Journal of Diabetes Research The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Influence of Melatonin on the Proliferative and Apoptotic Responses of the Prostate under Normal and Hyperglycemic Conditions Thu, 30 Jul 2015 12:12:35 +0000 The antitumor properties of melatonin (MLT) are known for prostate cancer cells. This study investigated whether MLT affects prostate maturation and interferes with tissue injuries induced by diabetes. MLT was administered to Wistar rats from 5 weeks of age in the drinking water (10 μg/kg b.w.), and diabetes was induced at the 13th week by streptozotocin (4.5 mg/100g b.w., i.p.). The animals were euthanized in the 14th and 21st weeks. MLT reduced the immunostained cells for androgen receptor (AR) by 10% in younger rats. Diabetes decreased cell proliferation and increased apoptosis. MLT treatment impeded apoptosis and augmented proliferation and PCNA content in prostate following long-term diabetes due to restoration of testosterone levels and expression of melatonin receptor type 1B. The effect of MLT (500 µM, 5 mM, and 10 mM) on androgen-dependent (22Rv1) and androgen-independent (PC3) cancer cells and human prostate epithelial cells (PNTA1) under normal and hyperglycemic conditions (HG, 450 mg/dL) was analyzed. Contrary to PNTA1 and 22Rv1 cells, MLT improved the proliferation of PC3 cells in hyperglycemic medium. The combined data indicated that MLT had proliferative and antiapoptotic effects in prostate cells subjected to HG levels and it seems to involve specific MLT pathways rather than AR. Marina G. Gobbo, Nishtman Dizeyi, Per-Anders Abrahamsson, Per-Anders Bertilsson, Viviane Sanches Masitéli, Eloisa Zanin Pytlowanciv, Sebastião R. Taboga, and Rejane M. Góes Copyright © 2015 Marina G. Gobbo et al. All rights reserved. Cross Talk between Lipid Metabolism and Inflammatory Markers in Patients with Diabetic Retinopathy Wed, 29 Jul 2015 07:12:59 +0000 Purpose. The purpose of this study was to examine the relationship between metabolic and inflammatory markers in patients with diabetic retinopathy (DR). Methods. 208 adult patients with type 2 diabetes participated in this study and were categorized into (1) mild nonproliferative diabetic retinopathy (NPDR) without clinically significant macular edema (CSME), (2) NPDR with CSME, (3) proliferative diabetic retinopathy (PDR) without CSME, and (4) PDR with CSME. Variable serum metabolic markers were assessed using immunoassays. Multinomial logistic regression analysis was performed. Results. Diabetes duration and hypertension are the most significant risk factors for DR. Serum Apo-B and Apo-B/Apo-A ratio were the most significant metabolic risk factors for PDR and CSME. For every 0.1 g/L increase in Apo-B concentration, the risk of PDR and CSME increased by about 1.20 times. We also found that 10 pg/mL increase in serum TNF-α was associated with approximately 2-fold risk of PDR/CSME while an increase by 100 pg/mL in serum VEGF concentration correlated with CSME. Conclusions. In conclusion, it seems that there is a link between metabolic and inflammatory markers. Apo-B/Apo-A ratio should be evaluated as a reliable risk factor for PDR and CSME, while the role of increased systemic TNF-α and VEGF should be explored in CSME. Roxanne Crosby-Nwaobi, Irini Chatziralli, Theodoros Sergentanis, Tracy Dew, Angus Forbes, and Sobha Sivaprasad Copyright © 2015 Roxanne Crosby-Nwaobi et al. All rights reserved. Association Analysis of Genetic Variants with Type 2 Diabetes in a Mongolian Population in China Tue, 28 Jul 2015 14:04:04 +0000 The large scale genome wide association studies (GWAS) have identified approximately 80 single nucleotide polymorphisms (SNPs) conferring susceptibility to type 2 diabetes (T2D). However, most of these loci have not been replicated in diverse populations and much genetic heterogeneity has been observed across ethnic groups. We tested 28 SNPs previously found to be associated with T2D by GWAS in a Mongolian sample of Northern China (497 diagnosed with T2D and 469 controls) for association with T2D and diabetes related quantitative traits. We replicated T2D association of 11 SNPs, namely, rs7578326 (IRS1), rs1531343 (HMGA2), rs8042680 (PRC1), rs7578597 (THADA), rs1333051 (CDKN2), rs6723108 (TMEM163), rs163182 and rs2237897 (KCNQ1), rs1387153 (MTNR1B), rs243021 (BCL11A), and rs10229583 (PAX4) in our sample. Further, we showed that risk allele of the strongest T2D associated SNP in our sample, rs757832 (IRS1), is associated with increased level of TG. We observed substantial difference of T2D risk allele frequency between the Mongolian sample and the 1000G Caucasian sample for a few SNPs, including rs6723108 (TMEM163) whose risk allele reaches near fixation in the Mongolian sample. Further study of genetic architecture of these variants in susceptibility of T2D is needed to understand the role of these variants in heterogeneous populations. Haihua Bai, Haiping Liu, Suyalatu Suyalatu, Xiaosen Guo, Shandan Chu, Ying Chen, Tianming Lan, Burenbatu Borjigin, Yuriy L. Orlov, Olga L. Posukh, Xiuqin Yang, Guilan Guilan, Ludmila P. Osipova, Qizhu Wu, and Narisu Narisu Copyright © 2015 Haihua Bai et al. All rights reserved. Insulin