Journal of Diabetes Research The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Intercellular Adhesion Molecule and Endogenous NOS Inhibitor: Asymmetric Dimethylarginine in Pregnant Women with Gestational Diabetes Mellitus Thu, 11 Feb 2016 06:53:35 +0000 Objective. The aim of the study was to evaluate the concentrations of soluble intercellular adhesion molecule-1 (s-ICAM-1) and endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA), as markers of endothelium dysfunction in patients with gestational diabetes mellitus (GDM). Patients and Methods. The levels of s-ICAM-1 and ADMA were analysed in the group of 56 patients with GDM and compared to 25 healthy pregnant women. The concentrations of s-ICAM-1 and ADMA were measured in serum using ELISA tests. Results. The groups did not differ by baseline descriptors: age ( versus years, NS) and gestational age ( versus hbd, NS). The patients with GDM were more obese (BMI versus  kg/m2, ) and had higher concentration of C-reactive protein ( versus  mg/L, ). In the GDM group the level of ADMA was lower ( versus  μmol/L, ) and the level of s-ICAM-1 was significantly higher (.12 versus  ng/mL, ) compared to controls. Conclusions. The pregnant women with GDM are characterized by higher concentration of s-ICAM-1 that reflects the activation and dysfunction of the endothelial cells. The decreased ADMA level in GDM patients seems to be preventive in the limitation of NO synthesis caused by the impaired insulin action and the endothelial dysfunction. Elżbieta Poniedziałek-Czajkowska, Radzisław Mierzyński, Dariusz Szymula, Bożena Leszczyńska-Gorzelak, and Jan Oleszczuk Copyright © 2016 Elżbieta Poniedziałek-Czajkowska et al. All rights reserved. Increased Autoreactivity of the Complement-Activating Molecule Mannan-Binding Lectin in a Type 1 Diabetes Model Wed, 10 Feb 2016 09:03:27 +0000 Background. Diabetic kidney disease is the leading cause of end-stage renal failure despite intensive treatment of modifiable risk factors. Identification of new drug targets is therefore of paramount importance. The complement system is emerging as a potential new target. The lectin pathway of the complement system, initiated by the carbohydrate-recognition molecule mannan-binding lectin (MBL), is linked to poor kidney prognosis in diabetes. We hypothesized that MBL activates complement upon binding within the diabetic glomerulus. Methods. We investigated this by comparing complement deposition and activation in kidneys from streptozotocin-induced diabetic mice and healthy control mice. Results. After 20 weeks of diabetes, glomerular deposition of MBL was significantly increased. Diabetic animals had 2.0-fold higher (95% CI 1.6–2.5) immunofluorescence intensity from anti-MBL antibodies compared with controls (). Diabetes and control groups did not differ in glomerular immunofluorescence intensity obtained by antibodies against complement factors C4, C3, and C9. However, the circulating complement activation product C3a was increased in diabetes as compared to control mice (). Conclusion. 20 weeks of diabetes increased MBL autoreactivity in the kidney and circulating C3a concentration. Together with previous findings, these results indicate direct effects of MBL within the kidney in diabetes. Jakob Appel Østergaard, Marieta Milkova Ruseva, Talat Habib Malik, Ingeborg Torp Hoffmann-Petersen, Matthew Caleb Pickering, Steffen Thiel, and Troels Krarup Hansen Copyright © 2016 Jakob Appel Østergaard et al. All rights reserved. Longitudinal Frequencies of Blood Leukocyte Subpopulations Differ between NOD and NOR Mice but Do Not Predict Diabetes in NOD Mice Thu, 04 Feb 2016 07:39:45 +0000 Immune phenotyping provides insight into disease pathogenesis and prognostic markers. Trajectories from age of 4 to 36 weeks were modeled for insulin autoantibodies and for leukocyte subpopulations in peripheral blood from female NOD () and NOR () mice. NOD mice had higher trajectories of insulin autoantibodies, CD4+ and CD8+ T lymphocytes, B lymphocytes, IgD+IgM− B lymphocytes, and NK cells and lower trajectories of CD4+CD25+ T lymphocytes, IgM+ B lymphocytes, granulocytes, and monocytes than NOR mice (all ). Of these, only the increased IAA trajectory was observed in NOD mice that developed diabetes as compared to NOD mice that remained diabetes-free. Therefore, the profound differences in peripheral blood leukocyte proportions observed between the diabetes-prone NOD mice and the diabetes-resistant mice do not explain the variation in diabetes development within NOD mice and do not provide markers for diabetes prediction in this model. Tanja Telieps, Meike Köhler, Irina Treise, Katharina Foertsch, Thure Adler, Dirk H. Busch, Martin Hrabě de Angelis, Admar Verschoor, Kerstin Adler, Ezio Bonifacio, and Anette-Gabriele Ziegler Copyright © 2016 Tanja Telieps et al. All rights reserved. Taurine Transporter Gene Expression in Mononuclear Blood Cells of Type 1 Diabetes Patients Wed, 03 Feb 2016 13:52:47 +0000 Background. Taurine transporter gene expression (RNA-TauT) has a role in retinal cell function and is modulated in vitro and in vivo by hyperglycemia and/or oxidative stress. This study was aimed at testing whether RNA-TauT gene expression is modified in blood mononuclear peripheral cells (MPCs) of type 1 diabetic patients, is related to plasma markers of oxidative stress or endothelial dysfunction, or, finally, is related to presence of retinopathy. Methods. RNA-TauT was measured in MPCs by real-time PCR-analysis