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Aims: To assess the cardiovascular (CV) safety of oral semaglutide, the first tablet formulation of a glucagon-like peptide-1 receptor agonist. Materials and methods: PIONEER 6 is a multinational, randomized, placebo-controlled, double-blind trial in patients with type 2 diabetes at high risk of CV events (defined as being aged ≥50 years and having established CV disease [CVD] or moderate [stage 3] chronic kidney disease [CKD], or being aged ≥60 years with ≥1 other CV risk factor). Patients were randomized to once-daily oral semaglutide (up to 14 mg) or placebo added to standard of care. The primary composite endpoint is time to first occurrence of CV death or non-fatal myocardial infarction or non-fatal stroke. The primary hypothesis was to exclude an excess in CV risk with oral semaglutide by assessing non-inferiority versus placebo for the primary endpoint (non-inferiority margin of 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio). PIONEER 6 is event-driven, with follow-up continuing until accrual of at least 122 primary outcome events. There is no pre-defined minimal duration. Results: Overall, 3183 patients have been enrolled (mean age 66.1 years, 31.6% females) in 214 sites across 21 countries. At baseline, the mean duration of diabetes was 14.9 years, mean glycated haemoglobin concentration was 66 mmol/mol (8.2%), and 84.6% of patients had established CVD/moderate CKD. Conclusions: PIONEER 6 will provide evidence regarding the CV safety of oral semaglutide in patients with type 2 diabetes and high CV risk.

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.

Purpose: The prevalence of type 2 diabetes mellitus (T2DM) is increasing in Turkey due to rising obesity rates, sedentary life styles and Turkey’s aging population; up-to-date and standardized data collection is required for the global fight against diabetes. The data collected from Turkey during the 5th wave of a multinational, multi-center and observational study are evaluated in this article. Material and Method: The International Diabetes Management Practices Study (IDMPS) which is an international, observational multicenter, cross-sectional study, evaluated demographic and clinical characteristics of diabetic patients, treatment modalities, complications, cardiovascular risk factors and also reported the results of the patient health questionnaire (PHQ-9). Results: This study consisted of 842 T2DM and 115 Type 1 diabetes mellitus (T1DM) patients and was carried out by 94 doctors in Turkey between December 13th 2011 and January 26th 2012. Data revealed that 52% of patients were treated with oral anti-diabetic (OAD) drugs only, 29% were treated with OAD + insulin, and 18% of subjects were treated with insulin alone. 88% of T2DM patients had at least one microvascular complication and 99% had at least one cardiovascular risk factor. Only 27% of T1DM and 28% of T2DM patients reached the target hemoglobin A1c value of

INTRODUCTION: The aim of this study was to optimise and automate a low cost fructosamine assay and then to investigate the relationship between serum fructosamine levels and long-term complications. METHODS: Serum fructosamine and HbA1c were measured in non-diabetic controls (n = 146) with a mean age of 60 ± 20 and diabetic subjects (n = 353) with a mean age of 61 ± 11. The optimization of fructosamine analysis by nitrobluetetrazolium method requires the optimal solubility of diformazan and mathematical correction of uric acid interferance. The within-day imprecision and between-day imprecision of the automated method were 0.7% (n=10) and 2.5% (n=10) respectively. RESULTS: Mean fructosamine concentrations were significantly increased in DM (342 ± 74 μmol/L) compared with control group (270 ± 47 μmol/L) (p 0.05). However, since it is highly correlated with HbA1c (r = 0.817, p, GİRİŞ ve AMAÇ: Bu çalışmanın amacı düşük maliyetli bir fruktozamin ölçüm yöntemini otoanalizöre uyarlamak ve optimize etmek; daha sonra serum fruktozamin seviyesi ile uzun dönemli komplikasyonlar arasındaki ilişkiyi araştırmaktır.YÖNTEM ve GEREÇLER: Yaşları ortalama 60 ± 20 sağlıklı kontroller (n = 146) ile yaşları ortalama 61 ± 11 diyabetik deneklerde (n = 353) serum fruktozamin ve HbA1c seviyeleri ölçüldü. Fruktozamin ölçümü için “Nitrobluetetrazolium yöntemi” otoanalizöre uyarlandı ve diformazanın yeterli çözünmesinin sağlanması ile ürik asit interferansının matematiksel düzeltmesi ile optimizasyonu sağlandı. Otomatize yönetimin gün içi ve günler arası tekrarlanabilirliği sırasıyla %0.7 (n=20) ve %2.5 (n=20) olarak saptandı.BULGULAR: Ortalama fruktozamin konsantrasyonu DM’lerde (342 ± 74 μmol/L) kontrol grubuna (270 ± 47 μmol/L) göre belirgin yüksekti (p 0.05). Bununla beraber HbA1c ile koreledir (r = 0.817, p

