ISRN Endocrinology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Lipoprotein Ratios as Surrogate Markers for Insulin Resistance in South Indians with Normoglycemic Nondiabetic Acute Coronary Syndrome Sun, 18 May 2014 07:47:39 +0000 Background. Insulin resistance has been associated with dyslipidemia and cardiovascular disease. Even though homeostasis model assessment of insulin resistance (HOMA-IR) is a well-known insulin resistance predictor, estimation of serum lipoprotein ratios has been recently suggested as a surrogate marker for insulin resistance. Here, we evaluated the relationship between lipoprotein ratios and insulin resistance in normoglycemic nondiabetic south Indians with acute coronary syndrome. Methods. 100 normoglycemic nondiabetic ACS patients and 140 controls were enrolled in the study. Levels of fasting glucose, fasting insulin, and lipid profile [total cholesterol (TC), triglycerides (TG), and high density lipoprotein cholesterol (HDL-C)], lipoprotein(a) [Lp(a)] levels were measured and lipoprotein ratios were computed. HOMA-IR was used to calculate the insulin resistance. Receiver operating characteristic curves (ROC) analysis was used to compare the power of these lipoprotein ratios to predict insulin resistance. Results. Lipoprotein ratios were significantly higher in normoglycemic nondiabetic ACS patients, as compared to healthy controls, and were significantly correlated with HOMA-IR by Spearman's rank correlation analysis. ROC curve showed that Lp(a)/HDL-C and TG/HDL-C ratios were the best surrogate predictors of insulin resistance in normoglycemic nondiabetic ACS. Conclusion. This study demonstrates that serum lipoprotein ratios significantly correlate with insulin resistance in normoglycemic nondiabetic ACS. Lp(a)/HDL-C and TG/HDL-C ratios could be used as surrogate markers of insulin resistance in atherosclerosis-prone south Indians with normoglycemic nondiabetic ACS. Medha Rajappa, M. G. Sridhar, J. Balachander, K. R. Sethuraman, and Kalai Selvi Rajendiran Copyright © 2014 Medha Rajappa et al. All rights reserved. Antihyperglycaemic Effect of Tetracarpidium Conophorum Nuts in Alloxan Induced Diabetic Female Albino Rats Tue, 06 May 2014 07:17:12 +0000 The antihyperglycaemic activity of Tetracarpidium conophorum nut (walnut) was investigated in albino rats. A total of 20 albino rats were used for the study. The rats were divided into five groups (A–E) of four rats each. Diabetes were induced in the rats except four which served as the positive control group A. Groups B (negative control), C, D, and E contain diabetic rats each with blood sugar level ≥17.00 mmol/L. Groups A and B were fed on 85.2 g of top feed grower over the test period. Test groups C, D, and E were fed on 21.3 g, 42.6 g, and 85.2 g of walnuts, respectively, and their fasting blood sugar (FBS) levels were checked on daily basis. Fasting blood glucose levels of the test groups were significantly lower than negative control , for 3rd, 7th, and 10th days of the test. There were also significant increase in the body weight and hemoglobin concentration and a decreased urine output of the test group compared with the controls. These results indicate that Tetracarpidium conophorum nut (walnut) has an antihyperglycemic effect in diabetic rats. Donatus Onukwufor Onwuli, Holy Brown, and Harrison Anaezichukwuolu Ozoani Copyright © 2014 Donatus Onukwufor Onwuli et al. All rights reserved. Effect of Aerobic Training on Glucose Control and Blood Pressure in T2DDM East African Males Tue, 04 Mar 2014 11:30:36 +0000 Background. Exercise training intervention is underused in the management of type 2 diabetes mellitus in East Africa. Methods. 41 physically-active males with type 2 diabetes mellitus living in Mozambique were recruited and randomly assigned to 12 weeks of supervised exercise of low intensity exercise (LEX), vigorous intensity exercise (VEX), or to a control group (CON). Since there were no differences for any outcome variables between the exercise groups, VEX and LEX were combined into one exercise group (EX). Results. Age and baseline body weight were similar between EX and CON. Plasma glucose at 120 min following glucose load (Glu 120) was significantly reduced in the EX group after training (Glu 120 : 17.3 mmol/L to 15.0 mmol/L, ), whereas Glu 120 remained unchanged in the CON (Glu 120 : 16.6 mmol/L to 18.7 mmol/L). After controlling for baseline blood pressure (BP), posttraining systolic BP and diastolic BP were lower in the EX group than in the CON group (EX: 129/77 mm Hg, CON: 152/83 mm Hg, ). Conclusion. Adding exercise to already active African men with type 2 diabetes improved glucose control and BP levels without concomitant changes in weight. Huimin Yan, Antonio Prista, Sushant M. Ranadive, Albertino Damasceno, Paula Caupers, Jill A. Kanaley, and Bo Fernhall Copyright © 2014 Huimin Yan et al. All rights reserved. Correlation between Body Mass Index and Waist Circumference in Patients with Metabolic Syndrome Tue, 04 Mar 2014 08:58:41 +0000 Metabolic syndrome is defined as a group of coexisting metabolic risk factors, such as central obesity, lipid disorders, carbohydrate disorders, and arterial hypertension. According to the 2005 IDF criteria, subsequently revised in 2009, abdominal obesity is identified as the waist circumference of ≥80 cm in women and ≥94 cm in men. It is responsible for the development of insulin resistance. The aim of our study was to demonstrate a correlation between waist circumference (WC) and body mass index (BMI) in patients with metabolic syndrome in relation with hypertension, lipid disorders, and