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The goals of Type 2 diabetes treatment are to eliminate the hyperglycemia resulting from insulin insufficiency and/or insulin resistance, delay beta cell damage/depletion, and prevent other metabolic co-morbidities and complications. In the current treatment algorithms, lifestyle changes (medical nutrition therapy, physical exercise) and oral anti-diabetics are followed by insulin therapy, which is considered a replacement therapy for Type 2 diabetes. Pre-mixed insulin preparations, which are an option for patients with poor blood glucose level control under oral anti-diabetics treatment, have been developed to meet both basal and prandial insulin needs by simulating the physiological changes in insulin levels. The consensus on the necessity of individualizing insulin therapy requires physicians to have a detailed knowledge of the various uses of insulin. Therefore, this comprehensive consensus statement has been prepared by a panel of expert endocrinologists from different regions of Turkey to help physicians use biphasic insulin aspart 30 in suitable patients at the right time. In this statement, expert panel opinions on (a) Recommendations for the appropriate initiation, titration, and intensification of insulin treatment, and (b) The treatment algorithms in initiation, titration, and intensification of biphasic insulin aspart 30 treatment and special conditions specific to changing treatment regimen are presented.

Contradictory results are encountered in literature regarding the effects of hypothyroidism on the risk factors of atherosclerosis. We aimed to explore the changes in atherosclerotic risk factors and insulin sensitivity before and after levothyroxine replacement therapy in women with primary hypothyroidism and compare with that of healthy controls.Twelve patients (mean age of 34±11.7years) without an evident disease except for primary hypothyroidism (TSH≥20mIU/L) and eleven euthyroid, age-matched (33.8±8.4years) female volunteers as controls were included. Baseline thyroid hormones, lipid parameters, homocysteine, fibrinogen levels were measured in both groups. Flow-mediated endothelial-dependent vasodilatation (FMD) method was used to evaluate endothelial dysfunction. Insulin sensitivity was assessed by M values based on euglycemic hyperinsulinemic clamp technique. The same measurements were performed after 6months of levothyroxine treatment and recovery of euthyroid state in hypothyroid patients.Treatment reduced total cholesterol (P0.005), LDL-cholesterol (P0.005), lipoprotein(a) (P0.01), fibrinogen (P0.0001) and homocysteine (P0.0005) levels. Treatment significantly improved M values of hypothyroid patients (3.68±1.53mg/kg.min vs 6.02±1.21mg/kg.min, P0.0001) and FMD (9.1±3.7% vs 16.4±4.4%, hypothyroid vs euthyroid, P0.0001). Significant correlations were found between M values and TSH (r=-0.6, P0.005), fibrinogen (r=-0.53, P0.01) measurements, free T3 (r=0.51, P0.02) and free T4 (r=0.49, P0.02) levels. FMD was significantly correlated with fibrinogen levels (r=-0.49, P0.05).Insulin resistance, endothelial dysfunction, atherosclerotic risk markers improves with treatment of hypothyroidism.

Epicardial adipose tissue (EAT) thickness is a novel cardiovascular risk indicator, whereas carotid intima media thickness (CIMT) is a known marker of subclinical atherosclerosis. The aim of this study was to measure EAT thickness and CIMT in subclinical hypothyroid (SCH) patients and to determine the effect of restoration of the euthyroid state on these variables. The study included 43 patients with SCH (mean age: 35.2 ± 10.7 years; F–M ratio: 42:1) and 30 healthy controls (mean age: 34.5 ± 8.2 years; F–M ratio: 25:5). EAT thickness and CIMT were measured via conventional echocardiography and ultrasonography. Among the patients, 23 were followed up with l-thyroxine replacement until restoration of the euthyroid state and re-evaluated 6 months after baseline. Basal EAT thickness was higher in the SCH patients than in the controls (3.2 ± 0.7 vs. 2.3 ± 0.3 mm—p < 0.0001), whereas CIMT was similar in both groups (0.50 ± 0.09 vs. 0.48 ± 0.04 mm). EAT thickness was correlated with CIMT in the patient group (r = 0.39, p = 0.01), but this correlation was not evident based on multivariate analysis when corrected for age and body mass index (r 2 = 0.47 and p = 0.0001 for the model). In the follow-up patient subgroup, both EAT thickness and CIMT decreased significantly following l-thyroxine treatment, when normal TSH levels were attained (3.4 ± 0.7 vs. 2.3 ± 0.5 mm—p = 0.007 and 0.51 ± 0.09 vs. 0.46 ± 0.07 mm—p = 0.01, respectively). EAT thickness was greater in the SCH patients than in controls, whereas CIMT was similar in both groups. Restoration of the euthyroid state with l-thyroxine treatment was associated with significant decreases in EAT thickness and CIMT in the group of patients that received l-thyroxine treatment and, as such, might reduce the cardiovascular risk associated with SCH.

Adipokines are markers of insulin resistance and play a role in the atherosclerotic process. The association of adipokines with the macrovascular complications of type 1 diabetes mellitus (DM) needs to be determined. The aim of this study was to measure serum adiponectin, leptin, and resistin levels in type 1 DM patients and investigate their relationship with carotid intima media thickness (CIMT), a clinical marker of atherosclerosis.Seventy-five type 1 DM patients and 115 sex and age-matched healthy controls were included in the study. Serum adiponectin, leptin, and resistin levels were measured by the enzyme-linked immunosorbent assay (ELISA method). CIMT was assessed by Doppler ultrasonography.Adiponectin levels in diabetics were higher (25.8±14.8 μg/mL vs. 5.5±7.3 μg/mL; P0.0001) and leptin levels were lower than controls (9.4±6.2 ng/mL vs. 12.8±8.6 ng/mL; P=0.01). Resistin levels were also higher in the diabetic group compared to controls (2.1±1.4 ng/mL vs. 1.6±0.8 ng/mL; P=0.04). Adiponectin was correlated negatively with CIMT (r=-0.24, P=0.03), age (r=-0.30, P=0.02), BMI (r=-0.33, P=0.02), waist-to-hip ratio (WHR) (r=-0.38, P=0.01) and positively with creatinine (r=0.44, P=0.004). Leptin levels were correlated with total cholesterol (r=0.53, P=0.01) and high-density lipoprotein (HDL) (r=0.67, P=0.001). Resistin was correlated with CIMT (r=0.24, P=0.03) and systolic blood pressure (r=0.48, P=0.009). Multivariate analysis revealed resistin and creatinine to be independent predictors of CIMT among adiponectin, leptin, resistin, WHR, glycosylated hemoglobin (HbA1c), and creatinine.Increased adiponectin correlates negatively and resistin positively with CIMT in type 1 diabetic patients, but adjusting for other known predictors reveals only resistin to be associated with subclinical atherosclerosis in this group of patients.