Objective Acromegaly is a multisystemic disorder caused by excessive secretion of growth hormone (GH). Sleep-disordered breathing (SDB) such as sleep apnea syndrome (SAS) may occur in acromegaly. The aim of study was to assess the presence of sleep disorders and evaluate the systemic complications on respiratory, cardiovascular, and upper airway systems in acromegalic patients. Methods The study group consisted of 30 acromegaly outpatients. GH and insulin-like growth factor 1 (IGF-1) measurements were obtained; body pletysmography, arterial blood gas analysis, tissue-doppler imaging, echocardiography, polysomnography, otorhinolaryngologic examination, and head-neck computed tomography were performed. Results Sixteen female (53.3%) and 14 male (46.7%) acromegalic patients had a mean age of 51.1 ± 13.2. GH was supressed in 19 patients (63.3%) when 11 had active acromegaly (36.7%). There were 17 patients with SAS (62.9%) (7: mild, 3:intermediate, 7:severe SAS) and average AHI was 16/h. Sixteen patients had predominantly obstructive SAS while one patient had predominantly central SAS. SAS was statistically more frequent in males than females (P = .015). The mean neck circumference was significantly longer in patients with SAS (P = .048). In SAS patients,the soft palate was elongated and thickened,which was statistically significant (P = .014 and P = .05).Vallecula-to-tongue distance was statistically longer in acromegalic patients with SAS (P = .007).There was a positive correlation between tonsil size,vallecula-to-tongue distance and AHI (r = 0.432, P = .045 and r = 0.512, P = .021, respectively). Conclusion SDB seems to be common and clinically important in patients with acromegaly, particularly in men. The most frequent type of apnea in acromegalics is obstructive. Hormonal activity of acromegaly does not seem to have an effect on the development of SAS. Despite its high prevalence, SAS is frequently under-assessed in patients with acromegaly. Systemic complications and SDB should be researched in acromegalics.

Mature cystic teratomas form approximately 20% of all ovarian tumours. Of these, approximately 15% include benign thyroid tissue

BACKGROUND: Cushing's disease is a rare debilitating endocrine disorder for which few prospective interventional studies have been done. We report results of the first phase 3 trial assessing long-acting intramuscular pasireotide in patients with Cushing's disease. METHODS: In this phase 3 clinical trial we recruited patients aged 18 years or older with persistent, recurrent, or de-novo (non-surgical candidates) Cushing's disease who had a mean urinary free cortisol (mUFC) concentration (from three 24 h samples) of 1·5-5·0 times the upper limit of normal (ULN), a normal or greater than normal morning plasma adrenocorticotropic hormone concentration, and a pituitary source of Cushing's syndrome, from 57 sites across 19 countries. Exclusion criteria included previous pasireotide treatment, mitotane therapy within 6 months, and pituitary irradiation within 10 years. We randomly allocated patients 1:1 (block size of four) using an interactive-response-technology system to intramuscular pasireotide 10 mg or 30 mgevery 4 weeks for 12 months (in the core phase). We stratified randomisation by screening mUFC concentration (1·5 to

Low plasma corticotropin is considered a useful parameter for the diagnosis of subclinical hypercortisolism in patients with an adrenal incidentaloma. However, immunoassays are vulnerable to interference from endogenous antibodies. In this study, subjects who underwent Hypothalamus-pituitary-adrenal axis evaluation for the assessment of subclinical hypercortisolism were evaluated. The objective of the study was to ascertain whether antibody interference in corticotropin immunoassay affected the diagnostic work-up and clinical decisions. The 437 consecutive patients with incidentally discovered adrenal adenomas were included in this single centre study. Patients who had a combination of a nonsuppressed corticotropin concentration (>4.4 pmol/L) and a non-suppressed cortisol concentration after 1 mg overnight dexamethasone suppression test (>50 nmol/L) were selected. Eight eligible subjects without specific features of Cushing's syndrome were identified and recruited for interference studies and follow-up. Nine controls including one patient with unilateral adrenalectomy and one patient with Cushing's disease were recruited as well. Eligible subjects and controls were subjected to hormonal tests and investigations for suspected interference. Interference studies included measurement of corticotropin on a different analytical platform, serial dilutions, polyethylene glycol precipitation and heterophilic antibody analysis. Patients were followed with clinical and laboratory parameters for a median duration of 30 (12–90) months. Antibody interference was identified in four patients. Rheumatoid factor was responsible for the interference in one patient. Clinical management of the patients was affected by the erroneous results. Interference tests were negative in control subjects. Erroneous results associated with analytical interference negatively impacted on clinical decision making in this patient group. This should be considered particularly in conditions such as subclinical hypercortisolism which decisions depend on laboratory investigations mainly. Analytical interference could explain the high variability observed both in field measurements from patients who were expected to have lower corticotropin concentrations and in subclinical hypercortisolism prevalence reported by different studies. Many problems can be resolved by ensuring good communication between clinical and laboratory staff.

Objective: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD). Increased body fat, particularly its central distribution, is a well-known risk factor for CVD. A change in body composition in RA has been described previously. However, in most of these studies, age- and sex- but not body mass index (BMI)-matched controls were used. The aim of this study was to evaluate body composition in RA patients and compare it with age-, sex-, and BMI-matched controls. Material and Methods: Sixty-five RA patients (55 females and 10 males; mean age 54.9 ± 10.8) and 31 healthy controls (25 females, 6 males; 53.8±8.6) were included in this study. Mean disease duration was 9.2±9.6 years. Body composition was assessed by anthropometric methods (skinfold thicknesses, body circumferences), bioimpedance analysis, and dual-energy X-ray absorptiometry (DXA). Visceral adipose tissue (VAT) was assessed with computed tomography. Results: There were no significant differences for total body fatness, regional fat distribution, and total body water and fat-free mass between RA patients and control subjects. Bone mineral content (BMC), assessed by DXA, was significantly lower in RA patients (p=0.004). Clinical disease activity indices and steroid treatment do not affect soft tissue body composition or BMC. Conclusion: At least some RA patients do not have soft tissue composition alterations and may have similar health risks in comparison with subjects with similar age, sex, and total adiposity.