carbohydrate disorders. A cross-sectional two-site study was conducted in the Kuyavian-Pomeranian Voivodeship for 24 months. The study group consisted of 839 patients with diagnosed metabolic syndrome: 345 men (41.1%) and 494 women (58.9%) aged 32–80. In the study group, WC was found to be significantly correlated with BMI (R = 0.78, P < 0.01). The presence of overweight in men (BMI 25, 84 kg/m2) and even normal body weight in women (BMI 21,62 kg/m2) corresponds to an increased volume of visceral tissue in the abdomen. Introduction of primary prophylaxis in those people to limit the development of diabetes mellitus type 2 and cardiovascular diseases should be considered. Marcin Gierach, Joanna Gierach, Marlena Ewertowska, Adam Arndt, and Roman Junik Copyright © 2014 Marcin Gierach et al. All rights reserved. Lower Plasma Creatinine and Urine Albumin in Individuals at Increased Risk of Type 2 Diabetes with Factor V Leiden Mutation Tue, 04 Mar 2014 07:18:01 +0000 The factor V Leiden (FVL) mutation is the most frequent genetic cause of venous thrombosis in Caucasians. However, protective effects have been suggested to balance the disadvantages. We have recently observed protective effects of FVL mutation on experimental diabetic nephropathy in mice as well as an association with reduced albuminuria in two human cohorts of diabetic patients. In the present study we aimed to reevaluate these findings in an independent, larger cohort of 1905 Caucasians at risk of developing type 2 diabetes and extend possible associations to earlier disease stages of nephropathy. Carriers of FVL mutation had a significantly lower urine albumin excretion () and tended to have lower plasma creatinine concentrations (). The difference in plasma creatinine concentrations was significant after adjustment for the influencing factors: age, gender, and lean body mass (). These observations at a very early “disease” stage are an important extension of previous findings and suggest that modification of glomerular dysfunction by FVL mutation is relevant during very early stages of diabetic nephropathy. This makes the underlying mechanism an interesting therapeutic target and raises the question whether FVL mutation may also exert protective effects in other glomerulopathies. Andreas Peter, Andreas Fritsche, Fausto Machicao, Peter P. Nawroth, Hans-Ulrich Häring, and Berend Isermann Copyright © 2014 Andreas Peter et al. All rights reserved. Resveratrol Promotes Foot Ulcer Size Reduction in Type 2 Diabetes Patients Thu, 20 Feb 2014 13:01:31 +0000 Objective. The effect of a proprietary formulation of trans-resveratrol (t-RSV) on manifestations of diabetic foot syndrome (DFS) was studied in type 2 diabetic patients with newly diagnosed diabetic foot ulcers. Method. Placebo-controlled, examiner-blinded, parallel-group randomized controlled pilot clinical trial (ACTRN Clinical Trial Registry number 12610000629033) involving 24 patients with DFS (15 males and 9 females, average age of years) divided into the placebo and RSV-treatment groups was performed. 50 mg of t-RSV or placebo capsules was given to each patient twice a day over a 60-day time period. Results. Reduction in the parameters reflecting diabetic ulcer size was more profound in the RSV group as compared to placebo. RSV-treated patients also had a marginally improved performance in the foot pressure test. A statistically significant decline in the plasma fibrinogen level, but not CRP, was also found in the RSV-treated patients. Some improvement in the plasma lipid profile and fasting glucose levels were not related to RSV-treatment, since they have been seen on both the RSV and placebo groups, revealing the effectiveness of medical supervision and education in the newly diagnosed patients with DFS. Conclusion. t-RSV supplementation promotes reduction of the foot ulcer size and reduces plasma fibrinogen level in type 2 diabetic patients. Yuriy K. Bashmakov, Samir H. Assaad-Khalil, Myriam Abou Seif, Ruzan Udumyan, Magdy Megallaa, Kamel H. Rohoma, Mohamed Zeitoun, and Ivan M. Petyaev Copyright © 2014 Yuriy K. Bashmakov et al. All rights reserved. Thyroid Hormone Status Interferes with Estrogen Target Gene Expression in Breast Cancer Samples in Menopausal Women Thu, 20 Feb 2014 07:35:52 +0000 We investigated thyroid hormone levels in menopausal BrC patients and verified the action of triiodothyronine on genes regulated by estrogen and by triiodothyronine itself in BrC tissues. We selected 15 postmenopausal BrC patients and a control group of 18 postmenopausal women without BrC. We measured serum TPO-AB, TSH, FT4, and estradiol, before and after surgery, and used immunohistochemistry to examine estrogen and progesterone receptors. BrC primary tissue cultures received the following treatments: ethanol, triiodothyronine, triiodothyronine plus 4-hydroxytamoxifen, 4-hydroxytamoxifen, estrogen, or estrogen plus 4-hydroxytamoxifen. Genes regulated by estrogen (TGFA, TGFB1, and PGR) and by triiodothyronine (TNFRSF9, BMP-6, and THRA) in vitro were evaluated. TSH levels in BrC patients did not differ from those of the control group (1.34 ± 0.60 versus 2.41 ± 1.10 μU/mL), but FT4 levels of BrC patients were statistically higher than controls (1.78 ± 0.20 versus 0.95 ± 0.16 ng/dL). TGFA was upregulated and downregulated after estrogen and triiodothyronine treatment, respectively. Triiodothyronine increased PGR expression; however 4-hydroxytamoxifen did not block triiodothyronine action on PGR expression. 