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Dyslipidemia is a risk factor for post- transplant diabetes mellitus, especially in patients who are taking tacrolimus. Although lipotoxicity of dyslipidemia leads to β-cell failure, the handling of lipids by β cells is a mystery in molecular endocrinology. Likewise, lipid droplet homeostasis is appreciated as a key component of lipid metabolism in cells like hepatocytes, but its role in β cells remains to be elucidated.To evaluate the morphologic changes in β cells with special focus on lipid droplets, we evaluated electron micrographs under metabolic stress conditions of glucotoxicity, lipotoxicity, and glucolipotoxicity in isolated rat insulinoma INS-1E β cells. Cells were treated with palmitic acid (0.5 mM), glucose (33 mM), or both for 16 hours, after which morphologic changes were observed with an electron microscope.Many lipid droplets were observed in the cytoplasm of healthy β cells in the control group (no treatment). Lipid droplets were also visible in the cytosol, and the cytoplasm was rich in organelles and insulin vesicles under high glucose stimulation. However, after treatment with palmitic acid, almost no lipid droplets were observed. Endocrine vesicles were also depleted, with severe morphologic disruption of other organelles. Under glucolipotoxic conditions, β cells showed a decreased number of lipid droplets and insulin vesicles compared with controls.Lipid droplet dynamics seemed important in the homeostasis of β-cell metabolism. In this preliminary study, healthy β cells appeared rich in lipid droplets under normal conditions. However, lipotoxicity depleted and glucolipotoxicity decreased the number of lipid droplets in β cells. Because dyslipidemia causing lipotoxicity is one of the most frequent metabolic problems in transplant patients and increases risk of posttransplant diabetes mellitus, understanding the mystery of lipid droplets in β cells and the pathophysiology of diabetes in transplant patients is important, especially for those taking tacrolimus.

Background: \ud Four glucagon-like peptide-1 (GLP-1) receptor agonists that are structurally similar to human GLP-1 have been shown to reduce the risk of adverse cardiovascular events among persons with type 2 diabetes. The effect of an exendin-based GLP-1 receptor agonist, efpeglenatide, on cardiovascular and renal outcomes in patients with type 2 diabetes who are also at high risk for adverse cardiovascular events is uncertain.\ud \ud Methods: \ud In this randomized, placebo-controlled trial conducted at 344 sites across 28 countries, we evaluated efpeglenatide in participants with type 2 diabetes and either a history of cardiovascular disease or current kidney disease (defined as an estimated glomerular filtration rate of 25.0 to 59.9 ml per minute per 1.73 m2 of body-surface area) plus at least one other cardiovascular risk factor. Participants were randomly assigned in a 1:1:1 ratio to receive weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg or placebo. Randomization was stratified according to use of sodium–glucose cotransporter 2 inhibitors. The primary outcome was the first major adverse cardiovascular event (MACE; a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or undetermined causes).\ud \ud Results: \ud A total of 4076 participants were enrolled; 2717 were assigned to receive efpeglenatide and 1359 to receive placebo. During a median follow-up of 1.81 years, an incident MACE occurred in 189 participants (7.0%) assigned to receive efpeglenatide (3.9 events per 100 person-years) and 125 participants (9.2%) assigned to receive placebo (5.3 events per 100 person-years) (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P

Differentiated thyroid carcinomas (DTC) are the most common form of endocrine malignancies. The role of genetic variations in the development of papillary thyroid carcinoma (PTC) is approximately 60.0-70.0%. The X-ray repair cross-complementing group 1 (XRCC1) protein has an important role in DNA repair mechanisms and genomic polymorphisms of XRCC1 gene affect the function of the protein. In the present case-control study, we aimed to compare the genotype frequency distributions of XRCC1 single nucleotide polymorphisms (SNPs) in terms of the presence of other risk factors (Hashimoto’s thyroiditis, smoking, obesity, radiation exposure) in patients with thyroid nodules who had fine-needle aspiration biopsy (FNAB) and/or thyroid surgery due to thyroid cancer. The genotype frequency distributions of three common XRCC1 SNPs (Arg194Trp, Arg399Gln, Arg280His) were compared to those with DTC (n = 228), benign thyroid nodules (BTN, n = 100) and healthy controls (n = 93) in terms of certain pre defined risk factors such as the presence of Hashimoto’s thyroiditis, smoking, obesity, a family history of thyroid cancer and radiation exposure. The frequency of the GA genotype of Arg280His in DTC cases was found to be higher than in those with BTN and the healthy control group (p p p = 0.004). The Arg280His GA genotype was more common in DTC than in cancer-free controls. The GA genotype frequency was also high in DTC cases with a family history of thyroid cancer.

Background/aim Advanced chronic periodontitis is observed rarely in acromegaly. Periodontal tissue including the alveolar bone is seemed to be spared from the systemic metabolic derangements of bone in this patient population. Chronic elevation of growth hormone, IGF-1, and bone morphogenetic proteins may play a role in periodontal tissue regeneration in acromegalics. In this study, we aimed to evaluate the potential roles of local gingival bone morphogenetic proteins (BMP) in periodontal tissue pathology in acromegaly. Materials and methods Thirty-five patients with acromegaly and 22 healthy subjects were recruited. All the participants were examined by the same periodontologist for the diagnosis of periodontal diseases. BMP-2 and -4 were studied in gingival crevicular fluid. Results Gingival BMP-2 and BMP-4 levels were similar in acromegaly and control groups in general, with and without chronic periodontitis. For all the participants, gingival BMP-2 levels were statistically lower in those participants with chronic periodontitis then those without periodontitis (29.4 ± 11.2 vs. 41.2 ± 23.2, respectively, p = 0.027). Causal relation between the gingival BMP levels and periodontal tissue health status was tested with one way ANOVA which revealed a significant difference between gingival BMP- 2 levels in those with different degrees of periodontal tissue pathology (p = 0.025). When analyzed separately, gingival BMP-2 levels revealed a causal relation with the degree of periodontal pathology with borderline significance only in patients with acromegaly (p = 0.057). Conclusion Acromegaly is a disease with an unexpectedly low frequency of advanced periodontitis, irrespective of the long disease duration and pathognomonic oral manifestations. BMP-2 might have a protective role against chronic advanced periodontitis in these patients.