Objective Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. Methods This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. Results Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Q variant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed. Conclusion We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity.

Objective To determine the intraobserver and interobserver agreement levels in the evaluation of technetium Tc 99m sestamibi parathyroid scintigraphic images. Methods Ninety-eight patients with hyperparathyroidism were included in the study, and their parathyroid images were evaluated by 4 experienced nuclear medicine observers. The 98 cases were evaluated twice by each observer within an interval of 2 weeks. The evaluations were performed directly on workstations with use of digital images. A questionnaire was completed by each observer. The presence of a lesion, the number and the localizations of the lesions, and whether the lesion was clear or doubtful were all evaluated. Cohen kappa statistics and total agreement percentages were calculated by using SPSS version 11.0 software. Results The 4 observers performed 8 different evaluations and identified a minimum of 38 and a maximum of 43 cases with a parathyroid lesion (or lesions). Both the intraobserver and the interobserver agreements were “very good” for the presence of a parathyroid lesion. The intraobserver agreement was also “very good” and the interobserver agreement was “good” (for only 1 pair of observers) or “very good” for the evaluation of the number of parathyroid lesions. The intraobserver agreement was “very good” or “good” and the interobserver agreement was “good” for the lesion localization and for the presence of a doubtful lesion. Conclusion Parathyroid scintigraphy seems to be an observer independent method in the detection of a parathyroid lesion, in the determination of the number of lesions, and in the localizations of the lesions. The measured high agreement between observers increases the reliability of parathyroid scintigraphy. (Endocr Pract. 2012;18: 538-548)

Left ventricular diastolic dysfunction (LVDD) develops in the early stages of acromegaly. The purpose of this study was to identify LVDD analyzing by new echocardiograpic criteria as well as to evaluate determinants of the LVDD in acromegaly. This cross-sectional study examined 42 patients with acromegaly; 16 in active disease (AA) and 26 cured/well controlled (CA), and compared them with 30 healthy controls (CG). Ventricular systolic and diastolic functions were studied by conventional and tissue Doppler imaging based on the E/Em ratio and myocardial performance index (MPI). Other clinical parameters possibly contributing to LVDD in acromegaly were also investigated. The prevalence of LV hypertrophy (33%) and LVDD (35.7%) were increased in acromegaly, however, there were no differences between the AA and CA groups. Acromegalic patients had higher LV volumes and LV mass, and septal E/Em ratio compared to CG, whereas LV ejection fraction and MPI were not different. The presence of acromegaly (r = 0.29, P = 0.013), diabetes mellitus (DM) (r = 0.41, P < 0.001), hypertension (r = 0.35, P = 0.002), and sleep apnea (r = 0.56, P = 0.003) were found to be correlated with LVDD, whereas duration and activity of acromegaly were not. In regression analysis, advanced age (OR: 8.53, P = 0.006) and DM (OR: 25.9, P = 0.007) were found to be independent risk factors for LVDD. The risk of LVDD according to new criteria increases in acromegaly. However, it seems to be related to the presence of DM and advanced age and is independent of disease duration and activity. (Int Heart J 2012; 53: 299-305)

Background The majority of the incidentally discovered adrenal masses are non-functioning adrenal adenomas; however data regarding traditional and novel cardiovascular risk predictors in these subjects is lacking. The objective of our study was to investigate the levels of PAI-1, IL-6 and Apelin along with several traditional cardiovascular risk markers in subjects with non-functioning adrenal adenomas. Methods 38 subjects with non-functioning adrenal adenomas and 30, age, gender and BMI matched healthy controls were enrolled. Participants underwent hormonal evaluation including morning cortisol, adrenocorticotrophic hormone (ACTH), post dexamethasone suppression test (DST) cortisol, dehydroepiandrosterone sulfate (DHEAS) and urinary cortisol. Anthropometric and metabolic parameters, body composition, PAI-1, IL-6 and Apelin were measured. Results Subjects with non-functioning adrenal adenomas had significant elevations in systolic blood pressure, mean arterial pressure, waist circumference, uric acid, and post DST cortisol and had significantly reduced levels of DHEAS when compared to BMI matched controls. No significant difference was observed in terms of PAI-1, IL-6 and Apelin between groups. PAI-1 and IL-6 were significantly correlated with mean arterial pressure, BMI, uric acid, total and LDL-cholesterol. Linear regression analysis showed that morning cortisol and Apelin levels independently predicted HOMA levels in subjects with adrenal adenomas. Conclusion Subjects with non-functioning adrenal adenomas feature several cardiovascular risk factors even when compared to BMI matched individuals. Subtle cortisol autonomy in adrenal adenomas may be associated with those findings.