Insulin resistance is getting important in the course of type 1 diabetes mellitus. Visceral fat depot is associated with insulin resistance and assessment of epicardial fat thickness is a way of measuring visceral fat. The aim of the study was to measure epicardial adipose tissue (EAT) thickness and to determine its relationship with waist-hip-ratio (WHR) and estimated glucose disposal rate (eGDR) in adult type 1 diabetic patients. Thirty-six type 1 diabetic patients (aged 31 ± 8 years; Female/Male: 22/14) and 43 age, gender and BMI matched healthy controls were included. Fasting blood glucose (FBG), hemoglobin A1c, and lipid profiles were measured. Waist-hip-ratio (WHR) was calculated. Daily insulin dose/kg of patients were recorded and eGDR of all subjects was calculated. Epicardial adipose tissue (EAT) thickness was evaluated by echocardiography. EAT thickness of the type 1 diabetic patients was significantly higher than controls (3.30 ± 1.06 vs. 2.30 ± 0.34 mm, P < 0.0001). EAT thickness was correlated with age (P = 0.05; r = 0.35), WHR (P = 0.003; r = 0.67), daily insulin dose/kg (r = 0.45, P = 0.005), and eGDR (r = −0.55, P = 0.0004). Multivariate analysis revealed WHR and eGDR to be related to EAT among age, WHR, daily insulin dose/kg, eGDR, FBG, and hemoglobin A1c (r2 of the model = 0.64). Epicardial adipose tissue thickness is increased in type 1 diabetic patients compared to controls and is related to WHR and eGDR in this group of patients. This measurement may point to the presence of insulin resistance in type 1 diabetic patients.

Zollinger-Ellison syndrome is characterized by elevated levels of serum gastrin associated with increased gastric acid secretion, gastrointestinal ulcerations and diarrhea. Most gastrinomas (75%) occur sporadically and are located within the gastrinoma triangle. Extraduodenal, extrapancreatic and extranodal gastrinomas have been shown in 5.6% of the patients with Zollinger-Ellison syndrome who underwent surgery. We report a 44-year-old female who had been complaining of nausea and diarrhea for 12 years. Abdominal computed tomography and magnetic resonance imaging detected a homogeneous, regular-shaped 6 x 7 cm solid mass, located between the liver, right kidney and inferior vena cava. Somatostatin receptor positive scanning led us to investigate a neuroendocrine tumor. Serum gastrin level was found very high and the patient underwent surgery. Local excision of the tumor was performed, and an 8x6x5 cm, well-capsulated, solitary mass, originating from the common bile duct was removed. The unique feature of our case is the unusual localization, and although the tumor was very large in size, only capsule invasion was observed with no evidence of distant metastasis.

Germline thyrotropin receptor (TSHR) mutations are associated with sporadic congenital nonautoimmune hyperthyroidism and familial nonautoimmune hyperthyroidism. Somatic TSHR mutations are associated with toxic thyroid nodules (TTNs). The objective of the study was to define a relation of the clinical appearance and the in vitro activity (IVA) of the TSHR mutations described by several authors for these thyroid disorders.We analyzed the IVAs published as linear regression analysis (LRA) of the constitutive activity as a function of the TSHR expression and the basal cyclic adenosine monophosphate (cAMP) values to determine differences between exclusively somatic, exclusively familial, and shared sporadic and somatic TSHR-mutations. Further, we investigated correlations of the LRAs/basal cAMP values with clinical activity characteristics (CACs) of TTNs, such as largest diameter of the TTN and the age of the patient at thyroid surgery.Shared sporadic and somatic mutations showed higher median LRA (14.5) and higher median basal cAMP values (fivefold) than exclusively familial mutations (6.1, p = 0.0002; 2.9-fold, p 0.0001, respectively). Moreover, mutations shared between sporadic congenital nonautoimmune hyperthyroidism and toxic thyroid nodules (TTNs) showed higher median LRA/basal cAMP values (p 0.0001) than exclusively somatic mutations in TTNs (5.1; 3.89-fold, respectively). Exclusively somatic mutations and exclusively familial mutations showed no significant difference in their median LRA values (p = 0.786) but a significant difference for basal cAMP values (p = 0.0006). The two examined CACs showed no correlation with the IVA characterized by LRA/basal cAMP values or with the presence or absence of a TSHR-mutation.This systematic analysis of published constitutively activating TSHR-mutations, their CACs, and their IVA provides evidence for higher IVA of shared sporadic and somatic TSHR mutations as compared with familial TSHR mutations. CACs of somatic TSHR mutations in TTNs did not have a clear association with the IVA as characterized by LRA or basal cAMP values.

Background Impaired glucose tolerance (IGT) forms an intermediate stage in the natural history of diabetes mellitus. Insulin-resistant states might be associated with dysfunction of the vascular endothelium. Objectives To determine the effects of chronic exercise and a low-calorie diet on plasma nitric oxide (NO) and endothelin-1 (ET-1) levels in patients with IGT and to elucidate the relationship between the oxidant stress markers and NO/ET-1 levels of blood before and after exercise. Methods Patients with IGT (n = 14) participated in a regular exercise program and exercised for 40 minutes each day, 3 days a week for 12 weeks. Physiological, anthropometric, and biochemical measurements were performed before, during the 6th week, and at the end of the program. Results There was a significant reduction in body mass index, body fat content, systolic and diastolic blood pressures, as well as NO and ET-1 concentrations after 12 weeks of exercise and diet program. Exercise training significantly elevated subjects' maximum oxygen consumption, whereas the resting metabolic rates of the patients did not change. The formation of thiobarbituric acid reactive substances were significantly reduced, whereas sulfhydryl groups were significantly increased on the 6th week (P Conclusion Our results demonstrate that exercise, along with low-calorie diet, induced reductions in the plasma of both ET-1 and NO. Beneficial effects were observed on anthropometric measurements and plasma oxidant stress markers, indicating weight loss associated with exercise training and calorie restriction may effectively improve endothelial dysfunction in patients with IGT.