Objective: Proton pump inhibitor (PPI) drugs reduce gastric acid secretion and lead to an increase in serum gastrin levels. Many preclinical and some clinical researches have established some positive effects of gastrin or PPI therapy on glucose regulation. The aim of this study was to prospectively investigate the short term effects of esomeprazole on glycaemic control in patients with type 2 diabetes mellitus. In addition, the presence of an association between this effect and gastrin levels was evaluated. Methods: Thirty-two subjects with type 2 diabetes mellitus were enrolled and grouped as intervention (n=16) and control (n=16). The participants in the intervention group were prescribed 40 mg of esomeprazole treatment for three months. At the beginning of the study and at the 3rd month, HbA1c level (%) and gastrin levels (pmol/L) of participants were assessed. Then, the groups were compared in terms of their baseline and 3rd month values. Results: In the intervention group, the mean gastrin level increased significantly from 34.3±14.4 pmol/L to 87.4±43.6 pmol/L (p Conclusion: Our study demonstrates that esomeprazole has no extra benefit for the controlled diabetic patient in three months. However, in only the metformin-treated subgroup, esomeprazole may prevent the rise in HbA1c level.

Background/aim Overt thyroidism is known to cause neuropsychiatric disorders but studies on subclinical hyperthyroidism (SCH) are limited. Subclinical hyperthyroidism induction by administering L-Thyroxine (LT4) is the standard treatment method in differentiated thyroid carcinoma (DTC) follow-up. Our aim was to investigate whether anxiety, depression and quality of life are affected in DTC patients followed-up with exogenous SCH. Materials and methods The patients were divided into exogenous SCH by LT4-DTC (n = 127), euthyroid-DTC (n = 66) and exogenous euthyroid-benign thyroid noduule (BTN) who underwent thyroidectomy for benign thyroid pathology (n = 85) groups. Results The rate of moderate/severe anxiety was significantly higher in SCH-DTC than euthyroid-BTN group (27.5%, n = 35 vs. 9.4%, n = 8) (P = 0.001). TSH levels and Beck anxiety inventory (BAI) scores were significantly negatively correlated(P = 0.009 r = –0.16). Free T4 and BAI were significantly positively correlated (P = 0.04 r = 0.4). The groups were similar in terms of depression severity (P = 0.15). Subclinical hyperthyroid-DTC group scored significantly lowerthan euthyroid-BTN group in all scales of SF-36 quality of life survey. Conclusion LT4-induced SCH, which is a part of traditional DTC treatment, can exacerbate the anxiety symptoms in patients and disrupt their quality of life, depending on the level of fT4.

Amac: Baska endikasyonlar ile yapilan goruntulemelerde tespit edilen adrenal insidentaloma (AI) vakalarinin cogu nonfonksiyone benign kitlelerdir. Otonom kortizol sekresyonu (OKS) genellikle AI’lerin degerlendirilmesi sirasinda tanimlanmis bir klinik antitedir. OKS’de Otonom kortizol sekresyonunda artmis kardiyovaskuler hastalik (KVH) riski bilinmektedir. Bu calismada amacimiz; merkezimizde takip edilen AI ve ozellikle OKS hastalarinin uzun donem klinik, radyolojik ve KVH risk parametrelerini degerlendirmektir. Yontemler: Toplam 279 AI vakasinin klinik, radyolojik, hormonal ve labaratuvar takiplerini retrospektif degerlendirdik. Bulgular: AI’lerin %76,7 ’si nonfonsiyone AI (NFAI), %13,3’i OKS, %3,9’u Cushing sendromu, %1,8’i feokromositoma, %3,6 ’si primer aldosteronizm, %0,7’si adrenokortikal karsinom (AKK) idi. Ortalama takip suresi 3,5±2,3 (1-14) yil idi. Feokromositoma ve AKK vakalari diger adrenal adenomlara gore anlamli buyuktu (sirasi ile 48±16,04, 71,5±16,23 ve ortalama 25,8±12,9 mm p

