International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Genetic Variations in the Kir6.2 Subunit (KCNJ11) of Pancreatic ATP-Sensitive Potassium Channel Gene Are Associated with Insulin Response to Glucose Loading and Early Onset of Type 2 Diabetes in Childhood and Adolescence in Taiwan Sun, 21 Sep 2014 09:31:58 +0000 To investigate the role of E23K polymorphism of the KCNJ11 gene on early onset of type 2 diabetes in school-aged children/adolescents in Taiwan, we recruited 38 subjects with type 2 diabetes (ages 18.6 ± 6.6 years; body mass index percentiles 83.3 ± 15.4) and 69 normal controls (ages 17.3 ± 3.8 years; body mass index percentiles 56.7 ± 29.0) from a national surveillance for childhood/adolescent diabetes in Taiwan. We searched for the E23K polymorphism of the KCNJ11 gene. We found that type 2 diabetic subjects had higher carrier rate of E23K polymorphism of KCNJ11 gene than control subjects (P = 0.044). After adjusting for age, gender, body mass index percentiles, and fasting plasma insulin, the E23K polymorphism contributed to an increased risk for type 2 diabetes (P = 0.047). K23-allele-containing genotypes conferring increased plasma insulin level during OGTT in normal subjects. However, the diabetic subjects with the K23-allele-containing genotypes had lower fasting plasma insulin levels after adjustment of age and BMI percentiles. In conclusion, the E23K variant of the KCNJ11 gene conferred higher susceptibility to type 2 diabetes in children/adolescents. Furthermore, in normal glucose-tolerant children/adolescents, K23 allele carriers had a higher insulin response to oral glucose loading. Yi-Der Jiang, Lee-Ming Chuang, Dee Pei, Yann-Jinn Lee, Jun-Nan Wei, Fung-Chang Sung, and Tien-Jyun Chang Copyright © 2014 Yi-Der Jiang et al. All rights reserved. Differences in the Cardiometabolic Control in Type 2 Diabetes according to Gender and the Presence of Cardiovascular Disease: Results from the eControl Study Sun, 21 Sep 2014 05:40:40 +0000 The objective of this cross-sectional study was to assess differences in the control and treatment of modifiable cardiovascular risk factors (CVRF: HbA1c, blood pressure [BP], LDL-cholesterol, body mass index, and smoking habit) according to gender and the presence of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) in Catalonia, Spain. The study included available data from electronic medical records for a total of 286,791 patients. After controlling for sex, age, diabetes duration, and treatment received, both men and women with prior CVD had worse cardiometabolic control than patients without previous CVD; women with prior CVD had worse overall control of CVRFs than men except for smoking; and women without prior CVD were only better than men at controlling smoking and BP, with no significant differences in glycemic control. Finally, although the proportion of women treated with lipid-lowering medications was similar to (with prior CVD) or even higher (without CVD) than men, LDL-cholesterol levels were remarkably uncontrolled in both women with and women without CVD. The results stress the need to implement measures to better prevent and treat CVRF in the subgroup of diabetic women, specifically with more intensive statin treatment in those with CVD. Josep Franch-Nadal, Manel Mata-Cases, Irene Vinagre, Flor Patitucci, Eduard Hermosilla, Aina Casellas, Bonaventura Bolivar, and Dídac Mauricio Copyright © 2014 Josep Franch-Nadal et al. All rights reserved. Better Understanding in the Differentiation of Thyroid Follicular Adenoma, Follicular Carcinoma, and Follicular Variant of Papillary Carcinoma: A Retrospective Study Thu, 18 Sep 2014 07:43:40 +0000 Background. To evaluate the role of ultrasonography (US), US-guided fine-needle aspiration (USFNA) and intraoperative frozen section (FS) in follicular neoplasm. Methods. US features, USFNA cytology, and FS results were compared based on the pathology results of patients with follicular adenoma (FA), follicular carcinoma (FC), and follicular variant of papillary thyroid carcinoma (FVPTC). Results. FC and FVPTC showed significantly higher rates of suspicious US features () and positive findings on either US or cytology, 80.0% and 90.7%, compared to FA, 64.5% (). Intraoperative FS showed higher malignant rates in FVPTC and FC (81.8% and 75.0%, resp.), compared to FA (3.8%, ). Conclusion. Suspicious US features were more significantly seen in FC and FVPTC compared to FA. Intraoperative FS is useful in the differential diagnosis of these lesions and supplements cytology results of USFNA. Jung Hyun Yoon, Eun-Kyung Kim, Ji Hyun Youk, Hee Jung Moon, and Jin Young Kwak Copyright © 2014 Jung Hyun Yoon et al. All rights reserved. Augmented β-Cell Function and Mass in Glucocorticoid-Treated Rodents Are Associated with Increased Islet Ir-β/AKT/mTOR and Decreased AMPK/ACC and AS160 Signaling Wed, 17 Sep 2014 09:37:33 +0000 Glucocorticoid (GC) therapies may adversely cause insulin resistance (IR) that lead to a compensatory hyperinsulinemia due to insulin hypersecretion. The increased β-cell function is associated with increased insulin signaling that has the protein kinase B (AKT) substrate with 160 kDa (AS160) as an important downstream AKT effector. In muscle, both insulin and AMP-activated protein kinase (AMPK) signaling phosphorylate and inactivate AS160, which favors the glucose transporter (GLUT)-4 translocation to plasma membrane. Whether AS160 phosphorylation is modulated in