Alterations in the neuroendocrine system occur during critical illness. Chronic obstructive pulmonary disease (COPD) itself causes hormonal changes. The aim of this study was to determine neu roendocrine hormones of COPD patients with acute respiratory failure and to investigate the relationship between hormonal changes, mortality, and morbidity.We enrolled 21 patients (13 F/8 M) with COPD exacerbation requiring artificial airway support. Blood samples were collected on admission to the ICU, and on the day of hospital discharge. Eighteen healthy people were included as controls.Female patients had lower luteinizing hormone (LH), follicle stimulating hormone (FSH), and free triiodothyronine (fT3), and higher prolactin (PRL) levels than controls on admission to the ICU (FSH: 70.3 vs. 29.3 mlU/mL; LH: 26.6 vs. 6.8 mlU/mL; fT3: 2.9 vs. 2.0 pg/mL; PRL: 12.4 vs. 21.3 ng/mL). Male patients had low testosterone and TSH and high PRL but only changes in TSH and PRL reached statistical significance (testosterone: 3.5 vs. 1.5 ng/mL, TSH: 1.1 vs. 0.5 ulU/mL, PRL: 9.7 vs. 14.2 ng/mL). Female patients had lower fT3 than males (fT3(female): 2.7 vs. fT3(male): 2.0 pg/mL). On follow-up, significantly elevated FSH and fT3 and decreased estradiol concentrations were documented among recovered women (FSH: 28.4 vs. 46.6 mlU/mL, fT3(,): 2.0 vs. 2.6 pg/mL, E(2): 27.7 vs. 19.0 pg/mL). Patients had high C-reactive protein levels and acute physiologic and chronic health evaluation II scores. Mortality rate was 9.5% and a negative correlation between E(2) and duration of noninvasive mechanical ventilation and length of hospital stay was found in male patients.Men and women with acute respiratory failure in the presence of COPD develop significant changes in the neuroendocrine axis. Hormonal suppression vanishes with disease improvement.

There is a plethora of partly contradictory reports on somatostatin receptor (SSTR) expression in thyroid tumors. Therefore, our goal was to systematically determine SSTR2 expression in benign cold thyroid nodules (CNs), hot thyroid nodules (HNs), papillary carcinomas (PCs), and Graves' disease (GD) in comparison with intraindividual control tissues by means of immunohistochemistry.Tissue sections from 19 HNs, 10 CNs, 17 PCs and their surrounding tissues, and 8 GD thyroids were immunostained for SSTR2. Membranous SSTR2 staining was quantitated by evaluating 10 high-power fields (HPFs) systematically distributed along the largest diameter of the tissue section.The area covered by thyroid epithelial cells in 10 HPFs expressed as median (in mm(2)) was 0.53 for CNs, 0.44 for HNs, 1.5 for PCs, 1.3 for GD, and 0.3 for the surrounding tissues. The SSTR2 staining density determined by dividing the area of SSTR2 positively stained thyroid epithelial cells (in mm(2)) by the area of all thyroid epithelial cells (in mm(2)) in 10 HPFs was 0.1662 for CNs, 0.0204 for HNs, 0.0369 for PCs, and 0.0386 for GD.SSTR2 expression is inhomogeneous in thyroid disease, with the highest density detected in CNs. It remains to be determined whether this finding could be of pathophysiologic or therapeutic relevance. The high SSTR2 density in CNs should be considered in the interpretation of SSTR scintigraphy-positive findings.

Magnesium has been shown to increase bone mineral density when used in the treatment of osteoporosis, yet its mechanism of action is obscure. In this study, the effects of daily oral magnesium supplementation on biochemical markers of bone turnover were investigated. Twenty postmenopausal women have been divided into two groups. Ten patients were given magnesium citrate (1,830 mg/day) orally for 30 days. Ten postmenopausal women of matching age, menopause duration, and BMI were recruited as the control group and followed without any medication. Fasting blood and first-void urine samples were collected on days 0, 1, 5, 10, 20, and 30, respectively. Total magnesium, calcium, phosphorus, iPTH and osteocalcin were determined in blood samples. Deoxypyridinoline levels adjusted for creatinine were measured in urine samples. Thirty consecutive days of oral magnesium supplementation caused significantly decrease in serum iPTH levels in the Mg-supplemented group (p

To determine the effect of radioiodine treatment on thyroid C cells, calcitonin (CT) levels were measured by RIA before and after intravenous calcium stimulation (2 mg/kg body-weight elemental calcium) in 22 women treated with 131I for hyperthyroidism. The results were compared with sex, age and weight-matched normal controls. There was a slight but statistically significant decrease in basal CT levels of the patients compared to the control group (mean +/- SE; 0.009 +/- 0.001 vs 0.011 +/- 0.001 pmol/l, P less than 0.05). The mean stimulated CT level of the patient group was significantly lower than that of the controls (0.010 +/- 0.001 vs. 0.018 +/- 0.003 pmol/l, P less than 0.001). The absence or presence of 131I-induced hypothyroidism at the time of the study did not influence basal or stimulated CT levels. Basal and stimulated CT levels were significantly lower in the patients with Graves' disease than in the patients with toxic nodular goitre. We conclude that 131I used to correct hyperthyroidism may cause marked CT deficiency.

Patients with diabetes have an increased cardiovascular morbidity and mortality despite interventions to prevent these outcomes. Abnormalities in diurnal blood pressure patterns are also associated with excess cardiovascular mortality. The aim of this study was to determine the effects of diurnal blood pressure patterns on endothelial function and oxidative stress in patients with uncomplicated type 1 diabetes mellitus. Thirty-two normotensive and normoalbuminuric type 1 diabetic patients (21 dipper and 11 nondipper) and 37 healthy (27 dipper and 10 nondipper) volunteers underwent 24-h ambulatory blood pressure monitoring. Their endothelial functions were evaluated using flow mediated dilatation (FMD) and by measuring nitric oxide and thiobarbituric acid reactive substances (TBARS). Dippers were defined as subjects who exhibited an average reduction in both systolic and diastolic blood pressure of greater than 10% between day and night periods. Nondipper type 1 diabetic patients and controls had nighttime systolic and diastolic blood pressure values that were significantly higher than those of dipper diabetic patients (p

Obesity is a well-recognized risk factor for the development of insulin resistance and the metabolic syndrome. Adipokines secreted from adipocytes play an important role in the pathogenesis of insulin resistance, hypertension, disorders of coagulation, dyslipidemia, and glucose abnormalities associated with insulin resistance or the metabolic syndrome. The selective ligands of the nuclear transcription factor PPARgamma, Thiazolidinediones (TZDs), induce differentiation of preadipocytes to mature and more insulin sensitive adipocytes. This review summarizes adipocyte biology, the role of the adipokines in the pathogenesis of insulin resistance, and the effects of TZDs on insulin resistance and the metabolic disorders associated with it.