Introduction Targeting better glycated hemoglobin (HbA1c) and blood pressure (BP) goals may endanger older adults with type 2 diabetes mellitus (T2DM). Overtreatment of T2DM and hypertension is a trending issue, although undertreatment is still common. We investigated the rates and predictors of overtreatment and undertreatment of glycemia and BP in older adults with T2DM and physicians' attitudes to deintensify or intensify treatment. Methods Data from older adults (>= 65 years) enrolled in a large nationwide T2DM survey in 2017 across Turkey were analyzed. Overtreatment of glycemia was defined as HbA1c < 6.5% plus the use of >= 2 oral antihyperglycemics or insulin, and BP overtreatment was defined as systolic BP (SBP) < 120 mmHg or diastolic BP (DBP) < 65 mmHg plus the use of >= 2 drugs. Undertreatment of glycemia was defined as HbA1c > 9%, and BP undertreatment was defined as SBP > 150 mmHg or DBP > 90 mmHg. Deintensification or intensification rates were calculated according to treatment modification initiated by the treating physician(s). Results the rate of overtreatment in the glycemia group (n = 1264) was 9.8% (n = 124) and that in the BP group (n = 1052) was 7.3% (n = 77), whereas the rate of undertreatment was 14.2% (n = 180) and 15.2% (n = 160), respectively. in the adjusted model, use of oral secretagogues (sulfonylureas or glinides) (odds ratio [OR] 1.94, 95% confidence interval [CI] 1.2-3.1) and follow-up at a private clinic (OR 1.81, 95% CI 1.0-3.3) were predictors of glycemia overtreatment. BP overtreatment was independently associated with the use insulin-based diabetes therapies (OR 1.86, 95% CI 1.14-3.04). There was no independent association of BP undertreatment to the study confounders. the deintensification and intensification rates were 25 and 75.6%, respectively, for glycemia and 10.9 and 9.2%, respectively, for BP. Conclusions the results show that one in ten older adults with T2DM are overtreated while one in four require modification of their current antihyperglycemic and antihypertensive treatments. Physicians are eager to intensify medications while they largely ignore deintensification in diabetes management. These results warrant enforced measures to improve the care of older adults with T2DM. Plain Language Summary Plain language summary is available for this article., Turkish Society of Endocrinology and Metabolism (TEMD) [04/10/2016-01], The TEMD study was funded by the Turkish Society of Endocrinology and Metabolism (TEMD) (Grant no. 04/10/2016-01). Automated blood pressure monitors were provided by Sanovel A/S. the funding agencies had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. No Rapid Service Fee was received by the journal for the publication of this article.

Background Kidney transplantation (KT) corrects secondary hyperparathyroidism. However, persistent hyperparathyroidism (pHPT) may be observed in some patients post-KT. This study aims to evaluate the risk factors and treatment options for pHPT. Materials and methods The study population comprises 1054 patients who underwent KT between January 2001 and May 2019. Serum samples were analyzed for calcium (Ca), phosphorus, creatinine, intact parathyroid hormone (iPTH) and estimated glomerular filtration rate. Results The prevalence of pHPT following KT is 14%. Ninety pHPT patients were compared with 550 non-pHPT patients. The median duration of pre-KT dialysis was longer, and pre-KT serum Ca, P, and iPTH levels were significantly higher in the pHPT group than the non-HPT group. The pHPT of 46 patients (51%) received medical treatment. The remaining 44 patients (49%) had parathyroidectomy (PTx) if symptoms or signs (or both) of pHPT continued. Subtotal PTx was performed in 35 patients, and minimally invasive PTx was performed in 9 patients. Conclusion Based on our study results, the most important risk factors for post-KT pHPT are long dialysis duration and high pre-KT iPTH levels. In patients who underwent KT, if pHPT lasts longer than 1 year, surgical treatment is the recommended approach. Based on our experience, the treatment method to be performed in pHPT should be 3+1/2 PTx.

Aims We aimed to evaluate the elastographic features of Achilles tendon with Acoustic Radiation Force Impulse in patients with and without diabetic neuropathy. Methods According to the presence of peripheral neuropathy, 45 patients with type 2 diabetes were divided into 2 subgroups. Those with peripheral neuropathy were defined as group I (22 patients) and those without peripheral neuropathy were defined as group II (23 patients). A total of thirty age-, gender-, and body mass index-matched healthy individuals were selected as controls. All participants underwent both ultrasonographic and Acoustic Radiation Force Impulse elastographic examination in order to evaluate Achilles Tendon thickness and stiffness. Results Achilles tendon thicknesses were similar between groups (p=0.991). Achilles tendon thicknesses of both patient groups were significantly higher than the control group (group I vs control p=0.01; group II vs control p=0.006). Stiffness values of Achilles tendons were similar between the control group and group II (p=0.993). Shear Wave Velocity was significantly lower in group I than group IIand control group (p Conclusion Diabetic patients with neuropathy have thicker and softer Achilles tendon while the elasticity of Achilles tendon in diabetic patients without neuropathy is similar to the healthy controls. Softening of the Achilles tendon may be an early sign of diabetic foot and reveal the patients with a risk of diabetic foot.

AIM. Posttransplant diabetes mellitus (PTDM) is a metabolic complication that usually occurs after liver transplantation (LT) due to immunosuppression. In this study, our aim was to identify PTDM incidence after LT in our center and the potential risk factors. MATERIALS AND METHODS. In this study, 238 adult LT patients were evaluated in terms of PTDM development. RESULTS. Of 238 patients included in the study, 170 (71.4%) were male, 68 (28.6%) were female and the mean age was 43.5± 13.7 years. Of all patients, PTDM developed in 24 (10.1%). Transient-Hyperglycemia (t-HG) was detected in 31 (13%) patients. PTDM and t-HG patients had a greater body weight than non-PTDM patients (BMI kg/m(2): 27.6± 5.3, 25.8± 4.3and 23.9± 3.3, respectively p