Resistance, Type 1 and Type 2 Diabetes, and Related Complications 2015 Tue, 28 Jul 2015 07:44:54 +0000 Joseph Fomusi Ndisang, Sharad Rastogi, and Alfredo Vannacci Copyright © 2015 Joseph Fomusi Ndisang et al. All rights reserved. Healthy Chilean Adolescents with HOMA-IR ≥ 2.6 Have Increased Cardiometabolic Risk: Association with Genetic, Biological, and Environmental Factors Mon, 27 Jul 2015 13:14:44 +0000 Objective. To determine the optimal cutoff of the homeostasis model assessment-insulin resistance (HOMA-IR) for diagnosis of the metabolic syndrome (MetS) in adolescents and examine whether insulin resistance (IR), determined by this method, was related to genetic, biological, and environmental factors. Methods. In 667 adolescents (16.8 ± 0.3 y), BMI, waist circumference, glucose, insulin, adiponectin, diet, and physical activity were measured. Fat and fat-free mass were assessed by dual-energy X-ray absorptiometry. Family history of type 2 diabetes (FHDM) was reported. We determined the optimal cutoff of HOMA-IR to diagnose MetS (IDF criteria) using ROC analysis. IR was defined as HOMA-IR values above the cutoff. We tested the influence of genetic, biological, and environmental factors on IR using logistic regression analyses. Results. Of the participants, 16% were obese and 9.4 % met criteria for MetS. The optimal cutoff for MetS diagnosis was a HOMA-IR value of 2.6. Based on this value, 16.3% of participants had IR. Adolescents with IR had a significantly higher prevalence of obesity, abdominal obesity, fasting hyperglycemia, and MetS compared to those who were not IR. FHDM, sarcopenia, obesity, and low adiponectin significantly increased the risk of IR. Conclusions. In adolescents, HOMA-IR ≥ 2.6 was associated with greater cardiometabolic risk. R. Burrows, P. Correa-Burrows, M. Reyes, E. Blanco, C. Albala, and S. Gahagan Copyright © 2015 R. Burrows et al. All rights reserved. Dysglycaemia and Other Predictors for Progression or Regression from Impaired Fasting Glucose to Diabetes or Normoglycaemia Mon, 27 Jul 2015 12:52:13 +0000 Aims. Diabetes mellitus is a growing health problem worldwide. This study aimed to describe dysglycaemia and determine the impact of body composition and clinical and lifestyle factors on the risk of progression or regression from impaired fasting glucose (IFG) to diabetes or normoglycaemia in Australian women. Methods. This study included 1167 women, aged 20–94 years, enrolled in the Geelong Osteoporosis Study. Multivariable logistic regression was used to identify predictors for progression to diabetes or regression to normoglycaemia (from IFG), over 10 years of follow-up. Results. At baseline the proportion of women with IFG was 33.8% and 6.5% had diabetes. Those with fasting dysglycaemia had higher obesity-related factors, lower serum HDL cholesterol, and lower physical activity. Over a decade, the incidence of progression from IFG to diabetes was 18.1 per 1,000 person-years (95% CI, 10.7–28.2). Fasting plasma glucose and serum triglycerides were important factors in both progression to diabetes and regression to normoglycaemia. Conclusions. Our results show a transitional process; those with IFG had risk factors intermediate to normoglycaemics and those with diabetes. This investigation may help target interventions to those with IFG at high risk of progression to diabetes and thereby prevent cases of diabetes. L. de Abreu, Kara L. Holloway, Mark A. Kotowicz, and Julie A. Pasco Copyright © 2015 L. de Abreu et al. All rights reserved. Association of the Genetic Polymorphisms in Transcription Factor 7-Like 2 and Peroxisome Proliferator-Activated Receptors-γ2 with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status in Emirati Population Mon, 27 Jul 2015 12:48:28 +0000 Background. Transcription factor 7-like 2 gene (TCF7L2) and peroxisome proliferator-activated receptors-γ2 (PPAR-γ2) have a profound effect on the incidence of type 2 diabetes mellitus (T2DM) and had previously been found to be associated with T2DM risk in various ppopulations. However, studies in the Arab population are inconsistent. We conducted a case control study to confirm the association of variants rs10885409 of TCF7L2 and Pro12Ala (rs1801282) of PPAR-γ2 with risk of T2DM and related complications in Emirati population of Arab origin. We also investigated the interaction of these associations with obesity status. Methods. DNA was extracted from the saliva samples of 272 T2DM patients and 216 nondiabetic Emiratis. Genotyping for rs10885409 (TCF7L2) and rs1801282 (PPAR-γ2 P12A) variants was accomplished with a TaqMan assay. The subgroups were constituted according to obesity status. Results. In the nonobese group, the rs10885409 C allele in the recessive model was significantly associated with the incidence of T2DM (OR 1.975 [95% CI 1.127–3.461], ), but this association was not observed in the obese group or when BMI was not considered. PPAR-γ2 risk allele Pro12 frequency (0.96) was similar in the groups tested and more than 90% population was homozygous for this allele. Conclusions. Our case-control study is the first of its kind in Emiratis which establishes TCF7L2 rs10885409 C allele as a T2DM risk