International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Diabetes Mellitus 2014 Mon, 25 May 2015 07:07:54 +0000 Ilias Migdalis, David Leslie, Anastasia Mavrogiannaki, Nikolaos Papanas, Paul Valensi, and Helen Vlassara Copyright © 2015 Ilias Migdalis et al. All rights reserved. Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D Sun, 24 May 2015 12:05:47 +0000 Background. The role of phospholipase D (PLD) as a positive modulator of glucose uptake activation by insulin in muscle and adipose cells has been demonstrated. The role of PLD in the regulation of glucose metabolism by insulin in the primary hepatocytes has been determined in this study. Methods. For this purpose, we studied effects of inhibitors of PLD on glucose uptake and glycogen synthesis stimulation by insulin. To determine the PLD activity, the method based on determination of products of transphosphatidylation reaction, phosphatidylethanol or phosphatidylbutanol, was used. Results. Inhibition of PLD by a general antagonist (1-butanol) or specific inhibitor, halopemide, or N-hexanoylsphingosine, or by cellular ceramides accumulated in doxorubicin-treated hepatocytes decreased insulin-stimulated glucose metabolism. Doxorubicin-induced hepatocytes resistance to insulin action could be abolished by inhibition of ceramide production. Halopemide could nullify this effect. Addition of propranolol, as well as inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) (wortmannin, LY294002) or suppressors of Akt phosphorylation/activity, luteolin-7-O-glucoside or apigenin-7-O-glucoside, to the culture media could block cell response to insulin action. Conclusion. PLD plays an important role in the insulin signaling in the hepatocytes. PLD is activated downstream of PI3-kinase and Akt and is highly sensitive to ceramide content in the liver cells. Nataliya A. Babenko and Vitalina S. Kharchenko Copyright © 2015 Nataliya A. Babenko and Vitalina S. Kharchenko. All rights reserved. Quality of Care for Patients with Type 2 Diabetes Mellitus in Dubai: A HEDIS-Like Assessment Sun, 24 May 2015 09:12:43 +0000 Objective. As little data are available on the quality of type 2 diabetes mellitus (T2DM) care in the Arabian Gulf States, we estimated the proportion of patients receiving recommended monitoring at the Dubai Hospital for T2DM over one year. Methods. Charts from 150 adults with T2DM were systematically sampled and quality of care was assessed during one calendar year, using a Healthcare Effectiveness Data and Information Set- (HEDIS-) like assessment. Screening for glycosylated haemoglobin (HbA1c), low-density lipoprotein (LDL), blood pressure, retinopathy, and nephropathy was considered. Patients were classified based on their most recent test in the period, and predictors of receiving quality care were examined. Results. Mean age was 58 years (standard deviation (SD): 12.4 years) and 33% were males. Over the year, 98% underwent HbA1c screening (50% had control and 28% displayed poor control); 91% underwent LDL screening (65% had control); 55% had blood pressure control; 30% had retinopathy screening; and 22% received attention for nephropathy. No individual characteristics examined predicted receiving quality care. Conclusion. Some guideline monitoring was conducted for most patients; and rates of monitoring for selected measures were comparable to benchmarks from the United States. Greater understanding of factors leading to high adherence would be useful for other areas of preventive care and other jurisdictions. Shelagh M. Szabo, Katherine M. Osenenko, Lara Qatami, Bonnie M. Korenblat Donato, Ellen E. Korol, Abdulrazzaq A. Al Madani, Fatheya F. Al Awadi, Jaber Al-Ansari, Ross Maclean, and Adrian R. Levy Copyright © 2015 Shelagh M. Szabo et al. All rights reserved. Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells Thu, 21 May 2015 13:55:28 +0000 Thyroid cancer and thyroid nodules are more prevalent in women than men, so female sex hormones may have an etiological role in these conditions. There are no data about direct effects of progesterone on thyroid cells, so the aim of the present study was to evaluate progesterone effects in the sodium-iodide symporter NIS, thyroglobulin TG, thyroperoxidase TPO, and KI-67 genes expression, in normal thyroid follicular cells, derived from human tissue. NIS, TG, TPO, and KI-67 mRNA expression increased significantly after TSH 20 μUI/mL, respectively: 2.08 times, ; 2.39 times, ; 1.58 times, ; and 1.87 times, . In thyroid cells treated with 20 μUI/mL TSH plus 10 nM progesterone, RNA expression of NIS, TG, and KI-67 genes increased, respectively: 1.78 times, ; 1.75 times, ; and 1.95 times, , and TPO mRNA expression also increased, though not significantly (1.77 times, ). These effects were abolished by mifepristone, an antagonist of progesterone receptor, suggesting that genes involved in thyroid cell function and proliferation are upregulated by progesterone. This work provides evidence that progesterone has a direct effect on thyroid cells, upregulating genes involved in thyroid function and growth. Ana Paula Santin Bertoni, Ilma Simoni Brum, Ana Caroline Hillebrand, and Tania Weber Furlanetto Copyright © 2015 Ana Paula Santin Bertoni et al. All rights reserved. The Cost of Managing Type 2 Diabetes Mellitus in Greece: A Retrospective Analysis of 10-Year Patient Level Data “The HERCULES Study” Thu, 21 May 2015 06:36:50 +0000 Objective. This study aimed to estimate the mean annual cost of treating type 2 diabetes mellitus patients (T2DM) including complications and comorbidities in Greece. Design. A noninterventional retrospective study was based on patient level data analysis (bottom-up approach) from medical records, with at least 10-year-follow-up data. Results. The total annual cost per