islets from GC-treated subjects is unknown. For this, two animal models, Swiss mice and Wistar rats, were treated with dexamethasone (DEX) (1 mg/kg body weight) for 5 consecutive days. DEX treatment induced IR, hyperinsulinemia, and dyslipidemia in both species, but glucose intolerance and hyperglycemia only in rats. DEX treatment caused increased insulin secretion in response to glucose and augmented β-cell mass in both species that were associated with increased islet content and increased phosphorylation of the AS160 protein. Protein AKT phosphorylation, but not AMPK phosphorylation, was found significantly enhanced in islets from DEX-treated animals. We conclude that the augmented β-cell function developed in response to the GC-induced IR involves inhibition of the islet AS160 protein activity. André O. P. Protzek, José M. Costa-Júnior, Luiz F. Rezende, Gustavo J. Santos, Tiago Gomes Araújo, Jean F. Vettorazzi, Fernanda Ortis, Everardo M. Carneiro, Alex Rafacho, and Antonio C. Boschero Copyright © 2014 André O. P. Protzek et al. All rights reserved. Fat, Muscle, and Bone Interactions in Obesity and the Metabolic Syndrome Mon, 15 Sep 2014 06:38:01 +0000 Reina Armamento-Villareal, Nicola Napoli, Debra Waters, and Dennis Villareal Copyright © 2014 Reina Armamento-Villareal et al. All rights reserved. Investigation of the Protective Effects of Taurine against Alloxan-Induced Diabetic Retinal Changes via Electroretinogram and Retinal Histology with New Zealand White Rabbits Sun, 14 Sep 2014 13:17:03 +0000 The purpose of this study was to investigate the protective role of orally administered taurine against diabetic retinal changes via electroretinogram (ERG) and retinal histology on rabbits. Rabbits were randomly assigned into groups: Group I (vehicle administration only); Group II (diabetes: induced by 100 mg/kg alloxan injection); Group III (diabetes and fed with 200 mg/kg taurine); and Group IV (diabetes and fed with 400 mg/kg taurine). The body weight and blood glucose levels of the rabbits were monitored weekly. The ERG was measured on weeks 5 and 15. Retinal histology was analyzed in the end of the experiment. Results revealed that a taurine supplement significantly ameliorates the alloxan-induced hyperglycemia and protects the retina from electrophysiological changes. Group II showed a significant change in the mean scotopic b-wave amplitude when compared to that of Group I, whereas the diabetic rabbits treated with taurine (Group III and IV) were analogous to Group I. Histologically, the amount of Bipolar and Müller cells showed no difference between all groups and when compared with those of Group I. Our study provides solid evidences that taurine possesses an antidiabetic activity, reduced loss of body weight, and less electrophysiological changes of the diabetic retina. Samuel Tung-Hsing Chiang, Shang-Min Yeh, Yi-Chen Chen, Shiun-Long Lin, and Jung-Kai Tseng Copyright © 2014 Samuel Tung-Hsing Chiang et al. All rights reserved. Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma Sun, 14 Sep 2014 07:53:16 +0000 Pheochromocytomas (PCC) are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL) tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A) for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described <10% VHL mutation rate cannot account for the high frequency of hypoxic response observed. Indeed, little is known about genetic mechanisms disrupting other complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL) of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation. David A. Rowbotham, Katey S. S. Enfield, Victor D. Martinez, Kelsie L. Thu, Emily A. Vucic, Greg L. Stewart, Kevin L. Bennewith, and Wan L. Lam Copyright © 2014 David A. Rowbotham et al. All rights reserved. Gender Differences in Ghrelin Association with Cardiometabolic Risk Factors in Arab Population Tue, 09 Sep 2014 00:00:00 +0000 Ghrelin is a stomach produced hormone that has been shown to have protective role against development of CVD which is a leading cause of death in the Arab world. The objective of this study is to examine the gender difference in association between traditional CVD risk factors and plasma ghrelin among Arabs. 359 Arab residents in Kuwait participated in a cross-sectional survey (≥20 years old): 191 were females and 168 were males. Plasma level of ghrelin was assessed using Luminex-based assay. Ghrelin levels were significantly higher in females (935 ± 78 pg/mL) than males (763 ± 65 pg/mL) (). Females showed inverse association with WC (, ) and HbA1C (, ) as well as SBP (, ) and DBP (, ), respectively. Higher levels of ghrelin were shown to associate with increased insulin resistance, as measured by HOMAIR, in male Arab subjects (-trend = 0.0202) but not in females. In this study we show that higher ghrelin level was negatively associated with measures of obesity, HbA1C, and blood pressure in females and positively associated with increased insulin resistance in Arab males. Mohamed Abu-Farha, Mohammed Dehbi, Fiona Noronha, Ali Tiss, Monira Alarouj, Kazem Behbehani, Abdullah Bennakhi, and Naser Elkum Copyright © 2014 Mohamed Abu-Farha et al. All rights reserved. Male Accessory Gland Infection: Relevance of Serum Total Testosterone Levels Mon, 08 Sep 2014 08:13:43 +0000 Aim of the present study was to evaluate the different ultrasound characterization of fertile symptomatic patients with MAGI (male accessory gland infection) according to different serum