in 35 type 1 diabetic patients and in 33 age- and sex-matched controls, additionally measuring plasma and cell taurine and markers of oxidative stress and endothelial dysfunction. Results. RNA-TauT, expressed as , was significantly higher in MPCs of type 1 diabetic patients than in controls [median (interquartile range): 1.32(0.31) versus 1.00(0.15); ]. In diabetic patients RNA-TauT was related to HbA1c (; ) and inversely to plasma homocysteine (; ) being additionally significantly higher in MPCs of patients without retinopathy [(); 1.36(0.34)] compared to those with retinopathy [(); 1.16(0.20)], independently from HbA1c or diabetes duration. Conclusions. RNA-TauT gene expression is significantly upregulated in MPCs of type 1 diabetes patients and is related to HbA1c levels and inversely to plasma homocysteine. Finally, in diabetes patients, RNA-TauT upregulation seems to be blunted in patients with retinopathy independently of their metabolic control or longer diabetes duration. Zaleida Napoli, Giuseppe Seghieri, Loria Bianchi, Roberto Anichini, Alessandra De Bellis, Ilaria Campesi, Ciriaco Carru, Stefano Occhioni, Angelo Zinellu, and Flavia Franconi Copyright © 2016 Zaleida Napoli et al. All rights reserved. Uptake and Effects of the e-Vita Personal Health Record with Self-Management Support and Coaching, for Type 2 Diabetes Patients Treated in Primary Care Wed, 03 Feb 2016 13:22:08 +0000 We studied the use, uptake, and effects of e-Vita, a personal health record, with self-management support and personalized asynchronized coaching, for type 2 diabetes patients treated in primary care. Patients were invited by their practice nurse to join the study aimed at testing use and effects of a personal health record. Patients were followed up for 6 months. Uptake and usage were monitored using log data. Outcomes were self-reported diabetes self-care, diabetes-related distress, and emotional wellbeing. Patients’ health status was collected from their medical chart. 132 patients agreed to participate in the study of which less than half (46.1%) did not return to the personal health record after 1st login. Only 5 patients used the self-management support program within the personal health record, 3 of whom asked a coach for feedback. Low use of the personal health record was registered. No statistical significant differences on any of the outcome measures were found between baseline and 6 month follow-up. This study showed minimal impact of implementing a personal health record including self-management support in primary diabetes care. Successful adoption of web-based platforms, as ongoing patient centered care, is hard to achieve without additional strategies aimed at enhancing patient motivation and engaging professionals. M. van Vugt, M. de Wit, F. Sieverink, Y. Roelofsen, S. H. Hendriks, H. J. G. Bilo, and F. J. Snoek Copyright © 2016 M. van Vugt et al. All rights reserved. Diabetic Retinopathy Is Strongly Predictive of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Wed, 03 Feb 2016 09:34:54 +0000 A well-established, comprehensive, and simple test battery was used here to re-evaluate risk factors for cardiovascular autonomic neuropathy (CAN) in type 2 diabetes. One hundred and seventy-four patients with type 2 diabetes were evaluated through the methods of deep breathing and Valsalva maneuver for correlation with factors that might influence the presence and severity of CAN. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment, and CAN was defined as a CASS score ≥2. Results showed that nephropathy, duration of diabetes, blood pressure, uric acid, and the presence of retinopathy and metabolic syndrome significantly correlated with the CASS score. Age may not be a risk factor for diabetic CAN. However, the effects of diabetes on CAN are more prominent in younger patients than in older ones. Diabetic retinopathy is the most significant risk factor predictive of the presence of CAN in patients with type 2 diabetes. Chih-Cheng Huang, Jong-Jer Lee, Tsu-Kung Lin, Nai-Wen Tsai, Chi-Ren Huang, Shu-Fang Chen, Cheng-Hsien Lu, and Rue-Tsuan Liu Copyright © 2016 Chih-Cheng Huang et al. All rights reserved. The IL-1β Receptor Antagonist SER140 Postpones the Onset of Diabetes in Female Nonobese Diabetic Mice Wed, 03 Feb 2016 07:57:58 +0000 The cytokine interleukin-1β (IL-1β) is known to stimulate proinflammatory immune responses and impair β-cell function and viability, all critical events in the pathogenesis of type 1 diabetes (T1D). Here we evaluate the effect of SER140, a small peptide IL-1β receptor antagonist, on diabetes progression and cellular pancreatic changes in female nonobese diabetic (NOD) mice. Eight weeks of treatment with SER140 reduced the incidence of diabetes by more than 50% compared with vehicle, decreased blood glucose, and increased plasma insulin. Additionally, SER140 changed the endocrine and immune cells dynamics in the NOD mouse pancreas. Together, the data suggest that SER140 treatment postpones the onset of diabetes in female NOD mice by interfering with IL-1β activated pathways. Helena Cucak, Gitte Hansen, Niels Vrang, Torben Skarsfeldt, Eva Steiness, and Jacob Jelsing Copyright © 2016 Helena Cucak et al. All rights reserved. miRNAs in Urine Extracellular Vesicles as Predictors of Early-Stage Diabetic Nephropathy Thu, 28 Jan 2016 13:06:53 +0000 Background. miR-192, miR-194, and miR-215 are enriched in the kidney and play roles in the pathogenesis of diabetic nephropathy (DN). Extracellular