The influence of thyroid dysfunction on haemostasis is complex and still not very well understood. Both bleeding tendency and hypercoagulable states have been reported. In this article, we attempt to discuss the possible relationship between thyroid dysfunction and secondary haemostasis and fibrinolysis. After the analysis of the recent literature, we conclude that thyroid dysfunction is associated with alterations in fibrin generation and fibrinolysis. Most of the evidence suggests that hyperthyroidism is associated with impaired fibrinolysis and enhanced coagulation. Although, former studies proposed that there was an increase in fibrinolytic activity in hypothyroidism, increasing number of recent reports advocated the opposite. We believe that further prospective comprehensive clinical studies involving large numbers of patients either with overt or subclinical thyroid dysfunctions should be performed to clarify the effect of thyroid dysfunction on secondary haemostasis and fibrinolysis. Recent important patents focusing on coagulation and thyroid dysfunction are also discussed in this review. © 2011 Bentham Science Publishers Ltd.

Reduced creatinine clearance is related to an increased risk for diabetic foot ulcer development. Wound healing has been reported to be worse in diabetic patients with impaired kidney functions than general diabetic population. This study aimed to investigate the effect of creatinine clearance on the short-term outcome of neuropathic diabetic foot ulcers. Data from 147 neuropathic diabetic foot ulcer episodes were included in this observational study. Patients were admitted to Dokuz Eylul University Hospital between January 2003 and June 2008. Patients were excluded if they had limb ischemia. Diabetic nephropathy was investigated by 24h urinary albumin excretion and serum creatinine levels. Creatinine clearance was calculated according to Cockcroft-Gault formula. Foot ulcers were followed up for 6 months to determine the outcome. Our short-term follow-up revealed that neuropathic diabetic ulcers healed worse in patients with decreased creatinine clearance than in those who had normal creatinine clearance. Amputation rates were also found to be higher. Our results suggest that creatinine clearance is an important factor affecting wound healing in patients with neuropathic diabetic foot ulcers.

Background: Because of the increased use of imaging interventions, more subjects have been diagnosed with adrenal incidentaloma in recent years. Aim: To evaluate the risk of mass enlargement, hormone hypersecretion and development of adrenal carcinomas during short-term follow- up. Subjects and methods: There were 317 subjects with in- cidentally discovered adrenal tumors in the registry. Forty subjects were excluded because of clinically overt hormone secretion at diagnosis and subjects with complete data were included in radiological (no.=150) and hormonal (no.=150) fol- low-up. Radiological evaluation was performed with comput- ed tomography (CT) and/or magnetic resonance imaging (MRI). There were 143 subjects with adrenal adenomas and 7 subjects with other tumor types (cyst or myelolipoma). Me- dian follow-up duration was 24 months. Results: Increase in tumor size was detected in 25 subjects (17.4%) with adeno- mas and 1 subject with adrenal myelolipoma (14.3%). De- crease in tumor size was found in 7 subjects (4.8%) with adrenal adenomas. One patient was diagnosed with adreno- cortical carcinoma during follow-up. In subjects with non-func- tioning adrenal adenoma (NFA, no.=120) or subclinical Cush- ing syndrome (sCS) (no.=30), no subject developed clinically overt hormone hypersecretion, while 8 (6%) subjects in the NFA group developed sCS. Tumor diameter and follow-up duration were significantly higher in subjects who developed sCS. Conclusion: In conclusion, we demonstrated that, despite being infrequent, adrenal tumors may increase in size, devel- op overt or subclinical hormone secretion or feature malig- nant transformation. Therefore, radiological and hormonal follow-up should be recommended to the patients. More in- vestigations are needed for the establishment of long-term follow-up protocols. (J. Endocrinol. Invest. 33: 32-36, 2010) ©2010, Editrice Kurtis

Data regarding cardiovascular risk in subjects with non-functioning adrenal adenoma are limited. The objectives of this study are to investigate carotid intima media thickness (IMT) as an indicator of atherosclerosis in subjects with non-functioning adrenal incidentaloma (AI) and to evaluate the factors that could be associated with IMT. Forty-nine subjects without findings of hypercortisolism or other adrenal gland disorders, 34 body mass index (BMI)-unmatched controls (C) and 18 BMI-matched controls (BC) were enrolled. Participants underwent hormonal evaluation including morning cortisol, adrenocorticotrophic hormone (ACTH), post dexamethasone suppression test cortisol (DST), dehydroepiandrosterone sulfate (DHEAS), and urinary free cortisol. Anthropometric and metabolic parameters and carotid IMT were measured. AI group had increased BMI, blood pressure, waist circumference, post DST cortisol, uric acid, and homeostasis model assessment (HOMA) levels when compared with C. Blood pressure, uric acid and, post DST cortisol remained significantly elevated in AI versus BC. Average IMT was increased significantly in AI versus C (0.74 mm vs. 0.68 mm, P = 0.029) and insignificantly elevated in AI versus BC (0.74 mm vs. 0.67 mm, P = 0.086). In all participants, IMT was correlated with age, BMI, HOMA, waist circumference, morning cortisol, and uric acid. Morning cortisol was independently associated with HOMA levels in both AI group and all participants. Increased IMT in non-functioning AI was a consequence of insulin resistant state associated with subtle cortisol autonomy rather than a direct effect of cortisol. The correlation between morning cortisol and IMT may be associated with the effect of hypothalamus-pituitary-adrenal axis disturbances on vasculature.