concentrations of total T (TT). We analyzed the ultrasound and hormonal data of 200 patients aged between 24.0 and 67.0 years. Patients were divided into six groups according to the sextile distribution of TT. Patients with serum concentrations of TT < 3.6 ng mL−1 had a higher mean duration of symptoms compared to the other examined groups. Patients with serum concentrations of TT > 6.6 ng mL−1 showed a frequency of ultrasound criteria suggestive for bilateral form of prostatitis and prostate-vesiculo-epididymitis and significantly lower compared to the other examined groups. At multivariate logistic regression analysis adjusted for age and BMI, TT was an independent predictive factor of prostatovesiculitis (OR = 0.818 [95% CI: 0.675–0.992]; ) and prostate-vesiculo-epididymitis (OR = 0.714 [95% CI: 0.578–0.880]; ), which represent the main forms of complicated MAGI. The results of this study suggest that male hypogonadism could be associated with a different ultrasound characterization of these patients. R. A. Condorelli, A. E. Calogero, E. Vicari, V. Favilla, S. Cimino, G. I. Russo, G. Morgia, and S. La Vignera Copyright © 2014 R. A. Condorelli et al. All rights reserved. The Effects of Soy Bean Flour Enriched Bread Intake on Anthropometric Indices and Blood Pressure in Type 2 Diabetic Women: A Crossover Randomized Controlled Clinical Trial Mon, 08 Sep 2014 00:00:00 +0000 Previous studies showed that soy bean has the potential to improve many aspects of diabetes state and provide metabolic benefits that aid in weight management. We aimed to determine the effects of soy bean flour enriched bread on anthropometric indices and blood pressure among type 2 diabetic patients. This randomized, crossover, clinical trial was performed in 30 type 2 diabetic women. There were two trial periods for 6 weeks and a wash-out period for 4 weeks. In the soy bread diet period, 120 g of soy bean flour enriched bread was consumed each day instead of the same amount of their usual bread or other cereal products. After a 4-week wash-out period, participants were crossed over for another 6 weeks. Mean (±SD) age of study participants was 45.7 ± 3.8 years. The results of our study showed no significant effects of soy bean flour enriched bread on anthropometric indices and blood pressure among diabetic patients. Despite the slight reduction in BMI, waist circumference, and percent of body fat, there were no significant differences in changes of these values between two groups. No significant changes in waist to hip ratio and blood pressure were seen. Asma Salari Moghaddam, Mohammad Hassan Entezari, Bijan Iraj, Gholamreza Askari, Elham Sharifi Zahabi, and Mohammad Reza Maracy Copyright © 2014 Asma Salari Moghaddam et al. All rights reserved. Endoscopic Retroperitoneal Adrenalectomy for Adrenal Metastases Mon, 08 Sep 2014 00:00:00 +0000 Objectives. To evaluate whether retroperitoneal approach for adrenalectomy is a safe and effective treatment for adrenal metastases (AM). Methods. From June 2004 to January 2014, nine consecutive patients with AM were treated with endoscopic retroperitoneal adrenalectomy (ERA). A retrospective study was conducted, and clinical data, tumor characteristics, and oncologic outcomes were acquired and analyzed. Results. Renal cancer was the primary site of malignancy in 44.4% of cases. The mean operative time was 132 ± 10.4 min. There were 5 synchronous and 4 metachronous AM. One patient required conversion to transperitoneal laparoscopic procedure. No mortality or perioperative complications were observed. The median overall survival was 11 months (range: 2–42 months). Survival rates of 50% and 25% were identified at 1 and 3 years, respectively. At the end of the study, 4 patients were alive with a mean observed follow-up of 20 months. No patients presented with local tumor relapse or port-site metastases. Conclusions. This study shows that ERA is a safe and effective procedure for resection of AM and advances the surgical treatment of adrenal disease. The use of the retroperitoneal approach for adrenal tumors less than 6 cm can provide very favorable surgical outcomes. Gintaras Simutis, Givi Lengvenis, Virgilijus Beiša, and Kęstutis Strupas Copyright © 2014 Gintaras Simutis et al. All rights reserved. Study of Microvessel Density and the Expression of Vascular Endothelial Growth Factors in Adrenal Gland Pheochromocytomas Wed, 03 Sep 2014 11:17:54 +0000 Angiogenesis (neoangiogenesis), a process of neovascularization, is an essential step for local tumor growth and distant metastasis formation. We have analysed angiogenesis status: vascular architecture, microvessel density, and vascular endothelial growth factors expression in 62 adrenal pheochromocytomas: 57 benign and 5 malignant. Immunohistochemical evaluation revealed that vascular architecture and vessel density are different in the central and subcapsular areas of the tumor. Furthermore, we have observed a strong correlation between number of macrophages and microvessel density in the central and subcapsular areas of the tumor and between the expression of VEGF-A in tumor cells and microvessel density in central and subcapsular areas of the tumor. Secondary changes in these tumors influence the results and both vascular architecture and microvessel density are markedly disturbed by hemorrhagic and cystic changes in pheochromocytomas. These changes are partially caused by laparoscopic operation technique. However, no differences in vascular parameters were found between pheochromocytomas with benign and malignant clinical behavior. Our observation showed that analysis of angiogenesis, as a single feature, does not help in differentiating malignant and benign pheochromocytomas and has no independent prognostic significance. On the other hand, high microvessel density in pheochromocytoma is a promising factor for antiangiogenic therapy in malignant cases. Magdalena Białas, Grzegorz Dyduch, Joanna Dudała, Monika Bereza-Buziak, Alicja Hubalewska-Dydejczyk, Andrzej Budzyński, and Krzysztof Okoń Copyright © 2014 Magdalena Białas et al. All rights reserved. Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications Wed, 03 Sep 2014 08:28:43 +0000 Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency) has been reported with neurological and magnetic resonance imaging (MRI) abnormalities (e.g., delayed myelination and brain atrophy) due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH), a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF) pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS) through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric) CNS seems to be particularly vulnerable to alterations induced by adrenal disorders and/or supraphysiological doses of corticosteroids. Physicians should be aware of potential neurological manifestations in children with adrenal dysfunction to achieve better prevention and timely diagnosis and treatment of these disorders. Further studies are needed to explore the potential neurological, cognitive, and psychiatric long-term consequences of high doses of prolonged corticosteroid administration in childhood. Vincenzo Salpietro, Agata Polizzi, Gabriella Di Rosa, Anna Claudia Romeo, Valeria Dipasquale, Paolo Morabito, Valeria Chirico, Teresa Arrigo, and Martino Ruggieri Copyright © 2014 Vincenzo Salpietro et al. All rights reserved. Circulating Sclerostin and Irisin Are Related and Interact with Gender to Influence Adiposity in Adults with Prediabetes Wed, 03 Sep 2014 07:54:30 +0000 Objectives. Sclerostin, an osteocyte-specific protein, has been found to be related to adiposity and glucose metabolism. Irisin, a myokine, can affect browning of white fat and influence glucose and energy homeostasis. Taken together, this suggests a probable network among fat, bone, and muscle that may influence health outcomes. The aims of this study were to investigate the relationship of circulating sclerostin and irisin and their association with adiposity (assessed by body mass index (BMI)). Materials/Methods. A cross-sectional study included 98 adults with impaired fasting glucose and/or impaired glucose tolerance. 75 gm OGTT was performed in all subjects. Fasting plasma samples were obtained for glycated hemoglobin, calcium, creatinine, serum sclerostin and irisin. Results. Circulating irisin and sclerostin were highly correlated . After controlling for age, gender, and BMI, irisin was significantly related to sclerostin . Multivariate linear regression analysis demonstrated that circulating sclerostin and irisin were negatively associated with BMI, independent of age in males. In females, no relationship of sclerostin or irisin to BMI was found. Conclusions. Circulating irisin and sclerostin are highly related. Interventions targeting irisin could affect sclerostin and vice versa. Theerawut Klangjareonchai, Hataikarn Nimitphong, Sunee Saetung, Nuttapimon Bhirommuang, Rattanapan Samittarucksa, Suwannee Chanprasertyothin, Rattana Sudatip, and Boonsong Ongphiphadhanakul Copyright © 2014 Theerawut Klangjareonchai et al. All rights reserved. Sexual Dysfunction in Women with Diabetic Kidney Wed, 03 Sep 2014 05:36:39 +0000 Few studies address alteration of sexual function in women with diabetes and chronic kidney disease (CKD). Quality of life surveys suggest that discussion of sexual function and other reproductive issues are of psychosocial assessment and that education on sexual function in the setting of chronic diseases such as diabetes and CKD is widely needed. Pharmacologic therapy with estrogen/progesterone and androgens along with glycemic control, correction of anemia, ensuring adequate dialysis delivery, and treatment of underlying depression are important. Changes in lifestyle such as smoking cessation, strength training, and aerobic exercises may decrease depression, enhance body image, and have positive impacts on sexuality. Many hormonal abnormalities which occur in women with diabetes and CKD who suffer from chronic anovulation and lack of progesterone secretion may be treated with oral progesterone at the end of each menstrual cycle to restore menstrual cycles. Hypoactive sexual desire disorder (HSDD) is the most common sexual problem reported by women with diabetes and CKD. Sexual function can be assessed in women, using the 9-item Female Sexual Function Index, questionnaire, or 19 items. It is important for nephrologists and physicians to incorporate assessment of sexual function into the routine evaluation protocols. Ersilia Satta, Carlo Magno, Alessandro Galì, Antonino Inferrera, Roberta Granese, Carmela Aloisi, Michele Buemi, Guido Bellinghieri, and Domenico Santoro Copyright © 2014 Ersilia Satta et al. All rights reserved. Factors Associated with Utilization of Dipeptidyl-4 Inhibitors in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Retrospective Study Tue, 02 Sep 2014 10:15:06 +0000 Dipeptidyl-4 (DPP-4) inhibitors are oral antidiabetic agents recently introduced to Malaysia. Thus, limited data is available on their utilization patterns and factors associated with their use. This study aims to analyse the utilization patterns of DPP-4 inhibitors, factors that influenced the choice of agent, and the rationale for treatment with DPP-4 inhibitors in patients with type 2 diabetes mellitus. This retrospective study was conducted to address the utilization pattern of DPP-4 inhibitors and factors that influence choice in type 2 diabetes mellitus patients. 