Objective: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a challenging complication of chronic bisphosphonate (BP) use. The hormone relaxin is able to induce the multistep differentiation process of human osteoclastogenesis, exhibits anti-fibrotic and anti-inflammatory actions, and promotes vasodilatation, wound healing, and angiogenesis. The present study aimed to evaluate the effects of relaxin in the prevention and management of BRONJ. Material and Methods: Thirty-six male Sprague Dawley rats were randomly divided into four groups. Rats in group 1 (n = 10) received relaxin and BP simultaneously for 12 weeks. Rats in group 2 (n = 10) received injections of BP for 12 weeks, followed by relaxin for another 12 weeks. Rats in group 3 (n = 10) received only BP injections, and those in group 4 (control, n = 6) received only saline. Necrosis and inflammation in the rats’ mandibles were evaluated as indicators of BRONJ. Results: Necrosis and inflammation were not detected in group 1 (BP + relaxin). In group 3 (BP only), incidence rates of necrosis and inflammation were 90% and 60%, respectively. Conclusions: Our findings suggest that relaxin may be potently effective in preventing BRONJ and have some benefit in the treatment of existing BRONJ. Objetivo: A osteonecrose da mandíbula relacionada ao bisfosfonato (BRONJ) é uma desafiadora complicação do uso crônico de bisfosfonato (BP). O hormônio relaxina é capaz de induzir o processo múltiplo de diferenciação da osteoclastogênese humana, exibe ações anti-fibróticas e anti-inflamatórias e promove vasodilatação, cicatrização de feridas e angiogênese. O presente estudo teve como objetivo avaliar os efeitos da relaxina na prevenção e tratamento do BRONJ. Material e Métodos: Trinta e seis ratos Sprague Dawley machos foram divididos aleatoriamente em quatro grupos. Os ratos do grupo 1 (n = 10) receberam relaxina e BP simultaneamente por 12 semanas. Os ratos do grupo 2 (n = 10) receberam injeções de BP por 12 semanas, seguidos de relaxina por mais 12 semanas. Os ratos do grupo 3 (n = 10) receberam apenas injeções de BP e os do grupo 4 (controle, n = 6) receberam apenas solução salina. Necrose e inflamação nas mandíbulas dos ratos foram avaliadas como indicadores de BRONJ. Resultados: Necrose e inflamação não foram detectadas no grupo 1 (BP + relaxina). No grupo 3 (somente BP), as taxas de incidência de necrose e inflamação foram de 90% e 60%, respectivamente. Conclusões: Nossos resultados sugerem que a relaxina pode ser potentemente eficaz na prevenção do BRONJ e ter algum benefício no tratamento do BRONJ existente. Consejo Nacional para Investigaciones Científicas y Tecnológicas

CONTEXT: Previous studies have associated overt/subclinical hypothyroidism and obesity but have failed to confirm a causative relationship between them. Confusion is even more for subjects with Hashimoto’s Thyroiditis (HT). OBJECTIVE: In this study, we aimed to evaluate the fat distribution and metabolic profile of subjects with euthyroid HT as well as to establish an appropriate cut-off level of TSH for the development of metabolic syndrome (Mets) in both groups. PATIENTS AND METHODS: All subjects were euthyroid whether under levothyroxine replacement or not. We recruited 301 volunteers (99 with HT and 202 without thyroid autoimmunity). Together with some metabolic variables, we measured the waist circumference, hip circumference, neck circumference manually; the total body fat with a body composition analyzer; and the visceral fat/trunk fat percentage via abdominal bioelectrical impedance analysis. RESULTS: A significant positive correlation was established between TSH levels and insulin, fasting plasma glucose, HOMA-IR and body mass index (r=0.28; p0.05). The prevalence of Mets was similar when HT subjects using levothyroxine or HT subjects with accompanying thyroid nodules were taken into consideration. Similarly, anthropometric and metabolic parameters were similar in both the HT group and the control group. We were unable to establish the TSH cut-off level by ROC analysis with desired sensitivity and specificity (AUC: 0.563 with 95% C.I. p=0.35; standard error 0.76). CONCLUSIONS: Although weight gain is frequently encountered in subjects with HT, such subjects with thyroid function tests in the euthyroid range have a similar prevalence of Mets and similar metabolic and anthropometric measurements compared to subjects without autoimmunity.

CONTEXT: Visceral adipose tissue (VAT) is a strong predictor of carbohydrate metabolism disorders. Abdominal bioelectrical impedance analysis (A-BIA) is a simple method for the measurement of VAT and is a promising tool in screening and follow-up of abdominal obesity. However the role of A-BIA in dieting individuals has not been evaluated adequately in longitudinal follow-up studies. OBJECTIVE: The aim of this study is to determine the role of A-BIA in identifying the changes in metabolic predictors after diet and/or exercise therapy. DESIGN: All patients who sought weight loss treatment underwent baseline assessment and were prescribed a program of diet. After a mean follow-up of 3.2 months, data were analyzed. SUBJECTS AND METHODS: Ultimately, 103 participants who reported adhering to the diet, enrolled to the study. We tested associations between changes in body composition measures and changes in laboratory measures using correlations and multivariate linear regression analysis. RESULTS: Mean loss of body weight was 3.4±2.8 kg. All but waist-to-hip ratio, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels changed significantly (p

Background Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by premature mortal cardiovascular complications. Liver transplantation (LT) is the only curative treatment option. In this study, the long-term clinical follow-up data of 8 patients who underwent LT with a diagnosis of FH in our center are presented. Materials and methods A total of 638 LT were performed between December 1985 and June 2019 at Baskent University, of which 8 patients underwent LT with a diagnosis of FH and were evaluated retrospectively. Results Of the 8 patients, 4 underwent deceased donor and 4 living donor transplantation. Five patients had preoperative cardiovascular disease and consequent interventional operations. There was significant reduction in postoperative LDL-C and TC levels starting from the first week, and stabilizing at the first month and first year. The median survival time of patients was 5 years (2-12 years). All patients are still alive. None of the complications of patients with preoperative cardiovascular complications had progressed. Conclusion Liver transplantation is the preferred curative treatment for the pathophysiology of FH. In our study, LDL-C levels were brought under control with LT performed on patients with FH. Median 5-year follow-up of patients showed that the progression of cardiac complications was abated.