patient for managing diabetes in Greece was estimated at € 7,111 and was, statistically significantly, higher for patients with inadequate glycemic control () versus patients with adequate control () (€ 7,783 versus € 6,366, resp.;   ). This was mainly attributed to difference in CV hospitalizations between groups 14/111 versus 4/100, respectively, (95% CI: 1.10–10.9) for inadequately controlled patients. The largest component of cost was management of comorbidities, accounting for 48% of costs, and pharmaceutical treatment at 35.9% while only 14.9% was attributed to diabetes treatment per se. Obese men and patients with poor education are the groups with higher treatment costs. Conclusions. This is the first study to capture all cost components and the real burden of diabetes in Greece. Comorbidities were found to account for almost half of total cost, significantly higher in nonoptimally controlled diabetes patients. Ilias Migdalis, Grigorios Rombopoulos, Magdalini Hatzikou, Christos Manes, Nikolaos Kypraios, and Nikolaos Tentolouris Copyright © 2015 Ilias Migdalis et al. All rights reserved. Body Image Disturbance in Acromegaly Patients Compared to Nonfunctioning Pituitary Adenoma Patients and Controls Wed, 20 May 2015 11:54:43 +0000 Purpose. Excess growth hormone secretion in adults results in acromegaly, a condition in which multiple physical changes occur including bony and soft tissue overgrowth. Over time these changes can markedly alter a person’s appearance. The aim of this study was to compare body image disturbance in patients with acromegaly to those with nonfunctioning pituitary adenomas (NFAs) and controls and assess the impact of obesity in these groups. Methods. A cross-sectional survey including quality of life, body image disturbance, anxiety and depression measures, growth hormone, and BMI measurement was carried out. Results. The groups did not differ with respect to body image disturbance. However separate analysis of obese participants demonstrated relationships between mood scales, body image disturbance, and pain issues, particularly for acromegaly patients. Conclusions. While the primary hypothesis that acromegaly might be associated with body image disturbance was not borne out, we have shown that obesity together with acromegaly and NFA can be associated with body image issues, suggesting that BMI rather than primary diagnosis might better indicate whether patients might experience body image disturbance problems. Helen M. Conaglen, Dennis de Jong, Veronica Crawford, Marianne S. Elston, and John V. Conaglen Copyright © 2015 Helen M. Conaglen et al. All rights reserved. Prevalence of Orthostatic Hypertension in Elderly Patients with Type 2 Diabetes Wed, 20 May 2015 07:14:04 +0000 Background. The aim of the present study was to determine the prevalence of orthostatic hypertension (OHT) in elderly patients with type 2 diabetes and its relation to metabolic and echocardiographic parameters. Methods. This was an analytical cross-sectional study in 97 patients normotensive or hypertensive. OHT was defined as a ≥10 mmHg increase in systolic blood pressure after four minutes in the standing position. Results. The prevalence of OHT was 20.6%. The mean body mass index was significantly higher in patients with OHT than in those without it ( versus  kg/m2; ). There were no statistically significant differences between the two groups for other metabolic parameters. Among the 68 patients who had an echocardiographic examination 27% of those with OHT had an increase in their left atrial volume index (LAVi) compared with 75% of those who did not have OHT (). The mean LAVi of patients with OHT was significantly lower than that of those without OHT ( versus , resp.; ). Conclusion. We found a high prevalence of orthostatic hypertension and a lower left atrial volume indexed in the patients with orthostatic hypertension. Patrícia Mesquita, Deborah Queiroz, Vanderson Lamartine de Lima Silva, Vanessa de Carvalho Texeira, Yasmin Rodrigues Vilaça de Lima, Edinaldo Rodrigues Fontes Júnior, Jéssica Garcia, and Francisco Bandeira Copyright © 2015 Patrícia Mesquita et al. All rights reserved. Treatment Compliance with Fixed-Dose Combination of Vildagliptin/Metformin in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin Monotherapy: A 24-Week Observational Study Tue, 19 May 2015 13:56:56 +0000 Objective. To evaluate the differences in treatment compliance with vildagliptin/metformin fixed-dose versus free-dose combination therapy in patients with type 2 diabetes mellitus (T2DM) in Greece. Design. Adult patients with T2DM, inadequately controlled with metformin monotherapy, (850 mg bid), participated in this 24-week, multicenter, observational study. Patients were enrolled in two cohorts: vildagliptin/metformin fixed-dose combination (group A) and vildagliptin metformin free-dose combination (group B). Results. 659 patients were enrolled, 360 were male, with mean BMI 30.1, mean T2DM duration 59.6 months, and mean HbA1c at baseline 8%; 366 patients were assigned to group A and 293 to group B; data for 3 patients was missing. In group A, 98.9% of patients were compliant with their treatment compared to 84.6% of group B. The odds ratio for compliance in group A versus B was (OR) 18.9 (95% CI: 6.2, 57.7; ). In group A mean HbA1c decreased from 8.1% at baseline to 6.9% () at the study end and from 7.9% to 6.8% () in group B. Conclusions. Patients in group A were more compliant than patients in group B. These results are in accordance with international literature suggesting that fixed-dose combination therapies lead to increased compliance to treatment. Grigorios Rombopoulos, Magdalini Hatzikou, Athanasios Athanasiadis, and Moyses Elisaf Copyright © 2015 Grigorios Rombopoulos et al. All rights reserved. The