299 subjects taking either sitagliptin or vildagliptin from September 2008 to September 2012 were included in the study. Sitagliptin was more frequently prescribed than vildagliptin. Of the patients prescribed DPP-4 inhibitors, 95% received combinations of these and other agents, whereas only 5% were prescribed DPP-4 inhibitors as monotherapy. Factors affecting the utilization of DPP-4 inhibitors included age and concomitant use of beta blockers and aspirin . Early identification of factors associated with DPP-4 inhibitors is essential to enhance quality use of the drugs. Hasniza Zaman Huri, NorFarahen Selamat, and Shireene Ratna Vethakkan Copyright © 2014 Hasniza Zaman Huri et al. All rights reserved. Markers of Systemic Inflammation and Apo-AI Containing HDL Subpopulations in Women with and without Diabetes Tue, 02 Sep 2014 09:49:14 +0000 Background. Besides their role in reverse cholesterol transport, HDL particles may affect the atherosclerotic process through the modulation of subclinical inflammation. HDL particles differ in size, composition, and, probably, anti-inflammatory properties. This hypothesis has never been explored in diabetic women, frequently having dysfunctional HDL. The potential relationship between lipid profile, Apo-AI containing HDL subclasses distribution, and common inflammatory markers (hsCRP, IL-6) was examined in 160 coronary heart disease- (CHD-) free women with and without type 2 diabetes. Results. Compared to controls, diabetic women showed lower levels of the atheroprotective large α-1, α-2, and pre-α-1 and higher concentration of the small, lipid-poor α-3 HDL particles ( all); diabetic women also had higher hsCRP and IL-6 serum levels (age- and BMI-adjusted ). Overall, HDL subclasses significantly correlated with inflammatory markers: hsCRP inversely correlated with α-1 and pre-α-1 ; IL-6 inversely correlated with α-1 , α-2 , and pre-α-1 and positively with α-3 HDL . Similar correlations were confirmed at univariate regression analysis. Conclusions. More atheroprotective HDL subclasses are associated with lower levels of inflammatory markers, especially in diabetic women. These data suggest that different HDL subclasses may influence CHD risk also through the modulation of inflammation. Giuseppina T. Russo, Annalisa Giandalia, Elisabetta L. Romeo, Angela Alibrandi, Katalin V. Horvath, Bela F. Asztalos, and Domenico Cucinotta Copyright © 2014 Giuseppina T. Russo et al. All rights reserved. Assessment of the Common Risk Factors Associated with Type 2 Diabetes Mellitus in Jeddah Mon, 01 Sep 2014 07:00:05 +0000 Risk factor management is important in avoiding life-threatening complications and preventing new-onset diabetes. We performed a case-control study in 2013 at ten primary health care centers in Jeddah, Saudi Arabia to determine the common risk factors of diabetes mellitus type 2 (DM2) and the demographic background of adult Saudi patients with DM2. Known diabetic patients were recruited as cases, while nondiabetic attendants were selected as controls. A pretested designed questionnaire was used to collect data from 159 cases and 128 controls. Cases were more likely than controls to be men (), less educated (), natives of eastern Saudi Arabia (), retired (), lower-salaried (), or married or divorced (). By univariate analysis cases were likely to be current smokers (), hypertensive (), or overweight/obese (). Cases were also more likely to have a history of DM in a first-degree relative (). By multivariate analysis, cases were more likely to be older than 40 years (), less educated (), married or divorced (), jobless/housewives (), or current smokers (). They were also more likely to have salaries <7000 Saudi riyals (). Overall, prediabetic and high risk groups should be identified and counseled early before the occurrence of diabetes. Manal A. Murad, Samia S. Abdulmageed, Rahila Iftikhar, and Bayan Khaled Sagga Copyright © 2014 Manal A. Murad et al. All rights reserved. Central Hypogonadotropic Hypogonadism: Genetic Complexity of a Complex Disease Mon, 01 Sep 2014 06:13:34 +0000 Central hypogonadotropic hypogonadism (CHH) is an emerging pathological condition frequently associated with overweight, metabolic syndrome, diabetes, and midline defects. The genetic mechanisms involve mutations in at least twenty-four genes regulating GnRH neuronal migration, secretion, and activity. So far, the mechanisms underlying CHH, both in prepubertal and in adulthood onset forms, remain unknown in most of the cases. Indeed, all detected gene variants may explain a small proportion of the affected patients (43%), indicating that other genes or epigenetic mechanisms are involved in the onset of CHH. The aim of this review is to summarize the current knowledge on genetic background of CHH, organizing the large amount of data present in the literature in a clear and concise manner, to produce a useful guide available for researchers and clinicians. Marco