International Journal of Endocrinology The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Lower Extremity Peripheral Arterial Disease Is an Independent Predictor of Coronary Heart Disease and Stroke Risks in Patients with Type 2 Diabetes Mellitus in China Sun, 21 May 2017 00:00:00 +0000 We aimed to determine the relationship between lower extremity peripheral arterial disease (PAD), 10-year coronary heart disease (CHD), and stroke risks in patients with type 2 diabetes (T2DM) using the UKPDS risk engine. We enrolled 1178 hospitalized T2DM patients. The patients were divided into a lower extremity PAD group (ankle-brachial or >1.4; 88 patients, 7.5%) and a non-PAD group (ankle-brachial and ≤1.4; 1090 patients, 92.5%). Age; duration of diabetes; systolic blood pressure; the hypertension rate; the use of hypertension drugs, ACEI /ARB, and statins; CHD risk; fatal CHD risk; stroke risk; and fatal stroke risk were significantly higher in the PAD group than in the non-PAD group ( for all). Logistic stepwise regression analysis indicated that ABI was an independent predictor of 10-year CHD and stroke risks in T2DM patients. Compared with those in the T2DM non-PAD group, the odds ratios (ORs) for CHD and stroke risk were 3.6 (95% confidence interval (CI), 2.2–6.0; ) and 6.9 (95% CI, 4.0–11.8; ) in those with lower extremity PAD, respectively. In conclusion, lower extremity PAD increased coronary heart disease and stroke risks in T2DM. Xiao-Hong Pang, Jue Han, Wan-Lan Ye, Xue Sun, Yue Ding, Wen-Juan Huang, Yi-Ming Zhao, Han-Yu Lou, Li-Zhen Shan, Ying-Xiu Kang, Xiao-Xiao Song, Song-Zhao Zhang, Wei Gu, and Peng-Fei Shan Copyright © 2017 Xiao-Hong Pang et al. All rights reserved. Relationship between IGF-I Concentration and Metabolic Profile in Children with Growth Hormone Deficiency: The Influence of Children’s Nutritional State as well as the Ghrelin, Leptin, Adiponectin, and Resistin Serum Concentrations Wed, 17 May 2017 06:24:19 +0000 Background. Some, however not all, children with growth hormone deficiency (GHD) reveal a tendency towards metabolic disorders. Insulin-like growth factor I (IGF-I) is the main mediator of GH anabolic effects. Objective. The aim of the study was to compare ghrelin, adiponectin, leptin, resistin, lipid, glucose, and insulin concentrations in GHD children, depending on the IGF-I bioavailability. Methods. The analysis comprised 26 children with GHD, aged 5.7–15.3 yrs. Fasting serum concentrations of IGF-I, IGFBP-3, ghrelin, leptin, adiponectin, resistin, lipids, glucose, and insulin were measured. The GHD children were divided into two subgroups: (1) with lower IGF-I/IGFBP-3 molar ratio and (2) with higher IGF-I/IGFBP-3 molar ratio. The control group consisted of 39 healthy children, aged 5.1–16.6 yrs, of normal height and body mass. Results. GHD children with lower IGF-I/IGFBP-3 molar ratio were found to have a significantly lower body mass and insulin and triglyceride concentrations, as well as significantly higher ghrelin and adiponectin concentrations than GHD children with higher IGF-I/IGFBP-3. Conclusions. A better metabolic profile characterised GHD children with low IGF-I bioavailability. This phenomenon may be the result of high adiponectin and ghrelin concentrations in those children and their influence on adipose tissue, glucose uptake, and orexigenic axis. Renata Stawerska, Joanna Smyczyńska, Maciej Hilczer, and Andrzej Lewiński Copyright © 2017 Renata Stawerska et al. All rights reserved. Corrigendum to “Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents” Tue, 16 May 2017 00:00:00 +0000 Amilton Dos Santos-Júnior, Taciane Barbosa Henriques, Maricilda Palandi de Mello, Osmar Henrique Della Torre, Lúcia Arisaka Paes, Adriana Perez Ferreira-Neto, Letícia Esposito Sewaybricker, Thiago Salum Fontana, Eloisa Helena Rubello Valler Celeri, Gil Guerra-Júnior, and Paulo Dalgalarrondo Copyright © 2017 Amilton Dos Santos-Júnior et al. All rights reserved. Relationship between Central Arterial Stiffness and Insulin Resistance in Chinese Community-Dwelling Population without Diabetes Mellitus Sun, 14 May 2017 09:04:38 +0000 Objective. Insulin resistance (IR) is a pathological condition present not only in patients with type 2 diabetes mellitus (DM), but also in community-dwelling population without DM. Both central arterial stiffness and IR are closely correlated with cardiovascular morbidity and mortality. The relationship between central arterial stiffness and IR has not been described in Chinese community-dwelling population without DM. The current analysis was designed to investigate the relationship between central arterial stiffness and IR in Chinese community-dwelling population without DM. Methods. There were 1150 participants fully assessed for not only homeostasis model assessment of insulin resistance (HOMA-IR) but also carotid-femoral pulse wave velocity (cfPWV). Results. Median age was 39 (18–80) years, and 69.7% were men. Bivariate correlation analysis showed that cfPWV was significantly related to HOMA-IR (). Logistic regression analysis indicated that cfPWV was independently associated with HOMA-IR (). Conclusions. This community-based analysis testified that the relationship between central arterial stiffness and IR was evident as early as during nondiabetic stage. Early interventions in Chinese community-dwelling population without DM to improve the IR are also important in the prevention of cardiovascular diseases. Shihui Fu, Ying Lin, Leiming Luo, and Ping Ye Copyright © 2017 Shihui Fu et al. All rights reserved. The Validity and Reliability between Automated Oscillometric Measurement of Ankle-Brachial Index and Standard Measurement by Eco-Doppler in Diabetic Patients with or without Diabetic Foot Tue, 09 May 2017 00:00:00 +0000 Objective. To evaluate the concordance between oscillometric ABI and standard Doppler ABI in diabetic Chinese patients with or without diabetic foot. Methods. 