Purpose: Cardiovascular effects of hypothyroidism are well known. Osteopontin (OPN) is a new inflammatory marker which was first isolated from the bone. Flow-mediated dilatation (FMD), a noninvasive technique to measure this endothelium-dependent function, has been used in several clinical studies to show cardiovascular risks. The aim of our study was to assess FMD value in hypothyroidism patients and to investigate whether plasma OPN level is a parameter which can predict cardiovascular risks in this group of patients. Material and Method: This study included 39 patients who had high levels of thyroid-stimulating hormone (TSH) and 11 healthy euthyroid controls. Plasma TSH, free thyroxine, fibrinogen, high-sensitive C-reactive protein (hsCRP), fasting plasma glucose, total cholesterol (T-chol), low density lipoprotein (LDL), triglyceride and OPN levels were measured at the time hypothyroidism was first detected and after euthyroid state was achieved with levothyroxine treatment. In parallel with these assessments, brachial FMD measurements were also performed. Results: In hypothyroid patients cardiovascular risk factors such as T-chol, LDL and triglyceride levels were higher than in control group but fibrinogen and hsCRP levels were not different between the groups. OPN levels were similar in patient and control groups, but basal FMD levels were lower in patients with hypothyroidism. After euthyroidism was achieved, OPN levels significantly decreased and FMD levels significantly increased, but a correlation was not detected between these two parameters. Discussion: Our study did not show a significant correlation between OPN and cardiovascular risk parameters. Further studies are needed to use OPN as a cardiovascular risk marker in hypothyroid patients.

OBJECTIVE The Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial reported neutral effects of insulin glargine on cardiovascular outcomes and cancers and reduced incident diabetes in high–cardiovascular risk adults with dysglycemia after 6.2 years of active treatment. Omega-3 fatty acids had neutral effects on cardiovascular outcomes. The ORIGIN and Legacy Effects (ORIGINALE) study measured posttrial effects of these interventions during an additional 2.7 years. RESEARCH DESIGN AND METHODS Surviving ORIGIN participants attended up to two additional visits. The hazard of clinical outcomes during the entire follow-up period from randomization was calculated. RESULTS Of 12,537 participants randomized, posttrial data were analyzed for 4,718 originally allocated to insulin glargine (2,351) versus standard care (2,367), and 4,771 originally allocated to omega-3 fatty acid supplements (2,368) versus placebo (2,403). Posttrial, small differences in median HbA1c persisted (glargine 6.6% [49 mmol/mol], standard care 6.7% [50 mmol/mol], P = 0.025). From randomization to the end of posttrial follow-up, no differences were found between the glargine and standard care groups in myocardial infarction, stroke, or cardiovascular death (1,185 vs. 1,165 events; hazard ratio 1.01 [95% CI 0.94–1.10]; P = 0.72); myocardial infarction, stroke, cardiovascular death, revascularization, or hospitalization for heart failure (1,958 vs. 1,910 events; 1.03 [0.97–1.10]; P = 0.38); or any cancer (524 vs. 529 events; 0.99 [0.88–1.12]; P = 0.91) or between omega-3 and placebo groups in cardiovascular death (688 vs. 700; 0.98 [0.88–1.09]; P = 0.68) or other outcomes. CONCLUSIONS During >6 years of treatment followed by >2.5 years of observation, insulin glargine had neutral effects on health outcomes and salutary effects on metabolic control, whereas omega-3 fatty acid supplementation had no effect.

Background Mitochondrial uncoupling proteins (UCP) 1, 2 and 3 are members of the anion carrier protein family located in the inner mitochondrial membrane. There are various controversial reports on UCP genotypes and obesity in adults and children. This study aims to investigate the link between mostly studied UCP polymorphisms (UCP1-3826A/G, UCP2 Insertion/Deletion (Ins/Del) polymorphism of exon 8, and UCP3-55C/T Polymorphisms) and obesity in Turkish children. Furthermore, the relationships of UCP polymorphisms are also analyzed within the scope of metabolic parameters of obese children. Methods Molecular screening of the UCP1, UCP2, and UCP3 gene polymorphisms was carried out in 189 children aged 6 to 18 years, 102 of who had exogenous obesity (54 girls) and 87 of whom were healthy controls (48 girls). In the obese group, fasting lipids, glucose and insulin levels were measured. In 60 obese children, an oral glucose tolerance test (OGTT) was performed with 0, 30, 60, 90 and 120 minutes of sampling for plasma glucose and insulin levels. Results The frequency of UCP polymorphisms was similar in obese and non-obese children. In obese children, fasting lipids, glucose and insulin levels were not different among the UCP 1, 2 and 3 genotypes. While no relationship was found between the UCP 1 and 3 genotypes and glucose/insulin levels during OGTT, carriers of the Insertion allele with UCP2 Ins/Del polymorphism had significantly higher 30-minute insulin levels (p=0.018). Conclusions Polymorphisms of the UCP1-3826A/G, UCP2 Ins/Del, and UCP3-55C/T are not associated with obesity and related pathologies in Turkish children. However, the presence of the Ins allele of the UCP2 gene has been found to have an unfavorable influence on early insulin excursion after glucose loading.

Objective: Colorectal polyps and thyroid nodules are common disorders linked to hyperinsulinemia and metabolic syndrome (Mets). The direct association between these two diseases is not clear. We aimed to analyze the prevalence of thyroid nodules in subjects with and without colorectal polyps. The secondary aim was to establish the prevalence of Mets and its parameters in both disorders and to determine if insulin resistance and hyperinsulinemia are common underlying pathophysiological mechanisms. Subjects and Methods: One hundred and five subjects with colorectal polyps (71 males, 34 females) and 68 controls (28 males, 40 females) were enrolled. The parameters of Mets together with TSH, insulin, low-density lipoprotein cholesterol, and homeostasis model for assessment of insulin resistance levels were calculated. We performed thyroid ultrasonography in all participants. Results: The prevalence of Mets was similar in the colorectal polyp and control groups (37.1 vs. 37.3%, p = 0.982). The prevalence of Mets was nonsignificantly higher in subjects with a documented thyroid nodule compared to subjects without a thyroid nodule (43.0 vs. 32.6%, p = 0.205). The prevalence of thyroid nodules in subjects with colorectal polyps was significantly higher than in subjects without polyps (52.9 vs. 35.3%, p = 0.017). Compared to subjects with no colorectal polyps, we established a significant increase in the odds of having thyroid nodules (OR 2.05; 95% CI: 1.097–3.860, p = 0.017). The presence of colorectal polyps and age in the adjusted model were established to be independent risk factors for having thyroid nodules (p = 0.025 and p = 0.007, respectively). Conclusion: These results may support the presence of other common mechanisms in the development of these two pathologies other than insulin resistance and hyperinsulinemia.

