Journal of Diabetes Research The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Atypical Diabetic Foot Ulcer Keratinocyte Protein Signaling Correlates with Impaired Wound Healing Thu, 20 Oct 2016 06:17:10 +0000 Diabetes mellitus is associated with chronic diabetic foot ulcers (DFUs) and wound infections often resulting in lower extremity amputations. The protein signaling architecture of the mechanisms responsible for impaired DFU healing has not been characterized. In this preliminary clinical study, the intracellular levels of proteins involved in signal transduction networks relevant to wound healing were non-biasedly measured using reverse-phase protein arrays (RPPA) in keratinocytes isolated from DFU wound biopsies. RPPA allows for the simultaneous documentation and assessment of the signaling pathways active in each DFU. Thus, RPPA provides for the accurate mapping of wound healing pathways associated with apoptosis, proliferation, senescence, survival, and angiogenesis. From the study data, we have identified potential diagnostic, or predictive, biomarkers for DFU wound healing derived from the ratios of quantified signaling protein expressions within interconnected pathways. These biomarkers may allow physicians to personalize therapeutic strategies for DFU management on an individual basis based upon the signaling architecture present in each wound. Additionally, we have identified altered, interconnected signaling pathways within DFU keratinocytes that may help guide the development of therapeutics to modulate these dysregulated pathways, many of which parallel the therapeutic targets which are the hallmarks of molecular therapies for treating cancer. Glenn D. Hoke, Corrine Ramos, Nicholas N. Hoke, Mary C. Crossland, Lisa G. Shawler, and Joseph V. Boykin Copyright © 2016 Glenn D. Hoke et al. All rights reserved. Lay Health Trainers Supporting Self-Management amongst Those with Low Heath Literacy and Diabetes: Lessons from a Mixed Methods Pilot, Feasibility Study Wed, 19 Oct 2016 13:42:01 +0000 This article reports a mixed methods process evaluation of a pilot feasibility randomised controlled trial comparing a Lay Health Trainer (LHT) intervention and usual care for those with poorly controlled Type 2 Diabetes Melitus (T2DM). Set in a deprived area in the UK, this research explores patient and health care practitioner (HCP) views on whether a structured interview between a patient and a Lay Health Trainer (LHT), for the purpose of developing a tailored self-management plan for patients, is acceptable and likely to change health behaviours. In doing so, it considers the implications for a future, randomised controlled trial (RCT). Participants were patients, LHTs delivering the intervention, service managers, and practice nurses recruiting patients to the study. Patients were purposively sampled on their responses to a baseline survey, and semistructured interviews were conducted within an exploratory thematic analysis framework. Findings indicate that the intervention is acceptable to patients and HCPs. However, LHTs found it challenging to work with older patients with long-term and/or complex conditions. In order to address this, given an ageing population and concomitant increases in those with such health needs, LHT training should develop skills working with these populations. The design of any future RCT intervention should take account of this. Bernadette Bartlam, Trishna Rathod, Gillian Rowlands, and Joanne Protheroe Copyright © 2016 Bernadette Bartlam et al. All rights reserved. The Feasibility of Health Trainer Improved Patient Self-Management in Patients with Low Health Literacy and Poorly Controlled Diabetes: A Pilot Randomised Controlled Trial Wed, 19 Oct 2016 12:25:14 +0000 Type 2 diabetes mellitus is most prevalent in deprived communities and patients with low health literacy have worse glycaemic control and higher rates of diabetic complications. However, recruitment from this patient population into intervention trials is highly challenging. We conducted a study to explore the feasibility of recruitment and to assess the effect of a lay health trainer intervention, in patients with low health literacy and poorly controlled diabetes from a socioeconomically disadvantaged population, compared with usual care. Methods. A pilot RCT comparing the LHT intervention with usual care. Patients with HbA1c > 7.5 (58 mmol/mol) were recruited. Baseline and 7-month outcome data were entered directly onto a laptop to reduce patient burden. Results. 