230 consecutive diabetic patients ( limbs) were included. The right and left ABIs were determined with both devices by the same investigator. The concordance and agreement were assessed by kappa index and the Bland-Altman method. Results. The average Doppler ABI was 1.003 ± 0.286 on the right and 0.990 ± 0.287 on the left, while oscillometric ABI was 1.002 ± 0.332 and 0.993 ± 0.319, which had no significance. The average time for oscillometric ABI was 8.600 versus 16.980 minutes for Doppler ABI (). There was good agreement between the two measurements, with a kappa value of 0.869 on the right and 0.919 on the left. Regarding the Doppler ABI as the gold standard, the accuracy, sensitivity, specificity, +LR, and −LR of oscillometric ABI reached 95.22%, 94.34%, 95.48%, 20.873%, and 0.059% on the right. For the left, it was 96.94%, 96.43%, 97.11%, 33.364%, and 0.036%. Conclusions. The oscillometric measurement is a reliable, convenient, and less time-consuming alternative to standard Doppler ABI in patients. It should be widely used for PAD detection. Jing Ma, Min Liu, Dawei Chen, Chun Wang, Guanjian Liu, and Xingwu Ran Copyright © 2017 Jing Ma et al. All rights reserved. Association of Baseline Neutrophil-to-Lymphocyte Ratio with Clinicopathological Characteristics of Papillary Thyroid Carcinoma Tue, 09 May 2017 00:00:00 +0000 Objective. To investigate the potential association of neutrophil-to-lymphocyte ratio (NLR), a surrogate systemic inflammatory biomarker, with clinical and pathological characteristics of papillary thyroid cancers. Methods. 205 patients with papillary carcinoma were identified from the institutional thyroid cancer database between 2006 and 2015 (55 males, 150 females, mean age 51.2 ± 14.7 years). NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count, based on the preoperative complete blood cell counts. Results. NLR was significantly higher in carcinomas with extrathyroidal invasion (2.74 ± 01.24 versus 2.39 ± 0.96, ) and bilateral (2.67 ± 1.15 versus 2.35 ± 0.96, ) and multifocal tumours (2.65 ± 1.08 versus 2.29 ± 0.96, ), as well as lymph node-positive tumours (3.12 ± 1.07 versus 2.41 ± 1.02, ). On the other hand, NLR values were not associated with gender, age, tumour size, histologic subtype, the presence of thyroiditis, and TNM staging. Conclusions. As an index of inflammation, NLR is inexpensive, readily available, and easy to extract from routine blood tests. We found increased NLR values in papillary carcinomas with poorer histopathological profile and more aggressive clinical behaviour. Whether this systemic inflammatory response, as expressed by the NLR, represents the inflammatory microenvironment leading to tumourigenesis, or is a tumour-associated phenomenon, remains to be elucidated and warrants further study. Dimitrios K. Manatakis, Sofia Tseleni-Balafouta, Dimitrios Balalis, Vasiliki N. Soulou, Dimitrios P. Korkolis, George H. Sakorafas, Georgios Plataniotis, and Emmanouil Gontikakis Copyright © 2017 Dimitrios K. Manatakis et al. All rights reserved. TSH Variability of Patients Affected by Differentiated Thyroid Cancer Treated with Levothyroxine Liquid Solution or Tablet Form Tue, 09 May 2017 00:00:00 +0000 Background. Recent guidelines from the American Thyroid Association (ATA) indicate that, in many patients affected by differentiated thyroid cancer (DTC), the serum TSH should be maintained between 0.1 and 0.5 mU/L. The purpose of this study was to evaluate the TSH variability of patients affected by DTC treated with liquid L-T4 formulation or in tablet form. Patients and Methods. Patients were eligible if (a) they were submitted to a total thyroidectomy and 131I remnant ablation for DTC in our institution and (b) they were classified low-risk patients according to ATA guidelines 2009. Patients were randomized (1 : 1) to receive treatment of hypothyroidism with liquid L-T4 or tablet form. The first check-up evaluation was made from 8 to 12 months after 131I remnant ablation. TSH values were established again after further 12 months. Results. A significant increase in TSH values (median) was observed in patients taking tablets [TSH (min–max): 0.28 (0.1–0.45) versus 0.34 (0.01–0.78) mIU/L, ] as compared to those taking liquid formulation [TSH (min–max): 0.28 (0.1–0.47) versus 0.30 (0.1–0.55) mIU/L, ]. Conclusions. The use of L-T4 liquid formulation, as compared to that of tablets, resulted in a significantly higher number of DTC patients maintaining TSH values in range for the ATA risk score, reducing TSH variability over the time. Carlo Cappelli, Ilenia Pirola, Elena Gandossi, Claudio Casella, Davide Lombardi, Barbara Agosti, Fiorella Marini, Andrea Delbarba, and Maurizio Castellano Copyright © 2017 Carlo Cappelli et al. All rights reserved. Review of Factors Related to the Thyroid Cancer Epidemic Sun, 07 May 2017 00:00:00 +0000 Thyroid cancer is the most common endocrine cancer, of which the incidence has dramatically increased worldwide in the past few decades. The reasons for the observed rapid increase still are not fully understood, but evidence suggests that overdiagnosis, with the advancement in detection methods and screening policies, is not the sole driver of the substantial increase