International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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. The Optimal Approach for Laparoscopic Adrenalectomy through Mono Port regarding Left or Right Sides: A Comparative Study Wed, 20 Aug 2014 12:47:52 +0000 Introduction. Several studies have shown the feasibility and safety of both transperitoneal and posterior retroperitoneal approaches for single incision laparoscopic adrenalectomy, but none have compared the outcomes according to the left- or right-sided location of the adrenal glands. Materials and Methods. From 2009 to 2013, 89 patients who received LAMP (laparoscopic adrenalectomy through mono port) were analyzed. The surgical outcomes attained using the transperitoneal approach (TPA) and posterior retroperitoneal approach (PRA) were analyzed and compared. Results and Discussion. On the right side, no significant differences were found between the LAMP-TPA and LAMP-PRA groups in terms of patient characteristics and clinicopathological data. However, outcomes differed in which LAMP-PRA group had a statistically significant shorter mean operative time (84.13 ± 41.47 min versus 116.84 ± 33.17 min; ), time of first oral intake (1.00 ± 0.00 days versus 1.21 ± 0.42 days; ), and length of hospitalization (2.17 ± 0.389 days versus 3.68 ± 1.38 days; ), whereas in left-sided adrenalectomies LAMP-TPA had a statistically significant shorter mean operative time (83.85 ± 27.72 min versus 110.95 ± 29.31 min; ). Conclusions. We report that LAMP-PRA is more appropriate for right-sided laparoscopic adrenalectomies due to anatomical characteristics and better surgical outcomes. For left-sided laparoscopic adrenalectomies, however, we propose LAMP-TPA as a more suitable method. Wooseok Byon, Keehoon Hyun, Ji-Sup Yun, Yong Lai Park, and Chan Heun Park Copyright © 2014 Wooseok Byon et al. All rights reserved. Albuminuria Is Associated with Left Ventricular Hypertrophy in Patients with Early Diabetic Kidney Disease Wed, 20 Aug 2014 11:44:52 +0000 Aims. Left ventricular hypertrophy (LVH) and albuminuria are both markers for cardiovascular diseases (CVDs) in patients with type 2 diabetes mellitus (T2DM). We speculate that albuminuria in T2DM patients with early diabetic kidney disease (DKD) could predict LVH. Methods. 333 diabetic patients (219 non-DKD and 114 early DKD) were enrolled. The association between albuminuria and LVMI was examined using multivariate linear regression and logistic regression. Results. The rate of LVH was significantly higher in patients with early DKD versus those without DKD (57.0% versus 32.9%; ). Multivariate linear regression analysis demonstrated that albuminuria status (no, micro-, and macroalbuminuria; ), age (), systolic blood pressure (), and the use of ACEI/ARB drug () were independently associated with LVMI. The risks were substantially higher for LVH in the microalbuminuria group (odds ratio 2.473 (95% confidence interval 1.370–4.464)) and macroalbuminuria group (odds ratio 3.940 (95% confidence interval 1.553–9.993)) compared with that in non-DKD group. Concentric hypertrophy was the most common geometric pattern in patients with early DKD (36.0%), followed by eccentric hypertrophy (21.0%). Conclusions. Albuminuria is associated with higher LVMI and higher rate of LVH in patients with early phase DKD. Nan Wu, Weiwei Zhao, Kuanping Ye, Yintao Li, Min He, Bin Lu, and Renming Hu Copyright © 2014 Nan Wu et al. All rights reserved. Polymorphism of the FTO Gene Influences Body Weight in Children with Type 1 Diabetes without Severe Obesity Tue, 19 Aug 2014 12:06:41 +0000 The objective was to compare the impact of clinical and genetic factors on body mass index (BMI) in children with type 1 diabetes (T1DM) without severe obesity. A total of 1,119 children with T1DM (aged 4–18 years) were qualified to take part