factor in Emiratis and this association is modulated by obesity status. We also confirmed that Pro12Ala mutation in PPAR-γ2 is not associated with T2DM risk in this population. Habiba Al-Safar, Ahmed Hassoun, Shaikha Almazrouei, Wala Kamal, Bachar Afandi, and Naushad Rais Copyright © 2015 Habiba Al-Safar et al. All rights reserved. Edible Bird’s Nest Prevents High Fat Diet-Induced Insulin Resistance in Rats Mon, 27 Jul 2015 12:09:03 +0000 Edible bird’s nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance. Zhang Yida, Mustapha Umar Imam, Maznah Ismail, Der-Jiun Ooi, Nadarajan Sarega, Nur Hanisah Azmi, Norsharina Ismail, Kim Wei Chan, Zhiping Hou, and Norhayati Binti Yusuf Copyright © 2015 Zhang Yida et al. All rights reserved. Effect of Rosiglitazone and Insulin Combination Therapy on Inflammation Parameters and Adipocytokine Levels in Patients with Type 1 DM Mon, 27 Jul 2015 12:06:55 +0000 Aim. To investigate the efficacy of combined therapy of insulin and rosiglitazone on metabolic and inflammatory parameters, insulin sensitivity, and adipocytokine levels in patients with type 1 diabetes mellitus (type 1 DM). Material and Methods. A total of 61 adults with type 1 DM were randomly and prospectively assigned in open-label fashion to take insulin and rosiglitazone 4 mg/day () or insulin alone () for a period of 18 weeks while undergoing insulin therapy without acute metabolic complications. Results. Combination therapy did not significantly improve metabolic and inflammatory parameters, insulin sensitivity, and adiponectin levels. While leptin and resistin levels decreased in both groups (group 1: resistin 6.96 ± 3.06 to 4.99 ± 2.64, ; leptin 25.8 ± 17.6 to 20.1 ± 12.55, ; group 2: resistin 7.16 ± 2.30 to , ; leptin 16.72 ± 16.1 to 14.0 ± 13.4, ) Hgb and fibrinogen levels decreased only in group 1 (Hgb 13.72 ± 1.98 to 13.16 ± 1.98, , and fibrinogen 4.00 ± 1.08 to 3.46 ± 0.90, ). Patients in both groups showed weight gain and the incidence of hypoglycemia was not lower. Discussion. The diverse favorable effects of TZDs were not fully experienced in patients with type 1 DM. These results are suggesting that insulin sensitizing and anti-inflammatory characteristics of TZDs were likely to be more pronounced in patients who were not totally devoid of endogenous insulin secretion. Metin Guclu, Ozen Oz Gul, Soner Cander, Oguzkaan Unal, Guven Ozkaya, Emre Sarandol, and Canan Ersoy Copyright © 2015 Metin Guclu et al. All rights reserved. GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective Mon, 27 Jul 2015 11:58:20 +0000 Growth differentiation factor-15 (GDF-15) is a stress responsive cytokine. It is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells in normal and pathological condition. GDF-15 increases during tissue injury and inflammatory states and is associated with cardiometabolic risk. Increased GDF-15 levels are associated with cardiovascular diseases such as hypertrophy, heart failure, atherosclerosis, endothelial dysfunction, obesity, insulin resistance, diabetes, and chronic kidney diseases in diabetes. Increased GDF-15 level is linked with the progression and prognosis of the disease condition. Age, smoking, and environmental factors are other risk factors that may increase GDF-15 level. Most of the scientific studies reported that GDF-15 plays a protective role in different tissues. However, few reports show that the deficiency of GDF-15 is beneficial against vascular injury and inflammation. GDF-15 protects heart, adipose tissue, and endothelial cells by inhibiting JNK (c-Jun N-terminal kinase), Bad (Bcl-2-associated death promoter), and EGFR (epidermal growth factor receptor) and activating Smad, eNOS, PI3K, and AKT signaling pathways. The present review describes the different animal and clinical studies and patent updates of GDF-15 in diabetes and cardiovascular diseases. It is a challenge for the scientific community to use GDF-15 information for patient monitoring, clinical decision-making, and replacement of current treatment strategies for diabetic and cardiovascular diseases. Ramu Adela and Sanjay K. Banerjee Copyright © 2015 Ramu Adela and Sanjay K. Banerjee. All rights reserved. NLRP3 Inflammasome Polymorphism and Macrovascular Complications in Type 2 Diabetes Patients Mon, 27 Jul 2015 11:42:26 +0000 Background. It is generally accepted that poor glycemic control, arterial hypertension and/or hyperlipidemia, and the associated oxidative stress may contribute to the development of macro- and microvascular complications in type 2 diabetes (T2D). Such metabolic damage signals may activate inflammasome and trigger chronic inflammation. We investigated common polymorphisms in inflammasome coding genes and the risk for macro- and microvascular complications in T2D. Methods. In total 181 clinically well-characterised T2D patients were genotyped for NLRP3 rs35829419 and CARD8 rs2043211. Risk for diabetic complications was assessed using logistic regression. Results. Patients with median duration of T2D 11 (6–17) years had relatively well controlled blood glucose and lipid levels and blood pressure on the prescribed treatment regimen. Duration of T2D and plasma cholesterol levels were the most