Marino, Valeria Moriondo, Eleonora Vighi, Elisa Pignatti, and Manuela Simoni Copyright © 2014 Marco Marino et al. All rights reserved. Evaluation of Postural Parathyroid Hormone Change in Patients with Primary Hyperparathyroidism Mon, 01 Sep 2014 00:00:00 +0000 Purpose. In the present study, we aimed to investigate postural change of PTH in normal individuals and in patients with primary hyperparathyroidism (PHPT). Methods. Twenty-two patients with PHPT and nine healthy controls were enrolled. Following 12 h of fast, patients stayed in recumbent position for an hour and PTH and total Ca measurements were performed at the 45th and 60th minutes of resting. Afterwards, the patients resumed an upright posture for an hour and again blood samples were taken at the 45th and 60th minutes of standing. Results. In the PHPT group, mean PTH was calculated as 153.9 pg/mL in the recumbent position while it was 206.3 during upright position (Δ change was 47.7) (). In the control group mean serum PTH was measured as 41.2 pg/mL in the recumbent position while it was 44.8 pg/mL in the upright position (Δ change was 1.7) (). In both groups, serum Ca was higher in the upright position compared to the recumbent position (). Conclusion. Postural change of serum PTH is significant only in PHPT group. Postural PTH test may give a clue to the clinician when the diagnosis of PHPT is equivocal. Cevdet Aydin, Sefika Burcak Polat, Ahmet Dirikoc, Berna Ogmen, Neslihan Cuhaci, Reyhan Ersoy, and Bekir Cakir Copyright © 2014 Cevdet Aydin et al. All rights reserved. The Study of Serum Vitamin D and Insulin Resistance in Chinese Populations with Normal Glucose Tolerance Mon, 01 Sep 2014 00:00:00 +0000 Objectives. The aim of this study was to investigate the relationship between serum vitamin D and insulin resistance in Chinese subjects without diabetes mellitus. Methods. Serum 25(OH)D was measured in 897 individuals with normal glucose tolerance (NGT). Oral glucose tolerance tests (OGTTs) were conducted to exclude cases with diabetes, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). Metabolic parameters were measured and compared between the highest and lowest 25(OH)D quartiles. The relationship between serum 25(OH)D and homeostatic model assessment-insulin resistance (HOMA-IR) was analyzed. Results. Indexes, such as HOMA-IR, FINS, and SBP, were negatively correlated with serum 25(OH)D concentrations. Compared with the lowest quartile, individuals in the highest group had decreased Lg (HOMA-IR), Lg (FINS), and SBP. Pearson correlation analyses showed that serum 25(OH)D was negatively associated with age, BMI, Lg (HOMA-IR), and Lg (FINS). Multivariate linear regression analysis confirmed the negative correlation of Lg (HOMA-IR) and 25(OH)D. Conclusions. This study showed that serum 25(OH)D could be regarded as an independent predictor of insulin resistance for subjects without diabetes mellitus in China. Adequate vitamin D supplementation may improve multiple metabolic disturbances. Lin Ding, Congcong Wang, Heliang Ma, Yuling Tian, Yong Lu, and Shuguang Pang Copyright © 2014 Lin Ding et al. All rights reserved. Effects of a New Flavonoid and Myo-Inositol Supplement on Some Biomarkers of Cardiovascular Risk in Postmenopausal Women: A Randomized Trial Sun, 31 Aug 2014 12:07:42 +0000 Background and Aim. Cardiovascular risk is increased in women with menopause and metabolic syndrome. Aim of this study was to test the effect of a new supplement formula, combining cocoa polyphenols, myo-inositol, and soy isoflavones, on some biomarkers of cardiovascular risk in postmenopausal women with metabolic syndrome. Methods and Results. A total of 60 women were enrolled and randomly assigned ( per group) to receive the supplement (NRT: 30 mg of cocoa polyphenols, 80 mg of soy isoflavones, and 2 gr of myo-inositol), or placebo for 6 months. The study protocol included three visits (baseline, 6, and 12 months) for the evaluation of glucose, triglycerides, and HDL-cholesterol (HDL-C), adiponectin, visfatin, resistin, and bone-specific alkaline phosphatase (bone-ALP). At 6 months, a significant difference between NRT and placebo was found for glucose ( versus  mg/dL), triglycerides ( versus  mg/dL), visfatin ( versus  ng/mL), resistin ( versus  µg/L), and b-ALP ( versus  µg/mL). No difference in HDL-C concentrations nor in adiponectin levels between groups was reported at 6 months. Conclusions. The supplement used in this study improves most of the biomarkers linked to metabolic syndrome. This Trial is registered with NCT01400724. Rosario D’Anna, Angelo Santamaria, Maria Letizia Cannata, Maria Lieta Interdonato, Grazia Maria Giorgianni, Roberta Granese, Francesco Corrado, and Alessandra Bitto Copyright © 2014 Rosario D’Anna et al. All rights reserved. Impact of NRAS Mutations on the Diagnosis of Follicular Neoplasm of the Thyroid Sun, 31 Aug 2014 11:08:40 +0000 Background. Most patients with a preoperative diagnosis of thyroid follicular neoplasm (FN) undergo diagnostic surgery to determine whether the nodule is benign or malignant. Point mutations at NRAS codon 61 are the most common mutations observed in FN. However, the clinical significance of NRAS mutation remains unclear. Methods. From 2012 to 2013, 123 consecutive patients undergoing thyroidectomy for FN were evaluated prospectively. Molecular analyses for NRAS codon 61 were performed with pyrosequencing. Results. The overall malignancy rate in FN was 48.8% (60/123). Of 123 