vesicles (EVs) can be detected in body fluids and may serve as disease biomarkers. Methods. Eighty type 2 diabetes patients with normoalbuminuria (), microalbuminuria (), or macroalbuminuria (), as well as 10 healthy controls, were enrolled in this study. Real-time PCR was used to evaluate urinary EV miRNAs expression. Results. The miR-192 levels were significantly higher than the miR-194 and miR-215 levels in urine EVs and all three miRNAs were significantly increased in the microalbuminuric group compared with the normoalbuminuric and control subjects but were decreased in the macroalbuminuric group. In patients with normoalbuminuria and microalbuminuria, miR-192 was positively correlated with albuminuria (, ) levels and transforming growth factor- (TGF-) β1 (, ) expression. Receiver operating characteristic (ROC) curve analysis revealed that miR-192 was better than miR-194 and miR-215 in discriminating the normoalbuminuric group from the microalbuminuric group. Exposure of human renal tubular epithelial cells to high glucose increased the expression of both miRNAs in cellular supernatant EVs, indicating a potential source. Conclusion. These results suggest the potential use of urinary EV miR-192 as a biomarker of the early stage of DN. Yijie Jia, Meiping Guan, Zongji Zheng, Qian Zhang, Chuan Tang, Wenwei Xu, Zhizhou Xiao, Ling Wang, and Yaoming Xue Copyright © 2016 Yijie Jia et al. All rights reserved. ClC-3 Expression and Its Association with Hyperglycemia Induced HT22 Hippocampal Neuronal Cell Apoptosis Tue, 26 Jan 2016 14:17:18 +0000 Although apoptosis plays an important role in the development of Diabetic Encephalopathy (DE), the underlying molecular mechanisms remain unclear. With respect to this, the present work aims to study the variation in chloride/proton exchanger ClC-3 expression and its association with HT22 hippocampal neuronal apoptosis under hyperglycemic condition in vitro. The cells were stimulated with added 0, 5, or 25 mM glucose or mannitol for up to 72 hours before assessing the rate of ClC-3 expression, cell viability, and apoptosis. In a consecutive experiment, cells received chloride channel blocker in addition to glucose. The rate of cellular death/apoptosis and viability was measured using Flow Cytometry and MTT assay, respectively. Changes in ClC-3 expression were assessed using immunofluorescence staining and western blot analysis. The results revealed a significant increase in cellular apoptosis and reduction in viability, associated with increased ClC-3 expression in high glucose group. Osmolarity had no role to play. Addition of chloride channel blocker completely abolished this effect. Thus we conclude that, with its increased expression, ClC-3 plays a major role in hyperglycemia induced hippocampal neuronal apoptosis. To strengthen our understanding of this aforesaid association, we conducted an extensive literature search which is presented in this paper. Feiyan Fan, Tao Liu, Xin Wang, Dongni Ren, Hui Liu, Pengxing Zhang, Zhen Wang, Nan Liu, Qian Li, Yanyang Tu, and Jianfang Fu Copyright © 2016 Feiyan Fan et al. All rights reserved. Interactions between Diabetes and the Heart Sun, 24 Jan 2016 12:55:08 +0000 John Skoularigis, Andreas Melidonis, Dirk Westermann, Vasiliki V. Georgiopoulou, Georgios Karagiannis, and Gregory Giamouzis Copyright © 2016 John Skoularigis et al. All rights reserved. Diabetic Retinopathy Screening Ratio Is Improved When Using a Digital, Nonmydriatic Fundus Camera Onsite in a Diabetes Outpatient Clinic Thu, 21 Jan 2016 08:35:16 +0000 Objective. To evaluate the effect of onsite screening with a nonmydriatic, digital fundus camera for diabetic retinopathy (DR) at a diabetes outpatient clinic. Research Design and Methods. This cross-sectional study included 502 patients, 112 with type 1 and 390 with type 2 diabetes. Patients attended screenings for microvascular complications, including diabetic nephropathy (DN), diabetic polyneuropathy (DP), and DR. Single-field retinal imaging with a digital, nonmydriatic fundus camera was used to assess DR. Prevalence and incidence of microvascular complications were analyzed and the ratio of newly diagnosed to preexisting complications for all entities was calculated in order to differentiate natural progress from missed DRs. Results. For both types of diabetes, prevalence of DR was 25.0% () and incidence 6.4% () (T1DM versus T2DM: prevalence: 35.7% versus 22.1%, incidence 5.4% versus 6.7%). 25.4% of all DRs were newly diagnosed. Furthermore, the ratio of newly diagnosed to preexisting DR was higher than those for DN () and DP () representing at least 13 patients with missed DR. Conclusions. The results indicate that implementing nonmydriatic, digital fundus imaging in a diabetes outpatient clinic can contribute to improved early diagnosis of diabetic retinopathy. Pia Roser, Hannes Kalscheuer, Jan B. Groener, Daniel Lehnhoff, Roman Klein, Gerd U. Auffarth, Peter P. Nawroth, Florian Schuett, and Gottfried Rudofsky Copyright © 2016 Pia Roser et al. All rights reserved. Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients: Increased Genetic Load of Islet-Expressed and Cytokine-Regulated Candidate Genes Predicts Poorer Glycemic Control Wed, 20 Jan 2016 08:00:48 +0000 Genome-wide association studies (GWAS) have identified over 40 type 1 diabetes risk loci. The clinical impact of these loci on β-cell function during disease progression is unknown. We aimed at testing whether a genetic risk score could predict glycemic control and residual β-cell function in type 1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease progression. Two-thirds of 46 GWAS candidate genes examined were expressed in human islets, and 11 of these significantly changed expression levels following exposure to proinflammatory cytokines (IL-1β + IFNγ + TNFα) for 48 h. Using the GWAS single nucleotide polymorphisms (SNPs) from each locus, we constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D. With each additional risk allele carried, HbA1c levels increased significantly within first year after diagnosis. Network and gene ontology (GO) analyses revealed that several of the 11 candidate genes have overlapping biological functions and interact in a common network. Our results may help predict disease progression in newly diagnosed children with T1D which can be exploited for optimizing treatment. Caroline A. Brorsson, Lotte B. Nielsen, Marie Louise Andersen, Simranjeet Kaur, Regine Bergholdt, Lars Hansen, Henrik B. Mortensen, Flemming Pociot, Joachim Størling, and Hvidoere Study Group on Childhood Diabetes Copyright © 2016 Caroline A. Brorsson et al. All rights reserved. Protective Effects of Celastrol on Diabetic Liver Injury via TLR4/MyD88/NF-κB Signaling Pathway in Type 2 Diabetic Rats Tue, 19 Jan 2016 16:17:35 +0000 Immune and inflammatory pathways play a central role in the pathogenesis of diabetic liver injury. Celastrol is a potent immunosuppressive and anti-inflammatory agent. So far, there is no evidence regarding the mechanism of innate immune alterations of celastrol on diabetic liver injury in type 2 diabetic animal models. The present study was aimed at investigating protective effects of celastrol on the liver injury in diabetic rats and at elucidating the possible involved mechanisms. We analyzed the liver histopathological and biochemical changes and the expressions of TLR4 mediated signaling pathway. Compared to the normal control group, diabetic rats were found to have obvious steatohepatitis and proinflammatory cytokine activities were significantly upregulated. Celastrol-treated diabetic rats show reduced hepatic inflammation and macrophages infiltration. The expressions of TLR4, MyD88, NF-κB, and downstream inflammatory factors IL-1β and TNFα in the hepatic tissue of treated rats were downregulated in a dose-dependent manner. We firstly found that celastrol treatment could delay the progression of diabetic liver disease in type 2 diabetic rats via inhibition of TLR4/MyD88/NF-κB signaling cascade pathways and its downstream inflammatory effectors. Li-ping Han, Chun-jun Li, Bei Sun, Yun Xie, Yue Guan, Ze-jun Ma, and Li-ming Chen Copyright © 2016 Li-ping Han et al. All rights reserved. Association between Self-Reported Habitual Snoring and Diabetes Mellitus: A Systemic Review and Meta-Analysis Tue, 19 Jan 2016 15:06:27 +0000 Aim. Several studies have reported an association between self-reported habitual snoring and diabetes mellitus (DM); however, the results are inconsistent. Methods. Electronic databases including PubMed and EMBASE were searched. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association between snoring and DM using a random-effects model. Heterogeneity, subgroup, and sensitivity analyses were also evaluated. Begg’s, Egger’s tests and funnel plots were used to evaluate publication bias. Results. A total of eight studies (six cross sectional and two prospective cohort studies) pooling 101,246 participants were included. Of the six cross sectional studies, the summary OR and 95% CI of DM in individuals that snore compared with nonsnorers were 1.37 (95% CI: 1.20–1.57, ). There was no heterogeneity across the included studies (%, ). When stratified by gender, the pooled OR (95% CI) was 1.59 (1.20–2.11) in females (), and 0.89 (0.65–1.22) in males (). Of the two prospective studies, the pooled RR was 1.65 (95% CI, 1.30–2.08). Conclusions. Self-reported habitual snoring is statistically associated with DM in females, but not in males. This meta-analysis indicates a need to paying attention to the effect of snoring on the occurrence of DM in females. Xiaolu Xiong, Anyuan Zhong, Huajun Xu, and Chun Wang Copyright © 2016 Xiaolu Xiong et al. All rights reserved. New Horizons in Diabetology Mon, 18 Jan 2016 13:03:22 +0000 Ali Tootee, Garth Warnock, Aziz Ghahari, and Bagher Larijani Copyright © 2016 Ali Tootee et al. All rights reserved. Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids Mon, 18 Jan 2016 12:51:12 +0000 Tacrolimus and sirolimus are important immunosuppressive drugs used in human islet transplantation; however, they are linked to detrimental effects on islets and reduction of long-term graft function. Few studies investigate the direct effects of these drugs combined in parallel with single drug exposure. Human islets were treated with or without tacrolimus (30 μg/L), sirolimus (30 μg/L), or a combination thereof for 24 hrs. Islet function as well as apoptosis was assessed by glucose-stimulated insulin secretion (GSIS) and Cell Death ELISA. Proinflammatory cytokines were analysed by qRT-PCR and Bio-Plex. Islets exposed to the combination of sirolimus and tacrolimus were treated with or without methylprednisolone (1000 μg/L) and the expression of the proinflammatory cytokines was investigated. We found the following: (i) No additive reduction in function and viability in islets existed when tacrolimus and sirolimus were combined compared to the single drug. (ii) Increased expression of