important clinical risk factors for macrovascular complications ( and ). NLRP3 rs35829419 was associated with increased risk for macrovascular complications (), with myocardial infarction in particular (). No association was observed between CARD8 polymorphism and any of T2D complications. Conclusions. Our preliminary data suggest the role of NLRP3 polymorphism in diabetic macrovascular complications, especially in myocardial infarction. Jasna Klen, Katja Goričar, Andrej Janež, and Vita Dolžan Copyright © 2015 Jasna Klen et al. All rights reserved. Study of Protein Biomarkers of Diabetes Mellitus Type 2 and Therapy with Vitamin B1 Mon, 27 Jul 2015 11:40:09 +0000 In the present research work, the levels of protein biomarkers specific to diabetes mellitus type 2 in the Pakistani population using proteomic technology have been identified and characterized and effect of high dose thiamine has been seen on the levels of these marker proteins. Diabetic patients and normal healthy controls were recruited from the Sheikh Zayed Hospital, Lahore, Pakistan. Total biochemical assays and proteins were estimated by modern proteomic techniques. Some proteins were up- and downregulated in diabetic samples as compared to control and decreased after thiamine therapy, while other protein markers did not show a significant change after the thiamine therapy. The effect of high dose thiamine on the levels of these identified protein biomarkers in the human urine has also been observed. Assessment of the levels of these biomarkers will be helpful in not only early diagnosis but also prognosis of diabetes mellitus type 2. Samreen Riaz Copyright © 2015 Samreen Riaz. All rights reserved. Inflammatory Cytokine Profile Associated with Metabolic Syndrome in Adult Patients with Type 1 Diabetes Mon, 27 Jul 2015 11:10:26 +0000 Objective. To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cut-off point of the estimated glucose disposal rate that accurately differentiated these groups. Design. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. Methods. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. Results. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (), 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. Conclusion. We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance. Aldo Ferreira-Hermosillo, Mario Molina-Ayala, Claudia Ramírez-Rentería, Guadalupe Vargas, Baldomero Gonzalez, Armando Isibasi, Irma Archundia-Riveros, and Victoria Mendoza Copyright © 2015 Aldo Ferreira-Hermosillo et al. All rights reserved. Adipose Tissues Characteristics of Normal, Obesity, and Type 2 Diabetes in Uygurs Population Mon, 27 Jul 2015 11:09:08 +0000 Our results showed that, at the same BMI level, Uygurs have greater WHR values, abdominal visceral fat content, and diabetes risks than Kazaks. In addition, values of HDL-C in Uygur subjects were lower than those in Kazak subjects, and values of creatinine, uric acid, diastolic blood pressure, blood glucose, and fructosamine in Uygur male subjects were lower than those in Kazak male subjects. In contrast, systolic blood pressure values in Uygur subjects were greater than those in Kazak subjects, and blood glucose values were greater in Uygur female subjects than in Kazak female subjects. Additionally, in Uygurs, visceral adipose tissue expression levels of TBX1 and TCF21 were greater in obesity group than in normal and T2DM groups and lower in T2DM group than in normal group (). The visceral adipose tissue expression levels of APN in normal group was greater than those in obesity and T2DM groups, and visceral adipose tissue expression levels of TNF-α and MCP-1 in normal group were lower than those in obesity and T2DM groups (). In conclusion, T2DM in Uygurs was mainly associated with not only distribution of adipose tissue in body, but also change in metabolic activity and adipocytokines secretion of adipose tissue. Jun Zhang, Zhiwei Zhang, Yulei Ding, Peng Xu, Tingting Wang, Wenjing Xu, Huan Lu, Jun Li, Yan Wang, Siyuan Li, Zongzhi Liu, Na An, Li Yang, and Jianxin Xie Copyright © 2015 Jun Zhang et al. All rights reserved. Population-Based Studies on the Epidemiology of Insulin Resistance in Children Mon, 27 Jul 2015 11:07:40 +0000 Background. In view of the alarming incidence of obesity in children, insight into the epidemiology of the prediabetic state insulin resistance (IR) seems important. Therefore, the aim of this systematic review was to give an overview of all population-based studies reporting on the prevalence and incidence rates of IR in childhood. Methods. PubMed, Embase, and Cochrane library were searched in order to find all available population-based studies describing the epidemiology of IR in pediatric populations. Prevalence rates together with methods and cut-off values used to determine IR were extracted and summarized with weight and sex specific prevalence rates of IR if available. Results. Eighteen population-based studies were identified, describing prevalence rates varying between 3.1 and 44%, partly explained by different definitions for IR. Overweight and obese children had higher prevalence rates than normal weight children. In seven out of thirteen studies