76 patients were recruited; 60.5% had low health literacy and 75% were from the most deprived areas of England. Participants in the LHT arm had significantly improved mental health () and illness perception (). The intervention was associated with lower resource use, better patient self-care management, and better QALY profile at 7-month follow-up. Conclusion. This study describes successful recruitment strategies for hard-to-reach populations. Further research is warranted for this cost-effective, relatively low-cost intervention for a population currently suffering a disproportionate burden of diabetes, to demonstrate its sustained impact on treatment effects, health, and health inequalities. Joanne Protheroe, Trishna Rathod, Bernadette Bartlam, Gillian Rowlands, Gerry Richardson, and David Reeves Copyright © 2016 Joanne Protheroe et al. All rights reserved. Linking High Risk Postpartum Women with a Technology Enabled Health Coaching Program to Reduce Diabetes Risk and Improve Wellbeing: Program Description, Case Studies, and Recommendations for Community Health Coaching Programs Tue, 18 Oct 2016 12:35:06 +0000 Background. Low-income minority women with prior gestational diabetes mellitus (pGDM) or high BMIs have increased risk for chronic illnesses postpartum. Although the Diabetes Prevention Program (DPP) provides an evidence-based model for reducing diabetes risk, few community-based interventions have adapted this program for pGDM women. Methods. STAR MAMA is an ongoing randomized control trial (RCT) evaluating a hybrid HIT/Health Coaching DPP-based 20-week postpartum program for diabetes prevention compared with education from written materials at baseline. Eligibility includes women 18–39 years old, ≥32 weeks pregnant, and GDM or BMI > 25. Clinic- and community-based recruitment in San Francisco and Sonoma Counties targets 180 women. Sociodemographic and health coaching data from a preliminary sample are presented. Results. Most of the 86 women included to date (88%) have GDM, 80% were identified as Hispanic/Latina, 78% have migrant status, and most are Spanish-speaking. Women receiving the intervention indicate high engagement, with 86% answering 1+ calls. Health coaching callbacks last an average of 9 minutes with range of topics discussed. Case studies presented convey a range of emotional, instrumental, and health literacy-related supports offered by health coaches. Discussion. The DPP-adapted HIT/health coaching model highlights the possibility and challenge of delivering DPP content to postpartum women in community settings. This trial is registered with NCT02240420. Priyanka Athavale, Melanie Thomas, Adriana T. Delgadillo-Duenas, Karen Leong, Adriana Najmabadi, Elizabeth Harleman, Christina Rios, Judy Quan, Catalina Soria, and Margaret A. Handley Copyright © 2016 Priyanka Athavale et al. All rights reserved. Administration of Traditional Chinese Blood Circulation Activating Drugs for Microvascular Complications in Patients with Type 2 Diabetes Mellitus Tue, 18 Oct 2016 08:12:04 +0000 Traditional Chinese medicine (TCM) is an important complementary strategy for treating diabetes mellitus (DM) in China. Traditional Chinese blood circulation activating drugs are intended to guide an overall approach to the prevention and treatment of microvascular complications of DM. The core mechanism is related to the protection of the vascular endothelium and the basement membrane. Here, we reviewed the scientific evidence underpinning the use of blood circulation activating drugs to prevent and treat DM-induced microvascular complications, including diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR). Furthermore, we summarized the effects and mechanism of TCM on improving blood rheology, inhibiting aggregation of platelet, forming advanced glycation end products (AGEs), regulating oxidative stress, reducing blood fat, and improving lipid metabolism. The paper provides a new theoretical basis for the clinical practice of TCM in the prevention and treatment of DM and its microvascular complications. Lisha He, Han Wang, Chengjuan Gu, Xinhui He, Linhua Zhao, and Xiaolin Tong Copyright © 2016 Lisha He et al. All rights reserved. Meeting the Challenge of Diabetes in Ageing and Diverse Populations: A Review of the Literature from the UK Mon, 17 Oct 2016 08:44:51 +0000 The impact of type 2 diabetes on ageing societies is great and populations across the globe are becoming more diverse. Complications of diabetes unequally affect particular groups in the UK older people, and people with a South Asian background are two population groups with increased risk whose numbers will grow in the future. We explored the evidence about diabetes care for older people with South Asian ethnicity to understand the contexts and mechanisms behind interventions to reduce inequalities. We used a realist