) enzyme to increase plasma concentration of incretins and their biologic effects. Because glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone with various anti‐diabetic actions including stimulation of glucose‐induced insulin secretion, inhibition of glucagon secretion, hepatic glucose production and gastric emptying, it has been evaluated as a novel therapeutic agent for the treatment of type 2 diabetes mellitus (T2DM). GLP‐1 also manifests trophic effects on pancreas such as pancreatic beta cell growth and differentiation. Because DPP‐4 is the enzyme responsible for the inactivation of GLP‐1, DPP‐4 inhibition represents another potential strategy to increase plasma concentration of GLP‐1 to enhance the incretin effect. Thus, anti‐diabetic properties of these two classes of drugs have stimulated substantial clinical interest in the potential of incretin‐based therapeutic agents as a means to control glucose homeostasis in T2DM patients. Despite this fact, clinical use of GLP‐1 mimetics and DPP‐4 inhibitors have raised substantial concerns owing to possible side effects of the treatments involving increased risk for pancreatitis, and C‐cell adenoma/carcinoma. Thus, controversial issues in incretin‐based therapies under development are reviewed and discussed in this manuscript. Copyright

Insulin resistance in chronic hepatitis C

Aim:  Insulin resistance (IR), glucose intolerance and diabetes mellitus are commonly associated with cirrhosis. The exact pathogenetic mechanisms responsible are still unknown; however, they may be related to both hepatitis C virus itself and to liver injury. IR may be the earliest abnormality, which in the following years may progress to clinical diabetes mellitus. The aim of this study was to investigate the presence of IR by euglycaemic hyperinsulinemic clamp technique, in chronic hepatitis C patients.

Comparison of Efficacy of Sibutramine or Orlistat Versus Their Combination in Obese Women

Objective: Sibutramine and orlistat are currently used for weight loss. We aimed to investigate the effect of orlistat and sibutramine combination therapy in treatment of obese women. Subjects and Design: Study population consisted of 89 obese women who had a body mass index ≥ 30 kg/m2, were normotensive, and had normal glucose tolerance. All patients were placed on a diet which contained fat approximately 30% of total calorie intake and the diet was designed to cause an energy deficit of approximately 2.51–3.56 megajoule/day. At the first month of diet (baseline), all patients were randomly divided into three therapy groups: Diet + Orlistat (group 1; n = 30 patients), Diet + Sibutramine (group 2; n = 29 patients), Diet + Orlistat + Sibutramine (group 3; n = 30 patients). Body weight, body fat distribution and serum lipid levels were evaluated baseline and after six months in all subjects. Results: Mean weight loss was 5.5 ± 4.9 kg (p = 0.024) in group 1, 10.1 ± 3.6 kg (p < 0.001) in group 2, 10.8 ± 6.6 kg (p < 0.001) in group 3 after the six months. Weight loss was significantly greater in group 2 (p = 0.003) and group 3 (p = 0.002) when compared with group 1. Percentage of mean weight loss was 5.5 ± 3.1% in group 1, 10.2 ± 4.8% in group 2, 10.6 ± 5.7% in group 3. Percentage of weight loss was higher in group 2 (p = 0.01) and group 3 (p = 0.009) when compared with group 1. Weight loss and percentage of weight loss were not different between group 2 and group 3. Conclusion: These three regimens had different results on weight loss in obese women. Combination drug therapy and sibutramine therapy were both more effective than orlistat therapy alone. However, no significant difference was noted between combination drug therapy and sibutramine treatment groups.

Incidental Thyroid Carcinoma in Thyrotoxic Patients Treated by Surgery

Background and Aims: Thyroid malignancy detected incidentally in patients who are operated for thyrotoxicosis has been reported at different rates. The aim of this study was to investigate the rate of incidental thyroid carcinoma in thyrotoxic patients managed with surgery in our institution. Methods: Of the 375 thyrotoxic patients who had thyroid surgery between the years of 1997–2004, 70.7% were females and 29.3% were males. Among thyrotoxic patients 65.3% (n = 245) had toxic multinodular goiter (TMG), 16.8% (n = 63) had toxic adenoma (TA) and 17.9% (n = 67) had Graves’ disease. Results: Twenty-six (6.9%) of all thyrotoxic patients had thyroid carcinoma. Eighteen (7.3%) of TMG, 4 (6.3%) of TA and 4 (6%) of Graves’ disease patients had thyroid carcinoma. Histologic examination revealed 18 papillary (9 microscopic), 5 follicular, 2 hurthle cell and 1 anaplastic carcinoma. Conclusion: In our study, incidental thyroid carcinoma was found in 6.9% of subjects with thyrotoxicosis. Papillary thyroid microcarcinomas constituted 34.6% (26/9) of these newly diagnosed thyroid carcinomas. The incidence of thyroid carcinoma was not higher in subjects with Graves’ disease compared to TMG and TA. The rate of incidental thyroid carcinoma in subjects with thyrotoxicosis treated with surgery was similar to previous studies reported from different countries.