Introduction: The normal circadian rhythm of hormones in critical patients becomes chaotic causing some hormones to increase and others to decrease abnormally. The goal of this study is to evaluate hormonal changes in severely ill patients and to investigate the relationship between hormonal changes and mortality and morbidity. Material and methods: We enrolled 20 patients (10 F/10 M). Blood samples were collected on day 0, day 5, and day 10. If a patient was discharged before these defined days, a sample was drawn on that day. Twenty healthy controls were included. Results: Female patients had lower LH, FSH, and fT 3 and higher PRL and cortisol levels than controls on admission to the intensive care unit (ICU) (p LH = 0.021, p FSH :0.001, p fT3 = 0.021, p PRL = 0.042, p Cortisol

Background: QT dispersion (QTd) is a good prognostic marker in type 2 diabetic patients without previous cardiovascular disease. Diabetic patients with an attenuated decline in nocturnal blood pressure (non-dippers) have been shown to have increased risk of diabetic complications, vascular events and mortality. Aim: The aim of this study was to evaluate the relationship between diurnal blood pressure rhythm, QTd and microvascular complications in type 2 diabetic patients. Methods: Cardiovascular autonomic function tests, 24-h ambulatory blood pressure monitoring and urinary albumin excretion measurements were performed in healthy controls (n = 25), normoalbuminuric (n = 34) and microalbuminuric (n = 23) type 2 diabetic patients. QTd was assessed manually from 12-lead surface electrocardiograms. Results: Compared with the controls, both normoalbuminuric and microalbuminuric diabetic patients had increased QTd (59.11 ± 15.86; 60.27 ± 17.95 vs. 40.48 ± 10.92, p

In the last decade, studies were first done to determine the frequency of Gsalpha and later thyrotropin receptor (TSHR) mutations in benign autonomously functioning thyroid nodules (AFTN). Different frequencies ranging from 0% to 38% for GSp mutations and from 20% to 86% for TSHR mutations were found. There were only some limited case reports related to TSHR genetic alterations in malignant AFTN. Their role in autonomously functioning thyroid carcinomas is not well established. We present a patient who had thyroidectomy for toxic multinodular goiter and a papillary carcinoma was demonstrated histopathologically. Genomic DNA was isolated from two solid areas in the hot nodule and peripheral leukocytes of the patient. After amplifying the related regions, TSHR and GSalpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. An activating mutation of the TSHR gene (Leu 512 Arg) was found in the autonomously functioning papillary carcinoma. It is believed that this mutation causes constitutive activation of the cyclic adenosine monophosphate (cAMP) signal transduction pathway and thereby causes thyrotoxicosis and a hot thyroid nodule in an autonomously functioning papillary carcinoma.

Increased oxidative stress has an important role in the pathogenesis of diabetic nephropathy. The aim of this study was to evaluate the effects of renin-anigiotensin system blockage, either by angiotensin-converting enzyme inhibition or angiotensin receptor blockage, on oxidative stress and nitric oxide release in diabetic rat kidneys. After induction of diabetes, six rats were given captopril, six rats were given losartan, and six rats served as diabetic controls. Six healthy rats were also included. At the end of an 8-week period nitric oxide release, lipid peroxidation and protein oxidation were measured in kidney cortices, and urinary albumin excretion (UAE) was determined in 24-h urine samples. Losartan- and captopril-treated diabetic rats had lower levels of UAE than diabetic controls. Diabetic rats had higher levels of lipid peroxidation and protein oxidation compared to healthy rats. NO release was significantly lower in diabetic groups than healthy controls. UAE levels showed a positive correlation with lipid peroxidation and a negative correlation with NO release. Inhibition of lipid peroxidation could be one of the protective mechanisms of renin-angiotensin axis inhibition in diabetic kidney tissues.

Summary objective The efficacy and the effective dose of levothyroxine suppressive therapy in the treatment of benign thyroid nodules are controversial. In this study, we aimed to determine the response of solitary thyroid nodules to low- or high-level TSH suppression in a placebo-controlled, randomized crossover trial. design Forty-nine patients with solitary thyroid nodules on palpation were randomized to high-level and low-level TSH suppression groups. In each group, patients were further randomized to placebo and active levothyroxine subgroups. Patients in each subgroup were crossed over to placebo or active levothyroxine at the end of the first year and were then followed up for an additional year. methods TSH levels were suppressed to 0·4–0·6 mIU/ml and ≤ 0·01 mIU/ml in the low-level and high-level TSH suppression groups, respectively. Nodule volumes were measured at baseline and every 6 months after the desired level of TSH was reached if the patients were in the active levothyroxine treatment group or every 6 months if they were in the placebo group. results In high-level TSH suppression groups, nodule volume decreased significantly at the end of the active treatment periods (4·99 ± 2·02 ml vs. 3·20 ± 1·50 ml, P

Nonenzymatic glycation of tissue and plasma proteins may stimulate the production of oxidant and carbonyl stress in diabetes. The aim of this study was to evaluate the effects of aminoguanidine (AG) on lipid peroxidation, protein oxidation and nitric oxide (NO) release in diabetic rat kidneys. After induction of diabetes with streptozotocin, female Wistar rats were divided into 2 groups. Group DAG (n=9) rats were given AG hydrogen carbonate (1 g/L) in drinking water and group D (n=8) was diabetic control rats given only tap water. Group H (n=8) was followed as healthy controls. At the end of an 8 week period, NO release, lipid and protein oxidation were determined in kidney tissues. NO release was significantly lower in diabetic rats compared with healthy controls (pAlthough AG treatment had no effect on NO release, it significantly decreased lipid peroxidation in diabetic rat cortices. Consequently increased lipid peroxidation -as well as- protein oxidation could be involved in the pathogenesis of diabetic albuminuria.

We investigated the effect of aminoguanidine (AG) administration on GBM thickness, glomerular heparan sulfate (HS) content, and urinary albumin and HS excretion in diabetic rats. After induction of diabetes, female Wistar rats were divided into 2 groups: Group AGDM (n=11) received 1g/L aminoguanidine bicarbonate in drinking water, group DC (n=12) was given only tap water. Control rats received AG (group AGH, n=8) or tap water (group HC, n=8). At the end of a period of 8 weeks, urinary albumin and glycosaminoglycan (GAG) excretion was detected. GBM heparan sulfate distribution and count was determined under the electron microscope. The AGDM group had lower urinary albumin and GAG excretion than diabetic controls. GBM thickness was increased in diabetic rats compared to groups of AGDM and HC. In AGDM group alcian blue stained particle distribution and count in the GBM was similar to healthy controls. In conclusion AG prevents the decrease of anionic charged molecules in the GBM and GBM thickening. This can be one of the mechanisms by which AG decreases albuminuria in diabetic rats.

No consensus exists as to the best time for starting insulin treatment in patients with type 2 diabetes. Glucose toxicity is a significant factor which affects the approach to treatment at various stages of the disease. Those who advocate early insulin use cite studies which have used CSII or intensive insulin therapy in newly-diagnosed type 2 diabetics and have achieved long-term glycemic control without medication, similar to the “honeymoon” in type 1 diabetic patients. Although there are studies showing improved control with maximal dose sulfonylurea therapy, glucose control takes longer to achieve and HbA1c levels remain higher than current targets. It is evident that without insulin, our patients will perpetually remain below target and suffer the consequences of hyperglycaemia, even if mild.

