International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Glycemic Control in Kenyan Children and Adolescents with Type 1 Diabetes Mellitus Thu, 01 Oct 2015 11:44:28 +0000 Background. Type 1 diabetes mellitus (T1DM) is the most common endocrine disorder in children and adolescents worldwide. While data about prevalence, treatment, and complications are recorded in many countries, few data exist for Sub-Saharan Africa. The aim of this study was to determine the degree of control in patients with T1DM aged 1–19 years over a 6-month period in 3 outpatient Kenyan clinics. It also sought to determine how control was influenced by parameters of patient and treatment. Methods. Eighty-two children and adolescents with T1DM were included in the study. Clinical history regarding duration of illness, type and dose of insulin, and recent symptoms of hypoglycemia/hyperglycemia were recorded. Glycaemia, HbA1c, and ketonuria were tested. HbA1c of 8.0% and below was defined as the cut-off for acceptable control. Results. The median HbA1c for the study population was 11.1% (range: 6.3–18.8). Overall, only 28% of patients had reasonable glycemic control as defined in this study. 72% therefore had poor control. It was also found that age above 12 years was significantly associated with poor control. Conclusions. African children and with T1DM are poorly controlled particularly in adolescents. Our data strongly support the necessity of Kenya children to receive more aggressive management and follow-up. Thomas Ngwiri, Fred Were, Barbara Predieri, Paul Ngugi, and Lorenzo Iughetti Copyright © 2015 Thomas Ngwiri et al. All rights reserved. Reported Diabetes Mellitus Prevalence Rates in the Colombia Healthcare System from 2009 to 2012: Analysis by Regions Using Data of the Official Information Sources Thu, 01 Oct 2015 06:52:22 +0000 The objective of this study was to describe the reported diabetes mellitus (DM) prevalence rates of the 20–79-year-old population in Colombia from 2009 to 2012 reported by the healthcare system. Information on number of patients treated for DM was obtained by the Integral Information System of Social Protection (SISPRO), the registry of the Ministry of Health and Social Protection, and the High Cost Account (CAC), an organization to trace high expenditure diseases. From both sources age-standardized reported DM prevalence rates per 100.000 inhabitants from 2009 to 2012 were calculated. Whereas the reported DM prevalence rates of SISPRO revealed an increase from 964/100.000 inhabitants (2009) to 1398/100.000 inhabitants in 2012 (mean annual increase 141/100.000; p value: 0.001), the respective rates in the CAC register were 1082/100.000 (2009) and 1593/100.000 in 2012 (mean annual increase 165/100.000; p value: 0.026). The number of provinces reporting not less than 19% of the highest national reported DM prevalence rates (1593/100.000) increased from two in 2009 to ten in 2012. Apparently, the registries and the information retrieving system have been improved during 2009 and 2012, resulting in a greater capacity to identify and report DM cases by the healthcare system. Noël C. Barengo and Diana Carolina Tamayo Copyright © 2015 Noël C. Barengo and Diana Carolina Tamayo. All rights reserved. A Retrospective Analysis of the Relationship between Ethnicity, Body Mass Index, and the Diagnosis of Gestational Diabetes in Women Attending an Australian Antenatal Clinic Thu, 01 Oct 2015 06:46:00 +0000 Purpose. To estimate the prevalence of gestational diabetes mellitus (GDM) in a multiethnic population, assess the association between country of birth (COB) and GDM, and assess whether the association varies by body mass index (BMI). Methods. A retrospective study of 5260 pregnant women attending Sunshine Hospital, Australia, between 1st July 2012 and 30th June 2013. We fitted logistic regression models to assess the association between COB and GDM. An interaction between BMI and COB was assessed by likelihood ratio test. Results. In the 4610 included in our analysis, most common were women born in Australia or New Zealand (ANZ, 1932, 41.9%) and in Southeast Asia (922, 20%). GDM was diagnosed in 606 (13.2%) women. After adjusting for confounders, women from East Asia were most likely to develop GDM (37, 24.0%) and 5-fold more likely than women from ANZ (OR = 4.77, 95% CI: 3.12, 7.31, ). Women from other Asian countries had a 3-fold increased risk of GDM compared to women from ANZ. There was no evidence of an interaction by BMI .  Conclusions. Women born in Asia have higher risk of GDM compared to women born in ANZ. These data provide support for including COB in GDM management policies. Rebecca McDonald, Amalia Karahalios, Thao Le, and Joanne Said Copyright © 2015 Rebecca McDonald et al. All rights reserved. Diabetes Burden in Urban and Rural Senegalese Populations: A Cross-Sectional Study in 2012 Wed, 30 Sep 2015 17:35:44 +0000 Diabetes represents a challenging global health issue in the 21st century. Data from sub-Saharan African populations are scarce and are usually restricted to urban settings. The objective of this study was to compare prevalence and risk factors of diabetes in rural and urban areas in Senegal. Methods. In a community-based survey between January and May 2012, we included 1027 adults aged 18 years living in northern Senegal. Sociodemographic, clinical, and biological data were collected during household visits. Multivariate logistic regression was performed to identify factors associated with diabetes. Results. Mean age of participants was years and 65.7% were female. Participants from urban area represented 55.7%. The age-standardized prevalence of diabetes was 7.6% (6.0% in men versus 9.0% in women). Prevalence of diabetes