Mehmet Tüzün

Association of the angiotensinogen M235T and angiotensin-converting enzyme insertion/deletion gene polymorphisms in Turkish type 2 diabetic patients with and without nephropathy

OBJECTIVE Recent studies have suggested an association between a deletion variant of the angiotensin-converting enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for the development and progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS We investigated the relationship of the ACE insertion/deletion (I/D) and AGT M235T gene polymorphisms in Turkish patients with type 2 diabetes mellitus (DM) with and without diabetic nephropathy. A total of 102 individuals were screened for the presence of the ACE I/D and AGT M235T polymorphism: 46 individuals who had type 2 DM with diabetic nephropathy and, as controls, 56 individuals who had type 2 DM without diabetic nephropathy. Gene polymorphisms were determined by the specific melting temperature (T(m)) values of the resulting amplicons after real-time online polymerase chain reaction and melting curve analysis. RESULTS The frequencies of the ACE DD, ID, and II genotypes were 34.8%, 37.0%, and 28.3%, respectively, among type 2 diabetic patients with nephropathy, and 33.9%, 42.9%, 23.2%, respectively (P=.788), in the control subjects without diabetic nephropathy. On the other hand, the frequencies of the AGT MM, MT, and TT genotypes among the same groups were 26.1%, 52.2%, 21.7% and 26.8%, 57.1%, 16.1%, respectively (P=.758). CONCLUSIONS There were no differences in the frequencies of the AGT M235T and ACE I/D genotypes between Turkish patients with type 2 DM with and without nephropathy.

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.

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 Hormone Replacement Therapy on Insulin Resistance and Platelet Function Tests

Objectives: The aim of this study was to evaluate measures of insulin resistance and platelet function in postmenopausal women with oral or transdermal hormone replacement therapy (HRT). Subjects and Methods: Eighty women divided into four groups of 20 each were enrolled in the study. Group 1: postmenopausal hysterectomized women who received only transdermal estradiol (13.9 mg/12.5 cm2); group 2: women with intact uterus who were treated with estrogen-progestin combination (HRT); group 3: postmenopausal women who were treated with the selective estrogen receptor modulator tibolone, and group 4: women who were not taking any drugs for HRT were chosen as a control group (group 4). Results: In group 2, homeostasis model assessment of insulin resistance and fasting insulin levels were 2.90 ± 0.37 and 9.3 ± 3.0 µU/ml, respectively, prior to administration of HRT. These levels were reduced to 1.91 ± 0.41 (p = 0.001) and 7.1 ± 2.7 µU/ml (p = 0.002), respectively, after drug therapy. Mean levels of high-sensitivity C-reactive protein (hsCRP) were decreased with HRT only in group 2 (p = 0.002). No changes for biochemical and hematological parameters were observed in the other groups. Platelet function tests showed no differences after HRT in any group. Conclusions: Estrogen-progestin combination HRT decreased measures of insulin resistance and hsCRP levels, but had no effect on platelet function tests in postmenopausal women.

Evaluation of beta cell dysfunction by mixed meal tolerance test and oral L-arginine in patients with newly diagnosed type 2 diabetes mellitus.

BACKGROUND AND AIMS Defective insulin secretion is required for the development of frank diabetes mellitus. We evaluated the secretory response of pancreatic beta cells after the ingestion of mixed meal plus oral L-arginine in newly diagnosed type 2 diabetic patients. MATERIALS AND METHODS Twenty-four newly diagnosed type 2 diabetic patients were enrolled in this study. All patients were ingested a mixed meal of 553 kcal. Serum insulin levels were measured at time 0 just before the mixed meal and at 1, 2, 3, 4 and 5 h after the ingestion of the mixed meal. Twenty-four hours later, all patients ingested mixed meal followed by oral 8 g L-Arginine, and insulin levels were again measured at 0, 1, 2, 3, 4 and 5 h after the ingestion of the meal. RESULTS Insulin levels reached to peak values at the 2 (nd) hour, and decreased to baseline levels at the 5 (th) hour measurements both after the ingestion of mixed meal only and after the ingestion of mixed meal plus oral L-Arginine. First and 2 (nd) hour insulin levels were significantly higher after the ingestion of mixed meal plus oral L-Arginine. CONCLUSION In this study we used for the first time the combination of oral L-arginine with mixed meal test to evaluate the beta cell dysfunction in type 2 diabetic patients. Increments regarding serum insulin levels after the ingestion of mixed meal plus oral L-Arginine suggest that oral L-Arginine could be benefical for the evaluation of beta cell function and secretory defects.

Preprandial repaglinide decreases exogenous insulin requirements and HbA1c levels in type 2 diabetic patients taking intensive insulin treatment.

In this study, we investigated the effects of combining preprandial repaglinide to the insulin therapy for reducing the exogenous insulin requirements and serum HbA1c levels in type 2 diabetic patients whose blood glucose levels were previously regulated by multiple dose intensive insulin therapy. Fifty patients with type 2 diabetes who had been initially treated with oral antidiabetic agents without a satisfactory response were included in this study. After adequate glycemic control was achieved with intensive insulin therapy, the patients were divided into two subgroups. The first group continued with intensive insulin therapy. The second group received a combination of multiple insulin injections and oral repaglinide (1.5 mgr tid). The doses of insulin injections were gradually decreased accordingly in the second group. Both groups were followed-up for 3 months. Repaglinide was well tolerated and had no toxicity. A significant reduction regarding exogenous insulin requirements and serum HbA1c levels were demonstrated in patients taking preprandial repaglinide (p<0.01). Combining repaglinide to intensive insulin therapy could be a safe and effective alternative to intensive insulin therapy alone for the glycemic control and for reducing exogenous insulin requirements in type 2 diabetic patients.

The prevalence of RET/PTC mutations in papillary thyroid cancers in Turkish population and its relation between tumor histopathology and prognostic factors.

OBJECTIVE In recent years, thyroid cancer has been at the forefront of molecular pathology as a result of the consequences of the Chernobyl disaster and the recognition of the role of RET/PTC rearrangements in papillary thyroid carcinomas (PTCs). Correlation of RET/PTC expression with clinical outcome is controversial. This study aims to identify the prevalence of RET/PTC oncogene expression in Turkey, and to investigate the correlation between RET/PTC oncogene expression and the known prognostic factors of PTC in 101 patients. METHODS The RET rearrangements were examined by means of reverse transcriptase-polymerase chain reaction analysis, with primers flanking the chimeric region. Statistical evaluation was performed by using Independent samples t-test, One-sample Chi-square test and Pearson Chi-square or Fishers Exact Test. RESULTS RET/PTC was determined positive in 67(66.3%) of totally 101 patients (p<0.001). RET/PTC1 in 32(31.7%), RET/PTC3 in 21(20.8%), RET/PTC1+RET/PTC3 both in 10(9.9%) patients were found to be positive. There was RET/PTC2 positiveness in two patients, RET/PTC2,3 positiveness in one patient, and RET/PTC1,2,3 positiveness in one patient. No statistical difference was found between RET/PTC1 and RET/PTC3. None of genetico-clinical analyses showed any significant association between RET/PTC expression and the clinical and pathological features of the cancers. CONCLUSION While this prevalence of the RET/PTC is less than RET/PTC frequency seen after Chernobyl in Belarus, its prevalence in our region is also high (66.3%). As a result, no significant correlation was found in between prognosis and RET/PTC frequency.