OZET Amac: Hiperglisemi hastane mortalite ve morbiditesini etkileyen faktorlerden birisidir. Yatan hastalarin yaklasik yarisinda hiperglisemi varliginin ilk kez tespit edildigi rapor edilmistir. Bu calismanin amaci, Marmara Universitesi Hastanesi’nde yatan hastalarda yattiklari ve taburcu olduklari donemlerde hiperglisemi sikliginin ve hipergliseminin yatis suresi ile iliskisinin belirlenmesidir. Hastalar ve Yontem: Calismaya, Subat-Temmuz 2007 tarihleri arasinda Marmara Universitesi Hastanesi kliniklerinde 24 saatten uzun sureli yatan 1971 eriskin hasta dahil edilmistir. Hastalarin yattiklari ve taburcu olduklari gunlerde kan sekerleri, kapiller kandan glukometre ile olculmustur. Glukometre ile olculen aclik kan sekeri 126 mg/dL veya tokluk kan sekeri 200 mg /dLuzerinde bulunan hastalarin damarlarindan alinan kan orneklerinde kan sekeri olcumleri laboratuvarda yapilmistir. Hastalarin diyabet oykuleri ve yatis sureleri kaydedilmistir. Bulgular: Hastalarin %23.8’inde bilinen diyabet (Grup 1), % 12.3’ unde yeni tanili diyabet (Grup 2) saptanmistir. Grup 1 en sik Koroner Yogun Bakim Unitesi’nde (%80) ve en seyrek Beyin Cerrahisi Servisi’nde (% 5.8) gorulurken, Grup 2’nin sikligi en yuksek Goz Servisi hastalarinda (%25), en dusuk ise Fizik Tedavi Servisi hastalarindadir (%2.7). Grup 1’de yatis ve cikis sirasinda kan sekeri degerleri sirasi ile cerrahi bolumlerde diyabet olan ve olmayanlarda (157.6 ± 49.0 vs 151.0 ± 60.0, p>0.05) (114.4 ± 37.7 vs 111.8 ± 26.6, p>0.05), dahili bolumlerde diyabet olan (173.9 ± 89.5 vs 155.6 ± 43.4, p>0.05) ve olmayanlarda (110.7 ± 38.3 vs 111.9 ± 28.0, p>0.05) olarak bulunmustur. Diyabetik hastalarin yatis suresi (14.1±19 gun) diyabetik olmayanlara (7.5±13 gun) gore daha uzundur (p

Previous studies have suggested an influence of vitamin D receptor alleles on bone metabolism and on susceptibility to type 1 diabetes mellitus in different ethnic populations. We aimed to investigate the distribution of vitamin D receptor (VDR) alleles in relation to biochemical bone turnover parameters and bone densitometry measurements in a group of Turkish type 1 diabetic patients. One hundred and seventeen patients (M/F 57/60, 27.6 +/- A 7.3 y duration of diabetes 8.1 +/- A 6.3 y) and 134 healthy controls (M/F 61/73, 26.2 +/- A 5.3 y) were included in the study. Bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DEXA). The vitamin D receptor gene (VDR) polymorphisms FokI, Bsm1, Apa1, and Taq1 were examined using a PCR-based restriction analysis. Serum levels of calcium, phosphor osteocalcin, intact parathyroid hormone, and C telopeptide were measured. Vitamin D receptor Bsm1 Fok1, Apa1, and Taq1 genotype distributions were not different between patient with diabetes and control groups. BMD was 0.77 +/- A 0.2 g/cm(2) vs. 0.97 +/- A 0.2 g/cm(2) (P = 0.0001) for the femur, 1.0 +/- A 0.1 g/cm(2) vs. 1.13 +/- A 0.1 g/cm(2) (P = 0.001) for type 1 diabetic patients and controls. Bone turnover markers were significantly lower in type 1 diabetic group. BMD measurements and bone metabolic markers were not different between the genotypes in either the patient with diabetes or the controls. The VDR gene polymorphisms, Bsm1, Fok 1, Apa1, and Taq1 showed no influence on bone metabolism in our group of type 1 diabetic patients. Turkish Diabetes Foundation

OBJECTIVE To compare the effects of erythromycin and metoclopramide on gastric emptying and symptoms of gastroparesis in diabetic patients with delayed gastric emptying. RESEARCH DESIGN AND METHODS The study group consisted of 13 patients with symptoms of severe gastroparesis and delayed gastric emptying. Gastric emptying was evaluated using a radionuclide method, and gastrointestinal symptoms were scored. The patients were given either erythromycin (250 mg 3 times/day) or metoclopramide (10 mg 3 times/day) in random order for 3 wk, and after a washout period of 3 wk they were crossed-over to the other medication for another 3 wk. Parameters of gastric emptying were assessed before treatment and after both erythromycin and metoclopramide administration. RESULTS The half-time of gastric emptying in diabetic subjects was 110 (77–120) min before treatment. At 60 and 90 min, the median value of residual isotope activity was 66.5 (55–83.5) and 55% (43–74.3), respectively. The half-time decreased to 55 min (28.6–115) after 3 wk of treatment with erythromycin and percentages of meal retention in the stomach at 60 and 90 min were 49.9 (38.4–70) and 40.5% (29.7–60), respectively. After taking metoclopramide, the median value of half-time was 67 min (15–115) and percentages of meal retention at 60 and 90 min were 51 (34.5–93.9) and 42% (24–71.2), respectively. When compared with baseline values a significant difference in gastric emptying parameters was found after both erythromycin and metoclopramide. A significant improvement of the total score for gastrointestinal symptoms was observed with both drugs, but this improvement was more pronounced with erythromycin. CONCLUSIONS Erythromycin, a macrolide antibiotic and a motilin receptor agonist, appears to stimulate intestinal motility and seems to be an alternative agent for the treatment of gastroparesis caused by diabetic autonomic neuropathy.