Guyana Diabetes and Foot Care Project: Improved Diabetic Foot Evaluation Reduces Amputation Rates by Two-Thirds in a Lower Middle Income Country Tue, 19 May 2015 11:28:59 +0000 Background. Type 2 diabetes is the fourth leading cause of death in Guyana, South America. A complex, interprofessional, quality improvement intervention to improve foot and diabetes care was rolled out in two phases. Methods & Findings. Phase 1: Establishment of an Interprofessional Diabetic Foot Center (DFC) of Excellence to improve foot care and reduce diabetes-related amputations at the national referral hospital. Phase 2: Regionalization to cover 90% of the Guyanese population and expansion to include improved management of diabetes and hypertension. Fourteen key opinion leaders were educated and 340 health care professionals from 97 facilities trained. Eight centers for the evaluation and treatment of foot ulcers were established and 7567 people with diabetes evaluated. 3452 participants had foot screening and 48% were deemed high risk; 10% of these had undocumented foot ulcers. There was a 68% reduction in rate of major amputations (); below knee amputations were decreased by 80%, while above knee amputations were unchanged. An increased association of diabetes with women (F/M = 2.09) and increased risk of major amputation in men [odds ratio 2.16 (95% CI 1.83, 2.56)] were documented. Conclusions. This intervention improved foot care with reduction in major amputations sustained over 5 years. Julia Lowe, R. Gary Sibbald, Nashwah Y. Taha, Gerald Lebovic, Madan Rambaran, Carlos Martin, Indira Bhoj, and Brian Ostrow Copyright © 2015 Julia Lowe et al. All rights reserved. Comparison of Lipoprotein-Associated Phospholipase A2 and High Sensitive C-Reactive Protein as Determinants of Metabolic Syndrome in Subjects without Coronary Heart Disease: In Search of the Best Predictor Tue, 19 May 2015 08:42:39 +0000 High sensitivity C-reactive protein (hsCRP) is a marker of metabolic syndrome (MS) and cardiovascular (CV) disease. Lipoprotein-associated phospholipase A2 (Lp-PLA2) also predicts CV disease. There are no reports comparing these markers as predictors of MS. Methods. Cross-sectional study comparing Lp-PLA2 and hsCRP as predictors of MS in asymptomatic subjects was carried out; 152 subjects without known atherosclerosis participated. Data were collected on demographics, cardiovascular risk factors, anthropometric and biochemical measurements, and hsCRP and Lp-PLA2 activity levels. A logistic regression analysis was performed with each biomarker and receiver operating characteristic (ROC) curves were constructed for MS. Results. Mean age was 46 ± 11 years, and 38% of the subjects had MS. Mean Lp-PLA2 activity was 185 ± 48 nmol/mL/min, and mean hsCRP was 2.1 ± 2.2 mg/L. Subjects with MS had significantly higher levels of Lp-PLA2 () and hsCRP () than those without MS. ROC curves showed that both markers predicted MS. Conclusion. Lp-PLA2 and hsCRP are elevated in subjects with MS. Both biomarkers were independent and significant predictors for MS, emphasizing the role of inflammation in MS. Further research is necessary to determine if inflammation predicts a higher risk for CV events in MS subjects. Mónica Acevedo, Paola Varleta, Verónica Kramer, Giovanna Valentino, Teresa Quiroga, Carolina Prieto, Jacqueline Parada, Marcela Adasme, Luisa Briones, and Carlos Navarrete Copyright © 2015 Mónica Acevedo et al. All rights reserved. Thyroid Autoimmunity in the Context of Type 2 Diabetes Mellitus: Implications for Vitamin D Tue, 19 May 2015 08:30:38 +0000 Vitamin D deficiency has been associated with both type 2 diabetes mellitus (T2DM) and autoimmune disorders. The association of vitamin D with T2DM and thyroid autoimmunity (TAI) has not been investigated. Thus, we aimed to explore the putative association between T2DM and thyroid autoimmunity (TAI) focusing on the role of 25-hydroxy-vitamin D (25(OH)D). Study population included 264 T2DM patients and 234 controls. To explore the potential association between 25(OH)D and thyroid autoimmunity while controlling for potential confounders—namely, age, gender, body mass index, and presence of T2DM—multivariate logistic regression analyses were undertaken. Patients with T2DM were younger () and had significantly lower 25(OH)D levels () and higher anti-TPO titers (). Multivariable logistic regression analyses suggested that T2DM and 25(OH)D levels were significantly associated with the presence of thyroid autoimmunity. In an elderly population of diabetic patients and controls with a high prevalence of vitamin D deficiency/insufficiency, a patient with T2DM was found to be 2.5 times more likely to have thyroid autoimmunity compared to a nondiabetic individual and the higher the serum 25(OH)D levels were, the higher this chance was. Konstantinos Toulis, Xanthippi Tsekmekidou, Evangelos Potolidis, Triantafyllos Didangelos, Anna Gotzamani-Psarrakou, Pantelis Zebekakis, Michael Daniilidis, John Yovos, and Kalliopi Kotsa Copyright © 2015 Konstantinos Toulis et al. All rights reserved. Do Behavioral Risk Factors for Prediabetes and Insulin Resistance Differ across the Socioeconomic Gradient? Results from a Community-Based Epidemiologic Survey Tue, 19 May 2015 07:31:03 +0000 To examine whether behavioral risk factors associated with diabetes (diet, BMI, waist circumference, physical activity, and sleep duration) are also related to both prediabetes and insulin resistance (IR), we used data from Boston Area Community Health (BACH) Survey (2010–2012, ). Logistic and linear regression models were used to test the association of lifestyle factors with prediabetes status, insulin resistance, and prediabetes or insulin resistance. All regression models were stratified by education and income levels (to examine whether risk factors had differential effects across socioeconomic factors) and adjusted for age, gender, race/ethnicity, family history of diabetes, and smoking status. We found that large waist circumference was consistently associated with higher levels of insulin resistance (IR) and increased odds of prediabetes. While the association between large waist circumference and IR was consistent across all levels of SES , the association between large waist circumference and prediabetes was only statistically significant in the highest socioeconomic strata with odds ratios of 1.68 (95% CI 1.07–2.62) and 1.88 (95% CI 1.22–2.92) for postgraduate degree and income strata, respectively. There was no association between diet, physical activity, sleep duration, and the presence of multiple risk factors and prediabetes or IR within SES strata. May H. Yang, Sue A. Hall, Rebecca S. Piccolo, Nancy N. Maserejian, and John B. McKinlay Copyright © 2015 May H. Yang et al. All rights reserved. Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy Tue, 19 May 2015 07:14:32 +0000 Aim. Our aim was (1) to determine the frequency of insulin resistance (IR) in patients with Duchenne/Becker muscular dystrophy (DMD/BMD), (2) to identify deleted exons of DMD gene associated with obesity and IR, and (3) to explore some likely molecular mechanisms leading to IR. Materials and Methods. In 66 patients with DMD/BMD without corticosteroids treatment, IR, obesity, and body fat mass were evaluated. Molecules involved in glucose metabolism were analyzed in muscle biopsies. Results show that 18.3%, 22.7%, and 68% were underweight, overweight, or obese, and with high adiposity, respectively; 48.5% and 36.4% presented hyperinsulinemia and IR, respectively. Underweight patients (27.3%) exhibited hyperinsulinemia and IR. Carriers of deletions in exons 45 (OR = 9.32; 95% CI = 1.16–74.69) and 50 (OR = 8.73; 95% CI = 1.17–65.10) from DMD gene presented higher risk for IR than noncarriers. We observed a greater staining of cytoplasmic aggregates for GLUT4 in muscle biopsies than healthy muscle tissue. Conclusion. Obesity, hyperinsulinemia, and IR were observed in DMD/BMD patients and are independent of corticosteroids treatment. Carriers of deletion in exons 45 or 50 from DMD gene are at risk for developing IR. It is suggested that alteration in GLUT4 in muscle fibers from DMD patients could be involved in IR. Maricela Rodríguez-Cruz, Raúl Sanchez, Rosa E. Escobar, Oriana del Rocío Cruz-Guzmán, Mardia López-Alarcón, Mariela Bernabe García, Ramón Coral-Vázquez, Guadalupe Matute, and Ana Claudia Velázquez Wong Copyright © 2015 Maricela Rodríguez-Cruz et al. All rights reserved. Diabetes, Endothelial Dysfunction, and Vascular Repair: What Should a Diabetologist Keep His Eye on? Mon, 18 May 2015 13:32:29 +0000 Cardiovascular complications are the most common complications of diabetes mellitus. A prominent attribute of diabetic cardiovascular complications is accelerated atherosclerosis, considered as a still incurable disease, at least at more advanced stages. The discovery of endothelial progenitor cells (EPCs), able to replace old and injured mature endothelial cells and capable of differentiating into healthy and functional endothelial cells, has offered the prospect of merging the traditional theories on the pathogenesis of atherosclerosis with evolving concepts of vascular biology. The literature supports the notion that EPC alterations are involved in the pathogenesis of vascular diseases in diabetics, but at present many questions remain unanswered. In this review the aspects linking endothelial progenitor cells to the altered vascular biology in diabetes mellitus are discussed. V. Altabas Copyright © 2015 V. Altabas. All rights reserved. Vascular Effects of Dietary Advanced Glycation End Products Mon, 18 May 2015 13:28:32 +0000 Evidence has accumulated lately demonstrating that advanced glycation end products (AGEs) play an important role in the development of diabetic and cardiovascular complications as well as the development of other chronic diseases. AGEs originating from diet have a significant contribution to the AGEs body pool and therefore dietary interventions aiming at reducing AGEs load are believed to exert health promoting effects. This review summarizes the evidence from clinical studies regarding effects of dietary AGEs on the vascular system, highlighting also the different aspects of vascular tests. It also advocates an extension of dietary recommendations towards the promotion of cooking methods that reduce dietary AGEs in consumed foods. Alin Stirban and Diethelm Tschöpe Copyright © 2015 Alin Stirban and Diethelm Tschöpe. All rights reserved. Trends in the Levels of Serum Lipids and Lipoproteins and the Prevalence of Dyslipidemia in Adults with Newly Diagnosed Type 2 Diabetes in the Southwest Chinese Han Population during 2003–2012 Mon, 18 May 2015 13:27:33 +0000 Objective. To determine the trends of serum lipid levels and dyslipidemia in adults newly diagnosed with type 2 diabetes mellitus during 2003–2012 in Southwest China. Methods. Serum lipid measurements of 994 adults were obtained from 5 independent, cross-sectional studies (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012). The main outcome measures were mean serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels; body mass index; hemoglobin A1C level; and the percentages of patients with dyslipidemia, hypertension, coronary heart disease, and cerebrovascular disease. Results. The mean total cholesterol and low-density lipoprotein cholesterol levels increased from 4.92 ± 1.15 to 5.30 ± 1.17 mmol/L (P = 0.039) and 2.72 ± 0.83 to 3.11 ± 1.09 mmol/L (P = 0.004), respectively, and the mean HDL cholesterol level declined from 1.22 ± 0.30 