Objectives To determine the predominant pulmonary function abnormality in overweight and moderately obese subjects and to evaluate the correlation between the severity of lung function impairment and the degree of obesity. Methods Fifty-three volunteers underwent physical examination, skin fold measurements, and standardized pulmonary function tests. Thirty-one women and 22 men with a mean age of 40.2 (18-66) years were studied. Results The reduction in functional residual capacity (FRC) and expiratory reserve volume (ERV) were the most common abnormalities in overweight and obese subjects. The reduction in static lung volume was correlated with the degree of obesity in women and men. Stepwise multiple regression coefficients were obtained separately for women and men. Subscapular skinfold was the best predictor in women for FRC and waist-to-hip ratio (WHR) and BMI were found the best for ERV. WHR was found predictive for forced vital capacity, total lung capacity, and FRC in men. Conclusions The lung volumes are substantially affected in our overweight and obese subjects. This influence is focused on different parameters of respiratory functions in men and women in relation to body fat distribution.

Background Although the role of cytokines in the development of Hashimoto's thyroiditis has already been established, its pathogenesis has not yet been clearly elucidated. The aim of our study was to investigate serum transforming growth factor-β1 (TGF-β1) levels in patients with Hashimoto's thyroiditis as well as the effect of achieving euthyroidism by levothyroxine replacement on TGF-β1 levels. Methods Twenty nine female, newly diagnosed hypothyroid Hashimoto's thyroiditis patients (16 overt, 13 subclinical hypothyroid) and 25 age- and sex-matched healthy controls were enrolled in the study. Results Serum TGF-β1 levels were lower in the Hashimoto's thyroiditis group when compared with control cases. Although significant differences were noted in lipid levels and in anthropometric measurements following levothyroxine replacement, serum TGF-β1 levels remained unchanged. Conclusions Our data suggest that altered TGF-β1 levels are associated with the presence of Hashimoto's thyroiditis, not with the treatment of thyroid dysfunction. Autoimmunity may have been triggered as a result of decreased immunosuppressive effect induced by depressed TGF-β1 levels in patients with Hashimoto's thyroiditis.

OBJECTIVE: a)To determine serum Transforming Growth Factor-beta 1 (TGF-beta 1) levels in patients with type 2 diabetes who do not have diabetes related complications and in healthy controls, b) to evaluate the effects of metformin and rosiglitazone on TGF-beta 1 levels. DESIGN: In the washout period, 61 patients with Fasting Plasma Glucose levels (FPG) higher than 140 mg/dl, Postprandial Glucose (PPG) levels higher than 180 mg/dl and A1c levels exceeding 6.5% were treated with glimperide. After 4 weeks, 39 of these patients were randomised to receive either metformin or rosiglitazone for 12 weeks. Thirty healthy controls were also studied. RESULTS: There were no significant differences with regard to age, gender, body weight and BMI between patients and healthy controls. Type 2 diabetics had higher waist circumference, FPG, total cholesterol, LDL-cholesterol and triglyceride levels. Baseline TGF-beta 1 levels in diabetics were higher than in controls (29.84 +/- 7.04 ng/ml vs 11.37 +/- 4.06 ng/ml, p < 0.001). Metformin or rosiglitazone did not significantly modify the TGF-beta 1 levels. In a multiple regression analysis FPG was the only variable that was significantly associated with plasma TGF-beta 1 levels. CONCLUSION: The elevated levels of TGF-beta 1 in subjects with type 2 diabetes possibly indicate a tendency for renal and endothelial damage in such patients. The association of TGF-beta 1 with FPG possibly links poor diabetic control to vascular damage, leading to diabetic complications. Lack of changes in the levels of TGF-beta 1 after therapy may reflect inadequate therapy duration.

Contains fulltext : 170859.pdf (Publisher’s version ) (Open Access) AIMS: To determine whether US and European participants in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial differ regarding risk factors for cardiovascular mortality and morbidity. METHODS: Baseline data, stratified for prior cardiovascular disease (CVD), were compared using multivariable logistic regression analysis to establish whether region is an independent determinant of achieved targets for glycated hemoglobin (HbA1c), blood pressure (BP), and low-density lipoprotein (LDL)-cholesterol. RESULTS: Independent of CVD history, US participants were more often of non-White origin and had a longer history of type 2 diabetes, higher body weight, and higher baseline HbA1c. They had substantially lower systolic and diastolic BP, and a marginally lower LDL-cholesterol level. Fewer US participants were diagnosed with left ventricular dysfunction. In the largest group of patients, those with prior CVD and the highest cardiovascular risk, US participants were more often female, had a higher waist circumference, and had a decreased estimated glomerular filtration rate, but less frequently prior myocardial infarction or angina pectoris. CONCLUSIONS: There were baseline differences between US and European participants. These differences may result from variation in regional targets for cardiovascular risk factor management, and should be considered in the analysis and reporting of the trial results. Clinical trial identifier: ClinicalTrials.gov, NCT01179048.