Diabetic cardiomyopathy is an important complication of type 1 diabetes mellitus. Diastolic heart failure is an early manifestation of diabetic cardiac disease. Nt-proBNP is a valuable marker of ventricular dysfunction. The aim of this study was to determine Nt-proBNP concentrations in type 1 diabetic patients and determine their relationship with ventricular diastolic dysfunction (DD) and carotid artery intima media thickness (CIMT) measurements. Sixty-seven type 1 diabetic patients (30.2 ± 8.0 years; W/M: 24/43) without known cardiovascular disease and 48 healthy controls (30.5 ± 6.4 years; W/M: 19/29) were recruited. Nt-proBNP levels were measured. Conventional and tissue Doppler echocardiography were used to evaluate left ventricular diastolic function and CIMT. Nt-proBNP in diabetic patients was significantly higher than in controls (38 ± 34.8 vs. 15.1 ± 12.7 pg/ml) (P = 0.004). Ea level was higher (12.3 ± 3 vs. 10.3 ± 4 cm/s, P = 0.003) and E/Ea ratio was lower in patients (6.6 ± 2.5 vs. 9.7 ± 5.9, P = 0.001) compared with controls. Ratio of DD was higher in patients than controls (11.1 vs. 2.1%, P = 0.01). CIMT measurements in diabetic patients were higher than controls (0.54 ± 0.11 vs. 0.48 ± 0.05 mm, P = 0.02). Logistic regression revealed age and HbA1c to be independently associated with the presence of DD. Nt-proBNP levels are elevated in type 1 diabetic patients without overt cardiovascular disease and the presence of DD is increased in diabetic patients in comparison with controls. Nt-proBNP levels do not seem to be related to the presence of DD and subclinical atherosclerosis in this group of patients.

Epicardial adipose tissue has shown to be related to cardiovascular risk. The aim of this study is to investigate the relationship between epicardial adiposity and endothelial function in metabolic syndrome.Fifty patients with metabolic syndrome were recruited. Anthropometric measurements, fasting blood glucose, insulin, lipid profile, high-sensitivity C-reactive protein (hsCRP), fibrinogen, apolipoprotein A (Apo A), Apo B1, and lipoprotein (a) [Lp(a)] were determined. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Epicardial fat thickness was measured via two-dimensional M-mode echocardiography. Endothelial function was assessed as flow-mediated dilatation at the brachial artery.Epicardial fat tissue thickness was shown to be correlated negatively with FMD and positively with age, diastolic blood pressure, hsCRP, fibrinogen, HOMA-IR, and lipid parameters. Multiple regression analysis showed epicardial fat tissue thickness to be an independent factor influencing the endothelial function.Epicardial fat tissue may be a useful parameter in the assessment of patients with metabolic syndrome.

ObjectiveCirculating endothelial cells (CECs) have emerged as vascular damage markers and are increased in type 2 diabetic patients. Since type 1 diabetes is associated with vascular damage, we hypothesized high CEC numbers in this patient population.MethodsThirty-nine patients with type 1 diabetes and 39 controls were included. CECs were isolated using anti-CD146-coated Dynabeads, stained with Ulex lectin-1, and counted by fluorescence microscopy. Endothelial function was measured as flow-mediated dilation (FMD). Thiobarbituric acid reactive substances (TBARS), total glutathione levels (GSH), and paraoxonase (PON) activity levels were measured as oxidative stress markers.ResultsPatients with type 1 diabetes mellitus had higher number of CECs (7.46±5.37 vs 2.13±1.13 cells/ml,PPPPPThere was positive correlation between CEC numbers and HbAlc levels (r=0.49,P=0.002). CECs and fasting glucose levels were not correlated. There was no correlation between the number of CECs and FMD. Furthermore, there were no correlations between the number of CECs and TBARS, GSH and PON activity levels. Multiple regression analysis showed that HbAlc levels (r2=0.40,PConclusionCECs are elevated in patients with type 1 diabetes mellitus reflecting endothelial damage. This increase is dependent on long-term glucose control.

Environmental factors have been implicated in the development of autoimmune thyroid disease (AITD). Anti-Saccaromyces Cerevisiae Antibodies (ASCA) were shown to be elevated in several autoimmune diseases. The aim of the study was to determine ASCA levels and their relationship with thyroid autoantibodies in patients with AITD. One-hundred and twelve patients with AITD (age 41.1 ± 12.8 years; F/M:96/16) and 103 healthy controls (38.5 ± 10.3 years; F/M:82/21) were included. Twenty-four patients had Graves disease (GD), and 88 had Hashimoto’s thyroiditis (HT). ASCA IgA and IgG, TSH, free T4, anti-thyroglobulin, and anti-thyroid peroxidase antibody concentrations were determined. ASCA IgA positivity in patients with GD (16.6%) was similar to patients with HT (13.6%) and was higher than controls (5.8%). No significant difference was present between the frequencies of IgG positivity among GD (12.5%), HT (7.9%), and control groups (5.8%). The mean levels of ASCA IgA and IgG were comparable within the groups. No correlation of ASCA and anti-thyroglobulin and anti-thyroid peroxidase levels was observed. Increased IgA ASCA positivity is observed in patients with GD, suggesting a role of environmental stimuli in its pathogenesis. The role of ASCA in the etiology of AITD needs to be further examined.

PubMedID: 19079066 The timely secretion of gonadal sex steroids is essential for the initiation of puberty, the postpubertal maintenance of secondary sexual characteristics and the normal perinatal development of male external genitalia. Normal gonadal steroid production requires the actions of the pituitary-derived gonadotropins, luteinizing hormone and follicle-stimulating hormone. We report four human pedigrees with severe congenital gonadotropin deficiency and pubertal failure in which all affected individuals are homozygous for loss-of-function mutations in TAC3 (encoding Neurokinin B) or its receptor TACR3 (encoding NK3R). Neurokinin B, a member of the substance P-related tachykinin family, is known to be highly expressed in hypothalamic neurons that also express kisspeptin, a recently identified regulator of gonadotropin-releasing hormone secretion. These findings implicate Neurokinin B as a critical central regulator of human gonadal function and suggest new approaches to the pharmacological control of human reproduction and sex hormone-related diseases. © 2009 Nature America, Inc. All rights reserved. National Space Biomedical Research Institute Wellcome Trust: 080952/Z/06/Z, 078986/Z/06/Z Firat University Scientific Research Projects Management Unit: TF-2006-BAP20 1001, 106S276 This work was supported by grants to A.K.T., N.O.M. and B.Y. from the Scientific and Technological Research Council of Turkey (TÜBİTAK): The Support Programme for Scientific and Technological Research Projects (1001), project 106S276; and from the Cukurova University Scientific Research Projects Support Unit, grant TF-2006-BAP20; by the Wellcome Trust (R.K.S., Intermediate Clinical Fellowship 080952/Z/06/Z; S.O., Programme Grant 078986/Z/06/Z; F.R., Senior Basic Science Fellowship) and the UK National Institute for Health Research Cambridge Biomedical Research Centre. F.R. has also received support from St. John’s College, Cambridge, UK.