to 1.06 ± 0.24 mmol/L (P < 0.001). The percentages of patients with dyslipidemia increased gradually. The incidence of coronary heart and cerebrovascular diseases increased from 8.2% to 19.1% and 6.6% to 15.3%, respectively (P < 0.05). Conclusion. Unfavorable upward trends were observed in serum lipid levels and the prevalence of dyslipidemia, coronary heart disease, and cerebrovascular disease in adults newly diagnosed with type 2 diabetes mellitus in Southwest China during 2003–2012. Jing Tian, Hewen Chen, Fang Jia, Gangyi Yang, Shengbing Li, Ke Li, Lili Zhang, Jinlin Wu, and Dongfang Liu Copyright © 2015 Jing Tian et al. All rights reserved. Decreased Insulin Sensitivity and Impaired Fibrinolytic Activity in Type 2 Diabetes Patients and Nondiabetics with Ischemic Stroke Mon, 18 May 2015 13:10:52 +0000 We analyzed (a) insulin sensitivity (IS), (b) plasma insulin (PI), and (c) plasminogen activator inhibitor-1 (PAI-1) in type 2 diabetes (T2D) patients with (group A) and without (group B) atherothrombotic ischemic stroke (ATIS), nondiabetics with ATIS (group C), and healthy controls (group D). IS was determined by minimal model (Si). Si was lower in A versus B ( versus  min−1/mU/L × 104; ) and in C versus D ( versus  min−1/mU/L × 104; ). PI and PAI-1 were higher in A versus B (PI: versus  mU/L; , PAI-1: versus  mU/L; ) and in C versus D (PI: versus  mU/L; , PAI-1: versus  mU/L; ). Si correlated with PAI-1 in T2D patients and nondiabetics, albeit stronger in T2D. Binary logistic regression identified insulin, PAI-1, and Si as independent predictors for ATIS in T2D patients and nondiabetics. The results imply that insulin resistance and fasting hyperinsulinemia might exert their atherogenic impact through the impaired fibrinolysis. Aleksandra Jotic, Tanja Milicic, Nadezda Covickovic Sternic, Vladimir S. Kostic, Katarina Lalic, Veljko Jeremic, Milija Mijajlovic, Ljiljana Lukic, Natasa Rajkovic, Milorad Civcic, Marija Macesic, Jelena P. Seferovic, Jelena Stanarcic, Sandra Aleksic, and Nebojsa M. Lalic Copyright © 2015 Aleksandra Jotic et al. All rights reserved. Inverse Levels of Adiponectin in Type 1 and Type 2 Diabetes Are in Accordance with the State of Albuminuria Mon, 18 May 2015 12:06:30 +0000 Aims. To investigate the behaviour of adiponectin (ApN) in patients with type 1 and type 2 diabetic nephropathy. Methods. ApN and inflammatory and other markers of the metabolic syndrome were compared across diabetes types, albumin excretion rate (AER), and creatinine clearance (CrCl) categories in 219 type 1 and type 2 diabetic patients. Results. Significant differences among ApN levels according to AER were found in both types of diabetes (, , ). With the progression of albuminuria, ApN increased in type 1 and decreased in type 2 diabetes. Patients with decreased CrCl had higher ApN levels than those with normal CrCl in either type of diabetes (, , ). The best model for ApN () obtained from stepwise regression in type 1 diabetes included CrCl, BMI, WBC, CRP, and age, while in type 2 diabetes () it included ppPG, LDL, and UA. Conclusion. ApN behaved differently in relation to albuminuria, increasing with its progression in type 1 diabetes and decreasing in type 2 diabetes. It was however increased in the subgroups with decreased CrCl in both types of diabetes. Albuminuria seems to be more important than renal insufficiency in the definition of ApN levels in type 1 and type 2 diabetes. Spomenka Ljubic, Anamarija Jazbec, Martina Tomic, Ante Piljac, Dubravka Jurisic Erzen, Branko Novak, Snjezana Kastelan, Marijana Vucic Lovrencic, and Neva Brkljacic Copyright © 2015 Spomenka Ljubic et al. All rights reserved. A Randomised Controlled Trial to Delay or Prevent Type 2 Diabetes after Gestational Diabetes: Walking for Exercise and Nutrition to Prevent Diabetes for You Mon, 18 May 2015 11:57:12 +0000 Aims. To develop a program to support behaviour changes for women with a history of Gestational Diabetes Mellitus (GDM) and a Body Mass Index (BMI) > 25 kg/m2 to delay or prevent Type 2 Diabetes Mellitus. Methods. Women diagnosed with GDM in the previous 6 to 24 months and BMI > 25 kg/m2 were randomized to an intervention (I) () or a control (C) () group. The intervention was a pedometer program combined with nutrition coaching, with the primary outcome increased weight loss in the intervention group. Secondary outcomes included decreased waist and hip measurements, improved insulin sensitivity and body composition, increased physical activity, and improved self-efficacy in eating behaviours. Results. Median (IQR) results were as follows: weight: I −2.5 (2.3) kg versus C +0.2 (1.6) kg (), waist: I −3.6 (4.5) cm versus C −0.1 (3.6) cm (), and hip: I −5.0 (3.3) cm versus C −0.2 (2.6) cm (). There was clinical improvement in physical activity and eating behaviours and no significant changes in glucose metabolism or body composition. Conclusion. A pedometer program and nutrition coaching proved effective in supporting weight loss, waist circumference, physical activity, and eating behaviours in women with previous GDM. A. S. Peacock, F. E. Bogossian, S. A. Wilkinson, K. S. Gibbons, C. Kim, and H. D. McIntyre Copyright © 2015 A. S. Peacock et al. All rights reserved. Effects of Aerobic Exercise Based upon Heart Rate at Aerobic Threshold in Obese Elderly Subjects with Type 2 Diabetes Mon, 18 May 2015 11:45:49 +0000 In obese diabetic subjects, a correct life style, including diet and physical activity, is part of a correct intervention protocol. Thus, the aim of this study was to evaluate the effects of aerobic training intervention, based on heart rate at aerobic gas exchange threshold (), on clinical and physiological parameters in obese elderly subjects with type 2 diabetes (OT2DM). Thirty OT2DM subjects were randomly assigned