in the study. All children were genotyped for variants of FTO, MC4R, INSIG2, FASN, NPC1, PTER, SIRT1, MAF, IRT1, and CD36. Results. Variants of FTO showed significant association with BMI-SDS in the T1DM group. The main factors influencing BMI-SDS in children with T1DM included female gender (), poor metabolic control (), and carriage of the A allele of the FTO rs9939609 gene (). Conclusion. Our research indicates, when assessing, the risk of overweight and obesity carriage of the A allele in the rs9939609 site of the FTO gene adds to that of female gender and poor metabolic control. This trial is registered with (NCT01279161). Włodzimierz Łuczyński, Wojciech Fendler, Anna Ramatowska, Agnieszka Szypowska, Agnieszka Szadkowska, Wojciech Młynarski, Miron Chumiecki, Przemysława Jarosz-Chobot, Joanna Chrzanowska, Anna Noczyńska, Agnieszka Brandt, Małgorzata Myśliwiec, Barbara Głowińska-Olszewska, Paweł Bernatowicz, Oksana Kowalczuk, and Artur Bossowski Copyright © 2014 Włodzimierz Łuczyński et al. All rights reserved. Obesity as a Risk Factor for Tendinopathy: A Systematic Review Tue, 19 Aug 2014 07:31:19 +0000 Purpose. In the last few years, evidence has emerged to support the possible association between increased BMI and susceptibility to some musculoskeletal diseases. We systematically review the literature to clarify whether obesity is a risk factor for the onset of tendinopathy. Methods. We searched PubMed, Cochrane Central, and Embase Biomedical databases using the keywords “obesity,” “overweight,” and “body mass index” linked in different combinations with the terms “tendinopathy,” “tendinitis,” “tendinosis,” “rotator cuff,” “epicondylitis,” “wrist,” “patellar,” “quadriceps,” “Achilles,” “Plantar Fascia,” and “tendon.” Results. Fifteen studies were included. No level I study on this subject was available, and the results provided are ambiguous. However, all the 5 level II studies report the association between obesity measured in terms of BMI and tendon conditions, with OR ranging between 1.9 (95% CI: 1.1–2.2) and 5.6 (1.9–16.6). Conclusions. The best evidence available to date indicates that obesity is a risk factor for tendinopathy. Nevertheless, further studies should be performed to establish the real strength of the association for each type of tendinopathy, especially because the design of the published studies does not allow identifying a precise cause-effect relationship and the specific role of obesity independently of other metabolic conditions. Francesco Franceschi, Rocco Papalia, Michele Paciotti, Edoardo Franceschetti, Alberto Di Martino, Nicola Maffulli, and Vincenzo Denaro Copyright © 2014 Francesco Franceschi et al. All rights reserved. MicroRNA Deregulation in Anaplastic Thyroid Cancer Biology Tue, 19 Aug 2014 00:00:00 +0000 Anaplastic thyroid cancer (ATC) is among the most lethal types of cancers, characterized as a fast-growing and highly invasive thyroid tumor that is unresponsive to surgery and radioiodine, blunting therapeutic efficacy. Classically, genetic alterations in tumor suppressor TP53 are frequent, and cumulative alterations in different signaling pathways, such as MAPK and PI3K, are detected in ATC. Recently, deregulation in microRNAs (miRNAs), a class of small endogenous RNAs that regulate protein expression, has been implicated in tumorigenesis and cancer progression. Deregulation of miRNA expression is detected in thyroid cancer. Upregulation of miRNAs, such as miR-146b, miR-221, and miR-222, is observed in ATC and also in differentiated thyroid cancer (papillary and follicular), indicating that these miRNAs’ overexpression is essential in maintaining tumorigenesis. However, specific miRNAs are downregulated in ATC, such as those of the miR-200 and miR-30 families, which are important negative regulators of cell migration, invasion, and