Angiotensin-converting enzyme (ACE) inhibitors may reduce urinary albumin excretion (UAE) by decreasing glomerular pressure and increasing glomerular charge selectivity through preservation of glycosaminoglycans. The effect of Angiotensin II antagonism on glomerular charge selectivity remains to be determined. The aim of this study was to compare the effects of an AT1 blocker losartan and an ACE inhibitor (ACE-I) enalapril on UAE, extracellular matrix proteins, glycosaminoglycan excretion (UGAG) and red blood cell anionic charge (RBCCh) which are the indirect markers of glomerular basement membrane anionic content in hypertensive Type 2 diabetic patients. Twenty-four patients were randomised into two groups and received either enalapril (5—20 mg/d) or losartan (50—100 mg/d). All parameters were measured at baseline and after six months of treatment. At the end of six months, systolic and diastolic blood pressures (BP), UAE rates, UGAG excretion and RBCCh were significantly and equally reduced in both treatment groups compared with baseline. RBCCh was negatively correlated with UAE (r=-0. O 57, pGAG excretion (r=-0.57, RpGAG excretion (r=0.58, pGAG excretion and preserving RBCCh in hypertensive Type 2 diabetic patients. ACE inhibition and AT1-receptor blockade may have favourable effects on preserving glomerular anionic content in hypertensive diabetic patients.

Advanced glycoxidation end products have been implicated in delayed diabetic wound healing. In this study, we evaluated the effects of aminoguanidine, which is an advanced glycation and nitric oxide (NO) synthase inhibitor, on extracellular matrix protein expression, collagen configuration, and nitrite/nitrate levels in wounds of diabetic rats. Sixteen Wistar male rats were made diabetic by streptozotocin. Of these, eight rats were given AG (aminoguanidine bicarbonate (AG) (group DAG) in their drinking water, and eight rats were followed as diabetic paired controls (group D). Eight healthy rats were followed as the healthy control group (group H). At the eighth week, a 2 x 2 cm area full-thickness skin defect was created. The degree of contraction of the open wounds was evaluated for 2 weeks duration. On the 15th postoperative day, wound surface areas were measured, and wound specimens and blood samples were collected. The shrinking percentage of the wounds was small in both groups H and DAG compared with group D (p < 0.05). Similar to healthy rats, the aminoguanidine-treated diabetic rats had very strong transforming growth factor (TGF)-beta1 expression in granulation tissue and intact skin in comparison with diabetic controls. In the diabetic group, the intact skin demonstrated sparsely distributed regular collagen fibers in the granulation zone, and the regular pattern of collagen fibers was lost. In conclusion, aminoguanidine improves wound healing, restores growth factor TGF-beta1 expression, and preserves collagen ultra structure, whereas it has no prominent effect on NO levels within wound tissue in diabetic rats.

Autonomously functioning thyroid nodules (AFTNs) can present as hyperfunctioning adenomas or toxic multinodular goiters. In the last decade, a large number of activating mutations have been identified in the thyrotropin receptor (TSHR) gene in autonomously functioning thyroid nodules. Most have been situated close to, or within the sixth transmembrane segment and third intracellular loop of the TSHR where the receptor interacts with the Gs protein. In this study we describe two novel mutations in the sixth transmembrane segment of the TSHR causing hyperfunctioning thyroid nodules. Genomic DNAs were isolated from four hyperfunctioning thyroid nodules, normal tissues and peripheral leukocytes of two patients with toxic multinodular goiter. After amplifying the related regions, TSHR and G(s)alpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. Functional studies were done by site-directed mutagenesis and transfection of a mutant construct into COS-7 cells. We identified two novel TSHR mutations in two hyperfunctioning thyroid nodules: Phe631Val in the first patient and Iso630Met in the second patient. Both mutant receptors display an increase in constitutive stimulation of basal cyclic adenosine monophosphate (cAMP) levels compared to the wild-type receptor. This confirms that these mutant receptors cause hyperfunctioning thyroid nodules.

Many studies have been carried out to determine G(s) alpha and TSHR mutations in autonomously functioning thyroid nodules. Variable prevalences for somatic constitutively activating TSHR mutations in hot nodules have been reported. Moreover, the increased prevalence of toxic multinodular goiters in iodine-deficient regions is well known. In Turkey, a country with high incidence rates of goiter due to iodine deficiency, the frequency of mutations in the thyrotropin receptor signal transduction pathway has not been evaluated up to now. In the present study, a part of the genes of the TSHR, G(s)alpha and the catalytic subunit of the PKA were checked for activating mutations. Thirty-five patients who underwent thyroidectomy for multinodular goiters were examined. Genomic DNAs were extracted from 58 hyperactive nodular specimens and surrounding normal thyroid tissues. Mutation screening was done by single-strand conformational polymorphism (SSCP) analysis. In those cases where a mutation was detected, the localization of the mutation was determined by automatic DNA sequencing. No G(s)alpha or PKA mutations were detected, whereas ten mutations (17%) were identified in the TSHR gene. All mutations were somatic and heterozygotic. In conclusion, the frequency of mutations in the cAMP signal transduction pathway was found to be lower than expected in the Turkish population most likely because of the use of SSCP as a screening method and sequencing only a part of TSHR exon 10.

The aim of this study was to evaluate the effects of quinapril, valsartan, and amlodipin on glucose tolerance in cyclosporine (CsA)-toxic rats. Among 40 male Wistar rats 32 were administered cyclosporine (CsA) (15 mg/kg) intraperitoneally for 6 weeks. Quinapril (10 mg/kg per day) (group Q), valsartan (40 mg/kg per day) (group V), and amlodipine (10mg/kg per day) (group A) were administered to individual sets of eight CsA-treated animals via the drinking water with the remaining untreated hosts followed as a control group (group C) and 8 healthy controls (group H). A Glucose-tolerance test was performed by administering oral glucose (2 g/kg) followed by blood samples obtained from the tail vein at baseline as well as 30,60,90, and 120 minutes after the glucose load. Glucose area under the curve (AUC) was calculated according to the trapezoidal rule. CsA levels were determined using an immunofluorescence method. Kruskal Wallis ANOVA test was used for statistical analysis. Median CsA levels were 1968 ng/mL, 1982 ng/mL, 1580 ng/mL, 1600 ng/mL; and glucose AUC, 232.4 +/- 130 mg/min per dL, 63.1 +/- 25 mg/min per dL, 115.0 +/- 90 mg/min per dL, 47.4 +/- 34 mg/min per dL 53.4 +/- 38 mg/min per dL for groups C,Q,V,A and H, respectively. Quinapril-treated and amilodipine-treated rats displayed a lower glucose AUC than group C (P.01), which had higher glucose levels than healthy controls (P.001). In summary, CsA treated rats show impaired glucose tolerance, which is improved by quinapril or amlodipine treatment. Angiotensin converting enzymes inhibitors and calcium channel blockers affect beta cell function rather than insulin sensitivity.