FNs, 33 (26.8%) were positive for the NRAS mutation. The sensitivity, specificity, positive predictive value, and negative predictive value of a NRAS mutation-positive FN specimen to predict malignancy were 37%, 83%, 67%, and 58%, respectively. Patients with a NRAS-positive FN had a higher malignancy rate in additional thyroid nodules beyond the FN than patients with a NRAS-negative FN. The overall malignancy rate of patients with a NRAS-positive FN was significantly higher than that of patients with a NRAS-negative FN (79% versus 52%; P = 0.008). Conclusions. Determining NRAS mutation status in FN helps to improve the accuracy of thyroid cancer diagnosis and to predict cancer risk in accompanying thyroid nodules. Ja-Seong Bae, Seung Kyu Choi, Sora Jeon, Yourha Kim, Sohee Lee, Youn Soo Lee, and Chan Kwon Jung Copyright © 2014 Ja-Seong Bae et al. All rights reserved. A Review on the Relationship between SGLT2 Inhibitors and Cancer Sun, 31 Aug 2014 07:51:57 +0000 Risk of increasing breast and bladder cancer remains a safety issue of SGLT2 (sodium glucose cotransporter type 2) inhibitors, a novel class of antidiabetic agent. We reviewed related papers published before January 29, 2014, through Pubmed search. Dapagliflozin and canagliflozin are the first two approved SGLT2 inhibitors for diabetes therapy. Although preclinical animal toxicology did not suggest a cancer risk of dapagliflozin and overall tumor did not increase, excess numbers of female breast cancer and male bladder cancer were noted in preclinical trials (without statistical significance). This concern of cancer risk hindered its approval by the US FDA in January, 2012. New clinical data suggested that the imbalance of bladder and breast cancer might be due to early diagnosis rather than a real increase of cancer incidence. No increased risk of overall bladder or breast cancer was noted for canagliflozin. Therefore, the imbalance observed with dapagliflozin treatment should not be considered as a class effect of SGLT2 inhibitors and the relationship with cancer for each specific SGLT2 inhibitor should be examined individually. Relationship between SGLT2 inhibition and cancer formation is still inconclusive and studies with larger sample size, longer exposure duration, and different ethnicities are warranted. Hao-Wen Lin and Chin-Hsiao Tseng Copyright © 2014 Hao-Wen Lin and Chin-Hsiao Tseng. All rights reserved. Relative Validity and Reproducibility of a Quantitative Food Frequency Questionnaire for Adolescents with Type 1 Diabetes: Validity of a Food Frequency Questionnaire Wed, 27 Aug 2014 08:25:37 +0000 Background. Food frequency questionnaires are used to assess dietary intake in epidemiological studies. Objective. The aim of the study was to assess the relative validity and reproducibility of a quantitative food frequency questionnaire (QFFQ) for adolescents with type 1 diabetes. Methods: Validity was evaluated by comparing the data generated by QFFQs to those of 24-hour recalls (24 hrs). QFFQs were applied twice per patient to assess reproducibility. Statistical analysis included performing t-tests, obtaining Pearson correlation coefficients when necessary, correcting measurements for randomness by the weighted kappa method, calculating intraclass correlation coefficients, and generating Bland-Altman plots (). Results. The total energy and nutrient intake as estimated by the QFFQs were significantly higher than those from 24 hrs. Pearson correlation coefficients for energy-adjusted, deattenuated data ranged from 0.32 (protein) to 0.75 (lipid, unsaturated fat and calcium). Weighted kappa values ranged from 0.15 (vitamin C) to 0.45 (calcium). Bland-Altman plots indicated acceptable validity. As for reproducibility, intraclass correlation coefficients ranged from 0.24 (calcium) to 0.65 (lipid), and the Bland-Altman plots showed good agreement between the two questionnaires. Conclusion: The QFFQ presented an acceptable ability to classify correctly and with good reproducibility, adolescents with type 1 diabetes according to their levels of dietary intake. Rosana de Moraes Borges Marques, Amanda Cristine de Oliveira, Sheylle Almeida da Silva Teles, Maria Luiza Ferreira Stringuini, Nélida Shimid Fornés, and Giulliano Gardenghi Copyright © 2014 Rosana de Moraes Borges Marques et al. All rights reserved. The Association between 25-Hydroxyvitamin D and Hemoglobin A1c Levels in Patients with Type 2 Diabetes and Stage 1–5 Chronic Kidney Disease Wed, 27 Aug 2014 07:52:06 +0000 Aim. To examine the relationship between plasma 25-hydroxyvitamin D (25(OH)D) levels and blood hemoglobin A1c (HbA1c) levels in diabetic patients at various stages of chronic kidney disease (CKD). Methods. We screened for data collected between 2003 and 2012. The correlation between 25(OH)D and HbA1c levels was studied in patients categorized according to the severity of CKD and their vitamin D status. A multivariate linear regression model was used to determine whether 25(OH)D and HbA1c levels were independently associated after adjustment for a number of covariates (including erythrocyte metformin levels). Results. We identified 542 reports from 245 patients. The mean HbA1c value was % in vitamin D sufficiency, % in insufficiency, and % in deficiency (). There was a negative correlation between 25(OH)D and HbA1c levels for the population as a whole (, ) and in the CKD severity subgroups (, and , for CKD stages 1–3 and 4-5, resp.). In the multivariate analysis, the 25(OH)D level was the only factor associated with HbA1c (). Conclusion. 