epithelial-to-mesenchymal transition (EMT), processes that are overactivated in ATC. Therefore, molecular interference to restore the expression of tumor suppressor miRNAs, or to blunt overexpressed oncogenic miRNAs, is a promising therapeutic approach to ameliorate the treatment of ATC. In this review, we will explore the importance of miRNA deregulation for ATC cell biology. Cesar Seigi Fuziwara and Edna Teruko Kimura Copyright © 2014 Cesar Seigi Fuziwara and Edna Teruko Kimura. All rights reserved. Glycemic Control Outcomes by Gender in the Pay-for-Performance System: A Retrospective Database Analysis in Patients with Type 2 Diabetes Mellitus Mon, 18 Aug 2014 08:32:49 +0000 Background. The purpose of this study was to investigate how the degree of glycemic control in patients with type 2 diabetes associated with lifestyle interventions as well as sociodemographic factors and further examine the differences by gender. Methods. This was a retrospective study using data collected from a diabetes quality improvement plan that began in 2002 in a medical center in Taiwan. Statistic analysis was used to determine the associations of sociodemographic data, lifestyle intervention, and treatment regimens with changes in HbA1c levels (between the initial visit and the latest follow-up measured level), and the differences were then sorted by the sex of the patients. Results. Our results showed that HbA1c averaged 7.50% for males and 7.80% for females at the initial visit, compared to levels averaging 7.50% for males and 7.70% for females at the most recent follow-up visit. There was no significant change () in HbA1c in males, but there was a 0.10% () reduction in females. The duration of the diabetes and medication regimen was associated with the decrease seen in the females. Conclusions. The results of these analyses provide important insights for policy makers to formulate healthcare policies related to chronic diseases or illnesses. Shao-Ping Yuan, Chien-Ning Huang, Hung-Chang Liao, Yu-Tzu Lin, and Ya-huei Wang Copyright © 2014 Shao-Ping Yuan et al. All rights reserved. Effects of Recombinant Human Thyrotropin Administration on 24-Hour Arterial Pressure in Female Undergoing Evaluation for Differentiated Thyroid Cancer Mon, 18 Aug 2014 06:57:52 +0000 Objective. Thyroid-stimulating-hormone (TSH) receptors are expressed in endothelial cells. We investigated whether elevated TSH levels after acute recombinant TSH (rhTSH) administration may result in alterations in blood pressure (BP) in premenopausal women with well-differentiated thyroid carcinoma (DTC). Designs. Thirty euthyroid DTC female patients were evaluated by rhTSH stimulation test (mean age years). A 24 h ambulatory systolic and diastolic blood pressure (SBP, DBP) monitoring (24 hr ABPM) was performed on days 2-3(D2-3). TSH was measured on day 1(D1), day 3(D3), and day 5(D5). Central blood pressure was evaluated on D3. Twenty-three patients were studied 1–4 weeks earlier (basal measurements). Results. TSH levels were D1: median 0.2 mU/L, D3: median 115.0 mU/L, and D5: median 14.6 mU/L. There were no significant associations between TSH on D1 and D3 and any BP measurements. Median D5 office-SBP and 24 h SBP, DBP, and central SBP were correlated with D5-TSH (). In those where a basal 24 h ABPM had been performed median pulse pressure was higher after rhTSH-test (). Conclusions. TSH, when acutely elevated, may slightly increase SBP, DBP, and central SBP. This agrees with previous reports showing positive associations of BP with TSH. Gianna Rentziou, Katerina Saltiki, Efstathios Manios, Kimon Stamatelopoulos, Eleni Koroboki, Anastasia Vemmou, Emily Mantzou, Nikolaos Zakopoulos, and Maria Alevizaki Copyright © 2014 Gianna Rentziou et al. All rights reserved. Relationship between the Prevalence of Thyroid Nodules and Metabolic Syndrome in the Iodine-Adequate