was higher in urban areas (8.1%) compared to rural areas (4.6%). Disease awareness rate was 43%. After multivariate analysis, age (OR = 1.63, ), familial history of diabetes (OR = 1.42, ), and abdominal obesity (OR = 1.17, ) were associated with diabetes. Conclusion. Diabetes is frequent in urban and rural areas in Senegal. Awareness rate is very low among populations. Age, family history of diabetes, and abdominal obesity are the main risk factors identified. S. M. Seck, D. G. Dia, D. Doupa, A. Diop-Dia, I. Thiam, M. Ndong, and L. Gueye Copyright © 2015 S. M. Seck et al. All rights reserved. Serum Bisphenol A Level in Boys with Cryptorchidism: A Step to Male Infertility? Mon, 28 Sep 2015 13:04:12 +0000 Cryptorchidism is the most common congenital birth defect in boys and affects about 2–4% full-term male neonates. Its etiology is multifactorial. Purpose. To evaluate the serum bisphenol A (BPA) levels in boys with cryptorchidism and healthy boys and to assess the risk of environmental exposure to BPA using the authors’ questionnaire. The data were acquired from a study on boys with cryptorchidism () and a control group (). Prior to surgery, all patients had BPA serum levels evaluated. The size, position, rigidity of the testis, and abnormality of the epididymis of the undescended testis were assessed. Parents also completed a questionnaire on the risks of exposure to BPA in everyday life. Results. The testes in both groups were similar in size. The turgor of the undescended testis in the group of boys with cryptorchidism was decreased. Free serum BPA level in cryptorchid boys and in the control group was not statistically significant (). The conjugated serum BPA level in cryptorchid boys and in the control group was statistically significant (). Total serum BPA level in cryptorchid boys and in the control group was statistically significant (). Serum total BPA level was related with a positive answer about problems with conception (). Conclusion. Our study indicated that high serum BPA was associated with cryptorchidism. Marta Diana Komarowska, Adam Hermanowicz, Urszula Czyzewska, Robert Milewski, Ewa Matuszczak, Wojciech Miltyk, and Wojciech Debek Copyright © 2015 Marta Diana Komarowska et al. All rights reserved. Sex/Gender Differences in Metabolism and Behavior: Influence of Sex Chromosomes and Hormones Mon, 28 Sep 2015 12:11:05 +0000 Haifei Shi, Lynda M. Brown, and Roshanak Rahimian Copyright © 2015 Haifei Shi et al. All rights reserved. Regulation of Estrogen Receptor α Expression in the Hypothalamus by Sex Steroids: Implication in the Regulation of Energy Homeostasis Sun, 27 Sep 2015 13:26:18 +0000 Sex differences exist in the complex regulation of energy homeostasis that utilizes central and peripheral systems. It is widely accepted that sex steroids, especially estrogens, are important physiological and pathological components in this sex-specific regulation. Estrogens exert their biological functions via estrogen receptors (ERs). ERα, a classic nuclear receptor, contributes to metabolic regulation and sexual behavior more than other ER subtypes. Physiological and molecular studies have identified multiple ERα-rich nuclei in the hypothalamus of the central nervous system (CNS) as sites of actions that mediate effects of estrogens. Much of our understanding of ERα regulation has been obtained using transgenic models such as ERα global or nuclei-specific knockout mice. A fundamental question concerning how ERα is regulated in wild-type animals, including humans, in response to alterations in steroid hormone levels, due to experimental manipulation (i.e., castration and hormone replacement) or physiological stages (i.e., puberty, pregnancy, and menopause), lacks consistent answers. This review discusses how different sex hormones affect ERα expression in the hypothalamus. This information will contribute to the knowledge of estrogen action in the CNS, further our understanding of discrepancies in correlation of altered sex hormone levels with metabolic disturbances when comparing both sexes, and improve health issues in postmenopausal women. Xian Liu and Haifei Shi Copyright © 2015 Xian Liu and Haifei Shi. All rights reserved. Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis Sun, 27 Sep 2015 13:05:37 +0000 The liver is one of the most essential organs involved in the regulation of energy homeostasis. Hepatic steatosis, a major manifestation of metabolic syndrome, is associated with imbalance between lipid formation and breakdown, glucose production and catabolism, and cholesterol synthesis and secretion. Epidemiological studies show sex difference in the prevalence in fatty liver disease and suggest that sex hormones may play vital roles in regulating hepatic steatosis. In this review, we summarize current literature and discuss the role of estrogens and androgens and the mechanisms through which estrogen receptors and androgen receptors regulate lipid and glucose metabolism in the liver. In females, estradiol regulates liver metabolism via estrogen receptors by decreasing lipogenesis, gluconeogenesis, and fatty acid uptake, while enhancing lipolysis, cholesterol secretion, and glucose catabolism. In males, testosterone works via androgen receptors to increase insulin receptor expression and glycogen synthesis, decrease glucose uptake and lipogenesis, and promote cholesterol storage in the liver. These recent integrated concepts suggest that sex hormone receptors could be potential promising targets for the prevention of hepatic steatosis. Minqian Shen and Haifei Shi Copyright © 2015 Minqian Shen and Haifei Shi. All rights reserved. Sodium Valproate Enhances the Urethane-Induced Lung Adenomas and Suppresses Malignization of Adenomas