to an intervention (IG) or control group (CG). The IG performed a supervised aerobic exercise training based on heart rate at whereas CG maintained their usual lifestyle. Anthropometric measures, blood analysis, peak oxygen consumption (), metabolic equivalent (), work rate (), and were assessed at baseline and after intervention. After training, patients enrolled in the IG had significantly higher () , , , and and significantly lower () weight, BMI, %FM, and waist circumference than before intervention. Both IG and CG subjects had lower glycated haemoglobin levels after intervention period. No significant differences were found for all the other parameters between pre- and posttraining and between groups. Aerobic exercise prescription based upon HR at could be a valuable physical intervention tool to improve the fitness level and metabolic equilibrium in OT2DM patients. Gian Pietro Emerenziani, Maria Chiara Gallotta, Marco Meucci, Luigi Di Luigi, Silvia Migliaccio, Lorenzo Maria Donini, Felice Strollo, and Laura Guidetti Copyright © 2015 Gian Pietro Emerenziani et al. All rights reserved. Sitagliptin: Is It Effective in Routine Clinical Practice? Mon, 18 May 2015 11:41:41 +0000 Aim. The present study was conducted to determine the glycaemic effects of sitagliptin in type 2 diabetes patients. Methods. Data was collected from patient medical records of a major teaching hospital in Malaysia, from 2009 to 2012. Glycated hemoglobin () values prior to and up to 12 months after the initiation of sitagliptin were analysed. The change in values was accounted for based on a generalized linear model generated using the Generalized Estimating Equations (GEE) method. Results and Discussion. Of the 457 patients, 53.6% were elderly and 81.4% were overweight. The mean (standard deviation) before initiation of sitagliptin was 8.5 (1.4)%. This dropped to 7.7 (1.4)%, 3 to 6 months after initiation of sitagliptin, with a mean difference of 0.8% (95% confidence interval (CI): 0.7–1.0; ). However, this value increased to 8.0 (1.7)% after 7 to 12 months on sitagliptin () with a mean difference from baseline of 0.6% (95% CI: 0.4–0.7; ). Conclusion. In routine clinical practice, sitagliptin produces a significant reduction in mean (0.8%) within the first 6 months of use which corresponds to efficacy data obtained in controlled clinical trials. However, this reduction was lesser, 7 to 12 month later. Rita Mohan Dallumal, Siew Siang Chua, David Bin-Chia Wu, and Shireene Ratna Vethakkan Copyright © 2015 Rita Mohan Dallumal et al. All rights reserved. The Difference Quantity of Urinary Peptides between Two Groups of Type 2 Diabetic Patients with or without Coronary Artery Disease Mon, 18 May 2015 10:30:43 +0000 Objectives. We aim to explore urinary biomarkers that could monitor CAD in type 2 diabetic patients. Materials and Methods. Urine samples from two groups, twenty-eight type 2 diabetic patients with coexisting CAD and thirty type 2 diabetic patients without CAD, were purified by MB-WCX and then analyzed by MALDI-TOF-MS. Subsequently, we compared the urinary peptide signatures of the two groups by use of ClinProTools2.1 and evaluated the potential ability of the differently expressed peptides to distinguish type 2 diabetic patients with coexisting CAD from type 2 diabetic patients without CAD by ROC analysis. Finally, the differently expressed peptides were identified by nanoliquid chromatography-tandem mass spectrometry. Results. There were six differently expressed peptides (m/z 1305.2, 1743.9, 2184.9, 2756.1, 3223.2, and 6196.1) between the two groups of subjects, and they were identified as fragments of isoform 1 of fibrinogen alpha chain precursor, prothrombin precursor, and interalpha-trypsin inhibitor heavy chain H4. The diagnostic efficacy of m/z 2756.1 and m/z 3223.2 was better than the other peptides. Area under ROC of the m/z 2756.1, and m/z 3223.2 was 0.98 and 0.93, respectively. Conclusions. These urinary peptides are potential urinary biomarkers for monitoring of type 2 diabetic patients with CAD. Guangzhen Fu, Mei Hu, Lina Chu, and Man Zhang Copyright © 2015 Guangzhen Fu et al. All rights reserved. Breaking Therapeutic Inertia in Type 2 Diabetes: Active Detection of In-Patient Cases Allows Improvement of Metabolic Control at Midterm Mon, 18 May 2015 10:25:30 +0000 Type 2 diabetes (T2D) exists in 25–40% of hospitalized patients. Therapeutic inertia is the delay in the intensification of a treatment and it is frequent in T2D. The objectives of this study were to detect patients admitted to surgical wards with hyperglycaemia (HH; fasting glycaemia > 140 mg/dL) as well as those with T2D and suboptimal chronic glycaemic control (SCGC) and to assess the midterm impact of treatment modifications indicated at discharge. A total of 412 HH patients were detected in a period of 18 months; 86.6% (357) had a diagnosed T2D. Their preadmittance was 7.7 ± 1.5%; 47% (189) had ≥ 7.4% (SCGC) and were moved to the upper step in the therapeutic algorithm at discharge. Another 15 subjects (3.6% of the cohort) had T2D according to their current . Ninety-four of the 189 SCGC patients were evaluated 3–6 months later. Their before in-hospital-intervention was 8.6 ± 1.2% and 7.5 ± 1.2% at follow-up (). Active detection of hyperglycaemia in patients admitted in conventional surgical beds permits the identification of T2D patients with SCGC as well as previously unknown cases. A shift to the upper step in the therapeutic algorithm at discharge improves this control. Hospitalization is an opportunity to break therapeutic inertia. Anna M. Lucas Martín, Elena Guanyabens, R. Zavala-Arauco, Joaquín Chamorro, Maria Luisa Granada, Didac Mauricio, and Manuel Puig-Domingo Copyright © 2015 Anna M. Lucas Martín et al. All rights reserved. Low