approach to review the literature, mapped the main areas where relevant evidence exists, and explored the concepts and mechanisms which underpinned interventions. From this we constructed a theoretical framework for a programme of research and put forward suggestions for what our analysis might mean to providers, researchers, and policy makers. Broad themes of cultural competency; comorbidities and stratification; and access emerged as mid-level mechanisms which have individualised, culturally intelligent, and ethical care at their heart and through which inequalities can be addressed. These provide a theoretical framework for future research to advance knowledge about concordance; culturally meaningful measures of depression and cognitive impairment; and care planning in different contexts which support effective diabetes care for aging and diverse populations. Emma Wilkinson, Muhammad Waqar, Alan Sinclair, and Gurch Randhawa Copyright © 2016 Emma Wilkinson et al. All rights reserved. Association between -308G/A TNFA Polymorphism and Susceptibility to Type 2 Diabetes Mellitus: A Systematic Review Sun, 16 Oct 2016 15:57:52 +0000 Diabetes mellitus (DM) is considered to be a worldwide epidemic disease and its type 2 form comprises more than 95% of all cases. Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine. Its dysregulation has been implicated in a variety of human diseases, including type 2 diabetes mellitus (T2DM). The control of expression of this cytokine is associated with insulin resistance and has a strong genetic influence. In order to understand this relationship, the literature from all case-control studies since 2000 to date was reviewed. The genotypes frequency results presented in ten publications with different ethnicities were compared. The correlation between the TNFA promoter genotypes and the risk of developing T2DM remains controversial due to the many discrepancies between the different studies available. Ethnic differences may play a role in these conflicting results, since the distribution of TNFA promoter polymorphisms is distinctive between individuals of dissimilar racial origin. Hence, although the relationship between T2DM incidence and presence of polymorphisms at position -308 of the TNFA gene is not entirely clear, the results of these studies suggest the need for further investigation. Geisa Izetti Luna, Izabel Cristina Rodrigues da Silva, and Mauro Niskier Sanchez Copyright © 2016 Geisa Izetti Luna et al. All rights reserved. Complications of Diabetes 2016 Sun, 16 Oct 2016 11:47:55 +0000 Konstantinos Papatheodorou, Nikolaos Papanas, Maciej Banach, Dimitrios Papazoglou, and Michael Edmonds Copyright © 2016 Konstantinos Papatheodorou et al. All rights reserved. Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice Sun, 16 Oct 2016 09:56:49 +0000 The importance of proximal tubules dysfunction to diabetic albuminuria is uncertain. OVE26 mice have the most severe albuminuria of all diabetic mouse models but it is not known if impaired tubule uptake and processing are contributing factors. In the current study fluorescent albumin was used to follow the fate of albumin in OVE26 and normal mice. Compared to normal urine, OVE26 urine contained at least 23 times more intact fluorescent albumin but only 3-fold more 70 kD fluorescent dextran. This indicated that a function other than size selective glomerular sieving contributed to OVE26 albuminuria. Imaging of albumin was similar in normal and diabetic tubules for 3 hrs after injection. However 3 days after injection a subset of OVE26 tubules retained strong albumin fluorescence, which was never observed in normal mice. OVE26 tubules with prolonged retention of injected albumin lost the capacity to take up albumin and there was a significant correlation between tubules unable to eliminate fluorescent albumin and total albuminuria. TUNEL staining revealed a 76-fold increase in cell death in OVE26 tubules that retained fluorescent albumin. These results indicate that failure to process and dispose of internalized albumin leads to impaired albumin uptake, increased albuminuria, and tubule cell apoptosis. Y. S. Long, S. Zheng, P. M. Kralik, F. W. Benz, and P. N. Epstein Copyright © 2016 Y. S. Long et al. All rights reserved. An Immunomodulatory Device Improves Insulin Resistance in Obese Porcine Model of Metabolic Syndrome Thu, 13 Oct 2016 08:38:57 +0000 Obesity is associated with tissue inflammation which is a crucial etiology of insulin resistance. This inflammation centers around circulating monocytes which form proinflammatory adipose tissue macrophages (ATM). Specific approaches targeting monocytes/ATM may improve insulin resistance without