in Ovariectomized Female Mice Sun, 27 Sep 2015 12:59:22 +0000 In the present study, the possible effect of sodium valproate (NaVP) on urethane-induced lung tumors in female mice has been evaluated. BALB/c mice (; 4–6 weeks old, females) were used in the following groups: (1) urethane-treated; (2) urethane-NaVP-treated; (3) only NaVP-treated; (4) control. In the same groups, ovariectomized female mice () were investigated. Urethane was given intraperitoneally, with a total dose of 50 mg/mouse. In NaVP-treated mice groups, 0.4% aqueous solution of NaVP was offered to mice ad libitum. The duration of the experiment was 6 months. The number of tumors per mouse in ovariectomized mice and in those treated with urethane and NaVP was significantly higher than in mice treated with urethane only ( versus , ). No significant difference in the number of tumors per mouse was revealed while comparing the nonovariectomized urethane- and urethane-NaVP-treated groups (). A significant decrease of adenocarcinoma number in ovariectomized mice treated with a urethane-NaVP as compared with ovariectomized mice treated with urethane only was found (). NaVP together with low estrogen may have a protective effect on the malignization of adenomas in ovariectomized mice. Donatas Stakisaitis, Raminta Mozuraite, Nomeda Juodziukyniene, Janina Didziapetriene, Saule Uleckiene, Paulius Matusevicius, and Angelija Valanciute Copyright © 2015 Donatas Stakisaitis et al. All rights reserved. A Role for Estrogen in Schizophrenia: Clinical and Preclinical Findings Sun, 27 Sep 2015 12:52:48 +0000 Gender differences in schizophrenia have been extensively researched and it is being increasingly accepted that gonadal steroids are strongly attributed to this phenomenon. Of the various hormones implicated, the estrogen hypothesis has been the most widely researched one and it postulates that estrogen exerts a protective effect by buffering females against the development and severity of the illness. In this review, we comprehensively analyse studies that have investigated the effects of estrogen, in particular 17β-estradiol, in clinical, animal, and molecular research with relevance to schizophrenia. Specifically, we discuss the current evidence on estrogen dysfunction in schizophrenia patients and review the clinical findings on the use of estradiol as an adjunctive treatment in schizophrenia patients. Preclinical research that has used animal models and molecular probes to investigate estradiol’s underlying protective mechanisms is also substantially discussed, with particular focus on estradiol’s impact on the major neurotransmitter systems implicated in schizophrenia, namely, the dopamine, serotonin, and glutamate systems. Andrea Gogos, Alyssa M. Sbisa, Jeehae Sun, Andrew Gibbons, Madhara Udawela, and Brian Dean Copyright © 2015 Andrea Gogos et al. All rights reserved. 17β Estradiol Modulates Perfusion Pressure and Expression of 5-LOX and CYP450 4A in the Isolated Kidney of Metabolic Syndrome Female Rats Sun, 27 Sep 2015 12:49:15 +0000 Prevalence of metabolic syndrome and progression of nephropathy depend on sex. We examined a protective effect of estradiol against nephropathy in metabolic syndrome through the modulation of the arachidonic acid metabolism by activating the 5-lipoxygenase and cytochrome p450 4A pathways. 28 female Wistar rats were divided into four groups of seven animals each: control, intact metabolic syndrome, ovariectomized metabolic syndrome, and metabolic syndrome ovariectomized plus estradiol. Blood pressure, body weight, body fat, triglycerides, insulin, HOMA-index, albuminuria, and TNF- were increased in ovariectomized metabolic syndrome rats (). The perfusion pressure in isolated kidneys of ovariectomized metabolic syndrome rats in presence of 4 g of arachidonic acid was increased. The inhibitors of the arachidonic acid metabolism Baicalein, Miconazole, and Indomethacin in these rats decreased the perfusion pressure by 57.62%, 99.83%, and 108.5%, respectively and they decreased creatinine clearance and the arachidonic acid percentage. Phospholipase A2 expression in the kidney of ovariectomized metabolic syndrome rats was not modified. 5-lipoxygenase was increased in metabolic syndrome ovariectomized rats while cytochrome p450 4A was decreased. In conclusion, the loss of estradiol increases renal damage while the treatment with estradiol benefits renal function by modulating arachidonic acid metabolism through the 5-lipoxygenase and cytochrome p450 4A pathways. A. M. Zúñiga-Muñoz, V. Guarner Lans, E. Soria-Castro, E. Diaz-Diaz, R. Torrico-Lavayen, E. Tena-Betancourt, and I. Pérez-Torres Copyright © 2015 A. M. Zúñiga-Muñoz et al. All rights reserved. Role of Sex Hormones in the Development and Progression of Hepatitis B Virus-Associated Hepatocellular Carcinoma Sun, 27 Sep 2015 10:56:10 +0000 Infection with hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC) in developed countries. Epidemiological reports indicate that the incidence of HBV-related HCC is higher in males and postmenopausal females than other females. Increasing evidence suggests that sex hormones such as androgens and estrogens play an important role in the progression of an HBV infection and in the development of HBV-related HCC. While androgen is supposed to stimulate the androgen signaling pathway and cooperate to the increased transcription and replication of HBV genes, estrogen may play a protecting role against the progression of HBV infections and in the development of HBV-related HCC through decreasing HBV RNA transcription and inflammatory cytokines levels. Additionally, sex hormones can also affect HBV-related hepatocarcinogenesis by inducing epigenetic changes such as the regulation