Objective: The objective of this study was to assess the antiproliferative pleiotropic effects of statins on thyroid function, volume, and nodularity. Subjects and Methods: One hundred and six hyperlipidemic patients were included in this prospective study. The 69 patients in the statin groups received atorvastatin (16 received 10 mg and 18 received 20 mg) or rosuvastatin (20 received 10 mg and 15 received 20 mg). The 37 patients in the control group, assessed as not requiring drugs, made only lifestyle changes. Upon admission and after 6 months, all patients were evaluated by ultrasonography as well as for lipid variables (total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides) and thyroid function and structure. Results: After 6 months, no differences in thyroid function, thyroid volume, the number of thyroid nodules, or nodule size were observed in the statin and control groups. In a subgroup analysis, total thyroid volume had decreased more in patients receiving 20 mg of rosuvastatin than that in the control group (p < 0.05). Maximum nodule size had decreased more in those receiving 10 mg of rosuvastatin (p < 0.05). Conclusions: Our results suggest an association between rosuvastatin treatment and smaller thyroid volume and maximum nodule diameter; this could be attributable to the antiproliferative effects of statin therapy on the thyroid.

Tutuncu, Neslihan Bascil/0000-0002-1816-3903; Gonen, Mustafa Sait/0000-0002-1089-623X; CORAPCIOGLU, DEMET/0000-0003-0940-9147; Satman, Ilhan/0000-0001-8613-1797; nuhoglu, irfan/0000-0003-0650-3242; Sahin, Ibrahim/0000-0002-6231-0034; Demirci, Ibrahim/0000-0003-0498-3115; Altuntas, Seher Cetinkaya/0000-0002-9733-9443; Yildiz, Bulent O./0000-0003-1797-7662; BALCI, Mustafa Kemal/0000-0002-6494-3249; Araz, Mustafa/0000-0001-6741-7474; Saydam, Basak Ozgen/0000-0001-9457-8919; Bozkus, Yusuf/0000-0002-6976-6659; Sabuncu, Tevfik/0000-0001-6504-5355; SELEK, ALEV/0000-0002-0646-8697; Ozturk, Feyza Yener/0000-0001-5584-4954; Salman, Serpil/0000-0003-4867-3725; AKBAS, EMIN MURAT/0000-0002-3033-0073; KIRIK, Ali Murat/0000-0002-5771-4843; Sonmez, Alper/0000-0002-9309-7715; Cesur, Fazil Mustafa/0000-0002-1029-2604, WOS:000452704800016, PubMed: 30244051, Aims: Turkey has the highest prevalence of diabetes in Europe. It is therefore essential to know the overall cardiovascular risk and reveal the predictors of metabolic control in Turkish adults with diabetes mellitus. Methods: A nationwide, multicenter survey consecutively enrolled patients who were under follow up for at least a year. Optimal control was defined as HbA1c, Turkish Society of Endocrinology and Metabolism, The TEMD study has been funded by the Turkish Society of Endocrinology and Metabolism. Automated blood pressure monitors were provided by Sanovel A/S. The funding agencies had no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; or the preparation, review or approval of the manuscript.

Purpose: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women in reproductive age. Conflicting results are reported in the studies examining insulin resistance in lean PCOS subjects. We aimed to observe the controversial presence of insulin resistance in lean PCOS subjects with the gold standard method and assess the impacts of family history of type 2 diabetes mellitus (T2DM) on insulin resistance in these patients. Material and Method: Nineteen patients with PCOS and nine age-BMI matched control subjects were recruited into the study. Patients with PCOS were divided into two groups according to their FH of T2DM among their first degree relatives (FHneg vs FHpos). Insulin resistance was evaluated with homeostasis model assessment of insulin resistance (HOMA-IR) and hyperinsulinemic euglycemic clamp technique for all participants. Results: Mean M values were significantly higher in the control group when compared with PCOS patients (p=0.003). There was no statistically significant difference for HOMA-IR and M values when FHneg and FHpos patients were compared. Although HOMA-IR values were similar between all groups, M values were lower in FHneg and FHpos groups compared to the controls (p=0.02 and 0.004 respectively). Discussion: Lean PCOS patients have evident insulin resistance when compared to healthy subjects, and FH of T2DM seems to not affect insulin resistance. Even non-obese PCOS patients should be encouraged for healthy eating style and exercise to prevent the potential risks associated with insulin resistance. Furthermore these patients can see benefits from medical therapies which improve insulin sensitivity. Turk Jem 2015; 19: 55-59