Area of Hangzhou, China: A Cross-Sectional and Cohort Study Sun, 17 Aug 2014 11:06:50 +0000 Objective. The association between thyroid nodule (TN) prevalence and metabolic syndrome (MetS) has only rarely been examined in iodine-adequate areas and needs further clarification. We investigated correlations between MetS and TN prevalence in the iodine-adequate area of Hangzhou, China. Material and Method. A cross-sectional study that screened and recruited individuals for cohort research 3 years later. The 13522 subjects (8926 men, 4596 women) were screened in 2009 for all MetS components, thyroid ultrasound (US), and thyroid function. Cohort research recruited 1610 subjects who were screened in both 2009 and 2012, of whom 1061 underwent follow-up research. Results. The prevalence of TN was higher in the MetS (+) group than in the MetS (−) group (χ2 = 69.63, P < 0.001) and higher in women than in men (χ2 = 11.65, P = 0.001). Waist circumference (WC) was positively related to the prevalence of TN (OR = 1.022, P < 0.001). Individuals with greater WC in 2009 were more likely to suffer from TN in 2012 (RR = 1.434, P = 0.024). Elevated triglyceride level was a risk factor for developing new TN (RR = 1.001, P = 0.035). Conclusion. Both greater WC and elevated triglycerides are risk factors for new TN in this iodine-adequate area in China. Junhua Yin, Changchun Wang, Qin Shao, Dihong Qu, Zhenya Song, Pengfei Shan, Tao Zhang, Jun Xu, Qin Liang, Songzhao Zhang, and Jian Huang Copyright © 2014 Junhua Yin et al. All rights reserved. Effectiveness of Multiple Daily Injections or Continuous Subcutaneous Insulin Infusion for Children with Type 1 Diabetes Mellitus in Clinical Practice Thu, 14 Aug 2014 09:48:36 +0000 Aims. To determine whether multiple daily injections (MDIs) or continuous subcutaneous insulin infusion (CSII) contributes to better glucose control in children with different type 1 diabetes duration. Methods. Subjects were grouped according to early (1 year after disease onset; 1A) or late (1–3 years after onset; 2A) MDIs/CSII treatment initiation. Corresponding control groups (1B, 2B) received insulin injections twice daily. Results. HbA1c levels were consistently lower in group 1A than in group 1B (6 months (T2): 7.37% versus 8.21%; 12 months (T3): 7.61% versus 8.41%; 24/36 months (T4/T5): 7.61% versus 8.72%; all ), but were lower in group 2A than in group 2B only at T2 (8.36% versus 9.19%; ). Levels were lower in group 1A than in group 2A when disease duration was matched (7.61% versus 8.49%; ). Logistic regression revealed no correlation between HbA1c level and MDIs/CSII therapy. HbA1c levels were only negatively related to insulin dosage. Conclusions. Blood glucose control was better in patients receiving MDIs/CSII than in those receiving conventional treatment. Early MDIs/CSII initiation resulted in prolonged maintenance of low HbA1c levels compared with late initiation. MDIs/CSII therapy should be combined with comprehensive management. Chun-xiu Gong, Li-ya Wei, Di Wu, Bing-yan Cao, Xi Meng, and Lin-lin Wang Copyright © 2014 Chun-xiu Gong et al. All rights reserved. Rare Mutations of Peroxisome Proliferator-Activated Receptor Gamma: Frequencies and Relationship with Insulin Resistance and Diabetes Risk in the Mixed Ancestry Population from South Africa Thu, 14 Aug 2014 08:21:12 +0000 Background. Genetic variants in the nuclear transcription receptor, PPARG, are associated with cardiometabolic traits, but reports remain conflicting. We determined the frequency and the clinical relevance of PPARG SNPs in an African mixed ancestry population. Methods. In a cross-sectional study, 820 participants were genotyped for rs1800571, rs72551362, rs72551363, rs72551364, and rs3856806, using allele-specific TaqMan technology. The homeostatic model assessment of insulin (HOMA-IR), β-cells function (HOMA-B%), fasting insulin resistance index (FIRI), and the quantitative insulin-sensitivity check index (QUICKI) were calculated. Results. No sequence variants were found except for the rs3856806. The frequency of the PPARG-His447His variant was 23.8% in the overall population group, with no difference by diabetes status (). The His447His allele T was associated with none of the markers of insulin resistance overall and by diabetes status. In models adjusted for 2-hour insulin, the T allele was associated with lower prevalent diabetes risk (odds ratio 0.56 (95% CI 0.31–0.95)). Conclusion. Our study confirms the almost zero occurrences of known rare PPARG SNPs and has shown for the first time in an African population that one of the common SNPs, His447His, may be protective against type 2 diabetes. Z. Vergotine, A. P. Kengne, R. T. Erasmus, Y. Y. Yako, and T. E. Matsha Copyright © 2014 Z. Vergotine et al. All rights reserved. Liraglutide Exerts Antidiabetic Effect via PTP1B and PI3K/Akt2 Signaling Pathway in Skeletal Muscle of KKAy Mice Mon, 11 Aug 2014 08:26:57 +0000 Background. Liraglutide (a glucagon-like peptide 1 analog) was used for the treatment of type 2 diabetes (T2DM) which could produce glucose-dependent insulin secretion. Aim. The aim was to investigate whether liraglutide could improve myofibril and mitochondria injury in skeletal muscle and the mechanisms in diabetic KKAy mice. Method. We divided the male KKAy mice into 2 groups: liraglutide group (250 μg/kg/day liraglutide subcutaneous injection) and model group; meanwhile, the male C57BL/6J mice were considered as the control. After 6 weeks, the ultrastructure of skeletal muscle was observed by electron microscope. The gene expressions of protein tyrosine phosphatase 1B (PTP1B), phosphatidylinositol 3-kinase (PI3K), and glucose transporter type 4 (GLUT4) were determined by real-time PCR. The protein levels of the above molecules and phospho-Akt2 (p-Akt2) were measured by Western blot. Results. Liraglutide significantly ameliorated the injury of mitochondria by increasing the number (+441%) and the area (+113%) of mitochondria and mitochondrial area/100 µm2 (+396%) in skeletal muscle of KKAy mice. The results of real-time PCR and Western blot showed that liraglutide downregulated PTP1B while it upregulated PI3K and GLUT4 (). The protein level of p-Akt2/Akt2 was also increased (). Conclusion. These results revealed that liraglutide could improve myofibril and mitochondria injury in skeletal muscle against T2DM via PTP1B and PI3K/Akt2 signaling pathway. Wenjun Ji, Xinlin Chen, Juan Lv, Meng Wang, Shuting Ren, Bingxiang Yuan, Bing Wang, and Lina Chen Copyright © 2014 Wenjun Ji et al. All rights reserved. Dipeptidyl Peptidase-4 Inhibitors as a Third-Line Oral Antihyperglycaemic Agent in Patients with Type 2 Diabetes Mellitus: The Impact of Ethnicity Sun, 10 Aug 2014 12:40:29 +0000 Aims. The aim of this study is to examine the efficacy of adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to patients with type 2 diabetes inadequately controlled by metformin and sulphonylurea combination treatment. The response of Asian and non-Asian patients to this regimen was also examined. Methods. The medical and computerized records of 80 patients were examined. These patients had baseline HbA1c levels ranging from 7.0 to 12.5% and had a DPP-4 inhibitor add-on therapy for a minimum period of 12 weeks. The primary endpoint was the change in HbA1c level before and after DPP-4 inhibitor treatment. Results. During oral triple therapy, there was a reduction of HbA1c from 8.3% (7.7–8.9) to 7.2% (6.8–7.6) and 26 patients (32.5%) achieved an HbA1c <7%. Poor baseline glycaemic control, lower BMI, and younger age were associated with a better response, but duration of diabetes and gender did not affect outcome. The HbA1c reduction was not different