of mRNA levels by microRNAs (miRNAs), DNA methylation, and histone modification in liver tissue. This review describes the molecular mechanisms underlying the gender disparity in HBV-related HCC with the aim of improving the understanding of key factors underneath the sex disparity often observed in HBV infections. Furthermore, the review will propose more effective prevention strategies and treatments of HBV-derived diseases. Maurizio Montella, Giovanni D’Arena, Anna Crispo, Mario Capunzo, Flavia Nocerino, Maria Grimaldi, Antonio Barbieri, Anna Maria D’Ursi, Mario Felice Tecce, Alfonso Amore, Massimiliano Galdiero, Gennaro Ciliberto, and Aldo Giudice Copyright © 2015 Maurizio Montella et al. All rights reserved. Male Osteoporosis in the Elderly Sun, 20 Sep 2015 11:33:05 +0000 Osteoporosis is now recognized as an important public health problem in elderly men as fragility fractures are complicated by increased morbidity, mortality, and social costs. This review comprises an overview of recent findings in pathophysiology, diagnosis, and treatment of male osteoporosis, with particular regard to the old population. Patrizia D’Amelio and Giovanni Carlo Isaia Copyright © 2015 Patrizia D’Amelio and Giovanni Carlo Isaia. All rights reserved. Methylation of the Corticotropin Releasing Hormone Gene Promoter in BeWo Cells: Relationship to Gene Activity Thu, 17 Sep 2015 13:16:32 +0000 Corticotropin releasing hormone (CRH) production by the human placenta increases exponentially as pregnancy advances, and the rate of increase predicts gestational length. CRH gene expression is regulated by cAMP in trophoblasts through a cyclic AMP-response element (CRE), which changes its transcription factor binding properties upon methylation. Here we determined whether methylation of the CRH proximal promoter controls basal and cAMP-stimulated CRH expression in BeWo cells, a well-characterized trophoblastic cell line. We treated the cells with 8-Br-cAMP and the DNA methyltransferase inhibitor 5-aza-2′ deoxycytidine (5-AZA-dC) and determined the effects on CRH mRNA level and promoter methylation. Clonal bisulfite sequencing showed partial and allele independent methylation of CpGs in the CRH promoter. CRH mRNA expression and the methylation of a subset of CpGs (including CpG2 in the CRE) increased spontaneously during culture. 8-Br-cAMP stimulated CRH expression without affecting the increase in methylation. 5-AZA-dC decreased methylation and augmented 8-Br-cAMP-stimulated CRH expression, but it blocked the spontaneous increase of CRH mRNA level. We conclude that the CRH promoter is a dynamically and intermediately methylated genomic region in BeWo cells. Promoter methylation did not inhibit CRH gene expression under the conditions employed; rather it determined the contribution of alternative cAMP-independent pathways and cAMP-independent mechanisms to CRH expression control. Xin Pan, Maria Bowman, Rodney J. Scott, John Fitter, Richard C. Nicholson, Roger Smith, and Tamas Zakar Copyright © 2015 Xin Pan et al. All rights reserved. Comorbidity between Type 2 Diabetes and Depression in the Adult Population: Directions of the Association and Its Possible Pathophysiological Mechanisms Thu, 17 Sep 2015 11:35:15 +0000 Type 2 diabetes and depression are regarded as comorbid conditions, and three possible directions of the association between the diseases can underlie this observation of comorbidity. First, common etiology can increase a person’s risk of both diseases; second, persons with type 2 diabetes have increased prevalence or risk of future development of depression; or third, persons with depression have increased prevalence or risk of development of type 2 diabetes. This review gives an overview over possible pathophysiological mechanisms for each of the directions of the association between type 2 diabetes and depression and further discusses epigenetics as an additional, direction independent approach. We argue that unspecific pathophysiological mechanisms involved in the stress response might, at least to some extent, explain each of the directions of the association between type 2 diabetes and depression, while changes in brain structure and function among persons with diabetes and possible increased risk of development of type 2 diabetes after use of antidepressant agents could represent more disease specific mechanisms underlying the comorbidity. Line Iden Berge and Trond Riise Copyright © 2015 Line Iden Berge and Trond Riise. All rights reserved. Role of Paricalcitol in Modulating the Immune Response in Patients with Renal Disease Tue, 15 Sep 2015 10:14:32 +0000 Introduction. The aim was to highlight the existence of a relationship between vitamin D deficiency, chronic inflammation, and proteinuria, by measuring neutrophil gelatinase associated lipocalin (NGAL) and common inflammatory markers after administration of paricalcitol, a vitamin D analog, in vivo and in vitro. Methods. 40 patients with end-stage chronic kidney disease (CKD) and secondary hyperparathyroidism and 40 healthy subjects were enrolled. Serum calcium, phosphorus, 25(OH)-vitamin D, parathyroid hormone (PTH), erythrocyte sedimentation rate, high-sensitivity C-reactive protein, interleukin- (IL-) 17, IL-6, IL-1β, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), plasmatic and urinary NGAL, and 24 h albuminuria and proteinuria were measured before and 24 h after an intravenous bolus of paricalcitol (5 mcg). Human peripheral blood mononuclear cells were isolated and stimulated with phytohaemagglutinin. NGAL, IL-1β, IL-17, IL-6, TNF-α, and IFN-γ were measured in the culture medium and in the 24 h urine collection. Results. 