of the incidence. However, the effect of environmental/lifestyle factors remains speculative other than that of radiation exposure at a young age. This review tries to give a balanced view of debated factors leading to the thyroid cancer epidemic, to offer some alternatives in understanding the controversies, and to suggest potential directions in the search of modifiable risk factors to help reduce thyroid cancer. Yihao Liu, Lei Su, and Haipeng Xiao Copyright © 2017 Yihao Liu et al. All rights reserved. Antithyroid Drug Therapy for Graves’ Disease and Implications for Recurrence Wed, 26 Apr 2017 00:00:00 +0000 Graves’ disease (GD) is the most common cause of hyperthyroidism worldwide. Current therapeutic options for GD include antithyroid drugs (ATD), radioactive iodine, and thyroidectomy. ATD treatment is generally well accepted by patients and clinicians due to some advantages including normalizing thyroid function in a short time, hardly causing hypothyroidism, and ameliorating immune disorder while avoiding radiation exposure and invasive procedures. However, the relatively high recurrence rate is a major concern for ATD treatment, which is associated with multiple influencing factors like clinical characteristics, treatment strategies, and genetic and environmental factors. Of these influencing factors, some are modifiable but some are nonmodifiable. The recurrence risk can be reduced by adjusting the modifiable factors as much as possible. The titration regimen for 12–18 months is the optimal strategy of ATD. Levothyroxine administration after successful ATD treatment was not recommended. The addition of immunosuppressive drugs might be helpful to decrease the recurrence rate of GD patients after ATD withdrawal, whereas further studies are needed to address the safety and efficacy. This paper reviewed the current knowledge of ATD treatment and mainly focused on influencing factors for recurrence in GD patients with ATD treatment. Jia Liu, Jing Fu, Yuan Xu, and Guang Wang Copyright © 2017 Jia Liu et al. All rights reserved. Melatonin in Tuberous Sclerosis Complex Analysis Using Modern Mathematical Modeling Methods Wed, 26 Apr 2017 00:00:00 +0000 Purpose. The aim of the study was to assess melatonin secretion pattern in children with TSC and to compare it with the secretion patterns in children with and without epilepsy. Material and Methods. Melatonin secretion was measured every three hours using the RIA method in four children with recognized TSC. The parameters of the melatonin secretion models were interpreted and compared with those obtained for the patients with epilepsy () and the children from the control, nonepileptic group (). To describe the diurnal melatonin secretion, mathematical model was constructed and nonlinear least squares method with the Levenberg-Marquardt optimization algorithm was applied to approximate its parameters. The dim light melatonin onset (DLMO) parameters were also estimated from the model. Results and Conclusions. Statistically significant differences were found between the TSC melatonin secretion profiles and the nonepileptic control group. The profiles for the epileptic and TSC groups were found to be similar. For the TSC group, though a small one, the variations in the MLT release amplitudes seem to be independent of the total number of seizures; however, the MLT release shift appears to depend on the number of seizures. Justyna Paprocka, Marek Kijonka, Łukasz Boguszewicz, and Maria Sokół Copyright © 2017 Justyna Paprocka et al. All rights reserved. Amino Acid Signatures to Evaluate the Beneficial Effects of Weight Loss Tue, 18 Apr 2017 00:00:00 +0000 Aims. We investigated the relationship between circulating amino acid levels and obesity; to what extent weight loss followed by weight maintenance can correct amino acid abnormalities; and whether amino acids are related to weight loss. Methods. Amino acids associated with waist circumference (WC) and BMI were studied in 804 participants from the Malmö Diet and Cancer Cardiovascular Cohort (MDC-CC). Changes in amino acid levels were analyzed after weight loss and weight maintenance in 12 obese subjects and evaluated in a replication cohort (). Results. Out of the eight identified BMI-associated amino acids from the MDC-CC, alanine, isoleucine, tyrosine, phenylalanine, and glutamate decreased after weight loss, while asparagine increased after weight maintenance. These changes were validated in the replication cohort. Scores that were constructed based on obesity-associated amino acids and known risk factors decreased in the ≥10% weight loss group with an associated change in BMI (, ), whereas the scores increased in the <10% weight loss group (). Conclusions. Weight loss followed by weight maintenance leads to differential changes in amino acid levels associated with obesity. Treatment modifiable scores based on epidemiological and interventional data may be used to evaluate the potential metabolic benefit of weight loss. Nina Geidenstam, Martin Magnusson, Anders P. H. Danielsson, Robert E. Gerszten, Thomas J. Wang, Lovisa E. Reinius, Hindrik Mulder, Olle Melander, and Martin Ridderstråle Copyright © 2017 Nina Geidenstam et al. All rights reserved. Synergistic Effect of Family History of Diabetes and Dietary Habits on the Risk of Type 2 Diabetes in Central China Thu, 13 Apr 2017 00:00:00 +0000 Background. Family history of diabetes (FHD) and lifestyle are associated with type 2 diabetes (T2DM), but little is known about the FHD diet interactions. We aimed to analyze the interactions of FHD and