between Asians and non-Asians group [−1.00% (0.6–1.3) vs −0.90% (0.4–1.6)]. Conclusions. DPP-4 inhibitor as a third-line add-on therapy can achieve significant glycaemic improvement in patients with type 2 diabetes inadequately controlled on the combination of metformin and sulphonylurea. The improvement in HbA1c was similar between Asian and non-Asian patients. X. Zhang, B. Brooks, L. Molyneaux, E. Landy, R. Banatwalla, T. Wu, J. Wong, B. Su, and D. K. Yue Copyright © 2014 X. Zhang et al. All rights reserved. No Obesity Paradox—BMI Incapable of Adequately Capturing the Relation of Obesity with All-Cause Mortality: An Inception Diabetes Cohort Study Thu, 07 Aug 2014 10:37:16 +0000 Background. To reconcile “the obesity paradox,” we tested if (1) the contribution of anthropometric measures to mortality was nonlinear and (2) the confounding of hip circumference contributed to the obesity paradox recently observed among diabetic patients. Methods. We analyzed data of diabetic patients attending a community-based prospective, “Tehran lipid and glucose study.” In the mortality analysis, anthropometric measures—body mass index (BMI), waist, and hip circumference—were assessed using Cox models incorporating cubic spline functions. Results. During 12 990 person-years follow-up, BMI levels below 27 and those above 40 kg·m−2 were associated with increased mortality. When we added waist circumference to the BMI in the multivariate-adjusted model, the steepness of BMI-mortality association curve slope for values below 27 kg·m−2 increased, whereas the steepness of BMI-mortality association curve slope for values above this threshold decreased. Further adjusting the model for hip circumference, the steepness of the slopes of the association curve moved towards null on both extremes and no associations between BMI and all-cause mortality remained. Conclusion. BMI harbors intermixed positive and negative confounding effects on mortality of waist and hip circumference. Failing to control for the confounding effect of hip circumference may stymie unbiased hazard estimation and render conclusions paradoxical. Mohammadreza Bozorgmanesh, Banafsheh Arshi, Farhad Sheikholeslami, Fereidoun Azizi, and Farzad Hadaegh Copyright © 2014 Mohammadreza Bozorgmanesh et al. All rights reserved. Glucocorticoid Functional Reserve in Full-Spectrum Intensity of Primary Hypothyroidism Thu, 07 Aug 2014 06:07:26 +0000 Adrenal function might be impaired in patients with primary hypothyroidism. The objective was to evaluate adrenocortical function using the low-dose cosyntropin test in patients with primary hypothyroidism. Consequently a prospective, longitudinal, controlled study of sixty adult patients with primary hypothyroidism was carried out. Patients naïve to L-T4 treatment were compared with control participants. A low-dose cosyntropin test was done before and after L-T4 therapy. Thirty and sixty minutes after the low-dose cosyntropin, the mean cortisol values were lower in the cases group (612.6 ± 133.1 and 603.4 ± 153.7 nmol/L) when compared to the control group (677.0 ± 82.4 and 669.9 ± 83.7 nmol/L) ( and 0.003), respectively. After L-T4 therapy, this difference was lost. Four out of 60 cases (6.7%) taking a cortisol cutoff value of 500 mmol/L and 11 out of 60 (18.3%) having 550 mmol/L as the cutoff had adrenal insufficiency before L-T4 therapy. After L-T4 therapy, 50% and 81% of the cases had normal cortisol response. In conclusion, patients with different degrees of intensity of primary hypothyroidism had improved cortisol response after reaching euthyroidism. The incidence of adrenal insufficiency was 6.7–18.3% and more than 50% of the cases had a normal cortisol response after L-T4 therapy. René Rodríguez-Gutiérrez, Camilo González-Velázquez, Gerardo González-Saldívar, Jesús Zacarías Villarreal-Pérez, and José