WOS: 000380224800019, PubMed ID: 27144933, Context: Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near-total lack of body fat. Objective: We aimed to study natural history and disease burden of various subtypes of CGL. Design: We attempted to ascertain nearly all patients with CGL in Turkey. Setting: This was a nationwide study. Patients or Other Participants: Participants included 33 patients (22 families) with CGL and 30 healthy controls. Main Outcome Measure(s): We wanted to ascertain genotypes by sequencing of the known genes. Whole-body magnetic resonance imaging was used to investigate the extent of fat loss. Metabolic abnormalities and end-organ complications were measured on prospective follow-up. Results: Analysis of the AGPAT2 gene revealed four previously reported and four novel mutations (CGL1; c.144C>A, c.667_705delinsCTGCG, c.268delC, and c.316 + 1G > T). Analysis of the BSCL2 gene revealed four different homozygous and one compound heterozygous possible disease-causing mutations (CGL2), including four novel mutations (c.280C > T, c. 631delG, c. 62A > T, and c. 465-468delGACT). Two homozygous PTRF mutations (c.481-482insGTGA and c. 259C > T) were identified (CGL4). Patients with CGL1 had preservation of adipose tissue in the palms, soles, scalp, and orbital region, and had relatively lower serum adiponectin levels as compared to CGL2 patients. CGL4 patients had myopathy and other distinct clinical features. All patients developed various metabolic abnormalities associated with insulin resistance. Hepatic involvement was more severe in CGL2. End-organ complications were observed at young ages. Two patients died at age 62 years from cardiovascular events. Conclusions: CGL patients from Turkey had both previously reported and novel mutations of the AGPAT2, BSCL2, and PTRF genes. Our study highlights the early onset of severe metabolic abnormalities and increased risk of end-organ complications in patients with CGL.

Introduction: Although the etiology of osteoporosis is different between men and women, the underlying pathophysiological mechanism is similar, namely an absolute or relative increase in bone resorption, leading to progressive bone loss. Transforming growth factor (TGF)-beta 1 is a growth factor in human bone, which is produced by osteoblasts, and which has various effects on osteoclasts and osteoblasts. The aim of our study was to determine serum TGF-beta 1 levels in male patients with idiopathic osteoporosis. Methods: Twenty five males with idiopathic osteoporosis and 25 age-matched controls were studied. Osteoporosis was defined by a T score of

The influence of hypothyroidism on haemostasis is an active research area. Not only bleeding tendency but also hypercoagulable states have been reported in hypothyroid patients. Decreased and increased fibrinolytic activity in hypothyroid patients has been shown in several studies. Thrombin activatable fibrinolysis inhibitor (TAFI) is an inhibitor of fibrinolysis, which has been recently isolated from human plasma. The aim of our study was to determine plasma TAFI antigen levels in overt and subclinical hypothyroidism, and to investigate the effect of levothyroxine treatment on TAFI levels. The study was performed in age- and sex- matched 30 overt hypothyroid, 30 subclinical hypothyroid patients, and 30 healthy controls. Blood samples were obtained from patients with overt and subclinical hypothyroidism before levothyroxine replacement, and one month after achieving a euthyroid state with levothyroxine. TAFI antigen levels were measured using Enzyme-Linked ImmunoSorbent Assay kits (Affinity Biologicals; Ontario, Canada). In baseline evaluation both the overt and subclinical hypothyroid groups had higher TAFI antigen levels than control group (p

Both increased and decreased fibrinolytic activity have been reported in patients with hyperthyroidism. Elevated levels of plasma plasminogen activator inhibitor-1 (PAI-1) antigen have been found in hyperthyroid patients. Thrombin activatable fibrinolysis inhibitor (TAFI) is a novel plasma protein, which inhibits fibrinolysis through removal of C-terminal lysines from partially degraded fibrin. Previously, we showed that plasma TAFI antigen levels were increased in patients with overt and subclinical hypothyroidism. The aim of this study is to investigate plasma levels of TAFI and PAI-1 antigens in hyperthyroid patients. PAI-1 and TAFI antigen levels were measured in the plasma of 29 patients with hyperthyroidism (14 overt hyperthyroid and 15 subclinical hyperthyroid), and 26 healthy individuals. Although there were increased levels of PAI-1 antigen in hyperthyroid patients, plasma TAFI antigen levels were significantly lower compared to controls (80.79 ng/ml vs. 32.42 ng/ml, p = 0.000 for PAI-1; 10.42 microg/ml vs. 12.24 microg/ml, p = 0.009 for TAFI). Elevated PAI-1 antigen levels were positively correlated with free thyroid hormones, although TAFI antigen levels were in negative correlation with free thyroxine. Furthermore, an inverse correlation between PAI-1 and TAFI antigen levels was found. Our study demonstrated that TAFI antigen levels were decreased in patients with hyperthyroidism. Inverse correlation with PAI-1 suggests that the decrease in TAFI antigen levels may be due to activation of TAFI pathway. Further studies evaluating the underlying mechanisms of low TAFI antigen levels in hyperthyroidism should be undertaken.