lifestyle factors in Chinese T2DM onset. Methods. This was a cross-sectional survey in central urban China ( patients with T2DM and non-T2DM subjects). The biological interactions, defined by Rothman interactions, between FHD and each dietary factor were analyzed by using the synergy index (S) scores. Results. After adjustment for age, gender, BMI, and WHR, a uniparental FHD (, 95% CI: 2.36–3.42, ), a paternal history of FHD (, 95% CI: 1.91–3.35, ), a maternal history of FHD (, 95% CI: 2.67–4.02, ), a biparental history of FHD (, 95% CI: 2.98–9.31, ), and a FHD, irrespective of the parent (, 95% CI: 3.08–4.17, ), were associated with T2DM onset. There were significant interactions between FHD and consuming <15 g/d of potatoes (, 95% CI: 1.12–2.12), <8 g/d of poultry (, 95% CI: 1.04–2.17), <85 g/d of fresh fruits (, 95% CI: 1.63–2.88), and no freshly squeezed juice (, 95% CI: 1.46–3.49). Conclusions. Risk of T2DM was synergistically affected by FHD and dietary habits. Nutrition educational intervention may decrease the prevalence of T2DM in the Chinese with FHD. Yanyan Zhao, Chunhua Song, Xiaokun Ma, Xiaojun Ma, Qingzhu Wang, Hongfei Ji, Feng Guo, and Guijun Qin Copyright © 2017 Yanyan Zhao et al. All rights reserved. Variations in the 3′UTR of the CYP21A2 Gene in Heterozygous Females with Hyperandrogenaemia Wed, 12 Apr 2017 00:00:00 +0000 Heterozygosity for CYP21A2 mutations in females is possibly related to increased risk of developing clinical hyperandrogenism. The present study was designed to seek evidence on the phenotype-genotype correlation in female children, adolescents, and women with CYP21A2 mutations and variants in the 3′UTR region of the gene. Sixty-six patients out of the 169 were identified as carriers of CYP21A2 mutations. Higher values of stimulated 17 hydroxyprogesterone (17-OHP) levels were found in the carriers of the p.Val281Leu mutation compared to the carriers of other mutations (mean: 24.7 nmol/l versus 15.6 nmol/l). The haplotype of the 52C>T, 440C>T, and 443T>C in the 3′UTR was identical in all heterozygous patients with p.Val281Leu and the haplotype of the 12C>T and 52C>T was identical in all heterozygous patients with the p.Gln318. In conclusion, hyperandrogenaemic females are likely to bear heterozygous CYP21A2 mutations. Carriers of the mild p.Val281Leu mutation are at higher risk of developing hyperandrogenism than the carriers of more severe mutations. The identification of variants in the 3′UTR of CYP21A2 in combination with the heterozygous mutation may be associated with the mild form of nonclassic congenital adrenal hyperplasia and reveal the importance of analyzing the CYP21A2 untranslated regions for the appropriate management of this category of patients. Vassos Neocleous, Pavlos Fanis, Meropi Toumba, Alexia A. P. Phedonos, Michalis Picolos, Elena Andreou, Tassos C. Kyriakides, George A. Tanteles, Christos Shammas, Leonidas A. Phylactou, and Nicos Skordis Copyright © 2017 Vassos Neocleous et al. All rights reserved. Inositol(s) from Bench to Bedside in Endocrinology and Gynecology Tue, 04 Apr 2017 00:00:00 +0000 Vittorio Unfer, John E. Nestler, Zdravko A. Kamenov, Nikos Prapas, and Fabio Facchinetti Copyright © 2017 Vittorio Unfer et al. All rights reserved. Benefits of Levothyroxine Replacement Therapy on Nonalcoholic Fatty Liver Disease in Subclinical Hypothyroidism Patients Tue, 04 Apr 2017 00:00:00 +0000 Objectives. To evaluate the effect of levothyroxine (LT4) replacement therapy on nonalcoholic fatty liver disease (NAFLD) in subclinical hypothyroidism (SCH) patients. Methods. This study was a post hoc analysis of a randomized controlled trial and involved 33 significant and 330 mild SCH patients. All of the significant SCH patients received LT4 supplement. The mild SCH patients were grouped as LT4 treated or not. After 15 months of follow-up, prevalence of NAFLD in each group was reevaluated. Subgroup analysis was conducted in mild SCH patients with dyslipidemia. Results. After treatment with LT4, the prevalence of NAFLD in significant SCH patients reduced from 48.5% to 24.2% (). In mild SCH patients, prevalence of NAFLD and serum alanine aminotransferase (ALT) was not significantly affected by LT4 supplementation. Nonetheless, mild SCH patients with dyslipidemia who received LT4 treatment experienced decreases in the prevalence of NAFLD and serum ALT levels ( for both). In contrast, these parameters remained comparably stable in patients who were not treated. Conclusion. LT4 supplementation has benefits on NAFLD in significant SCH patients or mild SCH patients with dyslipidemia. For NAFLD patients with SCH, appropriate supplementation of LT4 may be an effective means of controlling NAFLD. The original trial was registered with (NCT01848171). Lu Liu, Yong Yu, Meng Zhao, Dongmei Zheng, Xu Zhang, Qingbo Guan, Chao Xu, Ling Gao, Jiajun Zhao, and Haiqing Zhang Copyright © 2017 Lu Liu et al. All rights reserved. Gender, Estrogen, and Obliterative Lesions in the Lung Sun, 02 Apr 2017 00:00:00 +0000 Gender has been shown to impact the prevalence of several lung diseases such as cancer, asthma, chronic obstructive pulmonary disease, and pulmonary arterial hypertension (PAH). Controversy over the protective effects of estrogen on the cardiopulmonary system should be of no surprise as clinical trials of hormone replacement therapy have failed to show benefits observed in experimental models. Potential confounders to explain these inconsistent estrogenic effects include the dose, cellular context, and systemic versus local tissue levels of estrogen. Idiopathic