Purpose: To evaluate bone mineral density (BMD) measurements and the presence of periodontitis in patients with acromegaly, as well as to inquire the impact of interfering factors. Material and Method: Forty-seven acromegalic patients with any accompanying condition known to affect calcium-bone metabolism and 60 age-matched healthy controls were included. Age, gender, duration and activity of acromegaly, past-present therapy options, pituitary hormone profiles, replacement therapies, and the results of periodontal analysis were recorded. Results: Eighteen patients were male (38.3%), 29 were female (61.7%). The mean age of the patients was 46.6±11.5 years, twenty-five (53.1%) had active, 22 (46.8%) had inactive acromegaly. The latter were older and had longer disease duration (p=0.04, p=0.003, respectively). Serum calcium and phosphorus levels, 24-hour urinary calcium excretion and BMD at the lumbar spine and femur neck insignificantly associated with disease activity (p>0.05). Osteoporosis was detected in 6 patients (12.76%). Periodontitis and advanced periodontitis were more common in control group (66.7% vs. 44.7%), (43.3% vs. 12.8%) (p=0.022, p=0.0001, respectively). There was no difference in chronic periodontitis and severity between active and inactive groups (48% vs. 40.9%; p=0.279). No difference was noted in other study parameters, as well. Repeated measures analysis of variance demonstrated statistically insignificant distribution between GH change in time and periodontitis subgroups. Discussion: We demonstrated that acromegaly exerted no clear negative impact on vertebral BMD in the absence of overt hypogonadism. Regardless of disease activity, acromegaly cases exhibited lower rates of periodontitis with less severity which remained unchanged in the presence of accompanying metabolic disorders known to have negative impact on periodontal tissue. Chronic exposure to excess GH may have a protective role against periodontitis. Turk Jem 2015; 19: 42-48

BACKGROUND: Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1-receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event.METHODS: We randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina.RESULTS: The 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (PCONCLUSIONS: In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events. (Funded by Sanofi; ELIXA ClinicalTrials.gov number, NCT01147250.).

Objective Thyroid volume and the prevalence of thyroid nodules are higher in patients with insulin resistance. A relationship between thyroid volume and glucose metabolism disorders (GMD) has not as yet been clarified. The present retrospective study aimed to investigate the association between GMD and thyroid volume. Subjects and methods: We investigated the data of 2,630 patients who were evaluated for thyroid biopsy in our hospital. The study population included 602 patients with GMD, 554 patients with diabetes mellitus (DM) and 1,474 patients with normal glucose metabolism as a control group. We obtained the levels of serum thyroid stimulating hormone (TSH) and the thyroid volumes of those patients retrospectively. Results The median ages for the control group, GMD group and DM group were 55 (15‐91) years, 60 (27‐97) years, and 65 (27‐91) years respectively and there was a statistically significant difference between the groups with regard to age and gender (p

OBJECTIVE Hypoglycemia is a leading risk of glucose-lowering therapy. Treatment with insulin glargine compared with standard care early in the course of dysglycemia in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial provides information on the frequency and predictors of hypoglycemia in this setting. RESEARCH DESIGN AND METHODS A total of 12,537 people with high cardiovascular risk and dysglycemia treated with one or no oral glucose-lowering agents were randomized to add glargine titrated to a fasting glucose level of ≤5.3 mmol/L (≤95 mg/dL) or to use standard therapies. Independent associations of both nonsevere hypoglycemia (symptomatic and confirmed with a glucose level of ≤3 mmol/L [≤54 mg/dL]) and severe hypoglycemia with characteristics at baseline, treatment allocation, and average HbA1c were assessed by Cox proportional hazards models. RESULTS During a median follow-up period of 6.2 years, 28% of participants reported nonsevere hypoglycemia, and 3.8% reported severe hypoglycemia. Prior use of a sulfonylurea and allocation to glargine independently predicted a higher risk for both categories of participants. Nonsevere events were independently associated with younger age, lower BMI, the presence of diabetes, and higher baseline HbA1c level. Severe events were associated with older age, hypertension, higher serum creatinine level, and lower cognitive function, but not baseline glycemic status. Progressively higher on-treatment HbA1c level was associated with a lower risk of nonsevere events in both treatment groups; a lower risk of severe events in the glargine group, and a higher risk of severe events with standard care. CONCLUSIONS Hypoglycemia was relatively uncommon in the ORIGIN trial, but was more frequent with sulfonylurea use at baseline and allocation to glargine. Nonsevere and severe events were associated with different clinical characteristics, awareness of which may guide individualized therapy.

OBJECTIVE To assess the success and baseline predictors of maintaining glycemic control for up to 5 years of therapy using basal insulin glargine or standard glycemic care in people with dysglycemia treated with zero or one oral glucose-lowering agents. RESEARCH DESIGN AND METHODS Data from 12,537 participants in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial were examined by baseline glycemic status (with or without type 2 diabetes) and by therapeutic approach (titrated insulin glargine or standard therapy) using an intention-to-treat analysis. Median values for fasting plasma glucose (FPG) and A1C and percentages with A1C RESULTS Median A1C in the whole population was 6.4% at baseline; at 5 years, it was 6.2% with glargine treatment and 6.5% with standard care. Of those with diabetes at baseline, 60% using glargine and 45% using standard care had A1C CONCLUSIONS Systematic intervention with basal insulin glargine or standard care early in the natural history of dysglycemia can maintain glycemic control near baseline levels for at least 5 years, whether diabetes is present at baseline or not. Keeping mean A1C

Purpose: We aimed to investigate the presence of antibodies (Anti-BIP) against binding immunoglobulin protein (BIP), an endoplasmic reticulum (ER) chaperone with immune modulator and anti-apoptotic effects in Hashimoto’s thyroiditis (HT) patients. Material and Method: We included sixty-two autoimmune thyroiditis patients, 20 with euthyroid autoimmune thyroiditis, 27 with subclinical hypothyroidism and 15 with hypothyroid, and a control group of 37 healthy subjects. Results: No statistically significant difference was determined in anti-BIP levels among the HT subgroups or in comparison with the control group (p=0.889).Discussion: Although BIP activation has been shown in vitro in thyroid cells, no difference was determined in our study in anti-BIP levels between the HT patient subgroups and the control group. This suggests that antibodies developing against BIP through apoptosis and/or T cell response are either not related to HT or at levels that cannot be determined by measuring serum. Turk Jem 2013; 17: 53-6