Magnesium Levels and FGF-23 Dysregulation Predict Mitral Valve Calcification as well as Intima Media Thickness in Predialysis Diabetic Patients Mon, 18 May 2015 10:02:59 +0000 Background. Mitral valve calcification and intima media thickness (IMT) are common complications of chronic kidney disease (CKD) implicated with high cardiovascular mortality. Objective. To investigate the implication of magnesium and fibroblast growth factor-23 (FGF-23) levels with mitral valve calcification and IMT in CKD diabetic patients. Methods. Observational, prospective study involving 150 diabetic patients with mild to moderate CKD, divided according to Wilkins Score. Carotid-echodoppler and transthoracic echocardiography were used to assess calcification. Statistical tests used to establish comparisons between groups, to identify risk factors, and to establish cut-off points for prediction of mitral valve calcification. Results. FGF-23 values continually increased with higher values for both IMT and calcification whereas the opposite trend was observed for magnesium. FGF-23 and magnesium were found to independently predict mitral valve calcification and IMT . Using Kaplan-Meier analysis, the number of deaths was higher in patients with lower magnesium levels and poorer Wilkins score. The mean cut-off value for FGF-23 was 117 RU/mL and for magnesium 1.7 mg/dL. Conclusions. Hypomagnesemia and high FGF-23 levels are independent predictors of mitral valve calcification and IMT and are risk factors for cardiovascular mortality in this population. They might be used as diagnostic/therapeutic targets in order to better manage the high cardiovascular risk in CKD patients. Ana Paula Silva, Kristina Gundlach, Janine Büchel, Teresa Jerónimo, André Fragoso, Claudia Silva, Patrícia Guilherme, Nélio Santos, Marília Faísca, and Pedro Neves Copyright © 2015 Ana Paula Silva et al. All rights reserved. Psychometric Properties of the Diabetes Management Self-Efficacy Scale in Korean Patients with Type 2 Diabetes Mon, 18 May 2015 10:00:39 +0000 Objectives. The aims of this study were to perform a cultural translation of the DMSES and evaluate the psychometric properties of the translated scale in a Korean population with type 2 diabetics. Methods. This study was conducted in patients with diabetes recruited from university hospitals. The first stage of this study involved translating the DMSES into Korean using a forward- and backward-translation technique. The content validity was assessed by an expert group. In the second stage, the psychometric properties of the Korean version of the DMSES (K-DMSES) were evaluated. Results. The content validity of the K-DMSES was satisfactory. Sixteen-items clustered into four-subscales were extracted by exploratory factor analysis, and supported by confirmatory factor analysis. The construct validity of the K-DMSES with the Summary of Diabetes Self-Care Activities scale was satisfactory (, ). The Cronbach’s alpha and intraclass correlation coefficient were 0.92 and 0.85 (; 95% –0.91), respectively, which indicate excellent internal consistency reliability and test-retest reliability. Conclusions. The K-DMSES is a brief instrument that has demonstrated good psychometric properties. It is therefore feasible to use in practice, and is ready for use in clinical research involving Korean patients with type 2 diabetes. Eun-Hyun Lee, Jaap van der Bijl, Lillie M. Shortridge-Baggett, Seung Jin Han, and Seung Hei Moon Copyright © 2015 Eun-Hyun Lee et al. All rights reserved. Resistance to the Beneficial Metabolic Effects and Hepatic Antioxidant Defense Actions of Fibroblast Growth Factor 21 Treatment in Growth Hormone-Overexpressing Transgenic Mice Mon, 18 May 2015 09:59:47 +0000 Fibroblast growth factor 21 (FGF21) modulates a diverse range of biological functions, including glucose and lipid metabolism, adaptive starvation response, and energy homeostasis, but with limited mechanistic insight. FGF21 treatment has been shown to inhibit hepatic growth hormone (GH) intracellular signaling. To evaluate GH axis involvement in FGF21 actions, transgenic mice overexpressing bovine GH were used. Expectedly, in response to FGF21 treatment control littermates showed metabolic improvements whereas GH transgenic mice resisted most of the beneficial effects of FGF21, except an attenuation of the innate hyperinsulinemia. Since FGF21 is believed to exert its effects mostly at the transcriptional level, we analyzed and observed significant upregulation in expression of various genes involved in carbohydrate and lipid metabolism, energy homeostasis, and antioxidant defense in FGF21-treated controls, but not in GH transgenics. The resistance of GH transgenic mice to FGF21-induced changes underlines the necessity of normal GH signaling for the beneficial effects of FGF21. Ravneet K. Boparai, Oge Arum, Johanna G. Miquet, Michal M. Masternak, Andrzej Bartke, and Romesh K. Khardori Copyright © 2015 Ravneet K. Boparai et al. All rights reserved. Altered Daytime Fluctuation Pattern of Plasminogen Activator Inhibitor 1 in Type 2 Diabetes Patients with Coronary Artery Disease: A Strong Association with Persistently Elevated Plasma Insulin, Increased Insulin Resistance, and Abdominal Obesity Mon, 18 May 2015 09:48:02 +0000 This study was aimed at investigating daily fluctuation of PAI-1 levels in relation to insulin resistance (IR) and daily profile of plasma insulin and glucose levels in 26 type 2 diabetic (T2D) patients with coronary artery disease (CAD) (group A), 10 T2D patients without CAD (group B), 12 nondiabetics with CAD (group C), and 12 healthy controls (group D). The percentage of PAI-1 decrease was lower in group A versus group B (4.4 ± 2.7 versus 35.0 ± 5.4%; ) and in C versus D (14.0 ± 5.8 versus 44.7 ± 3.1%; ). HOMA-IR