PAH is disproportionately found to be up to 4 times more common in females than in males; however, estrogen levels cannot explain why males develop PAH sooner and have poorer survival. Since the sex steroid hormone 17β-estradiol is a mitogen, obliterative processes in the lung such as cell proliferation and migration may impact the growth of pulmonary tissue or vascular cells. We have reviewed evidence for biological differences of sex-specific lung obliterative lesions and highlighted cell context-specific effects of estrogen in the formation of vessel lumen-obliterating lesions. Based on this information, we provide a biological-based mechanism to explain the sex difference in PAH severity as well as propose a mechanism for the formation of obliterative vascular lesions by estrogens. Hamza Assaggaf and Quentin Felty Copyright © 2017 Hamza Assaggaf and Quentin Felty. All rights reserved. Chronic Administration of Tadalafil Improves the Symptoms of Patients with Amicrobic MAGI: An Open Study Thu, 30 Mar 2017 06:43:30 +0000 Aim of this study was to evaluate the effects of pharmacological treatment with Tadalafil 5 mg daily on symptoms and quality of sperm parameters in selected patients with amicrobic MAGI (male accessory gland inflammation). 120 patients with amicrobic MAGI (mean age 27.0 ± 6.0 years) with mild-moderate ED (erectile dysfunction) according to IIEF-5 (International Index of Erectile Function 5 Items) scores underwent pharmacological treatment with Tadalafil 5 mg daily for six months. Before and after treatment these patients were evaluated through IIEF-5, semen analysis (according to WHO Criteria, 2010), SI-MAGI (Structured Interview about Male Accessory Gland Inflammation), and ultrasound evaluation. Patients with PVE (prostate-vesciculo-epididymitis) showed a significant increase in the percentage of spermatozoa with total (16.0 ± 8.0 versus 30.0 ± 6.0%) and progressive motility (8.00 ± 10.0 versus 25.0 ± 6.00%). It was a significant reduction of the number of patients with complicated ultrasound forms (30.0 versus 52.0) and a significant increase of the number of patients with uncomplicated ultrasound form (90.0 versus 68.0). Finally, there was a significant reduction in the percentage of patients with alterations of sexual function different from DE, such as premature ejaculation (4.00 versus 8.00%), painful ejaculation (4.00 versus 10.0%), delayed ejaculation (12.50 versus 8.00%), and decreased libido (10.0 versus 25.0%). Sandro La Vignera, Rosita A. Condorelli, Laura M. Mongioi, and Aldo E. Calogero Copyright © 2017 Sandro La Vignera et al. All rights reserved. Nonalcoholic Fatty Liver Disease and Associated Metabolic Risks of Hypertension in Type 2 Diabetes: A Cross-Sectional Community-Based Study Sun, 26 Mar 2017 00:00:00 +0000 The mechanisms facilitating hypertension in diabetes still remain to be elucidated. Nonalcoholic fatty liver disease (NAFLD), which is a higher risk factor for insulin resistance, shares many predisposing factors with diabetes. However, little work has been performed on the pathogenesis of hypertension in type 2 diabetes (T2DM) with NAFLD. The aim of this study is to investigate the prevalence of hypertension in different glycemic statuses and to analyze relationships between NAFLD, metabolic risks, and hypertension within a large community-based population after informed written consent. A total of 9473 subjects aged over 45 years, including 1648 patients with T2DM, were enrolled in this cross-sectional study. Clinical and biochemical parameters of all participants were determined. The results suggested that the patients with prediabetes or T2DM were with higher risks to have hypertension. T2DM with NAFLD had significantly higher levels of blood pressure, triglyceride, uric acid, and HOMA-IR than those without NAFLD. Data analyses suggested that hypertriglyceridemia [OR = 1.773 (1.396, 2.251)], NAFLD [OR = 2.344 (1.736, 3.165)], hyperuricemia [OR = 1.474 (1.079, 2.012)], and insulin resistance [OR = 1.948 (1.540, 2.465)] were associated with the higher prevalence of hypertension independent of other metabolic risk factors in type 2 diabetes. Further studies are needed to focus on these associations. Xiaoying Ding, Ying Xu, Yufan Wang, Xiaohua Li, Chunhua Lu, Jing Su, Yuhang Ma, Yuting Chen, Yanhua Yin, Lijun Zhang, Yong Wu, Yaqiong Jin, Lijun Zheng, Songmei Xu, Xiuli Zhu, Jilin Ma, Lihua Yu, Junyi Jiang, Naisi Zhao, Qingwu Yan, Andrew S. Greenberg, Qianfang Huang, Qian Ren, Haiyan Sun, Mingyu Gu, Li Zhao, Yunhong Huang, Yijie Wu, Chunxian Qian, and Yongde Peng Copyright © 2017 Xiaoying Ding et al. All rights reserved. Crosstalk between Aryl Hydrocarbon Receptor and Glucocorticoid Receptor in Human Retinal Pigment Epithelial Cells Wed, 22 Mar 2017 02:26:35 +0000 The aryl hydrocarbon receptor (AHR) is known to mediate the cellular reaction involved in processing environmental contaminants and, ultimately, preventing accumulation of unfavorable extra lipids and proteins. Glucocorticoid receptor (GR) mediates the expression of genes associated with anti-inflammatory properties. Because AHR and GR are closely related in lipid metabolic dysregulation and inflammation, we speculate that AHR and GR may play a crucial role in AMD pathogenesis and focus on their crosstalk in human retinal pigment epithelial cells (ARPE-19). However, how AHR and GR regulate each other’s signaling pathways is still poorly understood. In this research, we demonstrate that GR attenuates AHR-mediated gene expression by inhibition of nuclear translocation of AHR