reporting sex specific results, girls seemed to be more affected than boys. Conclusion. Prevalence rates of IR reported in children vary widely which is partly due to the variety of definitions used. Overweight and obese children had higher prevalence and girls were more insulin resistant than boys. Consensus on the definition for IR in children is needed to allow for comparisons between different studies. M. P. van der Aa, S. Fazeli Farsani, C. A. J. Knibbe, A. de Boer, and M. M. J. van der Vorst Copyright © 2015 M. P. van der Aa et al. All rights reserved. The Genetic Profile from HLA and Non-HLA Loci Allows Identification of Atypical Type 2 Diabetes Patients Mon, 27 Jul 2015 11:04:00 +0000 The complex diagnosis and treatment of diabetes highlight the need for markers to define how to monitor patients correctly during the course of their disease. Different studies demonstrate the existence of patients who cannot be clearly classified. We have previously shown that it is possible to differentiate “atypical diabetic patients” based on genotyping the HLA. In this work we show that the analysis of non-HLA related to type 1 diabetes in the INS-VNTR, SNP rs689, and rs3842753 improves the identification of these patients. We genotyped 913 individuals comprising controls from the general population and “classic” and “atypical” diabetic patients. We compared the distribution of these loci and analyzed linkage disequilibrium. The haplotype was in LD for all the SNPs that were evaluated. Regarding their association with the disease, the haplotype IAC was associated with type 1 (odds 2.60, 1.82–3.72, CI 95%) and “atypical diabetes” (odds 1.50, 1.01–2.23, CI 95%), whereas we did not observe an association with type 2 diabetes. Therefore, our results confirm that atypical diabetes is a different entity of the disease where the patient presents with a genetic background of T1D and a T2D phenotype, findings that are likely to be relevant for patient diagnosis and management in the clinic. Matias Fabregat, Mariana Fernandez, Gerardo Javiel, Graciela Vitarella, and Adriana Mimbacas Copyright © 2015 Matias Fabregat et al. All rights reserved. MicroRNA-223 Expression Is Upregulated in Insulin Resistant Human Adipose Tissue Mon, 27 Jul 2015 10:03:37 +0000 MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression and influence many cellular functions including glucose and lipid metabolism. We previously reported that adipose tissue (AT) from women with polycystic ovary syndrome (PCOS) or controls with insulin resistance (IR) revealed a differentially expressed microRNA (miRNA) profile, including upregulated miR-93 in PCOS patients and in non-PCOS women with IR. Overexpressed miR-93 directly inhibited glucose transporter isoform 4 (GLUT4) expression, thereby influencing glucose metabolism. We have now studied the role of miR-223, which is also abnormally expressed in the AT of IR subjects. Our data indicates that miR-223 is significantly overexpressed in the AT of IR women, regardless of whether they had PCOS or not. miR-223 expression in AT was positively correlated with HOMA-IR. Unlike what is reported in cardiomyocytes, overexpression of miR-223 in human differentiated adipocytes was associated with a reduction in GLUT4 protein content and insulin-stimulated glucose uptake. In addition, our data suggests miR-223 regulates GLUT4 expression by direct binding to its 3′ untranslated region (3′UTR). In conclusion, in AT miR-223 is an IR-related miRNA that may serve as a potential therapeutic target for the treatment of IR-related disorders. Tung-Yueh Chuang, Hsiao-Li Wu, Chen-Chun Chen, Gloria Mabel Gamboa, Lawrence C. Layman, Michael P. Diamond, Ricardo Azziz, and Yen-Hao Chen Copyright © 2015 Tung-Yueh Chuang et al. All rights reserved. Association of Metabolic Syndrome with the Cardioankle Vascular Index in Asymptomatic Korean Population Mon, 27 Jul 2015 10:03:24 +0000 Aim. Metabolic syndrome is characterized by a cluster of atherosclerotic cardiovascular risk factors. The cardioankle vascular index (CAVI) reflects arterial stiffness and may be used as an indicator of atherosclerotic cardiovascular disease. In this study, we investigated the association of CAVI with metabolic syndrome. Methods. A total of 1,144 adults were included in this study. We measured CAVIs and examined blood samples to identify metabolic syndrome according to WHO Asia Pacific criteria and NCEP-ATPIII criteria. AST, ALT, r-GTP, BUN, creatinine, high sensitivity C-reactive protein, and uric acid were also measured. Results. CAVI values were significantly higher in subjects with metabolic syndrome than those without metabolic syndrome and increased according to the number of metabolic syndrome components present. Subjects with high fasting blood sugar levels or high blood pressure showed high CAVI values. Multiple regression analysis showed that age, sex, diastolic blood pressure, and uric acid were independent predictors of CAVI. Conclusion. Subjects with metabolic syndrome had high CAVIs, which indicated arterial stiffness, and were closely associated with an increase in the number of metabolic risk factors. The individual risk factors for metabolic syndrome have the synergistic effect of elevating arterial stiffness in asymptomatic Korean population. Su-Hyun Nam, Sung-Goo Kang, Yun-Ah Lee, Sang-Wook Song, and Jun-Seung Rho Copyright © 2015 Su-Hyun Nam et al. All rights reserved. Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update Mon, 27 Jul 2015 10:00:44 +0000 Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management. Pragya Tiwari Copyright © 2015 Pragya Tiwari. All rights reserved. Comment on “Alpha-Lipoic Acid and Antioxidant Diet Help to Improve Endothelial Dysfunction in Adolescents with Type 1 Diabetes: A Pilot Trial” Mon, 27 Jul 2015 09:23:57 +0000 Hitesh Verma and Rajeev Garg Copyright © 2015 Hitesh Verma and Rajeev Garg. All rights reserved. Comparative Evaluation of Two Venous Sampling Techniques for the Assessment of Pancreatic Insulin and Zinc Release upon Glucose Challenge Mon, 27 Jul 2015 08:43:49 +0000 Advances in noninvasive imaging modalities have provided opportunities to study β cell function through imaging zinc release from insulin secreting β cells. Understanding the temporal secretory pattern of insulin and zinc corelease after a glucose challenge is essential for proper timing of administration of zinc sensing probes. Portal venous sampling is an essential part of pharmacological and nutritional studies in animal models. The purpose of this study was to compare two different percutaneous image-guided techniques: transhepatic ultrasound guided portal vein access and transsplenic fluoroscopy guided splenic vein access for ease of access, safety, and evaluation of temporal kinetics of insulin and zinc release into the venous effluent from the pancreas. Both techniques were safe, reproducible, and easy to perform. The mean time required to obtain desired catheter position for venous sampling was 15 minutes shorter using the transsplenic technique. A clear biphasic insulin release profile was observed in both techniques. Statistically higher insulin concentration but similar zinc release after a glucose challenge was observed from splenic vein samples, as compared to the ones from the portal vein. To our knowledge, this is the first report of percutaneous methods to assess zinc release kinetics from the porcine pancreas. Anil Kumar Pillai, William Silvers, Preston Christensen, Matthew Riegel, Beverley Adams-Huet, Ildiko Lingvay, Xiankai Sun, and Orhan K. Öz Copyright © 2015 Anil Kumar Pillai et al. All rights reserved. Wide-Field Megahertz OCT Imaging of Patients with Diabetic Retinopathy Mon, 27 Jul 2015 06:05:37 +0000 Purpose. To evaluate the feasibility of wide-field Megahertz (MHz) OCT imaging in patients with diabetic retinopathy. Methods. A consecutive series of 15 eyes of 15 patients with diagnosed diabetic retinopathy were included. All patients underwent Megahertz OCT imaging, a close clinical examination, slit lamp biomicroscopy, and funduscopic evaluation. To acquire densely sampled, wide-field volumetric datasets, an ophthalmic 1050 nm OCT prototype system based on a Fourier-domain mode-locked (FDML) laser source with 1.68 MHz A-scan rate was employed. Results. We were able to obtain OCT volume scans from all included 15 patients. Acquisition time was 1.8 seconds. Obtained volume datasets consisted of 2088 1044 A-scans of 60° of view. Thus, reconstructed en face images had a resolution of 34.8 pixels per degree in x-axis and 17.4 pixels per degree. Due to the densely sampled OCT volume dataset, postprocessed customized cross-sectional B-frames through pathologic changes such as an individual microaneurysm or a retinal neovascularization could be imaged. Conclusions. Wide-field Megahertz OCT is feasible to successfully image patients with diabetic retinopathy at high scanning rates and a wide angle of view, providing information in all three axes. The Megahertz OCT is a useful tool to screen diabetic patients for diabetic retinopathy. Lukas Reznicek, Jan P. Kolb, Thomas Klein, Kathrin J. Mohler, Wolfgang Wieser, Robert Huber, Marcus Kernt, Josef Märtz, and Aljoscha S. Neubauer Copyright © 2015 Lukas Reznicek et al. All rights reserved. Glycemic Variability Assessed by Continuous Glucose Monitoring and Short-Term Outcome in Diabetic Patients Undergoing Percutaneous Coronary Intervention: An Observational Pilot Study Sun, 26 Jul 2015 11:44:03 +0000 Poor glycemic control is associated with unfavorable outcome in patients undergoing percutaneous coronary intervention (PCI), irrespective of diabetes mellitus. However a complete assessment of glycemic status may not be fully described by glycated hemoglobin or fasting blood glucose levels, whereas daily glycemic fluctuations may influence cardiovascular risk and have even more deleterious effects than sustained hyperglycemia. Thus, this paper investigated the effectiveness of a continuous glucose monitoring (CGM), registering the mean level of glycemic values but also the extent of glucose excursions during coronary revascularization, in detecting periprocedural outcome such as renal or myocardial damage, assessed by serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and troponin I levels. High glycemic variability (GV) has been associated with worse postprocedural creatinine and