the adverse side effects of generalized immunosuppression. In this regard, a biomimetic membrane leukocyte processing device, called the selective cytopheretic device (SCD), was evaluated in an Ossabaw miniature swine model of insulin resistance with metabolic syndrome. Treatment with the SCD in this porcine model demonstrated a decline in circulating neutrophil activation parameters and monocyte counts. These changes were associated with improvements in insulin resistance as determined with intravenous glucose tolerance testing. These improvements were also reflected in lowering of homeostatic model assessment- (HOMA-) insulin resistant (IR) scores for up to 2 weeks after SCD therapy. These results allow for the planning of first-in-man studies in obese type 2 diabetic patients. Angela J. Westover, Kimberly A. Johnston, Deborah A. Buffington, and H. David Humes Copyright © 2016 Angela J. Westover et al. All rights reserved. The Association of Retinopathy and Plasma Glucose and HbA1c: A Validation of Diabetes Diagnostic Criteria in a Chinese Population Tue, 11 Oct 2016 14:03:43 +0000 Aims. This study aimed to evaluate the associations of diabetic retinopathy (DR) with fasting plasma glucose (FPG), 2-hour postload plasma glucose (2hPG), and glycated hemoglobin A1c (HbA1c) in a Chinese population. Materials and Methods. A total of 3124 participants, identified from a population-based survey in Pinggu district, were examined by retinal photography (45°). DR was classified according to the Early Treatment Diabetic Retinopathy Study scale. FPG, 2hPG, and HbA1c were tested and categorized by deciles, with the prevalence of DR calculated in each decile. Results. The prevalence of DR increased sharply in the 10th deciles, when FPG exceeded 7.03 mmol/L and HbA1c exceeded 6.4%. Analysis of the receiver operating characteristic curves showed that the optimal cutoffs for detecting DR were 6.52 mmol/L and 5.9% for FPG and HbA1c, respectively. The World Health Organization (WHO) criteria for diagnosing diabetes showed high specificity (90.5–99.5%) and low sensitivity (35.3–65.0%). Further, 6 individuals with retinopathy had normal plasma glucose; however, their characteristics did not differ from those without retinopathy. Conclusions. Thresholds of FPG and HbA1c for detecting DR were observed, and the WHO criteria of diagnosing diabetes were shown to have high specificity and low sensitivity in this population. Rui Zhang, Yufeng Li, Simin Zhang, Xiaoling Cai, Xianghai Zhou, and Linong Ji Copyright © 2016 Rui Zhang et al. All rights reserved. Qualitative Parameters of the Colonic Flora in Patients with HNF1A-MODY Are Different from Those Observed in Type 2 Diabetes Mellitus Tue, 11 Oct 2016 13:48:04 +0000 Background. Type 2 diabetes mellitus (T2DM) is determined by genetic and environmental factors. There have been many studies on the relationship between the composition of the gastrointestinal bacterial flora, T2DM, and obesity. There are no data, however, on the gut microbiome structure in monogenic forms of the disease including Maturity Onset Diabetes of the Young (MODY). Methods. The aim of the investigation was to compare the qualitative parameters of the colonic flora in patients with HNF1A-MODY and T2DM and healthy individuals. 16S sequencing of bacterial DNA isolated from the collected fecal samples using the MiSeq platform was performed. Results. There were significant between-group differences in the bacterial profile. At the phylum level, the amount of Proteobacteria was higher () and the amount of Bacteroidetes was lower () in T2DM group in comparison to the control group. In HNF1A-MODY group, the frequency of Bacteroidetes was lower than in the control group (). At the order level, Turicibacterales was more abundant in HNF1A-MODY group than in T2DM group. Conclusions. It appears that there are differences in the gut microbiome composition between patients with HNF1A-MODY and type 2 diabetes. Further investigation on this matter should be conducted. Sandra Mrozinska, Piotr Radkowski, Tomasz Gosiewski, Magdalena Szopa, Malgorzata Bulanda, Agnieszka H. Ludwig-Galezowska, Iwona Morawska, Agnieszka Sroka-Oleksiak, Bartlomiej Matejko, Przemyslaw Kapusta, Dominika Salamon, Maciej T. Malecki, Pawel Wolkow, and Tomasz Klupa Copyright © 2016 Sandra Mrozinska et al. All rights reserved. Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats Mon, 10 Oct 2016 11:29:32 +0000 Purpose. Products of angiotensin (ANG) I metabolism may predispose to vascular complications of diabetes mellitus. Methods. Diabetes was induced with streptozotocin (75 mg/kg i.p.). Rat aorta fragments, isolated 4 weeks later, were pretreated with perindoprilat (3 μM), thiorphan (3 μM), or vehicle and incubated for 15 minutes with ANG I (1 μM). Products of ANG I metabolism through classical (ANG II, ANG III, and ANG IV) and alternative (ANG (1–9), ANG (1–7), and ANG (1–5)) pathways were measured in the buffer, using liquid chromatography-mass spectrometry. Results. Incubation with ANG I resulted in higher concentration of ANG II (P = 0.02, vehicle pretreatment) and lower of ANG (1–9) (, perindoprilat pretreatment) in diabetes. Preference for the classical pathway is suggested by higher ANG III/ANG (1–7) ratios in vehicle (), perindoprilat (), and thiorphan pretreated () diabetic rat. Within the classical pathway, ratios of ANG IV/ANG II () and of ANG IV/ANG III (), but not of ANG III/ANG II are lower in diabetes. Conclusions. Diabetes in rats led to preference toward deleterious (ANG II, ANG III) over protective (ANG IV, ANG (1–9), and ANG (1–7)) ANG I metabolites. P. P. Wołkow, B. Bujak-Giżycka, J. Jawień, R. Olszanecki, J. Madej, J. Rutowski, and R. Korbut Copyright © 2016 P. P. Wołkow et al. All rights reserved. Combining Donor Characteristics with Immunohistological Data Improves the Prediction of Islet Isolation Success Mon, 10 Oct 2016 10:12:15 +0000 Variability of pancreatic donors may significantly impact the success of islet isolation. The aim of this study was to evaluate donor factors associated with isolation failure and to investigate whether immunohistology could contribute to organ selection. Donor characteristics were evaluated for both successful () and failed () islet isolations. Samples of donor pancreatic tissue () were taken for immunohistochemical examination. Islet isolations with 250000 islet equivalents were considered successful. We confirmed that BMI of less than 25 kg/m2 (), cold ischemia time more than 8 hours (), hospitalization longer than 96 hours (), higher catecholamine doses (), and edematous pancreases () all unfavorably affected isolation outcome. Subsequent immunohistochemical examination of donor pancreases confirmed significant differences in insulin-positive areas (). ROC analyses then established that the insulin-positive area in the pancreas could be used to predict the likely success of islet isolation (). At the optimal cutoff point (>1.02%), sensitivity and specificity were 89% and 76%, respectively. To conclude, while the insulin-positive area, determined preislet isolation, as a single variable, is sufficient to predict isolation outcome and helps to improve the success of this procedure, its combination with the established donor scoring system might further improve organ selection. Zuzana Berkova, Frantisek Saudek, Peter Girman, Klara Zacharovova, Jan Kriz, Eva Fabryova, Ivan Leontovyc, Tomas Koblas, Lucie Kosinova, Tomas Neskudla, Ema Vavrova, David Habart, Sarka Loukotova, Martina Zahradnicka, Kvetoslav Lipar, Ludek Voska, and Jelena Skibova Copyright © 2016 Zuzana Berkova et al. All rights reserved. Salacia Extract Improves Postprandial Glucose and Insulin Response: A Randomized Double-Blind, Placebo Controlled, Crossover Study in Healthy Volunteers Mon, 10 Oct 2016 07:36:19 +0000 Thirty-five healthy subjects were randomly assigned to different doses of Salacia chinensis extract (200 mg, 300 mg, and 500 mg SCE) capsules and compared with placebo. It is a placebo controlled randomized crossover design study. Subjects were given oral sucrose solution along with capsules and plasma glucose and insulin responses were analyzed. Blood samples were collected at 0, 30, 60, 90, 120, and 180 minutes after administration. AUC insulin significantly lowered after ingestion of SCE. No significant adverse events were observed. Reducing glucose and insulin is very important in reducing postprandial hyperglycemia. Shankaranarayanan Jeykodi, Jayant Deshpande, and Vijaya Juturu Copyright © 2016 Shankaranarayanan Jeykodi et al. All rights reserved. Detection and Management of Diabetes during Pregnancy in Low Resource Settings: Insights into Past and Present Clinical Practices Mon, 10 Oct 2016 06:06:00 +0000 Background. Timely and adequate treatment is important to limit complications of diabetes affecting pregnancy, but there is a lack of knowledge on how these women are managed in low resource settings. Objective. To identify modalities of gestational diabetes detection and management in low and lower middle income countries. Methods. We conducted a scoping review of published literature and searched the databases PubMed, Web of Science, Embase, and African Index Medicus. We included all articles published until April 24, 2016, containing information on clinical practices of detection and management of gestational diabetes irrespective of publication