was higher in group A versus group B () and in C versus D (). Simultaneously, AUCs of PAI-1 and insulin were higher in group A versus group B () and in C versus D (), while AUC of glucose did not differ between groups. In multiple regression analysis waist-to-hip ratio and AUC of insulin were independent determinants of decrease in PAI-1. The altered diurnal fluctuation of PAI-1, especially in T2D with CAD, might be strongly influenced by a prolonged exposure to hyperinsulinemia in the settings of increased IR and abdominal obesity, facilitating altogether an accelerated atherosclerosis. Katarina Lalić, Aleksandra Jotić, Nataša Rajković, Sandra Singh, Ljubica Stošić, Ljiljana Popović, Ljiljana Lukić, Tanja Miličić, Jelena P. Seferović, Marija Maćešić, Jelena Stanarčić, Milorad Čivčić, Iva Kadić, and Nebojša M. Lalić Copyright © 2015 Katarina Lalić et al. All rights reserved. Role of the Insulin-Like Growth Factor Type 1 Receptor in the Pathogenesis of Diabetic Encephalopathy Mon, 18 May 2015 09:42:33 +0000 Defective cognitive function is common in patients with diabetes, suggesting that insulin normally exerts anabolic actions in neuron, namely, diabetic encephalopathy. However, because insulin can cross-activate the insulin-like growth factor type 1 receptor (IGF-1R), which also functions in most of tissues, such as muscle and bone, it has been difficult to establish the direct (IGF-1-independent) actions of insulin in the pathogenesis of diabetic encephalopathy. To overcome this problem, we examined insulin signaling and action in primary PC-12 cells engineered for conditional disruption of the IGF-1 receptor (ΔIGF-1R). The results showed that the lower glucose metabolism and high expression of IGF-1R occurred in the brain of the DE rat model. The results also showed the defect of IGF-1R could significantly improve the ability of glucose consumption and enhance sensitivity to insulin-induced IR and Akt phosphorylation in PC12 cells. And meanwhile, IGF-1R allele gene knockout (IGF-1Rneo) mice treated with HFD/STZ had better cognitive abilities than those of wild mice. Those results indicate that insulin exerts direct anabolic actions in neuron-like cells by activation of its cognate receptor and prove that IGF-1R plays an important role in the pathogenesis of diabetic encephalopathy. Duo Zhang, Shuang Jiang, and Heng Meng Copyright © 2015 Duo Zhang et al. All rights reserved. The Blocking on the Cathepsin B and Fibronectin Accumulation in Kidney Glomeruli of Diabetic Rats Mon, 18 May 2015 09:37:28 +0000 Hyperglycemia results in the activation of tissue angiotensin II. Angiotensin II stimulates the synthesis of ECM proteins and causes a decrease activity of proteolytic enzymes. The aim of this study was to assess the impact of multilevel blocking of the RAAS, cathepsin B activity, and fibronectin accumulation in the glomerular in the rats diabetes model. Sixty male Wistar rats were initially included. Diabetes was induced by intravenous administration of streptozotocin. The animals were randomized to six groups of ten rats in group. Rats in the four groups were treated with inhibitors of the RAAS: enalapril (EN), losartan (LOS), enalapril plus losartan (EN + LOS), and spironolactone (SPIR); another group received dihydralazine (DIH) and the diabetic rats (DM) did not receive any drug. After six weeks, we evaluated blood pressure, 24 h urine collection, and blood for biochemical parameters and kidneys. In this study, fluorometric, ELISA, and immunohistochemical methods were used. Administration of EN + LOS increased activity of cathepsin B in homogenates of glomeruli compared to DM. Losartan treatment resulted in reduction of the ratio kidney weight/body weight compared to untreated diabetic rats. SPIR resulted in the increase activity of cathepsin B in the homogenate of glomeruli. The values of cathepsin B in the plasma of rats in all studied groups were similar and showed no tendency. Aleksandra Wyczalkowska-Tomasik, Irena Bartlomiejczyk, Agnieszka Wirkowska, Lukasz Koperski, Barbara Gornicka, and Leszek Paczek Copyright © 2015 Aleksandra Wyczalkowska-Tomasik et al. All rights reserved. Prevalence of Self-Reported Diabetes and Its Associated Factors: A Population-Based Study in Brazil Mon, 18 May 2015 09:35:55 +0000 Aim. The aim of this study was to estimate the prevalence of diabetes and its associated risk factors in adults from Brasilia, Brazil. Methods. The present cross-sectional population-based study consisted of interviews with individuals aged 18–65 years. Participants were selected through two-stage probability sampling by clusters and stratified by sex and age. Demographic and clinical data were collected directly with participants from February to May 2012. Self-reported diabetes prevalence was calculated at a 95% confidence interval (CI). Prevalence ratios (PR) were adjusted by Poisson regression with robust variance. Results. In all, 1,820 individuals were interviewed. Diabetes prevalence in the adult population of Brasilia was 10.1% (95% CI, 8.5%–11.6%). Variables associated with diabetes were an age between 35 and 49 years (PR = 1.83; 95% CI, 1.19–2.82) or 50 and 65 years (PR = 1.95; 95% CI, 1.17–3.23), hypertension (PR = 4.04; 95% CI, 2.66–6.13), respiratory disease (PR = 1.67; 95% CI, 1.11–2.50), cardiovascular disease (PR = 1.74; 95% CI, 1.15–2.63), and pain/discomfort (PR = 1.71; 95% CI, 1.21–2.41). Conclusion. Diabetes is a prevalent condition in adults living in Brasilia, and disease risk increases with age and comorbidities. Future health policies should focus on screening programs and prevention for the more vulnerable groups. Fabiana A. F. Da-Mata, Tais F. Galvao, Mauricio G. Pereira, and Marcus T. Silva Copyright © 2015 Fabiana A. F. Da-Mata et al. All rights reserved.