4-Hydroxytamoxifen, alone or associated with triiodothyronine, modulated gene expression of TNFRSF9, BMP-6, and THRA, similar to triiodothyronine treatment. Thus, our work highlights the importance of thyroid hormone status evaluation and its ability to interfere with estrogen target gene expression in BrC samples in menopausal women. Sandro José Conde, Renata de Azevedo Melo Luvizotto, Maria Teresa de Síbio, and Célia Regina Nogueira Copyright © 2014 Sandro José Conde et al. All rights reserved. Serum Levels of the Adipokine Zinc-α2-glycoprotein Are Decreased in Patients with Hypertension Sun, 09 Feb 2014 09:36:04 +0000 Objective. Zinc-2-glycoprotein (ZAG) has recently been proposed as a new adipokine involved in body weight regulation. The purpose of this study is to investigate serum levels of ZAG in patients with hypertension and its association with related characteristics. Methods. 32 hypertension patients and 42 normal controls were recruited and the relationship between serum ZAG, total and high molecular weight (HMW) adiponectin, and tumor necrosis factor- (TNF) determined by enzyme-linked immunosorbent assay (ELISA) and metabolic-related parameters was investigated. Results. Serum ZAG concentrations were significantly lowered in patients with hypertension compared with healthy controls (61.4 ± 32 versus 78.3 ± 42 g/mL, ). The further statistical analysis demonstrated that serum ZAG levels were negatively correlated with waist-to-hip ratio (WHR) (, ) and alanine aminotransferase (ALT) (, ). Additionally, serum HMW adiponectin significantly decreased, while TNF greatly increased in hypertension patients as compared with healthy controls (2.32 ± 0.41 versus 5.24 ± 1.02 g/mL, 3.30 ± 1.56 versus 2.34 ± 0.99 pg/mL, ). Conclusions. Serum ZAG levels are significantly lowered in hypertension patients and negatively correlated with obesity-related item WHR, suggesting ZAG is a factor associated with hypertension. Hui Juan Zhu, Xiang qing Wang, Hui Pan, Feng ying Gong, Dian xi Zhang, Nai shi Li, Lin jie Wang, and Hong bo Yang Copyright © 2014 Hui Juan Zhu et al. All rights reserved. Pioglitazone Inhibits the Expressions of p22phox and p47phox in Rat Mesangial Cells In Vitro Mon, 03 Feb 2014 11:43:37 +0000 Aim. The purpose of this study was to investigate the effects of pioglitazone on oxidative stress and the expressions of p22phox and p47phox, subunits of NADPH oxidase, in mesangial cells (MCs). Method. Rat mesangial cells were cultured and randomly divided into normal glucose (NG) group, high glucose (HG) group, and pioglitazone group. After 48 h exposure, the supernatants and cells were collected. The expressions of p22phox and p47phox in MCs were detected by RT-PCR and western blot. The levels of intracellular ROS were determined by flow cytometry. Coloimetry method was used to detect malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) activities. Results. Compared with the NG group, the expression levels of p22phox, p47phox and ROS significantly increased, the activity of SOD decreased in HG group, while the concentration of MDA greatly increased (). Pioglitazone significantly suppressed HG-induced p22phox and p47phox expressions and oxidative stress. The protein and gene expressions of p22phox and p47phox were markedly reduced after pioglitazone treatment, so did the ROS generation. The activities of SOD in MCs increased, while the concentrations of MDA in the supernatant decreased greatly by pioglitazone. Conclusions. Pioglitazone can inhibit HG-induced oxidative stress in MCs through suppressing p22phox and p47phox expressions. Shan Wang, Shan-dong Ye, Wen-jia Sun, and Yuan-yuan Hu Copyright © 2014 Shan Wang et al. All rights reserved. The Response of Circulating Leptin Levels to Exercise Stress Testing in Subjects Diagnosed with Metabolic Syndrome Tue, 28 Jan 2014 06:47:06 +0000 Aim. To assess the plasma leptin responses after exercise stress testing in patients with metabolic syndrome (MS). Material and Methods. We investigated 67 patients with MS, with mean age of years. They underwent exercise stress testing on cycloergometer. The lot was divided into three groups: group 1—10 patients with a true positive test, group 2—18 patients with a true negative test, and group 3—39 patients with a false negative test. Leptin levels were measured using the ELISA method. Results. Leptin levels decreased after effort in patients with MS ( ng/mL before and  ng/mL after the exercise stress test, , ). In groups 1 ( at rest versus  ng/mL after the exercise test, ) and 3 ( at rest versus  ng/mL, ), lower leptin levels were recorded immediately after exercise testing. Leptin levels were not significantly lower in group 2 before effort ( ng/ml) and after ( ng/mL). We found no correlation between leptinemia and exercise stress testing parameters, regardless of group. Conclusion. Our research showed that short-term exercise lowers leptin levels in coronary patients, without a relationship between its parameters and leptin values. Dana Pop, Alexandra Dădârlat, Gyorgy Bodizs, Liana Stanca, and Dumitru Zdrenghea Copyright © 2014 Dana Pop et al. All rights reserved. Vitamin D and the Immune System from the Nephrologist's Viewpoint Wed, 22 Jan 2014 16:17:26 +0000 Vitamin D and its analogues are widely used as treatments by clinical nephrologists, especially when treating chronic kidney disease (CKD) patients with secondary hyperparathyroidism. As CKD progresses, the ability to compensate for elevations in parathyroid hormone (PTH) and fibroblast growth factor-23 and for decreases in 1,25(OH)2D3 becomes inadequate, which results in hyperphosphatemia, abnormal bone disorders, and extra-skeletal calcification. In addition to its calciotropic effect on the regulation of