25(OH)-vitamin D was lower in CKD than in controls (), while inflammatory markers were higher in CKD group (). In vivo and in vitro studies showed a downregulation of NGAL, IL-17, IL-6, IL-1β, TNF-α, and IFN-γ after paricalcitol administration (). Conclusions. 25(OH)-vitamin D regulates immune and inflammatory processes. Further studies are needed to confirm these data in order to improve the treatment of CKD patients. Silvia Lucisano, Adriana Arena, Giovanna Stassi, Daniela Iannello, Gaetano Montalto, Adolfo Romeo, Giuseppe Costantino, Rosaria Lupica, Valeria Cernaro, Domenico Santoro, and Michele Buemi Copyright © 2015 Silvia Lucisano et al. All rights reserved. Radioguided Parathyroidectomy with Portable Mini Gamma-Camera for the Treatment of Primary Hyperparathyroidism Tue, 15 Sep 2015 10:06:30 +0000 Background. A proper localisation of pathological parathyroid glands is essential for a minimally invasive approach in the surgical treatment of primary hyperparathyroidism (PHP). The recent introduction of portable mini gamma-cameras (pMGCs) enabled intraoperative scintigraphic scanning. The aim of our study is to evaluate the efficacy of this new method and compare it with the preoperative localisation surveys. Methods. 20 patients were studied; they were evaluated preoperatively by neck ultrasound and -sestaMIBI-scintigraphy and intraoperatively with the pMGC IP Guardian 2. The results obtained from the three evaluations were compared. Results. The pMGC presented a sensitivity of 95%, a specificity of 98.89%, and a diagnostic accuracy of 98.18%, which were higher than those of preoperative ultrasound (sensitivity 55%; specificity 95%; diagnostic accuracy 87%) and scintigraphy with -sestaMIBI (sensitivity 73.68%; specificity 96.05%; diagnostic accuracy 91.58%). Conclusions. The pMGC can be used effectively as an intraoperative method to find the correct location of the pathological parathyroid glands. The pMGC is more reliable than the currently used preoperative and intraoperative localisation techniques. Claudio Casella, Pierluigi Rossini, Carlo Cappelli, Chiara Nessi, Riccardo Nascimbeni, and Nazario Portolani Copyright © 2015 Claudio Casella et al. All rights reserved. Effects of a Short Educational Program for the Prevention of Foot Ulcers in High-Risk Patients: A Randomized Controlled Trial Thu, 10 Sep 2015 14:00:57 +0000 Background. Patient education is capable of reducing the risk for diabetic foot ulcers. However, specific education on foot ulcer prevention was either included in broader programs addressing different parts of diabetes care or provided with time- and resource-consuming curricula. The aim of the study is to assess the feasibility and efficacy of a brief educational program for the prevention of diabetic foot ulcers in high-risk patients. Methods. The study was performed on type 2 diabetic patients, randomized in a 1 : 1 ratio either to intervention or to control group. The principal endpoint was the incidence of foot ulcers. The intervention was a two-hour program provided to groups of 5–7 patients, including a 30-minute face-to-face lesson on risk factors for foot ulcers, and a 90-minute interactive session with practical exercises on behaviors for reducing risk. Results. The study was prematurely terminated due to a highly significant difference in outcome between the two treatment groups. The final sample was therefore composed of 121 patients. Six patients, all in the control group, developed ulcers during the 6-month follow-up (10% versus 0%, ). Conclusions. A brief, 2-hour, focused educational program is effective in preventing diabetic foot ulcers in high-risk patients. Matteo Monami, Stefania Zannoni, Marianna Gaias, Besmir Nreu, Niccolò Marchionni, and Edoardo Mannucci Copyright © 2015 Matteo Monami et al. All rights reserved. Expression of Intratumoral IGF-II Is Regulated by the Gene Imprinting Status in Triple Negative Breast Cancer from Vietnamese Patients Thu, 10 Sep 2015 06:49:35 +0000 African American women suffer higher incidence and mortality of triple negative breast cancer (TNBC) than Caucasian women. TNBC is very aggressive, causing the worst clinical outcome. We previously demonstrated that tumors from these patients express high IGF-II and exhibit high activation of the IGF signaling pathways. IGF-II gene expression is imprinted (monoallelic), promotes tumor progression, and metastasis and regulates Survivin, a TNBC prognostic marker. Since BC mortality has increased among young Vietnamese women, we analyzed 48 (paired) TNBC samples from Vietnamese patients to assess IGF-II expression. We analyzed all samples by qrtPCR for identification of IGF-II heterozygosity and to determine allelic expression of the IGF-II gene. We also analyzed the tissues for proIGF-II and Survivin by RT-PCR and Western blotting. A total of 28 samples displayed IGF-II heterozygosity of which 78% were biallelic. Tumors with biallelic IGF-II gene expression exhibited the highest levels of proIGF-II and Survivin. Although 100% of these tissues corresponding normal samples were biallelic, they expressed significantly lower levels of or no proIGF-II and Survivin. Thus, IGF-II biallelic gene expression is differentially regulated in normal versus tumor tissues. We propose that intratumoral proIGF-II is dependent on the IGF-II gene imprinting status and it will promote a more aggressive TNBC. Vinodh Kumar Radhakrishnan, Lorraine Christine Hernandez, Kendra Anderson, Qianwei Tan, Marino De León, and Daisy D. De León Copyright © 2015 Vinodh Kumar Radhakrishnan et al. All rights reserved. The Age-Specific Association of Waist Circumference and Risk of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus in Shandong, China Wed, 09 Sep 2015 06:31:07 +0000 Objective. To examine the association of three most