Subclinical Cushing’s syndrome (SCS) is a condition of slight but chronic cortisol excess in patients with adrenal incidentaloma (AI) without typical signs and symptoms of Cushing’s syndrome. Adiponectin has potent roles in modulating energy balance and metabolic homeostasis and acts in opposition to glucocorticoids. This study aimed to evaluate adiponectin level in SCS and nonfunctional AI (NAI) patients and its relation with metabolic parameters. Patients with AI (n=40) and metabolically healthy controls (n=30) were included. In AI patients and controls, detailed medical history assessment, physical examinations, anthropometric measurements, and laboratory measurements were performed. Age, body mass index, waist circumference, and lipid profiles were significantly higher and waist-to-hip ratio and adiponectin level were significantly lower in the AI patients than in the controls. The midnight cortisol and urinary free cortisol levels were significantly higher in the SCS patients (n=8) than in the NAI patients (n=32). Adiponectin level of the SCS group was significantly lower than those of the NAI and control groups. The sensitivity and specificity for an adiponectin level of ≤13.00 ng/mL in predicting the presence of SCS were 87.5% and 77.4%, respectively. In conclusion, adiponectin is valuable in predicting the presence of SCS in AI patients.

Approximately 30% of patients with thyroid nodules have indeterminate or suspicious fine-needle aspiration (FNA) biopsy results. These patients usually undergo thyroidectomy because of cancer risk. Our aim was to determine diagnostic value of cyclin A and cyclin B1 immunohistochemistry added to routine cytology and their expression on histological sections. We studied the expression of cyclin A and cyclin B1 in FNA biopsies and resection specimens of 168 indeterminate or suspicious FNA biopsy results retrospectively at an academic hospital using immunohistochemistry. Malignant histopathology consisted 64 of resection specimens (58 papillary, 4 follicular, 1 medullary, and 1 Hürthle cell carcinoma). Cyclin A was overexpressed in 51.5% of malignant cases in contrast to 31.7% of 104 benign pathology specimens (P = 0.025). Cyclin B1 was positive in 39.1% of malignant specimens in contrast to 15.4% of benign cases (P = 0.001). Cyclin A overexpression was not linked to cyclin B1 overexpression. No association was found between overexpression of cyclin A, cyclin B1 and age, thyroiditis, multifocality, tumor size, extra-thyroidal extension, capsule infiltration, lymph node and distant organ metastases and TNM stage in malignant cases. Female patients with thyroid carcinoma overexpressed significantly more cyclin B1 than male patients (P = 0.015). Retrospective analysis of cyclin A and cyclin B1 in FNA biopsies yielded negative results for both benign and malignant cases. In conclusion, cyclin A and cyclin B1 are useful markers in the distinction of benign and malignant thyroid tumors and can increase diagnostic accuracy.

Insulin resistance, which provides a convenient milieu for platelet activation, has been closely associated with atherosclerotic disorders. Although it often accompanies hyperprolactinemia, findings conflict concerning its clinical impact in macroprolactinemia. In order to investigate the relationship between hyperprolactinemia and platelet activation evidenced by ADP-stimulated P-selectin expression on flow cytometry, we studied hyperprolactinemic, macroprolactinemic, and normoprolactinemic subjects. Thirty-four hyperprolactinemic and 44 age- and body mass index-matched euprolactinemic premenopausal women were included. They were matched regarding insulin sensitivity status, waist circumference, blood pressures, and plasma lipids. In order to detect macroprolactinemia among hyperprolactinemic cases, prolactin was measured before and after polyethylene glycol (PEG) precipitation in patients’ sera. P-selectin expression was significantly higher in the hyperprolactinemic group (P = 0.001), and 41.2% of them exhibited macroprolactinemia. Expression of P-selectin was comparable between the macroprolactin-negative (monomeric hyperprolactinemia; n = 20) and -positive (n = 14) subgroups (P = 0.90). Both subgroups showed greater expression compared with normoprolactinemic controls (P = 0.014 and 0.005, respectively). Platelet activation accompanies the atherosclerotic disorders closely associated with insulin resistance. Among groups matched with regard to insulin-sensitivity markers, both monomeric hyperprolactinemia and macroprolactinemia appeared to promote platelet activation.

Summary Background Mitochondria are the main production site of free oxygen radicals, which can cause organ dysfunction by oxidation of cellular macromolecules such as carbohydrates, lipids and proteins. Oxidative stress may result from either overproduction of these species or from failure of the antioxidant defence systems. Thyroid hormones have well-known effects on mitochondrial oxygen consumption, but data about how hypothyroidism affects oxidative stress are controversial, and little is known about oxidative stress in subclinical hypothyroidism. Total antioxidant status (TAS) gives information about all of the antioxidants in the organism, while malondialdehyde (MDA) is a lipid peroxidation marker used to assess lipid peroxidation due to increased oxidative stress. We aimed to determine how hypothyroidism and subclinical hypothyroidism affect serum MDA and TAS. Subjects and methods Serum TAS, MDA, C-reactive protein levels and lipid compositions were studied in 20 hypothyroid, 40 subclinical hypothyroid and 40 healthy subjects. Results MDA was elevated in both hypothyroid and subclinical hypothyroid patients compared with controls, while TAS levels show no significant differences between groups. Low-density lipoprotein (LDL) cholesterol levels were significantly high in both hypothyroid and subclinical hypothyroid patients. Triglyceride levels were high only in hypothyroid patients when compared with the controls. MDA showed a correlation with LDL cholesterol, total cholesterol and triglyceride. Conclusions These results suggest an increased oxidative stress in both hypothyroid and subclinical hypothyroidism states, which can be explained by both the insufficient increase in the antioxidant status and the altered lipid metabolism in these cases.