NGAL variations. Moreover, GV, and predominantly hypoglycemic variations, has been observed to increase in patients with periprocedural myocardial infarction. Thus, our study investigated the usefulness of CGM in the setting of PCI where an optimal glycemic control should be achieved in order to prevent complications and improve outcome. Annunziata Nusca, Angelo Lauria Pantano, Rosetta Melfi, Claudio Proscia, Ernesto Maddaloni, Rocco Contuzzi, Fabio Mangiacapra, Andrea Palermo, Silvia Manfrini, Paolo Pozzilli, and Germano Di Sciascio Copyright © 2015 Annunziata Nusca et al. All rights reserved. Beyond Culture and Language: Access to Diabetes Preventive Health Services among Somali Women in Norway Wed, 22 Jul 2015 11:49:50 +0000 Despite the high prevalence of type 2 diabetes in some immigrant and refugee communities in Norway, there is very little information available on their utilization of diabetes prevention interventions, particularly for women from Somali immigrant communities. A qualitative study of 30 Somali immigrant women aged 25 years and over was carried out in the Oslo area. Unstructured interviews were used to explore women’s knowledge of diabetes, their access to preventive health facilities, and factors impeding their reception of preventive health programs targeted for the prevention of type 2 diabetes. The study participants were found to have a good knowledge of diabetes. They knew that a sedentary lifestyle and unhealthy diet are among the risk factors for diabetes. Regardless of their knowledge, participants reported a sedentary lifestyle accompanied with the consumption of an unhealthy diet. This was attributed to a lack of access to tailored physical activity services and poor access to health information. Considering gender-exclusive training facilities for Somali immigrant women and others with similar needs, in addition to access to tailored health information on diet, may encourage Somali women to adopt a healthy lifestyle, and it will definitely contribute to a national strategy for the prevention of diabetes. Abdi A. Gele, Liv Elin Torheim, Kjell Sverre Pettersen, and Bernadette Kumar Copyright © 2015 Abdi A. Gele et al. All rights reserved. Type 1 Diabetes Modifies Brain Activation in Young Patients While Performing Visuospatial Working Memory Tasks Wed, 22 Jul 2015 06:47:13 +0000 In recent years, increasing attention has been paid to the effects of Type 1 Diabetes (T1D) on cognitive functions. T1D onset usually occurs during childhood, so it is possible that the brain could be affected during neurodevelopment. We selected young patients of normal intelligence with T1D onset during neurodevelopment, no complications from diabetes, and adequate glycemic control. The purpose of this study was to compare the neural BOLD activation pattern in a group of patients with T1D versus healthy control subjects while performing a visuospatial working memory task. Sixteen patients and 16 matched healthy control subjects participated. There was no significant statistical difference in behavioral performance between the groups, but, in accordance with our hypothesis, results showed distinct brain activation patterns. Control subjects presented the expected activations related to the task, whereas the patients had greater activation in the prefrontal inferior cortex, basal ganglia, posterior cerebellum, and substantia nigra. These different patterns could be due to compensation mechanisms that allow them to maintain a behavioral performance similar to that of control subjects. Geisa B. Gallardo-Moreno, Andrés A. González-Garrido, Esteban Gudayol-Ferré, and Joan Guàrdia-Olmos Copyright © 2015 Geisa B. Gallardo-Moreno et al. All rights reserved. Hypoglycemic Activity through a Novel Combination of Fruiting Body and Mycelia of Cordyceps militaris in High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice Thu, 16 Jul 2015 05:50:45 +0000 Diabetes mellitus (DM) is currently ranked among leading causes of death worldwide in which type 2 DM is reaching an epidemic proportion. Hypoglycemic medications for type 2 DM have either proven inadequate or posed adverse effects; therefore, the Chinese herbal products are under investigation as an alternative treatment. In this study, a novel combination of fruiting body and mycelia powder of herbal Cordyceps militaris number 1 (CmNo1) was administered to evaluate their potential hypoglycemic effects in high-fat diet- (HFD-) induced type 2 DM in C57BL/6J mice. Body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and blood biochemistry indexes were measured. Results indicated that CmNo1 lowered the blood glucose level by increasing insulin sensitivity, while no change in body weight was observed. Increased protein expression of IRS-1, pIRS-1, AKT, pAKT, and GLUT-4 in skeletal muscle and adipose tissue was found indicating restoration of insulin signaling. Additionally, PPAR-γ expression in adipose tissue restored the triglyceride and cholesterol levels. Finally, our results suggest that CmNo1 possesses strong hypoglycemic, anticholesterolemic, and antihypertriglyceridemic actions and is more economical alternate for DM treatment. Sung-Hsun Yu, Szu-Yu Tina Chen, Wei-Shan