Gerardo González-González Copyright © 2014 René Rodríguez-Gutiérrez et al. All rights reserved. Glucose Intolerance after a Recent History of Gestational Diabetes Thu, 07 Aug 2014 05:30:45 +0000 Aim. Our aim was to evaluate the uptake of our current screening strategy postpartum and the risk factors for glucose intolerance in women with a recent history of gestational diabetes (GDM). Methods. Retrospective analysis of files of women with a recent history of GDM diagnosed with the Carpenter and Coustan criteria from 01-01-2010 till 31-12-2013. Multivariable logistic regression was used to adjust for confounders. Results. Of all 231 women with a recent history of GDM, 21.4% (46) did not attend the scheduled postpartum OGTT. Of the women tested, 39.1% (66) had glucose intolerance and 5.3% (9) had diabetes. These women were more often overweight (39.7% versus 25.3%, = 0.009), were more often treated with basal-bolus insulin injections (52.0% versus 17.4%, = 0.032), and had a lower beta-cell function and lower insulin sensitivity, remaining significant after adjustment for age, BMI, and ethnicity (insulin secretion sensitivity index-2 (ISSI-2) in pregnancy 1.5 ± 0.5 versus 1.7 ± 0.4, = 0.029; ISSI-2 postpartum 1.5 (1.2–1.9) versus 2.2 (1.8–2.6), = 0.020; Matsuda index postpartum 3.8 (2.6–6.2) versus 6.0 (4.3–8.8), = 0.021). Conclusion. Glucose intolerance is frequent in early postpartum and these women have a lower beta-cell function and lower insulin sensitivity. One fifth of women did not attend the scheduled OGTT postpartum. Katrien Benhalima, Liesbeth Leuridan, Peggy Calewaert, Roland Devlieger, Johan Verhaeghe, and Chantal Mathieu Copyright © 2014 Katrien Benhalima et al. All rights reserved. Tuberculosis of the Adrenal Gland: A Case Report and Review of the Literature of Infections of the Adrenal Gland Wed, 06 Aug 2014 00:00:00 +0000 Infections of the adrenal glands remain an important cause of adrenal insufficiency, especially in the developing world. Indeed, when Thomas Addison first described the condition that now bears his name over 150 years ago, the vast majority of cases were attributable to tuberculosis. Here we describe a classic, but relatively uncommon, presentation in the United States of adrenal insufficiency followed by a review of the current literature pertaining to adrenal infections. Jagriti Upadhyay, Praveen Sudhindra, George Abraham, and Nitin Trivedi Copyright © 2014 Jagriti Upadhyay et al. All rights reserved. Vitamin D and Its Relationship with Obesity and Muscle Tue, 05 Aug 2014 00:00:00 +0000 The skin synthesis of vitamin D represents the first step of a metabolic pathway whose features have been extensively studied and clarified in the last decades. In particular, the production of active and inactive forms of the hormone and the actions of the corresponding enzymes have offered new insights into the knowledge of vitamin D metabolism. Additionally, the description of the different organs and tissues expressing the vitamin D receptor and its possible functions, as well as its genetic determinants, have allowed focusing on the interrelationship between vitamin D and many physiological and pathological functions. In this context, many studies reported the association between vitamin D and adipose tissue metabolism, as well as the possible role of the hormone in obesity, weight, and fat mass distribution. Finally, many reports focused on the vitamin D-related effects on skeletal muscle, particularly on the mechanisms by which vitamin D could directly affect muscle mass and strength. This paper is mainly aimed to review vitamin D metabolism and its relationship with obesity and skeletal muscle function. Cristiana Cipriani, Jessica Pepe, Sara Piemonte, Luciano Colangelo, Mirella Cilli, and Salvatore Minisola Copyright © 2014 Cristiana Cipriani et al. All rights reserved.