calcium, phosphate, and parathyroid hormone, vitamin D has many other noncalciotropic effects, including controlling cell differentiation/proliferation and having immunomodulatory effects. There are several immune dysregulations that can be noted when renal function declines. Physicians need to know well both the classical and nonclassical functions of vitamin D. This review is an analysis from the nephrologist's viewpoint and focuses on the relationship between the vitamin D and the immune system, together with vitamin's clinical use to treat kidney diseases. Cheng-Lin Lang, Min-Hui Wang, Chih-Kang Chiang, and Kuo-Cheng Lu Copyright © 2014 Cheng-Lin Lang et al. All rights reserved. Are Plasma Thyroid-Stimulating Hormone Levels Associated with Degree of Obesity and Metabolic Syndrome in Euthyroid Obese Patients? A Turkish Cohort Study Thu, 02 Jan 2014 09:46:35 +0000 We aimed to observe the association between degree of obesity and metabolic syndrome and plasma thyrotropin levels in obese, euthyroid Turkish patients. 947 obese and overweight patients who admitted to our outpatient clinic were assessed retrospectively. 150 healthy euthyroid cases were also recruited as the control group. Cases with metabolic syndrome were determined. Patients were divided into various subgroups as overweight, obese, morbid obese, men, and women. No statistical significance was determined when all the patients’ and subgroups’ plasma thyrotropin levels were compared to normal weight control group. No association was shown between the presence of metabolic syndrome and plasma thyrotropin levels for both all patients and subgroups. Also there was not any association between each component of metabolic syndrome and plasma thyrotropin levels. In conclusion, we did not found any significant association between plasma thyrotropin levels and obesity and metabolic syndrome in our euthyroid subjects. Okan Bakiner, Emre Bozkirli, Gulhan Cavlak, Kursad Ozsahin, and Eda Ertorer Copyright © 2014 Okan Bakiner et al. All rights reserved. Effects of Glucose Control and Variability on Endothelial Function and Repair in Adolescents with Type 1 Diabetes Sun, 29 Dec 2013 13:41:13 +0000 Background. Endothelial dysfunction and increased inflammation are precursors of cardiovascular disease in type 1 diabetes (T1D) and occur even in adolescents with T1D. The goal of this study was to determine the relationship of endothelial dysfunction to various measures of glycemia. Research Design and Methods. Forearm blood flow (FBF, venous occlusion plethysmography) was measured before and after 5 min of upper arm vascular occlusion in 17 adolescents with uncomplicated type 1 diabetes. Endothelial function was assessed as postocclusion FBF and forearm vascular resistance (FVR, mean arterial pressure/FBF). Fasting glucose, 72 hour mean glucose and standard deviation from continuous glucose monitoring, hemoglobin A1c, and hemoglobin A1c by duration area under the curve were used to assess immediate, short-term, and intermediate- and long-term glycemia. Results. Postocclusion FBF (, ) negatively correlated and postocclusion FVR positively correlated (, ) with hemoglobin A1c levels. FVR was positively associated with log 3 day mean glucose (, ). Postocclusion FBF ( versus  mL/dL/min, mean ± SE, ) tended to be lower and FVR ( versus  mmHg dL min/mL, ) was significantly higher in subjects with hemoglobin A1c above the median (8.3%) compared to those with lower hemoglobin A1c levels. Conclusions. These results demonstrate that poor intermediate-term glycemic control is associated with impaired endothelial function. Robert P. Hoffman, Amanda S. Dye, Hong Huang, and John A. Bauer Copyright © 2013 Robert P. Hoffman et al. All rights reserved. Carotid Atherosclerosis as a Surrogate Maker of Cardiovascular Disease in Diabetic Patients Sun, 10 Nov 2013 09:12:02 +0000 Many studies have shown that carotid intima-media thickness (IMT) is associated with cardiovascular disease (CVD). Although it remains inconclusive whether assessment of carotid IMT is useful as a screening test for CVD in Japanese diabetic patients, a total of 271 patients (151 men aged 66 ± 10 (standard deviation) years and 220 women aged 71 ± 8 years) were divided into two groups based on the presence of CVD. We cross-sectionally assessed the ability of carotid IMT to identify CVD corresponding to treatment that was examined by receiver-operating characteristic (ROC) curve analyses. Among the 271 diabetic patients, 199 non-CVD and 72 CVD patients were examined. Multiple linear regression analysis using the presence of CVD as an objective variable showed that carotid IMT (, ) as well as other confounding factors was a significant independent contributing factor. The ROC curve analysis showed that the best marker of CVD was carotid IMT, with an area under the ROC curve of 0.718 (95% confidence interval (CI), 0.650–0.785). The greatest sensitivity and specificity were obtained when the cut-off value of mean carotid IMT was set at 0.95 mm (sensitivity = 0.71, specificity = 0.60, and accuracy = 0.627). Our study suggests that carotid IMT may be useful for screening diabetic patients with CVD. Ryuichi Kawamoto, Tateaki Katoh, Tomo Kusunoki, and Nobuyuki Ohtsuka Copyright © 2013 Ryuichi Kawamoto et al. All rights reserved. Insulin Sensitivity Assessed by Stable Isotopes with Oral Glucose Administration: Validation with Euglycaemic Clamp Thu, 31 Oct 2013 14:36:39 +0000 Methods of determining insulin sensitivity that use an oral challenge of glucose are preferred to those using intravenous administration since the measurement is made in conditions more