proinflammatory cytokines mRNA and protein levels in islets took place. (iii) Methylprednisolone significantly decreased the proinflammatory response in islets induced by the drug combination. Although human islets are prone to direct toxic effect of tacrolimus and sirolimus, we found no additive effects of the drug combination. Short-term exposure of glucocorticoids could effectively reduce the proinflammatory response in human islets induced by the combination of tacrolimus and sirolimus. Kristine Kloster-Jensen, Afaf Sahraoui, Nils Tore Vethe, Olle Korsgren, Stein Bergan, Aksel Foss, and Hanne Scholz Copyright © 2016 Kristine Kloster-Jensen et al. All rights reserved. High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia Mon, 18 Jan 2016 10:50:08 +0000 Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX). Diabetes was induced via multiple low-dose injections of streptozotocin and blood glucose was maintained at moderate hyperglycemia (9–17 mM) through insulin supplementation. Exercise training consisted of daily treadmill running for 10 weeks. Compared to C, D had blunted baroreflex sensitivity, increased vascular sympathetic tone, increased serum neuropeptide Y (NPY), and decreased intrinsic heart rate. In contrast, DX differed from D in all measures of CAN (except NPY), including heart rate variability. These findings demonstrate that this T1DM model elicits deficits and exercise-mediated improvements to CV autonomic function which are reflective of clinical T1DM. Kenneth N. Grisé, T. Dylan Olver, Matthew W. McDonald, Adwitia Dey, Mao Jiang, James C. Lacefield, J. Kevin Shoemaker, Earl G. Noble, and C. W. James Melling Copyright © 2016 Kenneth N. Grisé et al. All rights reserved. Clinical Trial Assessing the Efficacy of Gabapentin Plus B Complex (B1/B12) versus Pregabalin for Treating Painful Diabetic Neuropathy Sun, 17 Jan 2016 08:29:11 +0000 Introduction. Painful diabetic neuropathy (PDN) is a prevalent and impairing disorder. The objective of this study was to show the efficacy and safety of gabapentin (GBP) plus complex B vitamins: thiamine (B1) and cyanocobalamine (B12) compared to pregabalin in patients with moderate to severe intensity PDN. Method. Multicenter, randomized, blind study. Two hundred and seventy patients were evaluated, 147 with GBP/B1/B12 and 123 with PGB, with a 7/10 pain intensity on the Visual Analog Scale (VAS). Five visits (12 weeks) were scheduled. The GBP/B1 (100 mg)/B12 (20 mg) group started with 300 mg at visit 1 to 3600 mg at visit 5. The PGB group started with 75 mg/d at visit 1 to 600 mg/d at visit 5. Different safety and efficacy scales were applied, as well as adverse event assessment. Results. Both drugs showed reduction of pain intensity, without significant statistical difference (). In the GBP/B1/B12 group, an improvement of at least 30% on VAS correlated to a 900 mg/d dose, compared with PGB 300 mg/d. Likewise, occurrence of vertigo was lower in the GBP/B1-B12 group, with a significant statistical difference, . Conclusions. Our study shows that GPB/B1-B12 combination is as effective as PGB. Nonetheless, pain intensity reduction is achieved with 50% of the minimum required gabapentin dose alone (800 to 1600 mg/d) in classic NDD trials. Less vertigo and dizziness occurrence was also observed in the GBP/B1/B12 group. This trial is registered with NCT01364298. Alberto Mimenza Alvarado and Sara Aguilar Navarro Copyright © 2016 Alberto Mimenza Alvarado and Sara Aguilar Navarro. All rights reserved. Vitamin D Deficiency Is Not Associated with Diabetic Retinopathy or Maculopathy Thu, 14 Jan 2016 10:25:40 +0000 Background. Experimental and clinical studies suggest a possible association between vitamin D deficiency and both diabetic retinopathy and maculopathy. Methods. We have performed a cross-sectional study in adults with types 1 and 2 diabetes mellitus. The relationship between the presence and severity of diabetic retinopathy and maculopathy with serum 25-hydroxyvitamin D concentration was evaluated using logistic regression analyses in the presence of demographic and clinical covariates. Results. 657 adults with diabetes were stratified based on retinopathy grading: No Diabetic Retinopathy (39%), Background Diabetic Retinopathy (37%), Preproliferative Diabetic Retinopathy (21%), and Proliferative Diabetic Retinopathy (3%), respectively. There were no differences in serum 25-hydroxyvitamin D concentrations (25(OH)D) between the groups ( versus versus versus  ng/mL, ). Logistic regression analysis demonstrated no statistically significant relationship between the severity of retinopathy and serum 25(OH)D. Furthermore, there was no difference in serum 25(OH)D between those with (, 14%) and those without (, 86%) Diabetic Maculopathy ( versus , ) and no relationship was demonstrated by logistic regression analyses between the two variables. Conclusions. This study has found no association between serum 25(OH)D and the presence and severity of diabetic retinopathy or maculopathy. Uazman Alam, Yasar Amjad, Anges Wan Shan Chan, Omar Asghar, Ioannis N. Petropoulos, and Rayaz A. Malik Copyright © 2016 Uazman Alam et al. All rights reserved. Erratum to “NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia” Wed, 13 Jan 2016 08:47:56 +0000 Pan Gao, Fang-Fang He, Hui Tang, Chun-Tao Lei, Shan Chen, Xian-Fang Meng, Hua Su, and Chun Zhang Copyright © 2016 Pan Gao et al. All rights reserved. Lifestyle Interventions to Prevent Type 2 Diabetes: A Systematic Review of Economic