mediated by TCDD. Chromatin immunoprecipitation analysis demonstrated that GR repress AHR recruitment and chromatin accessibility response to TCDD + Dex treatment leading to repression of AHR target genes. In contrast, AHR facilitates GR-mediated expression in ARPE-19. AHR increases GR recruitment on GRE of GR target genes. Coimmunoprecipitation assay revealed that AHR is associated with GR in ARPE-19 cells and the interaction is enhanced by the addition of TCDD and Dex. Taken together, these studies provide a molecular mechanism of crosstalk between AHR and GR in target gene expression in ARPE-19 cells. Hong Lan Jin, Yujin Choi, and Kwang Won Jeong Copyright © 2017 Hong Lan Jin et al. All rights reserved. Self-Monitoring of Blood Glucose to Assess Dawn Phenomenon in Chinese People with Type 2 Diabetes Mellitus Tue, 21 Mar 2017 09:04:51 +0000 Aims. We investigated whether self-monitoring of blood glucose could be used to assess dawn phenomenon in Chinese people with type 2 diabetes mellitus (T2DM). Methods. A total of 306 people with T2DM underwent continuous glucose monitoring and self-monitoring of blood glucose for 72 h. A linear model was used to fit the optimal linear formula of the magnitude of dawn phenomenon (ΔDawn) and self-monitoring of blood glucose values. Results. The prevalence of dawn phenomenon was similar within different oral antidiabetic drug groups (42.5%, 31.5%, and 40.9%, ). Multiple variable linear regression showed that prebreakfast, prelunch, and predinner glucose measurements were independently and significantly correlated with ΔDawn. The linear formula between ΔDawn and blood glucose was as follows: (adjusted , ). Conclusions. Dawn phenomenon could be partly assessed by blood glucose self-monitoring in Chinese people with T2DM using the abovementioned formula. The incidence of dawn phenomenon was similar among patients in different oral antidiabetic drug groups. Wen Wu, Yuxin Huang, Jieyuzhen Qiu, Jiao Sun, and Haidong Wang Copyright © 2017 Wen Wu et al. All rights reserved. Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain Tue, 21 Mar 2017 00:00:00 +0000 The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30–50% (4–6 mM versus 7–9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced. Vivi F. H. Jensen, Anne-Marie Mølck, Melissa Chapman, Lene Alifrangis, Lene Andersen, Jens Lykkesfeldt, and Ingrid B. Bøgh Copyright © 2017 Vivi F. H. Jensen et al. All rights reserved. XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T Gene Polymorphisms Associated with Male Infertility Risk: Evidences from Case-Control and In Silico Studies Tue, 21 Mar 2017 00:00:00 +0000 We evaluate the association between genetic polymorphisms of XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T with male infertility susceptibility. A total of 392 men including 178 infertile males (102 idiopathic azoospermia and 76 severe oligozoospermia) and 214 healthy controls were recruited. XRCC6 -61C>G and XRCC7 6721G>T genotyping was performed by PCR-RFLP whereas XRCC5 VNTR was performed by PCR. The 2R allele and 2R allele carriers of XRCC5 VNTR polymorphism significantly decreased risk of male infertility. The mutant GG genotypes and carriers of the CG and GG genotypes of XRCC6 -61C>G showed increased risk for the male infertility. Furthermore, the G allele of the XRCC6 -61C>G was correlated with increased susceptibility to male infertility. Likewise, the T allele of the XRCC7 6721G>T polymorphism was associated with increased susceptibility to male infertility in azoospermia. In silico analysis predicted that the presence of tandem repeats in XRCC5 gene prompter can be sequence to bind to more nuclear factors. Also, rs2267437 (C>G) variant was located in a well-conserved region in XRCC6 promoter and this variation might lead to differential allelic expression. The XRCC7 6721G>T gene polymorphism occurred in an acceptor-splicing site, but this polymorphism has no severe modification on XRCC7 mRNA splicing. Our results indicate the association of XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T gene polymorphisms with male infertility in Iranian men. Danial Jahantigh and Abasalt Hosseinzadeh Colagar Copyright © 2017 Danial Jahantigh and Abasalt Hosseinzadeh Colagar. All rights reserved. Combination Therapy with a Sodium-Glucose Cotransporter 2 Inhibitor and a Dipeptidyl Peptidase-4 Inhibitor Additively Suppresses Macrophage Foam Cell Formation and Atherosclerosis in Diabetic Mice Sun, 19 Mar 2017 00:00:00 +0000 Dipeptidyl peptidase-4 inhibitors (DPP-4is), in addition to their antihyperglycemic roles, have antiatherosclerotic effects. We reported that sodium-glucose cotransporter 2 inhibitors (SGLT2is) suppress atherosclerosis in a glucose-dependent manner in diabetic mice. Here, we investigated the effects of combination therapy with SGLT2i and DPP-4i on atherosclerosis in diabetic mice. SGLT2i (ipragliflozin, 1.0 mg/kg/day) and DPP-4i (alogliptin, 8.0 mg/kg/day), either alone or in combination, were administered to db/db mice or streptozotocin-induced diabetic apolipoprotein E-null (Apoe−/−) mice. Ipragliflozin and alogliptin monotherapies improved glucose intolerance; however, combination therapy did not show further improvement. The foam cell formation of peritoneal macrophages was suppressed by both the ipragliflozin and alogliptin monotherapies and was further enhanced by combination therapy. Although foam cell formation was closely associated with HbA1c levels in all groups, DPP-4i alone or the combination group showed further suppression of foam cell formation compared