akin to normal physiology. One previously reported protocol (ODILE) studies glucose uptake in isolation from absorption and endogenous production by the intravenous administration of tracer approximately forty-five minutes after the oral dose is given. However, this methodology has not been validated against other accredited procedures. This study utilizes the euglycemic hyperinsulinemic clamp in order to validate the ODILE method. Leslie Bluck, Rachel Williams, Sarah Jackson, Burak Salgin, Carlo Acerini, and David Dunger Copyright © 2013 Leslie Bluck et al. All rights reserved. No Association between Glycemia and Wound Healing in an Experimental db/db Mouse Model Tue, 22 Oct 2013 08:34:06 +0000 Impaired wound healing is a frequent problem in diabetes. Hyperglycemia may be an operative mechanism, but a link between glycemic control and wound healing has never been established. Wounds in db/db mice have been extensively studied. This study was undertaken to see if plasma glucose was a predictor of wound healing. An excisional wound was made (149 db/db mice). Wound closure was studied versus metabolic variables. The animals were weeks (mean ± standard error of the mean), obese ( g), and hyperglycemic (fasting plasma glucose  mmol/L). Wound closure at day 13 was . In linear mixed model analyses neither fasting plasma glucose nor its change from start to end of experiment was a significant predictor of wound closure (, , 95% CI: −0.01 to 0.31 and , , 95% CI: −0.11 to 0.23, resp.). However, increase in body weight significantly and independently predicted wound closure (for weight change, , , 95% CI: 0.06 to 0.38). This study strongly suggests that wound healing in db/db mice is independent of prevailing glycemia but dependent on anabolic changes such as weight gain over time. Margrete Berdal and Trond Jenssen Copyright © 2013 Margrete Berdal and Trond Jenssen. All rights reserved. Hypovitaminosis D in Patients with Type 2 Diabetes Mellitus: A Relation to Disease Control and Complications Tue, 22 Oct 2013 08:30:08 +0000 Aims. This study aims at assessing the relationship between 25 (OH) vitamin D (25-OHD) levels and microvascular complications in patients with type 2 diabetes mellitus (DM2). Methods. 136 patients (59 ± 11 years) with DM2 (disease duration 8.6 ± 7 years) participated in this cross-sectional study. Anthropometric data, HbA1c, 25-OHD levels, serum creatinine, and urine microalbumin/creatinine ratio were collected. Dilated retinal exam was performed, and diabetic neuropathy was assessed using the United Kingdom Screening Score. Results. Serum 25-OHD correlated negatively with HbA1c (  ). Mean 25-OHD levels were lower in subjects with diabetic retinopathy compared to those without retinopathy (12.3 ± 5.5 versus 21.8 ± 13.7, ) and lower in subjects with diabetic neuropathy compared to those without neuropathy (16.4 ± 10.4 versus 23.5 ± 14.5, ). After adjustment for BMI, diabetes duration, and smoking, 25-OHD was an independent predictor of HbA1c (β  −0.14; ). After adjustment for HbA1c, age, smoking, BMI and disease duration, 25-OHD were independent predictors for diabetic retinopathy: OR 2.8 [95% CI 2.1–8.0] and neuropathy: OR 4.5 [95% CI 1.6–12] for vitamin D < 20 versus vitamin D ≥ 20 ng/mL. Conclusion. Low serum 25-OHD level was an independent predictor of HbA1c, diabetic neuropathy, and diabetic retinopathy in patients with DM2. Hala Ahmadieh, Sami T. Azar, Najla Lakkis, and Asma Arabi Copyright © 2013 Hala Ahmadieh et al. All rights reserved. A Longitudinal Study of Changes in Thyroid Related Hormones among Pregnant Women Residing in an Iodine Deficient Urban Area Mon, 21 Oct 2013 08:32:53 +0000 Problem Statement. Thyroid gland in women undergoes functional changes during pregnancy. A few studies have described such changes in pregnant women residing in iodine deficient areas. Objective. To document these changes in pregnant women residing in Lahore, a low iodine intake urban area of Pakistan. Patients and Methods. In 254 pregnant women, data of FT4, FT3, and TSH during the first and subsequent trimesters were obtained and compared with those of 110 nonpregnant women. These hormones were determined in serum by radioimmunoassay (RIA) techniques using commercial kits. Results. Compared to nonpregnant women mean FT4 level was decreased, and FT3 and TSH increased significantly () in pregnant women. A negative correlation of FT4 with TSH was observed in all three trimesters. Serum FT3 was positively correlated with TSH only during the third trimester. As a function of gestation time, FT4 levels progressively decreased, and FT3 and TSH levels increased significantly (one-way ANOVA = 108.2, 17.3, and 44.8, resp.; all ) exhibiting thyroid gland adaptations. Conclusion. Pregnancy is associated with significant alterations in thyroid function due to low iodine intake in women residing in study area. The compensated thyroid function poses a risk of thyroid failure in a number of pregnant women. Shan Elahi and Zaib Hussain Copyright © 2013 Shan Elahi and Zaib Hussain. All rights reserved. Improving Compliance with Screening of Diabetic Patients for Microalbuminuria in Primary Care Practice Wed, 09 Oct 2013 08:45:51 +0000 Studies showed suboptimal compliance rate of primary care physicians with microalbuminuria screening. This study evaluated impact of electronic medical records (EMR) and computerized physicians reminders on compliance rate and showed small to modest improvement. Combining EMR with quality control monitoring has significantly improved compliance [OR 1.556, 95% CI 1.251–1.935, ]. Abeer Anabtawi and L. Mary Mathew Copyright © 2013 Abeer Anabtawi and L. Mary Mathew. All rights reserved. Risk of Cancer in Diabetes: The Effect of Metformin Tue, 24 Sep 2013 16:01:28 +0000 Cancer is the second cause of death. Association of diabetes as a growing and costly disease with cancer is a major health concern. Meanwhile, preexisting diabetes is associated with an increased risk of all-cause and cancer-specific mortalities. Presence of diabetes related comorbidities, poorer response to cancer treatment, and excess mortality related to diabetes are among the most important explanations. Although diabetes appear to be a risk factor for cancer and is associated with the mortality risk in cancer patients, several factors such as diabetes duration, multiple drug therapy, and the presence of diabetes comorbidities make the assessment of the effect of diabetes treatment on cancer risk and mortality difficult. Metformin is the drug of choice for the treatment of type 2 diabetes. The available evidence from basic science, clinical, and population-based research supports the anticancer effect of metformin. However, randomized controlled clinical trials do not provide enough evidence for a strong protective effect of metformin on cancer incidence or mortality. One of the most important limitations of these trials is the short duration of the followup. Further long-term randomized controlled clinical trials specifically designed to determine metformin effect on cancer risk are needed to provide the best answer to this challenge. Mojtaba Malek, Rokhsareh Aghili, Zahra Emami, and Mohammad E. Khamseh Copyright © 2013 Mojtaba Malek et al. All rights reserved. A Clinical Review of the Association of Thyroid Stimulating Hormone and Cognitive Impairment Mon, 23 Sep 2013 13:45:01 +0000 Clinical and subclinical hypothyroidism as well as overt hyperthyroidism in middle-aged and elderly adults are both associated with decreased cognitive functioning as memory, reaction time, and visuospatial organization. Subclinical hyperthyroidism (SH) or low serum concentrations of TSH concentrations have been associated with dementia in previous epidemiological studies, but the association in the elderly has not been established. There is little or no consensus regarding how thyroid function is associated with cognitive performance in the elderly. In this focused review, we have performed an examination between eleven studies from the last five years examining the association between thyroid function and cognitive performance in elderly people, a group who is overrepresented among individuals with minor abnormalities in serum TSH and thyroid hormone concentration. Six of the studies showed a consistent finding of an association between SH with cognitive impairment or dementia. In general, taking into account the largest and most powerfully designed studies, there is a strong body of evidence supporting the association between SH and cognitive impairment. The scarce number of publications on these topics indicates the need of more research especially regarding longitudinal and interventional studies thus hopefully enabling confirmation or rejection of causality between TSH abnormalities and dementia. Sylvia Annerbo and Johan Lökk Copyright © 2013 Sylvia Annerbo and Johan Lökk. All rights reserved. Aryl Hydrocarbon Receptor Ligands Inhibit IGF-II and Adipokine Stimulated Breast Cancer Cell Proliferation Mon, 23 Sep 2013 09:16:07 +0000 Obesity increases human cancer risk and the risk for cancer recurrence. Adipocytes secrete paracrine factors termed adipokines that stimulate signaling in cancer cells that induce proliferation. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays roles in tumorigenesis, is regulated by exogenous lipophilic chemicals, and has been explored as a therapeutic target for cancer therapy. Whether exogenous AHR ligands modulate adipokine stimulated breast cancer cell proliferation has not been investigated. We provide evidence that adipocytes secrete insulin-like growth factor 2 (IGF-2) at levels that stimulate the proliferation of human estrogen receptor (ER) positive breast cancer cells. Using highly specific AHR ligands and AHR short interfering RNA (AHR-siRNA), we show that specific ligand-activated AHR inhibits adipocyte secretome and IGF-2-stimulated breast cancer cell proliferation. We also report that a highly specific AHR agonist significantly () inhibits the expression of E2F1, CCND1 (known as Cyclin D1), MYB, SRC, JAK2, and JUND in breast cancer cells. Collectively, these data suggest that drugs that target the AHR may be useful for treating cancer in human obesity. Travis B. Salisbury, Gary Z. Morris, Justin K. Tomblin, Ateeq R. Chaudhry, Carla R. Cook, and Nalini Santanam Copyright © 2013 Travis B. Salisbury et al. All rights reserved. Diagnostic Value of the Combined Measurement of Serum Hcy, Serum Cys C, and Urinary Microalbumin in Type 2 Diabetes Mellitus with Early Complicating Diabetic Nephropathy Wed, 18 Sep 2013 18:56:15 +0000 Diabetic nephropathy (DN) is a major cause of end-stage kidney disease, and therefore early diagnosis and intervention may help reverse renal damage. One hundred and sixty-eight patients with T2DM and 56 healthy volunteers (control group) were enrolled at Shandong University Qilu Hospital between April 2010 and October 2012. All subjects underwent blood sampling for sera homocysteine (Hcy) and cystatin C (Cys C) assays and a urine microalbumin test. The patients were divided into three groups according to the urine microalbumin excretion rate (UMAER): the simple DM group (SDM group, ), the early-stage DN group (EDN group, ), and the