High TRAIL death receptor 4 and decoy receptor 2 expression correlates with significant cell death in pancreatic ductal adenocarcinoma patients.

Objectives: The importance of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor expression in pancreatic carcinoma development is not known. To reveal the putative connection of TRAIL and TRAIL receptor expression profile to this process, we analyzed and compared the expression profile of TRAIL and its receptors in pancreatic tissues of both noncancer patients and patients with pancreatic ductal adenocarcinoma (PDAC). Methods: Thirty-one noncancer patients and 34 PDAC patients were included in the study. TRAIL and TRAIL receptor expression profiles were determined by immunohistochemistry. Annexin V binding revealed the apoptotic index in pancreas. Lastly, the tumor grade, tumor stage, tumor diameter, perineural invasion, and number of lymph node metastasis were used for comparison purposes. Results: TRAIL decoy receptor 2 (DcR2) and death receptor 4 expression were up-regulated in PDAC patients compared with noncancer patients, and the ductal cells of PDAC patients displayed significant levels of apoptosis. In addition, acinar cells from PDAC patients had higher DcR2 expression but lower death receptor 4 expression. Increased DcR2 expression was also observed in Langerhans islets of PDAC patients. Conclusions: Differential alteration of TRAIL and TRAIL receptor expression profiles in PDAC patients suggest that the TRAIL/TRAIL receptor system may play a pivotal role during pancreatic carcinoma development.

High levels of endogenous tumor necrosis factor-related apoptosis-inducing ligand expression correlate with increased cell death in human pancreas.

Objectives: Type 1 diabetes (T1D) has been characterized by the T cell-mediated destruction of pancreatic &bgr; cells. Although various members of the tumor necrosis factor (TNF) family, such as Fas ligand or TNF, have recently been implicated in the development of T1D, the lack of TNF-related apoptosis-inducing ligand (TRAIL) expression or function facilitates the onset of T1D. Thus, the goal of the present study was to investigate the expression profiles of TRAIL and its receptors in human pancreas. Methods: Pancreata of 31 patients were analyzed by immunohistochemistry using antibodies developed against TRAIL and its receptors. Apoptosis was confirmed by Annexin V-fluorescein isothiocyanate binding and terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate nick end labeling assays. Results: Acinar cells displayed high levels of TRAIL and death receptor 4, but only low levels of death receptor 5. In contrast, only TRAIL and TRAIL decoy receptors (DcR1, DcR2) were detected in ductal cells. Similarly, Langerhans islets expressed only TRAIL and TRAIL decoy receptor. High levels of TRAIL expression in pancreas correlated with increased number of apoptotic cells. Conclusions: Although the expression of TRAIL decoy receptors might be necessary for defense from TRAIL-induced apoptosis, high levels of TRAIL may provide protection for Langerhans islets from the immunological attack of cytotoxic T cells.

Hypocalcemic Cardiomyopathy due to Untreated Hypoparathyroidism

Hypocalcemic cardiomyopathy due to hypoparathyroidism is a very rare condition which is usually refractory to conventional treatment for cardiac failure but which responds favorably to restoration of normocalcemia. A 55-year-old man and a 46-year-old woman with a history of postoperative hypoparathyroidism presented with symptoms of cardiac failure and hypocalcemia. A presumptive diagnosis of dilated cardiomyopathy was considered by echocardiography and endomyocardial biopsies were consistent with cardiomyopathy. The coronary angiograms were normal and there was no apparent cause for dilated cardiomyopathy in these patients. The history of the patients and partial recovery of cardiac function after restoration of normocalcemia suggest that hypocalcemia was the cause of dilated cardiomyopathy.

Therapeutic potential of VIP vs PACAP in diabetes

Type 2 diabetes (T2D) is characterized by chronic insulin resistance and a progressive decline in beta-cell function. Although rigorous glucose control can reduce morbidity and mortality associated with diabetes, achieving optimal long-term glycemic control remains to be accomplished in many diabetic patients. As beta-cell mass and function inevitably decline in T2D, exogenous insulin administration is almost unavoidable as a final outcome despite the use of oral antihyperglycemic agents in many diabetic patients. Pancreatic islet cell death, but not the defect in new islet formation or beta-cell replication, has been blamed for the decrease in beta-cell mass observed in T2D patients. Thus, therapeutic approaches designed to protect islet cells from apoptosis could significantly improve the management of T2D, because of its potential to reverse diabetes not just ameliorate glycemia. Therefore, an ideal beta-cell-preserving agent is expected to protect beta cells from apoptosis and stimulate postprandial insulin secretion along with increasing beta-cell replication and/or islet neogenesis. One such potential agent, the islet endocrine neuropeptide vasoactive intestinal peptide (VIP) strongly stimulates postprandial insulin secretion. Because of its broad spectrum of biological functions such as acting as a potent anti-inflammatory factor through suppression of Th1 immune response, and induction of immune tolerance via regulatory T cells, VIP has emerged as a promising therapeutic agent for the treatment of many autoimmune diseases including diabetes.