with the control or SGLT2i group at corresponding HbA1c levels. Both ipragliflozin and alogliptin monotherapies decreased scavenger receptors and increased cholesterol efflux regulatory genes in peritoneal macrophages, and combination therapy showed additive changes. In diabetic Apoe−/− mice, combination therapy showed the greatest suppression of plaque volume in the aortic root. In conclusion, combination therapy with SGLT2i and DPP4i synergistically suppresses macrophage foam cell formation and atherosclerosis in diabetic mice. Michishige Terasaki, Munenori Hiromura, Yusaku Mori, Kyoko Kohashi, Hideki Kushima, Makoto Ohara, Takuya Watanabe, Olov Andersson, and Tsutomu Hirano Copyright © 2017 Michishige Terasaki et al. All rights reserved. Activities of Amphioxus GH-Like Protein in Osmoregulation: Insight into Origin of Vertebrate GH Family Sun, 19 Mar 2017 00:00:00 +0000 GH is known to play an important role in both growth promotion and osmoregulation in vertebrates. We have shown that amphioxus possesses a single GH-like hormone (GHl) gene encoding a functional protein capable of promoting growth. However, if GHl can mediate osmoregulation remains open. Here, we demonstrated clearly that GHl increased not only the survival rate of amphioxus but also the muscle moisture under high salinity. Moreover, GHl induced the expression of both the ion transporter Na+-K+-ATPase (NKA) and Na+-K+-2Cl− cotransporter (NKCC) in the gill as well as the mediator of GH action IGFl in the hepatic caecum, indicating that GHl fulfills this osmoregulatory activity through the same mechanisms of vertebrate GH. These results together suggest that the osmoregulatory activities of GH had emerged in the basal chordate amphioxus. We also proposed a new model depicting the origin of pituitary hormone family in vertebrates. Mengyang Li, Chengyan Jiang, Yu Zhang, and Shicui Zhang Copyright © 2017 Mengyang Li et al. All rights reserved. Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health Thu, 16 Mar 2017 05:32:53 +0000 It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testosterone decline in men on bone health are less well known. Much of our knowledge comes from observational studies and retrospective analysis on small groups of men with variable causes of primary or secondary hypogonadism and mild to overt testosterone deficiencies. This review aims to present the current knowledge of the consequences of adult male hypogonadism on bone metabolism. The direct and indirect effects of testosterone on bone cells will be explored as well as the important differences in male osteoporosis and assessment as compared to that in females. The clinical consequence of both primary and secondary hypogonadism, as well as testosterone decline in older males, on bone density and fracture risk in men will be summarized. Finally, the therapeutic options and their efficacy in male osteoporosis and hypogonadism will be discussed. Gary Golds, Devon Houdek, and Terra Arnason Copyright © 2017 Gary Golds et al. All rights reserved. Associations of Two Obesity-Related Single-Nucleotide Polymorphisms with Adiponectin in Chinese Children Wed, 15 Mar 2017 05:04:17 +0000 Purpose. Genome-wide association studies have found two obesity-related single-nucleotide polymorphisms (SNPs), rs17782313 near the melanocortin-4 receptor (MC4R) gene and rs6265 near the brain-derived neurotrophic factor (BDNF) gene, but the associations of both SNPs with other obesity-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNPs and adiponectin that has a regulatory role in glucose and lipid metabolism. Methods. We examined the associations of the SNPs with adiponectin in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study. Results. The SNP rs6265 was significantly associated with adiponectin under an additive model ( and 0.024, resp.) after adjustment for age, gender, and BMI or obesity statuses. The SNP rs17782313 was significantly associated with low adiponectin under a recessive model. No statistical significance was found between the two SNPs and low adiponectin after correction for multiple testing. Conclusion. We demonstrate for the first time that the SNP rs17782313 near MC4R and the SNP rs6265 near BDNF are associated with adiponectin in Chinese children. These novel findings provide important evidence that adiponectin possibly mediates MC4R and BDNF involved in obesity. Lijun Wu, Liwang Gao, Xiaoyuan Zhao, Meixian Zhang, Jianxin Wu, and Jie Mi Copyright © 2017 Lijun Wu et al. All rights reserved. Muscarinic Receptors Types 1 and 2 in the Preoptic-Anterior Hypothalamic Areas Regulate Ovulation Unequally in the Rat Oestrous Cycle Wed, 15 Mar 2017 00:00:00 +0000 Muscarinic receptors types 1 (m1AChR) and 2 (m2AChR) in the preoptic and anterior hypothalamus areas (POA-AHA) were counted, and the effects of blocking these receptors on spontaneous ovulation were analysed throughout the rat oestrous cycle. Rats in each phase of the oestrous cycle were assigned to the following experiments: (1) an immunohistochemical study of the number of cells expressing m1AChR or m2AChR in the POA-AHA and (2) analysis of the effects of the unilateral blockade of the m1AChR (pirenzepine, PZP) or m2AChR (methoctramine, MTC) on either side of the POA-AHA on the ovulation rate. The number of m2AChR-immunoreactive cells was significantly higher at 09:00 h on each day of the oestrous cycle in the POA-AHA region, while no changes in the expression profile of m1AChR protein were observed. The ovulation rate in rats treated with PZP on the oestrous day was lower than