Objective Partial lipodystrophy of the limbs (PLL) is a newly described form of lipodystrophy that is characterized by symmetrical distal lipoatrophy of the limbs and insulin resistant diabetes. Research design and methods In this study, we prospectively screened our patients with type 2 diabetes for the presence of PLL phenotype. Metabolic parameters of PLL patients were compared to those with type 2 diabetes who applied to our diabetes clinic during the same period of time. Results Between Sep 2013 and Mar 2015, 2020 patients with type 2 diabetes were evaluated for the presence of PLL. PLL was confirmed in 16 patients. The prevalence of PLL was calculated as 0.79% in our diabetes clinic. The most common phenotypic presentations were loss of subcutaneous fat in the forearms, calves and thighs, and loss of fat in forearms and calves. Patients with PLL had poor metabolic control and marked insulin resistance compared to subjects with type 2 diabetes. Diabetes had been diagnosed at a younger age in patients with PLL. Patients with PLL also had more atherogenic lipid profiles. Conclusions Our data suggests that PLL is a relatively common form of lipodystrophy in diabetes clinics, which is associated with poor metabolic control and marked insulin resistance. The recognition of PLL in patients with type 2 diabetes can help better clinical management by alerting the physician to these associated co-morbidities.

Objective Acquired partial lipodystrophy (APL) is a rare disorder characterized by progressive selective fat loss. In previous studies, metabolic abnormalities were reported to be relatively rare in APL, whilst they were quite common in other types of lipodystrophy syndromes. Methods In this nationwide cohort study, we evaluated 21 Turkish patients with APL who were enrolled in a prospective follow-up protocol. Subjects were investigated for metabolic abnormalities. Fat distribution was assessed by whole body MRI. Hepatic steatosis was evaluated by ultrasound, MRI and MR spectroscopy. Patients with diabetes underwent a mix meal stimulated C-peptide/insulin test to investigate pancreatic beta cell functions. Leptin and adiponectin levels were measured. Results Fifteen individuals (71.4%) had at least one metabolic abnormality. Six patients (28.6%) had diabetes, 12 (57.1%) hypertrigylceridemia, 10 (47.6%) low HDL cholesterol, and 11 (52.4%) hepatic steatosis. Steatohepatitis was further confirmed in 2 patients with liver biopsy. Anti-GAD was negative in all APL patients with diabetes. APL patients with diabetes had lower leptin and adiponectin levels compared to patients with type 2 diabetes and healthy controls. However, contrary to what we observed in patients with congenital generalized lipodystrophy (CGL), we did not detect consistently very low leptin levels in APL patients. The mix meal test suggested that APL patients with diabetes had a significant amount of functional pancreatic beta cells, and their diabetes was apparently associated with insulin resistance. Conclusions Our results show that APL is associated with increased risk for developing metabolic abnormalities. We suggest that close long-term follow-up is required to identify and manage metabolic abnormalities in APL.

Background/aim: To determine the prevalence of malignancy in thyroid incidentalomas (TIs) detected by fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). Materials and methods: 18F-FDG PET/CT images were evaluated prospectively for the presence of thyroid uptake. The patients with a TI were evaluated by an endocrinologist according to the predefined diagnostic algorithm. The final diagnosis was obtained clinically and/or by pathology. Results: TI was detected in 4.2% of 4204 patients. A malignant thyroid nodule was diagnosed in 29% and 33% of the focal and diffuse-focal uptake groups, respectively. However, no malignancy was detected in the diffuse uptake group. The standardized maximum uptake values (SUVmax) of the nodules were significantly higher in patients with thyroid malignancy than in patients with benign nodules (P = 0.006). The calculated cut-off value of SUVmax for malignancy was 3.5. In 2 patients in whom the cytopathological diagnosis was benign, malignancy was diagnosed after total thyroidectomy. Conclusion: A malignant nodule was present in one-third of the patients with focal or diffuse-focal uptake. A SUVmax value of 3.5 was considered as a cut-off value for the differentiation of a malignant lesion. Benign cytology in fine-needle aspiration biopsy for 2 patients underestimated a thyroid malignancy.

The diagnostic accuracy of dehydroepiandrosterone sulfate (DHEAS) to predict subclinical Cushing's syndrome (sCS) has been a matter of debate. The primary objective of this study was to assess the diagnostic power of DHEAS in predicting sCS. This retrospective study was conducted in a tertiary referral center and based on subjects referred between 2004 and 2014. Data of 249 subjects with adrenal incidentalomas were evaluated. We also reviewed 604 DHEAS measurements from adults, which were performed during the same period in our laboratory (LB group). Adrenocortical function, tumor size, and clinical characteristics were assessed. We diagnosed sCS in 15.2 % of the participants in the presence of >= 2 of the following; 1 mg dexamethasone suppression test >3.0 mu g/dl, urinary free cortisol >70 mu g/24 h, and corticotrophin (ACTH)