Evaluation Studies Wed, 13 Jan 2016 06:56:40 +0000 Objective. To summarize key findings of economic evaluations of lifestyle interventions for the primary prevention of type 2 diabetes (T2D) in high-risk subjects. Methods. We conducted a systematic review of peer-reviewed original studies published since January 2009 in English, French, and Spanish. Eligible studies were identified through relevant databases including PubMed, Medline, National Health Services Economic Evaluation, CINHAL, EconLit, Web of sciences, EMBASE, and the Latin American and Caribbean Health Sciences Literature. Studies targeting obesity were also included. Data were extracted using a standardized method. The BMJ checklist was used to assess study quality. The heterogeneity of lifestyle interventions precluded a meta-analysis. Results. Overall, 20 studies were retained, including six focusing on obesity control. Seven were conducted within trials and 13 using modeling techniques. T2D prevention by physical activity or diet or both proved cost-effective according to accepted thresholds, except for five inconclusive studies, three on diabetes prevention and two on obesity control. Most studies exhibited limitations in reporting results, primarily with regard to generalizability and justification of selected sensitivity parameters. Conclusion. This confirms that lifestyle interventions for the primary prevention of diabetes are cost-effective. Such interventions should be further promoted as sound investment in the fight against diabetes. Koffi Alouki, Hélène Delisle, Clara Bermúdez-Tamayo, and Mira Johri Copyright © 2016 Koffi Alouki et al. All rights reserved. Community-Based Diabetes Screening and Risk Assessment in Rural West Virginia Tue, 12 Jan 2016 11:18:50 +0000 This project utilized a cross-sectional study design to assess diabetes risk among 540 individuals from 12 counties using trained extension agents and community organizations in West Virginia. Individuals were screened for diabetes using (1) the validated 7-item diabetes risk assessment survey and (2) hemoglobin A1c tests. Demographic and lifestyle behaviors were also collected. The average age, body mass index, and A1c were , , and , respectively. The majority were females, Non-Hispanic Whites with no prior diagnosis of diabetes. Screenings showed that 61.8% of participants were at high risk for diabetes. Family history of diabetes (siblings or parents), overweight or obese status, sedentary lifestyle, and older age were commonly prevalent risk factors. Higher risk scores computed from the 7-item questions correlated positively with higher A1c (, ). In multivariate logistic regression analyses, higher diabetes risk was predicted by obesity, older age, family history of hypertension, and gestational diabetes. Females were 4 times at higher risk than males. The findings indicated that community-based screenings were an effective way to assess diabetes risk in rural West Virginia. Linking diabetes screenings with referrals to lifestyle programs for high risk individuals can help reduce the burden of diabetes in the state. Ranjita Misra, Cindy Fitch, David Roberts, and Dana Wright Copyright © 2016 Ranjita Misra et al. All rights reserved. Metabolic Health Has Greater Impact on Diabetes than Simple Overweight/Obesity in Mexican Americans Sun, 10 Jan 2016 13:20:46 +0000 Purpose. To compare the risk for diabetes in each of 4 categories of metabolic health and BMI. Methods. Participants were drawn from the Cameron County Hispanic Cohort, a randomly selected Mexican American cohort in Texas on the US-Mexico border. Subjects were divided into 4 phenotypes according to metabolic health and BMI: metabolically healthy normal weight, metabolically healthy overweight/obese, metabolically unhealthy normal weight, and metabolically unhealthy overweight/obese. Metabolic health was defined as having less than 2 metabolic abnormalities. Overweight/obese status was assessed by BMI higher than 25 kg/m2. Diabetes was defined by the 2010 ADA definition or by being on a diabetic medication. Results. The odds ratio for diabetes risk was 2.25 in the metabolically healthy overweight/obese phenotype (95% CI 1.34, 3.79), 3.78 (1.57, 9.09) in the metabolically unhealthy normal weight phenotype, and 5.39 (3.16, 9.20) in metabolically unhealthy overweight/obese phenotype after adjusting for confounding factors compared with the metabolically healthy normal weight phenotype. Conclusions. Metabolic health had a greater effect on the increased risk for diabetes than overweight/obesity. Greater focus on metabolic health might be a more effective target for prevention and control of diabetes than emphasis on weight loss alone. Shenghui Wu, Susan P. Fisher-Hoch, Belinda Reninger, Kristina Vatcheva, and Joseph B. McCormick Copyright © 2016 Shenghui Wu et al. All rights reserved. Conserved Metabolic Changes in Nondiabetic and Type 2 Diabetic Bariatric Surgery Patients: Global Metabolomic Pilot Study Sun, 10 Jan 2016 12:18:55 +0000 The goal of this study was to provide insight into the mechanism by which bariatric surgical procedures led to weight loss and improvement or resolution of diabetes. Global biochemical profiling was used to evaluate changes occurring in nondiabetic and type 2 diabetic (T2D) patients experiencing either less extreme sleeve gastrectomy or a full gastric bypass. We were able to identify changes in metabolism that were affected by standard preoperation liquid weight loss diet as well as