25(OH)D levels were negatively correlated with HbA1c levels independently of study covariates. Farshad Kajbaf, Romuald Mentaverri, Momar Diouf, Albert Fournier, Said Kamel, and Jean-Daniel Lalau Copyright © 2014 Farshad Kajbaf et al. All rights reserved. Diagnosis and Treatment of Adrenal Medullary Hyperplasia: Experience from 12 Cases Wed, 27 Aug 2014 00:00:00 +0000 Objective. To dissect the characteristics of adrenal medullary hyperplasia (AMH) and share our experience of diagnosis and treatment of AMH. Methods. From 1999 to 2013, 12 cases of AMH have been pathologically diagnosed after operation in our hospital. The clinical characteristics, process of diagnosis, treatment, and prognosis during follow-up of all patients are summarized retrospectively. Results. Four cases were trended to be AMH and 6 cases were trended to be pheochromocytoma before operation; moreover, the other two patients were diagnosed accidentally. All patients, except for the patient with mucinous tubular and spindle cell carcinoma of left kidney by open surgery, experienced a smooth laparoscopic adrenalectomy, including 2 with radical nephrectomy, 10 of which experienced unilateral adrenalectomy, 1 was bilaterally partial adrenalectomy, and the remaining one was unilaterally complete removal and then 2/3 partially contralateral excision. After a medium follow-up of 6.5 years, it demonstrated a satisfactory outcome of 8 cured patients and 4 symptomatic improved patients. Conclusions. AMH presents a mimicking morphology and clinical manifestation with pheochromocytoma. Surgery could be the only effective choice for the treatment of AMH and showed a preferable prognosis after a quite long follow-up. Lu Yang, Liang Gao, Xiao Lv, Shengqiang Qian, Siyuan Bu, Qiang Wei, Jiuhong Yuan, and Tianyong Fan Copyright © 2014 Lu Yang et al. All rights reserved. Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of the Most Aggressive Thyroid Cancer Thu, 21 Aug 2014 06:54:26 +0000 Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features. Moira Ragazzi, Alessia Ciarrocchi, Valentina Sancisi, Greta Gandolfi, Alessandra Bisagni, and Simonetta Piana Copyright © 2014 Moira Ragazzi et al. All rights reserved. Serum Thyrotropin Is Positively Correlated with the Metabolic Syndrome Components of Obesity and Dyslipidemia in Chinese Adolescents Thu, 21 Aug 2014 06:54:12 +0000 Metabolic syndrome is a medical disorder characterized by obesity, hyperglycemia, dyslipidemia, and hypertension. Thyroid hormone has been shown to affect many metabolic processes. This study was undertaken to explore the relationship between serum thyrotropin and components of metabolic syndrome in Chinese adolescents. Waist circumference (76.4 ± 10.7 versus 70.0 ± 10.6 cm, = 0.006) and body mass index (23.90 ± 4.20 versus 21.51 ± 4.16 kg/m2, = 0.011) were significantly greater among adolescents with subclinical hypothyroidism compared with euthyroid subjects. The risk of obesity in the subclinical hypothyroid group was 3.444 times that in the euthyroid group (odds ratio = 3.444, 95% confidence interval (CI): 1.570–7.553). Serum TSH was significantly positively correlated with waist circumference (β = 1.512, = 0.019), TC (β = 0.160, = 0.003), LDL-C (β = 0.032, = 0.008), and TG (β = 0.095, = 0.001). The TSH level in the metabolic syndrome group was significantly higher than that in nonmetabolic syndrome group (2.65 [2.28–3.80] versus 2.53 [1.92–3.45] mIU/L, = 0.032). Serum TSH within the reference range was positively associated with TC (β = 0.173, = 0.013), LDL-C (β = 0.031, = 0.043), and TG (β = 0.132, = 0.021). Increased serum TSH in adolescents may be a potential risk factor for metabolic syndrome. Jingfan Zhang, Ranhua Jiang, Ling Li, Ping Li, Xue Li, Zinan Wang, Liang Li, and Weiping Teng Copyright © 2014 Jingfan Zhang et al. All rights reserved. Clinical Characteristics Related to Central Lymph Node Metastasis in cN0 Papillary Thyroid Carcinoma: A Retrospective Study of 916 Patients Thu, 21 Aug 2014 00:00:00 +0000 Background. Papillary thyroid carcinoma (PTC) is a form of thyroid cancer with high risk of cervical lymph node metastasis. Aim. The aim of this study was to investigate the incidence and the predictive factors for occult ipsilateral central lymph node (CLN) metastasis in the patients with papillary thyroid carcinoma. Methods. A total of 916 PTC patients (1017 lesions) undergoing central lymph node dissection in our hospital from 2005 to 2011 were enrolled. The relationship between CLN metastasis and clinical factors such as gender, age, tumor size, tumor number, capsule invasion, and tumor location was analyzed. Results. Occult CLN metastasis was observed in 52.41% (533/1017) of PTC lesions, respectively. Multivariate analysis showed that age ≤ 35 years, tumor size > 1.5 cm, present capsule invasion/extracapsular invasion, and tumor located in upper/middle pole/whole lobe were risk factors of CLN metastasis. Conclusions. Tumor located in upper/middle pole/whole lobe, less than 35 years old, tumor size > 1.5 cm, and present capsule invasion/extracapsular invasion were risk factors of CLN metastasis. We recommend performing ipsilateral prophylactic CLN dissection in cN0 PTC patients. Lie-Hao Jiang, Chao Chen, Zhuo Tan, Xiao-Xiao Lu, Si-Si Hu, Qing-Liang Wang, Xiu-Xiu Hou, Jun Cao, and Ming-Hua Ge Copyright © 2014 Lie-Hao Jiang et al. All rights reserved.