clinical DN and renal failure group (CDN group, ). Correlation analysis was performed to examine the association between sera Hcy and Cys C levels with UMAER. Our findings showed that sera Hcy level, Cys C level, and UMAER increased significantly in the SDM group (, ), the EDN group (), and the CDN group () as compared with the control group. These three biochemical markers also increased significantly with DN progression (). Correlation analysis showed that sera Hcy and Cys C levels were positively correlated with UMAER (, ; , ). In conclusion, our results showed that sera Hcy and Cys C levels increased consistently with the development and progression of DN as indicated by UMAER. Sera Hcy and Cys C are sensitive biomarkers for the detection of early-stage DN and monitoring its progression. Tengkai Wang, Qian Wang, Zhimei Wang, Zuomin Xiao, and Lunqin Liu Copyright © 2013 Tengkai Wang et al. All rights reserved. Gestational Diabetes Mellitus: Screening and Outcomes in Southern Italian Pregnant Women Thu, 05 Sep 2013 08:32:40 +0000 Recent Italian guidelines exclude women <35 years old, without risk factors for gestational diabetes mellitus (GDM), from screening for GDM. To determine the effectiveness of these measures with respect to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria, we evaluated 2,448 pregnant women retrospectively enrolled in Calabria, southern Italy. GDM was diagnosed following the IADPSG 2010 criteria. Among 538 women <35 years old, without risk factors, who would have not been tested according to the Italian guidelines, we diagnosed GDM in 171 (31.8%) pregnants (7.0% of total pregnants). Diagnosis was made at baseline (55.6%), 1 hour (39.8%), or 2 hours (4.7%) during OGTT. Despite of appropriate treatment, GDM represented a risk factor for cesarean section, polyhydramnios, increased birth weight, admission to neonatal intensive care units, and large for gestational age. These outcomes were similar to those observed in GDM women at high risk for GDM. In conclusion, Italian recommendations failed to identify 7.0% of women with GDM, when compared to IADPSG criteria. The risk for adverse hyperglycaemic-related outcomes is similar in low-risk and high-risk pregnants with GDM. To limit costs of GDM screening, our data suggest to restrict OGTT to two steps (baseline and 1 hour). Carmelo Capula, Eusebio Chiefari, Anna Vero, Biagio Arcidiacono, Stefania Iiritano, Luigi Puccio, Vittorio Pullano, Daniela P. Foti, Antonio Brunetti, and Raffaella Vero Copyright © 2013 Carmelo Capula et al. All rights reserved. Impact of Neonatal Manipulation of Androgen Receptor Function on Endocrine-Metabolic Programming in the Juvenile Female Rat Wed, 28 Aug 2013 07:51:21 +0000 The impact of neonatal androgen receptor (AR) stimulation/blockage, due to testosterone propionate (TP)/AR antagonist treatment, on individual anthropometry and neuroendocrine-metabolic function was evaluated in the juvenile female rat. Pups (age 5 days) were s.c. injected with TP (1.25 mg), flutamide (F; 1.75 mg), and TP + F or vehicle (control, CT) and studied on day 30 of age. Body weight (BW), parametrial adipose tissue (PMAT) mass, food intake, adipoinsular axis, and steroidogenic functions were examined. Opposite to TP-rats, F-treated rats developed hypophagia, grew slowly (BW and PMAT), and displayed heightened peripheral insulin sensitivity. These F effects were abrogated in TP + F animals. Accordingly, TP rats displayed hyperleptinemia, an effect fully prevented by F cotreatment. Finally, androgen-treated animals bore an irreversible ovarian dysfunction (reduced circulating levels of 17HOP4 and ovary 17HOP4 content and P450c17 mRNA abundance). These data indicate that early stimulation of AR enhanced energy store, blockage of AR activity resulted in some beneficial metabolic effects, and neonatally androgenized rats developed a severe ovarian dysfunction. Our study highlights the important role of AR in the early organizational programming of metabolic and neuroendocrine functions. Luisina Ongaro, Andres Giovambattista, and Eduardo Spinedi Copyright © 2013 Luisina Ongaro et al. All rights reserved. Comparison of In Vitro and In Situ Methods for Studying Lipolysis Mon, 19 Aug 2013 10:47:13 +0000 Lipolysis is a highly regulated process and is controlled by nervous system, hormones, and paracrine/autocrine factors. Dysregulation of lipolysis is associated with some pathophysiological conditions including diabetes, metabolic syndrome, and obesity. Nowadays, special attention isthereforepaid to study lipolysis using different experimental models. This review summarizes the current experimental methods for studying lipolysis. Culture of preadipocyte cell lines, use of differentiated stroma-vascular cells, primary culture of adipocyte, organ culture of adipose tissue, and microdialysis technique are the most widely used techniques to study lipolysis. The advantages and limitations of using these methods are discussed. Ahmad Ghorbani and Mahmood Abedinzade Copyright © 2013 Ahmad Ghorbani and Mahmood Abedinzade. All rights reserved. Liraglutide Suppresses the Plasma Levels of Active and Des-Acyl Ghrelin Independently of Active Glucagon-Like Peptide-1 Levels in Mice Tue, 13 Aug 2013 10:50:13 +0000 Glucagon-like peptide-1 (GLP-1), an insulinotropic gastrointestinal peptide that is primarily produced by intestinal endocrine L-cells, stimulates satiety. Ghrelin, a hormone that is produced predominantly by the stomach stimulates hunger. There are two forms of ghrelin: active ghrelin and inactive des-acyl ghrelin. After depriving mice of food for 24 h, we demonstrated that