Li, Navneet Kumar Dubey, Wei-Hong Chen, Jiunn-Jye Chuu, Sy-Jye Leu, and Win-Ping Deng Copyright © 2015 Sung-Hsun Yu et al. All rights reserved. Effect of Cinnamon Tea on Postprandial Glucose Concentration Tue, 14 Jul 2015 07:50:56 +0000 Glycaemic control, in particular at postprandial period, has a key role in prevention of different diseases, including diabetes and cardiovascular events. Previous studies suggest that postprandial high blood glucose levels (BGL) can lead to an oxidative stress status, which is associated with metabolic alterations. Cinnamon powder has demonstrated a beneficial effect on postprandial glucose homeostasis in animals and human models. The purpose of this study is to investigate the effect of cinnamon tea (C. burmannii) on postprandial capillary blood glucose level on nondiabetic adults. Participants were given oral glucose tolerance test either with or without cinnamon tea in a randomized clinical trial. The data revealed that cinnamon tea administration slightly decreased postprandial BGL. Cinnamon tea ingestion also results in a significantly lower postprandial maximum glucose concentration and variation of maximum glucose concentration (p < 0.05). Chemical analysis showed that cinnamon tea has a high antioxidant capacity, which may be due to its polyphenol content. The present study provides evidence that cinnamon tea, obtained from C. burmannii, could be beneficial for controlling glucose metabolism in nondiabetic adults during postprandial period. Maria Alexandra Bernardo, Maria Leonor Silva, Elisabeth Santos, Margarida Maria Moncada, José Brito, Luis Proença, Jaipaul Singh, and Maria Fernanda de Mesquita Copyright © 2015 Maria Alexandra Bernardo et al. All rights reserved. Impact of Inherited Prothrombotic Disorders on the Long-Term Clinical Outcome of Percutaneous Transluminal Angioplasty in Patients with Diabetes Mon, 13 Jul 2015 11:43:28 +0000 The aim of our study was to analyse inherited thrombotic disorders that influence the long-term outcome of PTA. Methods. Diabetic patients with peripheral arterial disease (PAD) treated by PTA in our centre between 2008 and 2011 were included in the study. Patients were divided into unsuccessful PTA group (75 patients), successful PTA group (58 patients), and control group (65 patients, with diabetes but no PAD). Diagnosis of inherited thrombotic disorders included mutation in factor V (Leiden), factor II (prothrombin), and mutation in genes for methylenetetrahydrofolate reductase—MTHFR (C677T and A1298C). Results. The genotypic frequency of Leiden allele G1691A was significantly associated with a risk of unsuccessful PTA in comparison with successful PTA group and control group (OR 8.8 (1.1–70.6), , and OR 9.8 (1.2–79.2), , resp.). However, we only observed a trend for the association of the prothrombin allele G20210A and risk of PTA failure. The frequencies of alleles of MTHFR 677 or 1298 did not differ significantly among the groups. Conclusion. Our study showed higher frequency of heterozygous form of Leiden mutation in diabetic patients with unsuccessful outcome of PTA in comparison with patients with successful PTA and diabetic patients without PAD. Michal Dubský, Alexandra Jirkovská, Libuše Pagáčová, Robert Bém, Andrea Němcová, Vladimíra Fejfarová, Veronika Wosková, and Edward B. Jude Copyright © 2015 Michal Dubský et al. All rights reserved. Complications of Diabetes Sun, 12 Jul 2015 06:57:44 +0000 Konstantinos Papatheodorou, Maciej Banach, Michael Edmonds, Nikolaos Papanas, and Dimitrios Papazoglou Copyright © 2015 Konstantinos Papatheodorou et al. All rights reserved. Meat Intake and Insulin Resistance in Women without Type 2 Diabetes Thu, 09 Jul 2015 12:03:43 +0000 Purpose. To examine the relationship between meat intake and insulin resistance (IR) in 292 nondiabetic women. Methods. IR was evaluated using the homeostasis model assessment (HOMA). Diet was assessed via 7-day weighed food records. Servings of very lean meat (VLM) and regular meat (meat) were indexed using the ADA Exchange Lists Program. Physical activity was assessed using accelerometers and body fat was measured using the Bod Pod. Results. Meat intake was directly related to HOMA (F = 7.4; P = 0.007). Women with moderate or high meat intakes had significantly higher HOMA levels than their counterparts. Adjusting for body fat weakened the relationship (F = 1.0; P = 0.3201). Odds ratio results showed that the low meat quartile had 67% lower odds of being IR (75th percentile) compared to their counterparts (OR = 0.33; 95% CI = 0.16–0.71). These findings changed little after adjusting for all covariates simultaneously (OR = 0.34; 95% CI = 0.14–0.83). Conversely, VLM intake was not related to HOMA, with or without the covariates. Conclusion. Moderate and high meat intakes are associated with increased insulin resistance in nondiabetic women. However, differences in body fat contribute significantly to the relationship. VLM is not predictive of IR. Prudence in the amount and type of meat consumed may be helpful in decreasing the likelihood of IR. Larry A. Tucker, James D. LeCheminant, and Bruce W. Bailey Copyright © 2015 Larry A. Tucker et al. All rights reserved.