Nitric oxide (NO), the key mediator synthesized by different NO synthase isoenzymes, plays an important role in endothelial function. It was recently shown that hyperhomocysteinemia is an important regulator of NO synthase. We investigated the role of homocysteine (Hcys) in erectile dysfunction (ED), which is associated with the defect in NO generation. Thirty-one nondiabetic patients and 33 control cases were evaluated. Patients with diabetes, coronary artery disease, vitamin B,, or folate deficiency were excluded in the study. The International Index of Erectile Function questionnaire was used to gauge identified erectile quality. Fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, vitamin B,2, folic acid, and Hcys levels of patients were measured. Penile color Dupplex ultrasound was used to detect vascular abnormalities in nondiabetic patients with ED. Patients with ED were older than the control subjects (55.6 +/- 8.4 vs 44.5 +/- 4.7 years, respectively; P < .001). Patients with ED had higher fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol, and Hcys levels. There was a significant negative correlation between mean Hcys level and mean International Index of Erectile Function domain score (P < .001). The penile color Doppler ultrasound findings showed that there was a negative significant correlation between mean Hcys level and the 1st, 5th, and 10th minute's peak-systolic velocity. Logistic regression analysis revealed that age and Hcys levels were the main determinants in ED. Hyperhomocysteinemia, known to be an important risk factor in endothelial dysfunction, seems to be an important determinant in ED. These data suggest that slightly elevated Hcys levels are significantly related with arterial and probably endothelial dysfunction in patients with ED. (c) 2006 Published by Elsevier Inc.

Leptin is mainly synthesised in white adipose tissue. Besides its effects on body weight and metabolic homeostasis, leptin also has effects on puberty, sexual Maturation and reproduction. In this study the relationship between leptin, IGF-1, oestradiol (E-2) and progesterone levels were investigated in serum and follicular fluid from cows. This Study included 72 healthy, Brown Swiss cows aged 45 years. Samples from the jugular vein and follicular fluids were collected. Phases of the oestrus cycle of cows were classified according to their serum progesterone levels (< 3.18 nmol/l, follicular phase and the others as luteal phase). Follicles were grouped as large (

Insulinoma is a rare islet cell tumor with typical clinical and biochemical characteristics caused by excessive insulin secretion. The malignant form is characterized by metastases for which a curative resection is rarely possible. Chemotherapy is usually ineffective. We achieved control of serum glucose levels with fluocortolone in a patient with malignant insulinoma and hypoglycemia. We then administered high dose folinic acid and 5-fluorouracil (5-FU) bolus, then 5-FU by continuous in, fusion for 2 consecutive days every 2 weeks (this method is abbreviated as HDLV5FU). The plasma insulin and C-peptide levels remained unchanged and the neoplasm was stable for 4 months with this therapy. According to the authors' literature review, this is the first malignant insulinoma case treated with both fluocortolone and HDLV5FU. Prospective studies are needed to determine more effective treatment modalities for malignant insulinoma.

Pleural effusion is a common diagnostic problem. The analysis of serum and body fluids for tumor markers has been intensively applied to clinical diagnosis. The aim of the present study was to determine the usefulness of simultaneous quantification of carbohydrate antigen 19.9, carbohydrate antigen 125, neuron specific enolase, mucinous-carcinoma-associated antigen, and ferritin in samples of pleural fluids in the malign pleural effusion and its differentiation from benign effusions. A total of 61 pleural effusions were collected from the patients, who were subjected either to simple needle aspiration or to tube drainage for the diagnosis of pleural effusion. Tumor markers were determined in benign patient groups with nonspecific pleurisy, tuberculous pleurisy, empyema, congestive heart failure and in malignancy groups consisting of adenocarcinoma, small cell lung carcinoma, mesothelioma, epidermoid lung cancer. The tumor markers CA-19.9, CA-125, NSE, and ferritin levels were quantified by the sandwich assay using the streptavidin technology of ELISA in an ES-300 Boehringer-Mannheim analyser. MCA was measured by employing a two-side solid phase EIA method. MCA measurements were done by the Cobas-Core. For all patients, the effusions correctly or incorrectly identified by the different procedures as being malignant or nonmalignant are defined as true positive, false positive, true negative, and false negative, the term 'positive' referring to histologically proven malignant pleural effusion while nonmalignant effusions are referred to as 'negative'. Therefore, sensitivity, specificity, positive predictive value, and negative predictive value were defined as diagnostic parameters. The cut-off values calculated were 352 U/ml for CA-125, 54 U/ml for CA-19.9. 555 for ferritin, 11.1 for MCA and 8.7 for NSE. In our study, the highest sensitivity is found to be MCA with 100%; specificity, CA-19.9 with 97%; PPV, CA-19.9 and MCA with 95% and NPV, MCA with 100%. Our data imply that the co-measurement of MCA + CA-19.9 + CA-125 levels may further improve their diagnostic value in malignant pleural effusion compared with that of each tumour marker alone and may be useful in distinguishing malignant from benign pleural effusions. (C) 2000 Elsevier Science B.V. All rights reserved.

Thyrotoxic hypokalemic periodic paralysis (THPP) is a rare complication of hyperthyroidism and an uncommon form of hypokalemic periodic paralysis. Its differentiation of more common forms of periodic paralysis is important because aggressive treatment can place the patient at risk for rebound hyperkalemia. Treatment of the underlying thyroid dysfunction cures the muscle symptoms. Here we describe a 37-year-old Turkish male with THPP whose paralysis attack recurred soon after administration of radioactive iodine.