that in the vehicle group. Animals treated on dioestrous-1 with PZP or MTC had a higher ovulation rate than those in the vehicle group. In contrast, on dioestrous-2, the MTC treatment decreased the ovulation rate. These results suggest that m1AChR or m2AChR in the POA-AHA could participate in the regulation of spontaneous ovulation in rats. Yadira L. López-Ramírez, Kayro López-Ramírez, Isabel Arrieta-Cruz, Angélica Flores, Luciano Mendoza-Garcés, Raúl A. Librado-Osorio, Roger Gutiérrez-Juárez, Roberto Domínguez, and María Esther Cruz Copyright © 2017 Yadira L. López-Ramírez et al. All rights reserved. Expression of Somatostatin Receptor 2 in Somatotropinoma Correlated with the Short-Term Efficacy of Somatostatin Analogues Wed, 15 Mar 2017 00:00:00 +0000 The expression of somatostatin receptor subtypes (SSTRs) in pituitary growth hormone- (GH-) secreting adenomas may predict the response to somatostatin analogues (SSA). Our aim was to evaluate the value of the immunohistochemical (IHC) scores of 2 subtypes, SSTR2 and SSTR5, in predicting the short-term efficacy of SSA therapy in patients with active acromegaly. Ninety-three newly diagnosed acromegalic patients were included in our study. These patients were categorized into either a SSA-pretreated group (SA, ) or a direct-surgery group (DS, ), depending on whether or not presurgical SSA treatment was received. IHC analysis, using a 12-grade scoring system, with rabbit monoclonal antibodies against SSTR2 and SSTR5, was performed on all adenoma tissues. The reduction of GH, IGF-1, and tumor size after treatment with SSA for 3 months was measured. Compared with that in the DS group, SSTR2 expression was lower in the SA group. Additionally, in the SA group, SSTR2 expression was positively correlated with the reduction of IGF-1 and tumor volume. However, there was no correlation between the SSTR5 score and the efficacy of SSA. In conclusion, the protein expression of SSTR2, but not of SSTR5, is a valuable indicator in predicting biochemical and tumor size response to short-term SSA treatment in acromegalic patients. Wenjuan Liu, Lina Xie, Min He, Ming Shen, Jingjing Zhu, Yeping Yang, Meng Wang, Ji Hu, Hongying Ye, Yiming Li, Yao Zhao, and Zhaoyun Zhang Copyright © 2017 Wenjuan Liu et al. All rights reserved. Metabolic Syndrome in People Living with Human Immunodeficiency Virus: An Assessment of the Prevalence and the Agreement between Diagnostic Criteria Tue, 14 Mar 2017 00:00:00 +0000 Objectives. We determined metabolic syndrome (MetS) prevalence and assessed the agreement between different diagnostic criteria in HIV-infected South Africans. Method. A random sample included 748 HIV-infected adult patients (79% women) across 17 HIV healthcare facilities in the Western Cape Province. MetS was defined using the Joint Interim Statement (JIS 2009), International Diabetes Federation (IDF 2005), and Adult Treatment Panel III (ATPIII 2005) criteria. Results. Median values were 38 years (age), 5 years (diagnosed HIV duration), and 392 cells/mm3 (CD4 count), and 93% of the participants were on antiretroviral therapy (ART). MetS prevalence was 28.2% (95%CI: 25–31.4), 26.5% (23.3–29.6), and 24.1% (21–27.1) by the JIS, IDF, and ATPIII 2005 criteria, respectively. Prevalence was always higher in women than in men (all ), in participants with longer duration of diagnosed HIV (all ), and in ART users not receiving 1st-line regimens (all ). The agreement among the three criteria was very good overall and in most subgroups (all ). Conclusions. The three most popular diagnostic criteria yielded similarly high MetS prevalence in this relatively young population receiving care for HIV infection. Very good levels of agreement between criteria are unaffected by some HIV-specific features highlighting the likely comparable diagnostic utility of those criteria in routine HIV care settings. Kim Anh Nguyen, Nasheeta Peer, Anniza de Villiers, Barbara Mukasa, Tandi E. Matsha, Edward J. Mills, and Andre Pascal Kengne Copyright © 2017 Kim Anh Nguyen et al. All rights reserved. Cholesterol Synthesis Increased in the MMI-Induced Subclinical Hypothyroidism Mice Model Sun, 12 Mar 2017 10:02:58 +0000 Subclinical hypothyroidism (SCH) is defined as increased serum thyroid-stimulating hormone (TSH) concentrations and normal serum thyroid hormone (TH) levels as well as an increased serum cholesterol level, which is an important cause of secondary hypercholesterolemia and cardiovascular diseases. Some studies have demonstrated a direct effect of TSH on cholesterol metabolism via in vivo and in vitro experiments. However, because no suitable SCH model has been established until now, the changes in cholesterol synthesis that occur in SCH patients remain unknown. Here, we establish an SCH mouse model by using long-term low-dose MMI administered in drinking water. Compared with the control group, the MMI-treated mice had elevated circulating TSH levels, but the serum FT3 levels in these mice did not change. Additionally, the TC levels increased in both the serum and liver of the experimental mice. Both the protein expression and activity of hepatic HMGCR, the rate-limiting enzyme for cholesterol synthesis in the liver, increased in these mice. We also found that the SCH mice had decreased phospho-HMGCR and phospho-AMPK expression, while the expression of AMPK showed no change. In conclusion, we established a suitable SCH model in which cholesterol synthesis is increased. Yongfeng Song, Xiujuan Zhang, Wenbin Chen, and Ling Gao Copyright © 2017 Yongfeng Song et al. All rights reserved.