the systemic administration of liraglutide (100 μg/kg), a human GLP-1 analog that binds to the GLP-1 receptor, increased (1.4-fold) the plasma levels of active GLP-1 and suppressed the plasma levels of active and des-acyl ghrelin after 1 h. Despite the elevated plasma levels of active GLP-1 (11-fold), liraglutide had no effect on the plasma levels of active or des-acyl ghrelin after 12 h. These findings demonstrated that liraglutide suppresses the plasma levels of active and des-acyl ghrelin independently of active GLP-1 levels in fasted mice, suggesting a novel in vivo biological effect of liraglutide beyond regulating plasma GLP-1. Katsunori Nonogaki and Marina Suzuki Copyright © 2013 Katsunori Nonogaki and Marina Suzuki. All rights reserved. Predictors of Postpartum Glucose Tolerance Testing in Italian Women with Gestational Diabetes Mellitus Wed, 17 Jul 2013 08:11:56 +0000 Postpartum screening is critical for early identification of type 2 diabetes in women previously diagnosed with gestational diabetes mellitus (GDM). Nevertheless, its rate remains disappointingly low. Thus, we plan to examine the rate of postpartum glucose tolerance test (ppOGTT) for Italian women with GDM, before and after counseling, and identify demographic, clinical, and/or biochemical predictors of adherence. With these aims, we retrospectively enrolled 1159 women with GDM, in Calabria, Southern Italy, between 2004 and 2011. During the last year, verbal and written counseling on the importance of followup was introduced. Data were analyzed by multiple regression analysis. A significant increase of the return rate was observed following introduction of the counseling [adjusted odds ratio (AOR) 5.17 (95% CI, 3.83–6.97), ]. Interestingly, previous diagnosis of polycystic ovary syndrome (PCOS) emerged as the major predictor of postpartum followup [AOR 5.27 (95% CI, 3.51–8.70), ], even after stratification for the absence of counseling. Previous diagnosis of GDM, higher educational status, and insulin treatment were also relevant predictors. Overall, our data indicate that counseling intervention is effective, even if many women fail to return, whereas PCOS represents a new strong predictor of adherence to postpartum testing. Carmelo Capula, Eusebio Chiefari, Anna Vero, Stefania Iiritano, Biagio Arcidiacono, Luigi Puccio, Vittorio Pullano, Daniela Foti, Antonio Brunetti, and Raffaella Vero Copyright © 2013 Carmelo Capula et al. All rights reserved. Paradoxically Low Levels of Total and HMW Adiponectin in Relation to Metabolic Parameters in a Tongan Population Tue, 09 Jul 2013 14:35:13 +0000 Aim. Adiponectin has demonstrated anti-inflammatory and insulin sensitising properties, and low circulating levels may be an important risk factor for diabetes. We examined levels of adiponectin and its insulin-sensitising HMW isoform and their relationship with metabolic parameters in Tongans, a population prone to type II diabetes. Methods. Adiponectin and its HMW isoform were quantitated by Elisa in specimens from a randomly recruited, multistage cluster population survey of Tongans and from a group of Caucasians. Anthropometric, clinical, and biochemical data were collected on each subject. Results. Both male and female Tongans had lower levels of total and HMW adiponectin than their Caucasian counterparts. Levels of total and HMW adiponectin were higher in females than males in each group. Adiponectin levels were inversely related to BMI, weight, and HOMA in Tongan males and females, as well as to dyslipidemia in both sexes. Conclusion. Tongans had lower levels of both total and HMW adiponectin than Caucasians population, even after matching Tongans to their Caucasian counterparts based on BMI, age, and sex. These findings may reflect differences in body composition between the populations not adequately assessed by BMI, lifestyle factors, or a genetic variant likely in a genetically homogenous population. Philip Peake, Stephen Colagiuri, Lesley V. Campbell, and Yvonne Shen Copyright © 2013 Philip Peake et al. All rights reserved. Estrogen Signaling and the Aging Brain: Context-Dependent Considerations for Postmenopausal Hormone Therapy Sun, 07 Jul 2013 10:33:57 +0000 Recent clinical studies have spurred rigorous debate about the benefits of hormone therapy (HT) for postmenopausal women. Controversy first emerged based on a sharp increase in the risk of cardiovascular disease in participants of the Women’s Health Initiative (WHI) studies, suggesting that decades of empirical research in animal models was not necessarily applicable to humans. However, a reexamination of the data from the WHI studies suggests that the timing of HT might be a critical factor and that advanced age and/or length of estrogen deprivation might alter the body's ability to respond to estrogens. Dichotomous estrogenic effects are mediated primarily by the actions of two high-affinity estrogen receptors alpha and beta (ERα & ERβ). The expression of the ERs can be overlapping or distinct, dependent upon brain region, sex, age, and exposure to hormone, and, during the time of menopause, there may be changes in receptor expression profiles, post-translational modifications, and protein:protein interactions that could lead to a completely different environment for E2 to exert its effects. In this review, factors affecting estrogen-signaling processes will be discussed with particular attention paid to the expression and transcriptional actions of ERβ in brain regions that regulate cognition and affect. Natasha N. Mott and Toni R. Pak Copyright © 2013 Natasha N. Mott and Toni R. Pak. All rights reserved.