common obesity measures including body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with chronic kidney disease (CKD) risk in patients with type 2 diabetes mellitus (T2D). Design. Cross-sectional evaluation of the effect of anthropometric measures on CKD risk. Setting. Outpatient Department. Subjects. T2D patients who were treated between October 2012 and May 2013. Intervention. None. Main Outcome Measure. CKD risk. Results. On average, the patients had a mean age of 60.2 years, and 40% were males. CKD was present in 46% of all the patients. In multivariate logistic regression using the imputed data, higher WC was associated with greater odds of CKD (OR = 1.019, 95% CI = 1.002–1.006, ), but not BMI and WHR. Interestingly, we found that patients with very small WC seemed to have greater odds of CKD. We observed age-specific effect of WC such that the effect of WC on CKD risk is significant only in middle-aged T2D patients. Conclusion. Our study provides evidence for the association of WC with CKD in Chinese patients with T2D. T2D patients, especially middle-aged T2D patients, should reduce their WC to decrease CKD risk. Lingling Xu, Weihong Yu, Ping Huang, Chunying Li, Yan Li, Meng Wang, Qun Xu, Jing Wang, Caixia Zheng, Bin Qu, Yanping Zhao, Meng Niu, Ou Wang, and Fengying Gong Copyright © 2015 Lingling Xu et al. All rights reserved. Switching from Twice-Daily Basal Insulin Injections to Once-Daily Insulin Degludec Injection for Basal-Bolus Insulin Regimen in Japanese Patients with Type 1 Diabetes: A Pilot Study Mon, 07 Sep 2015 11:59:26 +0000 The aim of this study was to investigate the efficacy of insulin degludec used for basal-bolus insulin regimen after switching from twice-daily basal insulin in Japanese patients with type 1 diabetes mellitus. The subjects were 22 type 1 diabetes patients treated with basal-bolus insulin regimen with twice-daily basal insulin. Basal insulin was switched to once-daily injection of insulin degludec with 10% dose reduction. HbA1c and fasting plasma glucose (FPG) were measured before and 12 weeks after switching. The frequency of hypoglycemic episodes, standard deviation (SD) of blood glucose, and mean of daily difference (MODD) were evaluated by continuous glucose monitoring (CGM) before and 4 weeks after switching. HbA1c and FPG before and 12 weeks after switching were comparable (HbA1c 8.5 ± 1.4 versus 8.7 ± 1.6%, ; FPG 203.2 ± 81.2 versus 206.5 ± 122.4 mg/dL, ). The frequency of hypoglycemia during nighttime was not significantly different at 4 weeks after switching (14.4 ± 17.0 versus 11.1 ± 15.0%, ). In addition, SD and MODD before and 4 weeks after switching were also comparable. In conclusion, glycemic control under once-daily insulin degludec injection was almost comparable to that under twice-daily basal insulin injections in Japanese type 1 diabetes patients. This study was registered with ID: UMIN000010474. Yuka Tosaka, Akio Kanazawa, Fuki Ikeda, Mayu Iida, Junko Sato, Kazuhisa Matsumoto, Toyoyoshi Uchida, Yoshifumi Tamura, Takeshi Ogihara, Tomoya Mita, Tomoaki Shimizu, Hiromasa Goto, Chie Ohmura, Yoshio Fujitani, and Hirotaka Watada Copyright © 2015 Yuka Tosaka et al. All rights reserved. Thyroid Dysfunction and Associated Risk Factors among Nepalese Diabetes Mellitus Patients Mon, 07 Sep 2015 08:16:45 +0000 Objectives. To assess thyroid function and associated risk factors in Nepalese diabetes mellitus patients. Methods. A cross-sectional study was carried out among 419 diabetes mellitus patients at B. P. Koirala Institute of Health Sciences, Dharan, Nepal. Information on demographic and anthropometric variables and risk factors for thyroid dysfunction was collected. Blood samples were analysed to measure thyroid hormones, blood sugar, and lipid profile. Results. Prevalence rate of thyroid dysfunction was 36.03%, with subclinical hypothyroidism (26.5%) as the most common thyroid dysfunction. Thyroid dysfunction was much common in females (42.85%) compared to males (30.04%) and in type 1 diabetes (50%) compared to type 2 diabetes mellitus (35.41%) . Diabetic patients with thyroid dysfunction had higher total cholesterol, HDL cholesterol, and LDL cholesterol in comparison to patients without thyroid dysfunction. Significant risk factors for thyroid dysfunction, specifically hypothyroidism (overt and subclinical), were smoking (relative risk of 2.56 with 95% CI (1.99–3.29, )), family history of thyroid disease (relative risk of 2.57 with 95% CI (2.0–3.31, )), and female gender (relative risk of 1.44 with 95% CI (1.09–1.91, )). Conclusions. Thyroid dysfunction is common among Nepalese diabetic patients. Smoking, family history of thyroid disease, and female gender are significantly associated with thyroid dysfunction. Saroj Khatiwada, Rajendra KC, Santosh Kumar Sah, Seraj Ahmed Khan, Rajendra Kumar Chaudhari, Nirmal Baral, and Madhab Lamsal Copyright © 2015 Saroj Khatiwada et al. All rights reserved. Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action Wed, 02 Sep 2015 09:51:44 +0000 In the last decade, ample evidence has demonstrated the growing importance of androgen receptor (AR) CAG repeat polymorphism in andrology. This genetic parameter is able to condition the peripheral effects of testosterone and therefore to influence male sexual function and fertility, cardiovascular risk, body composition, bone metabolism, the risk of prostate and testicular cancer, the psychiatric status, and the onset of neurodegenerative disorders. In this review, we extensively discuss the literature data and identify a role for AR CAG repeat polymorphism in conditioning the systemic testosterone effects. In particular, our main purpose was to provide an updated text able to shed light on the many and often contradictory findings reporting an influence of CAG repeat polymorphism on the targets of testosterone action. Giacomo Tirabassi, Angelo Cignarelli, Sebastio Perrini, Nicola delli Muti, Giorgio Furlani, Mariagrazia Gallo, Francesco Pallotti, Donatella Paoli, Francesco Giorgino, Francesco Lombardo, Loredana Gandini, Andrea Lenzi, and Giancarlo Balercia Copyright © 2015 Giacomo Tirabassi et al. All rights reserved. Low Growth Hormone Levels in Short-Stature Children with Pituitary Hyperplasia Secondary to Primary Hypothyroidism Wed, 02 Sep 2015 08:19:08 +0000 Objective. The follow-up of GH levels in short-stature children with pituitary hyperplasia secondary to primary hypothyroidism (PPH) is reported in a few cases. We aimed to observe changes in GH secretion in short-stature children with PPH. Methods. A total of 11 short-stature children with PPH accompanied by low GH levels were included. They received levothyroxine therapy after diagnosis. Their thyroid hormones, IGF-1, PRL, and pituitary height were measured at baseline and 3 months after therapy. GH stimulation tests were performed at baseline and after regression of thyroid hormones and pituitary. Results. At baseline, they had decreased GH peak and FT3 and FT4 levels and elevated TSH levels. Decreased IGF-1 levels were found in seven children. Elevated PRL levels and positive thyroid antibodies were found in 10 children. The mean pituitary height was  mm. After 3 months, FT3, FT4, and IGF-1 levels were significantly increased (all ), and values of TSH, PRL, and pituitary height were significantly decreased (all ). After 6 months, pituitary hyperplasia completely regressed. GH levels returned to normal in nine children and were still low in two children. Conclusion. GH secretion can be resolved in most short-stature children with PPH. Minghua Liu, Yanyan Hu, Guimei Li, and Wenwen Hu Copyright © 2015 Minghua Liu et al. All rights reserved. Changes in Bone Mineral Density and Metabolic Parameters after Pulsatile Gonadorelin Treatment in Young Men with Hypogonadotropic Hypogonadism Mon, 31 Aug 2015 06:03:58 +0000 To assess the prevalence of osteoporosis in young men with hypogonadotropic hypogonadism (HH) and to investigate the changes of BMD and metabolic parameters, a total of 22 young male patients with HH and 20 healthy controls were enrolled in the study. BMD, biochemical, and hormonal parameters were measured in two groups. Osteoporosis was more prevalent in HH patients (45.45%) than the control subjects (10.00%) (). The patients with HH had lower BMD in lumbar spine 2–4, femoral neck, and total hip (, for all) and higher fasting insulin (), HOMA-IR (), and SHBG () compared to the controls. After 6 months of pulsatile gonadorelin treatment, BMI () and BMD in lumbar spine 2–4, femoral neck, and total hip (, , and , resp.) increased dramatically and total cholesterol (), fasting insulin (), HOMA-IR (), and SHBG () decreased significantly in HH patients. The study shows a higher prevalence of osteoporosis in young men with HH. Long-term pulsatile gonadorelin treatment indicates a positive effect on BMD and metabolic parameters of HH patients. Chen-Xi Li, Song-Tao Tang, and Qiu Zhang Copyright © 2015 Chen-Xi Li et al. All rights reserved. Comparison of Conventional Open Thyroidectomy and Endoscopic Thyroidectomy via Breast Approach for Papillary Thyroid Carcinoma Wed, 26 Aug 2015 07:24:47 +0000 Purpose. The aim of this study was to evaluate the feasibility of endoscopic thyroidectomy via breast approach for papillary thyroid carcinoma (PTC). Methods. Between March 2008 and March 2013, 34 patients with PTC received endoscopic thyroidectomy (endo group) and 30 patients received conventional open thyroidectomy (open group). Patients in two groups underwent ipsilateral central compartment node dissection. The two groups were compared in terms of patient characteristics, perioperative clinical results, and postoperative complication. Results. The rates of lymph node metastasis in endo group and open group were 23.5% (8/34) and 13.3% (4/30), respectively, without statistically significant difference (). The mean number of lymph nodes dissected was 2.4 ± 2.9 in endoscopic group and 2.2 ± 1.9 in open group (). During the follow-up period, there was no recurrence or metastatic patients in two groups. All patients received the excellent cosmetic results in endo group, while 25 patients were satisfied with the cosmetic result and 5 were unsatisfied in the open group. Conclusions. The efficacy of endoscopic thyroidectomy via breast approach could be comparable to conventional open thyroidectomy in selected patients with PTC. Zhuo Tan, JiaLei Gu, QianBo Han, WenDong Wang, KeJing Wang, MingHua Ge, and JinBiao Shang Copyright © 2015 Zhuo Tan et al. All rights reserved. Tumor-Associated Mast Cells in Thyroid Cancer Wed, 26 Aug 2015 07:11:41 +0000 There is compelling evidence that the tumor microenvironment plays a major role in mediating aggressive features of cancer cells, including invasive capacity and resistance to conventional and novel therapies. Among the different cell populations that infiltrate cancer stroma, mast cells (MCs) can influence several aspects of tumor biology, including tumor development and progression, angiogenesis, lymphangiogenesis, and tissue remodelling. Thyroid cancer (TC), the most frequent neoplasia of the endocrine system, is characterized by a MC infiltrate, whose density correlates with extrathyroidal extension and invasiveness. Recent evidence suggests the occurrence of epithelial-to-mesenchymal transition (EMT) and stemness in human TC. The precise role of immune cells and their mediators responsible for these features in TC remains unknown. Here, we review the relevance