BACKGROUND: Hyperprolactinemia has been reported to be associated with abnormalities of carbohydrate metabolism. The aim of this study was to evaluate the effects of hyperprolactinemia and bromocriptine (Brc) treatment on endothelial function, insulin sensitivity and inflammatory markers in pre-menopausal women. METHODS: Sixteen hyperprolactinemic pre-menopausal women with pituitary adenomas were recruited and 20 healthy subjects were included as controls. Patients were given Brc in doses of 2.5-20 mg/dl until normal levels of prolactin were reached. Prior to treatment and 2 months after prolactin levels were normalized, the following tests were performed. Insulin sensitivity was determined by an oral glucose tolerance test based on a formula named the insulin sensitivity index (ISI composite). Endothelial function was measured as flow-mediated dilatation (FMD) on a brachial artery using high resolution ultrasound. RESULTS: Serum glucose, insulin, estrogen, highly sensitive C-reactive protein (hsCRP), fibrinogen, homocysteine and uric acid levels were measured. Calculated ISI composite and FMD were significantly lower in the hyperprolactinemic group in comparison with the controls and improved after Brc treatment. Serum homocysteine, hsCRP and uric acid levels were significantly higher in hyperprolactinemic patients than in the controls and returned to normal levels with Brc treatment. Serum prolactin concentrations were inversely correlated with FMD measurements (r=-0.68; P

The efficacy and the effective dose of levothyroxine suppressive therapy in the treatment of benign thyroid nodules are controversial. In this study, we aimed to determine the response of solitary thyroid nodules to low- or high-level TSH suppression in a placebo-controlled, randomized crossover trial.Forty-nine patients with solitary thyroid nodules on palpation were randomized to high-level and low-level TSH suppression groups. In each group, patients were further randomized to placebo and active levothyroxine subgroups. Patients in each subgroup were crossed over to placebo or active levothyroxine at the end of the first year and were then followed up for an additional year.TSH levels were suppressed to 0.4-0.6 mIU/ml andor = 0.01 mIU/ml in the low-level and high-level TSH suppression groups, respectively. Nodule volumes were measured at baseline and every 6 months after the desired level of TSH was reached if the patients were in the active levothyroxine treatment group or every 6 months if they were in the placebo group.In high-level TSH suppression groups, nodule volume decreased significantly at the end of the active treatment periods (4.99 +/- 2.02 ml vs. 3.20 +/- 1.50 ml, P0.01, in Group 1; and 3.72 +/- 1.79 ml to 2.05 +/- 0.64 ml, P0.001, in Group 2). In the low-level TSH suppression groups, nodule volume also decreased significantly at the end of the active treatment periods (4.43 +/- 1.76 ml vs. 3.04 +/- 1.32, P0.05, in Group 3; and 3.59 +/- 0.89 ml to 2.22 +/- 0.59 ml, P0.01, in Group 4). Nodule volumes regained their original volumes during the placebo treatment periods. The percentage decline in clinically relevant nodule volume reduction (or = 50%) was similar in the low-level and high-level TSH suppression groups.Low- and high-level TSH suppression were equally effective in reducing nodule volume and thus, considering the complications of high-level TSH suppression, low-level TSH suppression should be used if one considers levothyroxine suppressive therapy to reduce thyroid nodule size.

Çelik I, Akalin S, Erbaş T. Serum levels of interleukin 6 and tumor necrosis factor-α in hyperthyroid patients before and after propylthiouracil treatment. Eur J Endocrinol 1995;132:668–72. ISSN 0804–4643 Contrary to the usual inhibitory role of tumor necrosis factor-α (TNF-α) thyroid metabolism, it also has specific stimulatory effects in autoimmune thyroid disorders, including induction of HLA class II antigen-presenting cell—T cell interaction. Despite high intrathyroidal concentrations, various studies were not able to demonstrate high serum levels of TNF-α in patients with Graves' disease. To investigate this discrepancy we determined TNF-α and interleukin 6 (IL-6) levels in 25 hyperthyroid patients who responded to propylthiouracil treatment (16 with Graves' disease and nine with toxic multinodular goiter) and compared them with the levels found in euthyroid patients with simple diffuse goiter (n = 15) and normal healthy controls (n = 15). Median IL-6 levels were high in both Graves' disease and toxic multinodular goiter patients before propylthiouracil treatment (23 and 26.5 pg/ml, respectively). After restoring euthyroidism there was a statistically significant decline to near-normal levels (3 and 10 pg/ml, respectively). On the other hand, median serum TNF-α levels were high only in Graves' disease patients (20 pg/ml) and could not be normalized with antithyroid medication (20 pg/ml) compared to that of controls (5 pg/ml). Tumor necrosis factor-α, but not IL-6, was found to be high in the sera of Graves' disease patients when euthyroid, which may be due to an ongoing antigen–antibody interaction, a feature of autoimmune attack. It remains to be determined whether the degree of TNF-α and/or IL-6 elevation will be a predictor of disease recurrence. Ismail Çelik, Section of Oncology, Dept. of Medicine, Hacettepe University Institute of Oncology, Ankara 06100, Turkey

Acute effects of 20 mg oral enalapril (E), and angiotensin-converting enzyme inhibitor, on renal function and the renin-angiotensin-aldosterone system were investigated in 13 patients with type II diabetes mellitus (8 female, 5 male) and 10 hypertensive controls using a radionuclide method. Plasma glucose control was evaluated with fructosamine (F) determinations. After intravenous administration of 370 MBq 99mTc-DTPA, sequential images were recorded. Glomerular filtration rate (GFR), perfusion index (PI), time to maximum activity and reno index values of the kidneys were calculated. Two days later, renal scintigraphy was repeated after oral administration of E. Plasma levels of renin, angiotensin II and aldosterone were analyzed using RIA. Basal GFR values (mean: 92.6 ml/min) correlated with F (r = 0.364; p0.05). In the diabetic group, 5 patients had a decrease in GFR and an increase in PI after oral E. The mean percent change of GFR was 12 +/- 32 for patients and 20 +/- 12 for controls, respectively. Percent change of GFR had a slightly negative correlation with F values (r = -0.51; p0.05) and with PI (r = -0.65; p0.001). The patients with good metabolic control had an increase in GFR and a decrease in PI indicating an increase in renal blood flow and glomerular filtration. In patients with proteinuria and poorly controlled diabetes, in response to E-induced efferent arteriolar dilation, there is a decrease in GFR and an increase in PI which indicates a fall in filtration and renal blood flow. This glomerular hemodynamic pathology precedes morphological changes due to diabetes.

Left ventrical performance was assessed by systolic and diastolic time intervals measured echocardiographically in 24 diabetic patients without clinical heart disease and in 18 healthy subjects. It was found that diabetics had longer PEP, higher PEP/LVET ratio and longer IVRT (p less than 0.01). The possible pathogenetic explanations of these abnormalities are discussed and it is concluded that the measurement of time intervals is a useful method for detecting this myocardial dysfunction on the preclinical stage.