by bariatric surgery itself. Preoperation weight-loss diet was associated with a strong lipid metabolism signature largely related to the consumption of adipose reserves for energy production. Glucose usage shift away from glycolytic pyruvate production toward pentose phosphate pathway, via glucose-6-phosphate, appeared to be shared across all patients regardless of T2D status or bariatric surgery procedure. Our results suggested that bariatric surgery might promote antioxidant defense and insulin sensitivity through both increased heme synthesis and HO activity or expression. Changes in histidine and its metabolites following surgery might be an indication of altered gut microbiome ecology or liver function. This initial study provided broad understanding of how metabolism changed globally in morbidly obese nondiabetic and T2D patients following weight-loss surgery. Konrad Sarosiek, Kirk L. Pappan, Ankit V. Gandhi, Shivam Saxena, Christopher Y. Kang, Heather McMahon, Galina I. Chipitsyna, David S. Tichansky, and Hwyda A. Arafat Copyright © 2016 Konrad Sarosiek et al. All rights reserved. Characteristics of Type 2 Diabetes with Ketosis in Baoshan, Yunnan of China Sun, 10 Jan 2016 11:38:08 +0000 Objectives. The study provided data to demonstrate the characteristics of type 2 diabetes (T2D) with ketosis in rural parts of south-west border of China in order to help health professionals with optimizing diabetic care. Methods. All hospitalized adult diabetic patients consecutively between January 2011 and July 2015 in Baoshan People’s Hospital, Yunnan province of China, were evaluated. T2D with ketosis, ordinary T2D (without ketosis), and type 1 diabetes (T1D) patients were analyzed according to the clinical and biochemical parameters and chronic complications in these subjects. Results. The prevalence of T2D with ketosis was 12% in the whole study subjects. Overweight and obese patients were predominant (49.1%) in T2D patients with ketosis. The mean HbA1c (%, ), fasting plasma glucose ( mmol/L, ), and plasma triglyceride ( mmol/L, ) in T2D patients with ketosis were significantly higher than ordinary T2D patients without ketosis. Infections were the most common inducements in T2D patients with ketosis. Chronic complications including peripheral neuropathy (34.9%), retinopathy (12.7%), diabetic foot (18.1%), and persistent microalbuminuria (11.7%) were common in T2D patients with ketosis. Conclusions. This study indicated the poor glycemic control in diabetic patients in rural areas of south-west part of China. More efforts were urgently required to popularize public health education and improve medical quality in diabetic treatment in these regions. Shichun Du, Xia Yang, Degang Shi, and Qing Su Copyright © 2016 Shichun Du et al. All rights reserved. Effect of Ranirestat on Sensory and Motor Nerve Function in Japanese Patients with Diabetic Polyneuropathy: A Randomized Double-Blind Placebo-Controlled Study Sun, 10 Jan 2016 11:33:30 +0000 We conducted a 26-week oral-administration study of ranirestat (an aldose reductase inhibitor) at a once-daily dose of 20 mg to evaluate its efficacy and safety in Japanese patients with diabetic polyneuropathy (DPN). The primary endpoint was summed change in sensory nerve conduction velocity (NCV) for the bilateral sural and proximal median sensory nerves. The sensory NCV was significantly () improved by ranirestat. On clinical symptoms evaluated with the use of modified Toronto Clinical Neuropathy Score (mTCNS), obvious efficacy was not found in total score. However, improvement in the sensory test domain of the mTCNS was significant () in a subgroup of patients diagnosed with neuropathy according to the TCNS severity classification. No clinically significant effects on safety parameters including hepatic and renal functions were observed. Our results indicate that ranirestat is effective on DPN (Japic CTI-121994). Jo Satoh, Nobuo Kohara, Kenji Sekiguchi, and Yasuyuki Yamaguchi Copyright © 2016 Jo Satoh et al. All rights reserved. Knowledge and Lifestyle-Associated Prevalence of Obesity among Newly Diagnosed Type II Diabetes Mellitus Patients Attending Diabetic Clinic at Komfo Anokye Teaching Hospital, Kumasi, Ghana: A Hospital-Based Cross-Sectional Study Sun, 10 Jan 2016 08:59:31 +0000 This study aimed to determine the knowledge and prevalence of obesity among Ghanaian newly diagnosed type 2 diabetics. This cross-sectional study was conducted among diagnosed type 2 diabetics. Structured questionnaire was used to obtain data. Anthropometric measurements and fasting blood sugar levels were also assessed. Participants had adequate knowledge about the general concept of obesity (72.0%) and method of weight measurement (98.6%) but were less knowledgeable of ideal body weight (4.2%). The commonly known cause, complication, and management of obesity were poor diet (76.9%), hypertension (81.8%), and diet modification (86.7%), respectively. The anthropometric measures were higher among females compared to males. Prevalence of obesity was 61.3% according to WHR classification, 40.8% according to WHtR classification, 26.1% according to WC, and 14.8% according to BMI classification. Being female was significantly associated with high prevalence of obesity irrespective of the anthropometric measure used (). Taking of snacks in meals, eating meals late at night, physical inactivity, excessive fast food intake, and alcoholic beverage intake were associated with increased prevalence of obesity (). Prevalence of obesity is high among diabetic patient and thus increasing effort towards developing and making education programs by focusing on adjusting to lifestyle modifications is required. Yaa Obirikorang, Christian Obirikorang, Enoch Odame Anto, Emmanuel Acheampong, Nyalako Dzah, Caroline Nkrumah Akosah, and Emmanuella Batu Nsenbah Copyright © 2016 Yaa Obirikorang et al. All rights reserved. JNK1 Deficient Insulin-Producing Cells Are Protected against Interleukin-1β-Induced Apoptosis Associated with Abrogated Myc Expression Sun, 10 Jan 2016 08:02:53 +0000 The relative contributions of the JNK subtypes in inflammatory β-cell failure and apoptosis are unclear. The JNK protein family consists of JNK1, JNK2, and JNK3 subtypes, encompassing many different isoforms. INS-1 cells express JNK1α1, JNK1α2, JNK1β1, JNK1β2, JNK2α1, JNK2α2, JNK3α1, and JNK3α2 mRNA isoform transcripts translating into 46 and 54 kDa isoform JNK proteins. Utilizing Lentiviral mediated expression of shRNAs against JNK1, JNK2, or JNK3 in insulin-producing INS-1 cells, we investigated the role of individual JNK subtypes in IL-1β-induced β-cell apoptosis. JNK1 knockdown prevented IL-1β-induced INS-1 cell apoptosis associated with decreased 46 kDa isoform JNK protein phosphorylation and attenuated Myc expression. Transient knockdown of Myc also prevented IL-1β-induced apoptosis as well as caspase 3 cleavage. JNK2 shRNA potentiated IL-1β-induced apoptosis and caspase 3 cleavage, whereas JNK3 shRNA did not affect IL-1β-induced β-cell death compared to nonsense shRNA expressing INS-1 cells. In conclusion, JNK1 mediates INS-1 cell death associated with increased Myc expression. These findings underline the importance of differentiated targeting of JNK subtypes in the development of inflammatory β-cell failure and destruction. Michala Prause, Christopher Michael Mayer, Caroline Brorsson, Klaus Stensgaard Frederiksen, Nils Billestrup, Joachim Størling, and Thomas Mandrup-Poulsen Copyright © 2016 Michala Prause et al. All rights reserved. Gmelina arborea Roxb. (Family: Verbenaceae) Extract Upregulates the β-Cell Regeneration in STZ Induced Diabetic Rats Wed, 06 Jan 2016 12:42:54 +0000 Gmelina arborea Roxb. (common name: Et-demata, Family: Verbenaceae) has been used traditionally in Sri Lanka as a remedy against diabetes mellitus. The objective of the present study was to evaluate antidiabetic mechanisms of the aqueous bark extract of G. arborea in streptozotocin induced (STZ) diabetic male Wistar rats. Aqueous bark extract of G. arborea (1.00 g/kg) and glibenclamide as the standard drug (0.50 mg/kg) were administered orally using a gavage to STZ diabetic rats (65 mg/kg, ip) for 30 days. The antidiabetic mechanisms of aqueous extract of G. arborea (1.00 g/kg) were determined at the end of the experiment. The fasting blood glucose concentration was significantly lowered and the serum insulin and C-peptide concentrations were increased by 57% and 39% in plant extract treated rats on day 30, respectively (). The histopathology and immunohistochemistry results of the plant extract treated group showed a regenerative effect on β-cells of the pancreas in diabetic rats. In addition, serum lipid parameters were improved in G. arborea extract treated diabetic rats. The results revealed that the aqueous stem bark extract of G. arborea (1.00 g/kg) showed beneficial effects against diabetes mellitus through upregulating the β-cell regeneration and biosynthesis of insulin in diabetic rats. Anoja Priyadarshani Attanayake, Kamani Ayoma Perera Wijewardana Jayatilaka, Chitra Pathirana, and Lakmini Kumari Boralugoda Mudduwa Copyright © 2016 Anoja Priyadarshani Attanayake et al. All rights reserved. Noninsulin Antidiabetic Drugs for Patients with Type 2 Diabetes Mellitus: Are We Respecting Their Contraindications? Wed, 06 Jan 2016 12:20:15 +0000 Aim. To assess prescribing practices of noninsulin antidiabetic drugs (NIADs) in T2DM with several major contraindications according to prescribing information or clinical guidelines: renal failure, heart failure, liver dysfunction, or history of bladder cancer. Methods. Cross-sectional, descriptive, multicenter study. Electronic medical records were retrieved from all T2DM subjects who attended primary care centers pertaining to the Catalan Health Institute in Catalonia in 2013 and were pharmacologically treated with any NIAD alone or in combination. Results. Records were retrieved from a total of 255,499 pharmacologically treated patients. 78% of patients with some degree of renal impairment (glomerular filtration rate (GFR) < 60 mL/min) were treated with metformin and 31.2% with sulfonylureas. Even in the event of severe renal failure (GFR < 30 mL/min), 35.3% and 22.5% of patients were on metformin or sulfonylureas, respectively. Moreover, metformin was prescribed to more than 60% of patients with moderate or severe heart failure. Conclusion. Some NIADs, and in particular metformin, were frequently used in patients at high risk of complications when they were contraindicated. There is a need to increase awareness of potential inappropriate prescribing and to monitor the quality of prescribing patterns in order to help physicians and policymakers to yield better clinical outcomes in T2DM. Irene Ruiz-Tamayo, Josep Franch-Nadal, Manel Mata-Cases, Dídac Mauricio, Xavier Cos, Antonio Rodriguez-Poncelas, Joan Barrot, Gabriel Coll-de-Tuero, and Xavier Mundet-Tudurí Copyright © 2016 Irene Ruiz-Tamayo et al. All rights reserved.