of MC-derived mediators (e.g., the chemokines CXCL1/GRO-α, CXCL10/IP-10, and CXCL8/IL-8) in the context of TC. CXCL1/GRO-α and CXCL10/IP-10 appear to be involved in the stimulation of cell proliferation, while CXCL8/IL-8 participates in the acquisition of TC malignant traits through its ability to induce/enhance the EMT and stem-like features of TC cells. The inhibition of chemokine signaling may offer novel therapeutic approaches for the treatment of refractory forms of TC. Carla Visciano, Nella Prevete, Federica Liotti, and Gianni Marone Copyright © 2015 Carla Visciano et al. All rights reserved. Mechanisms of Normalisation of Bone Metabolism during Recovery from Hyperthyroidism: Potential Role for Sclerostin and Parathyroid Hormone Sun, 23 Aug 2015 12:12:22 +0000 Sclerostin, a protein expressed by osteocytes, is a negative regulator of bone formation. The aim of the study was to investigate the relationship between parathyroid hormone (PTH) and markers of bone metabolism and changes of sclerostin concentrations before and after treatment of hyperthyroidism. Patients and Methods. The study involved 33 patients (26 women), age (mean ± SD) 48 ± 15 years, with hyperthyroidism. Serum sclerostin, PTH, calcium, and bone markers [osteocalcin (OC) and collagen type I cross-linked C-telopeptide I (CTX)] were measured at diagnosis of hyperthyroidism and after treatment with thiamazole. Results. After treatment of hyperthyroidism a significant decrease in free T3 (FT3) and free T4 (FT4) concentrations was accompanied by marked decrease of serum sclerostin (from 43.7 ± 29.3 to 28.1 ± 18.4 pmol/L; ), OC (from 35.6 ± 22.0 to 27.0 ± 14.3 ng/mL; ), and CTX (from 0.49 ± 0.35 to 0.35 ± 0.23 ng/dL; ), accompanied by an increase of PTH (from 29.3 ± 14.9 to 39.8 ± 19.8; ). During hyperthyroidism there was a positive correlation between sclerostin and CTX (, ) and between OC and thyroid hormones (with FT3  , with FT4  , ). Conclusions. Successful treatment of hyperthyroidism results in a significant decrease in serum sclerostin and bone markers concentrations, accompanied by an increase of PTH. Elżbieta Skowrońska-Jóźwiak, Krzysztof C. Lewandowski, Zbigniew Adamczewski, Kinga Krawczyk-Rusiecka, and Andrzej Lewiński Copyright © 2015 Elżbieta Skowrońska-Jóźwiak et al. All rights reserved. Effect of Repetitive Glucose Spike and Hypoglycaemia on Atherosclerosis and Death Rate in Apo E-Deficient Mice Thu, 20 Aug 2015 12:51:49 +0000 Epidemiological data suggest that postprandial hyperglycaemia and hypoglycaemia are potential risk factors for cardiovascular disease. However, the effects of repetitive postprandial glucose spikes, repetitive hypoglycaemia, and their combination on the progression of atherosclerosis remain largely unknown. The present study investigated the effects of rapid rises and falls in glucose, and their combination, on the progression of atherosclerosis in apolipoprotein (apo) E-deficient mice. In this study, apo E-deficient mice with forced oral administration of glucose twice daily for 15 weeks were used as a model of repetitive postprandial glucose spikes, and apo E-deficient mice given an intraperitoneal injection of insulin once a week for 15 weeks were used as a model of repetitive hypoglycaemia. In addition, we established a model of both repetitive postprandial glucose spikes and hypoglycaemia by combining the above interventions. Atherosclerosis was evaluated in all mice by oil red O staining. Administration of ipragliflozin, a selective inhibitor of sodium-glucose cotransporter 2, in the mouse model of repetitive glucose spikes inhibited the progression of atherosclerosis, whereas long-term repetitive glucose spikes, repetitive hypoglycaemia, and their combination had no significant impact on atherosclerosis. However, repetitive hypoglycaemia was associated with poor survival rate. The results showed that repetitive hypoglycaemia reduces the survival rate without associated progression of atherosclerosis in apo E-deficient mice. Kenichi Nakajima, Tomoya Mita, Yusuke Osonoi, Kosuke Azuma, Toshiyuki Takasu, Yoshio Fujitani, and Hirotaka Watada Copyright © 2015 Kenichi Nakajima et al. All rights reserved. Multiple Factors Related to the Secretion of Glucagon-Like Peptide-1 Thu, 20 Aug 2015 11:53:08 +0000 The glucagon-like peptide-1 is secreted by intestinal L cells in response to nutrient ingestion. It regulates the secretion and sensitivity of insulin while suppressing glucagon secretion and decreasing postprandial glucose levels. It also improves beta-cell proliferation and prevents beta-cell apoptosis induced by cytotoxic agents. Additionally, glucagon-like peptide-1 delays gastric emptying and suppresses appetite. The impaired secretion of glucagon-like peptide-1 has negative influence on diabetes, hyperlipidemia, and insulin resistance related diseases. Thus, glucagon-like peptide-1-based therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) are now well accepted in the management of type 2 diabetes. The levels of glucagon-like peptide-1 are influenced by multiple factors including a variety of nutrients. The component of a meal acts as potent stimulants of glucagon-like peptide-1 secretion. The levels of its secretion change with the intake of different nutrients. Some drugs also have influence on GLP-1 secretion. Bariatric surgery may improve metabolism through the action on GLP-1 levels. In recent years, there has been a great interest in developing effective methods to regulate glucagon-like peptide-1 secretion. This review summarizes the literature on glucagon-like peptide-1 and related factors affecting its levels. XingChun Wang, Huan Liu, Jiaqi Chen, Yan Li, and Shen Qu Copyright © 2015 XingChun Wang et al. All rights reserved.