date or language. Results. We identified 23 articles mainly from Asia and sub-Saharan Africa. The majority of studies were conducted in large tertiary care centers and hospital admission was reported in a third of publications. Ambulatory follow-up was generally done by weekly to fortnightly visits, whereas self-monitoring of blood glucose was not the norm. The cesarean section rate for pregnancies affected by diabetes ranged between 20% and 89%. Referral of newborns to special care units was common. Conclusion. The variety of reported provider practices underlines the importance of promoting latest consensus guidelines on GDM screening and management and the dissemination of information regarding their implementation. Bettina Utz, Alexandre Delamou, Loubna Belaid, and Vincent De Brouwere Copyright © 2016 Bettina Utz et al. All rights reserved. Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration Tue, 04 Oct 2016 06:53:03 +0000 Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development. We orally and intravenously administered 33-mer and 19-mer gliadin peptide to NOD, BALB/c, and C57BL/6 mice and found that the peptides readily crossed the intestinal barrier in all strains. Several degradation products were found in the pancreas by mass spectroscopy. Notably, the exocrine pancreas incorporated large amounts of radioactive label shortly after administration of the peptides. The study demonstrates that, even in normal animals, large gliadin fragments can reach the pancreas. If applicable to humans, the increased gut permeability in prediabetes and type 1 diabetes patients could expose beta cells directly to gliadin fragments. Here they could initiate inflammation and induce beta cell stress and thus contribute to the development of type 1 diabetes. Susanne W. Bruun, Knud Josefsen, Julia T. Tanassi, Aleš Marek, Martin H. F. Pedersen, Ulrik Sidenius, Martin Haupt-Jorgensen, Julie C. Antvorskov, Jesper Larsen, Niels H. Heegaard, and Karsten Buschard Copyright © 2016 Susanne W. Bruun et al. All rights reserved. Training Does Not Alter Muscle Ceramide and Diacylglycerol in Offsprings of Type 2 Diabetic Patients Despite Improved Insulin Sensitivity Thu, 29 Sep 2016 16:57:42 +0000 Ceramide and diacylglycerol (DAG) may be involved in the early phase of insulin resistance but data are inconsistent in man. We evaluated if an increase in insulin sensitivity after endurance training was accompanied by changes in these lipids in skeletal muscle. Nineteen first-degree type 2 diabetes Offsprings (Offsprings) (age:  yrs; BMI:  kg/m2) and sixteen matched Controls (age:  yrs; BMI:  kg/m2) performed 10 weeks of endurance training three times a week at 70% of VO2max on a bicycle ergometer. Before and after the intervention a hyperinsulinemic-euglycemic clamp and VO2max test were performed and muscle biopsies obtained. Insulin sensitivity was significantly lower in Offsprings compared to control subjects () but improved in both groups after 10 weeks of endurance training (Off: %; Con: %, ). The content of muscle ceramide, DAG, and their subspecies were similar between groups and did not change in response to the endurance training except for an overall reduction in C22:0-Cer (). Finally, the intervention induced an increase in AKT protein expression (Off: %; Con: %, ). This study showed no relation between insulin sensitivity and ceramide or DAG content suggesting that ceramide and DAG are not major players in the early phase of insulin resistance in human muscle. Ditte Søgaard, Torben Østergård, Agnieszka U. Blachnio-Zabielska, Marcin Baranowski, Andreas Hansen Vigelsø, Jesper Løvind Andersen, Flemming Dela, and Jørn Wulff Helge Copyright © 2016 Ditte Søgaard et al. All rights reserved. Changes of Regulatory T Cells and of Proinflammatory and Immunosuppressive Cytokines in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis Thu, 29 Sep 2016 13:59:45 +0000 Objective. The aim of this study was to investigate the changes of regulatory T cells (Treg), interleukin-6 (IL-6), IL-10, transforming growth factor-β (TGF-β), and tumor necrosis factor-alpha (TNF-α) in patients with type 2 diabetes mellitus (T2DM). Methods. We performed a comprehensive search up to July 2016 for all clinical studies about the changes of Treg, IL-6, IL-10, IL-17, TGF-β, and TNF-α in T2DM patients versus healthy controls. Results. A total of 91 articles (5642 cases and 7378 controls) were included for this meta-analysis. Compared with the controls (all ), the patients had increased serum levels of IL-6, TGF-β, and TNF-α but decreased the percentage of peripheral CD4+CD25+Foxp3+Treg and serum IL-10 level. Furthermore, the percentage of peripheral CD4+CD25+Foxp3+Treg () and serum IL-10 level () were significantly lower in the patients with complication and in the patients without complication, respectively. No significant changes about the percentage of CD4+CD25+Treg () and serum IL-17 level () were found in T2DM patients. Conclusions. T2DM patients have decreased the percentage of peripheral CD4+CD25+Foxp3+Treg and levels of serum IL-10 but elevated serum levels of IL-6, TGF-β, and TNF-α. Presence of diabetic complications further lowers the peripheral CD4+CD25+Foxp3+Treg number. Yong-chao Qiao, Jian Shen, Lan He, Xue-zhi Hong, Fang Tian, Yan-hong Pan, Ling Liang, Xiao-xi Zhang, and Hai-lu Zhao Copyright © 2016 Yong-chao Qiao et al. All rights reserved. Optimal Revascularization Strategy on Medina 0,1,0 Left Main Bifurcation Lesions in Type 2 Diabetes Thu, 29 Sep 2016 12:34:53 +0000 Aim. Diabetes mellitus (DM) is a major risk factor for cardiovascular disease. The implications of a diagnosis of DM are as severe as the diagnosis of coronary artery disease. For many patients with complex coronary artery disease, optimal revascularization strategy selection and optimal medical therapy are equally important. In this study, we compared the hemodynamic results of different stenting techniques for Medina 0,1,0 left main bifurcation lesions. Methods. We use idealized left main bifurcation models and computational fluid dynamics analysis to evaluate hemodynamic parameters which are known to affect the risk of restenosis and thrombosis at stented bifurcation. The surface integrals of time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI) at bifurcation site were quantified. Results. Crossover stenting without final kissing balloon angioplasty provided the most favorable hemodynamic results (integrated values of TAWSS = 2.96 × 10−4 N, OSI = 4.75 × 10−6 m2) with bifurcation area subjected to OSI values >0.25, >0.35, and >0.45 calculated as 0.39 mm2, 0.06 mm2, and 0 mm2, respectively. Conclusion. Crossover stenting only offers hemodynamic advantages over other stenting techniques for Medina 0,1,0 left main bifurcation lesions and large bifurcation angle is associated with unfavorable flow profiles. Xuwei Zheng, Hongyu Peng, Donghui Zhao, Qin Ma, Kun Fu, Guo Chen, Qian Fan, and Jinghua Liu Copyright © 2016 Xuwei Zheng et al. All rights reserved. The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Worse Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis Thu, 29 Sep 2016 12:09:11 +0000 Objective. Type 2 deiodinase (Dio2) is an enzyme responsible for the conversion of T4 to T3. The Thr92Ala polymorphism has been shown related to an increased risk for developing type 2 diabetes mellitus (T2DM). The aim of this study is to assess the association between this polymorphism and glycemic control in T2DM patients as marked by the HbA1C levels. Design and Methods. The terms “rs225014,” “thr92ala,” “T92A,” or “dio2 a/g” were used to search for eligible studies in the PubMed, Embase, and Cochrane databases and Google Scholar. A systematic review and meta-analysis of studies including both polymorphism testing and glycated hemoglobin (HbA1C) assays were performed. Results. Four studies were selected, totaling 2190 subjects. The pooled mean difference of the studies was 0.48% (95% CI, 0.18–0.77%), indicating that type 2 diabetics homozygous for the Dio2 Thr92Ala polymorphism had higher HbA1C levels. Conclusions. Homozygosity for the Dio2 Thr92Ala polymorphism is associated with higher HbA1C levels in T2DM patients. To confirm this conclusion, more studies of larger populations are needed. Xiaowen Zhang, Jie Sun, Wenqing Han, Yaqiu Jiang, Shiqiao Peng, Zhongyan Shan, and Weiping Teng Copyright © 2016 Xiaowen Zhang et al. All rights reserved. Sweet Bones: The Pathogenesis of Bone Alteration in Diabetes Thu, 29 Sep 2016 08:57:07 +0000 Diabetic patients have increased fracture risk. The pathogenesis underlying the status of bone alterations in diabetes mellitus is not completely understood but is multifactorial. The major deficits appear to be related to a deficit in mineralized surface area, a decrement in the rate of mineral apposition, deceased osteoid surface, depressed osteoblast activity, and decreased numbers of osteoclasts due to abnormal insulin signaling pathway. Other prominent features of diabetes mellitus are an increased urinary excretion of calcium and magnesium, accumulation of advanced glycation end products, and oxidative stress leading to sweet bones (altered bone’s strength, metabolism, and structure). Every diabetic patient should be assessed for risk factors for fractures and osteoporosis. The pathogenesis of the bone alterations in diabetes mellitus as well as their molecular mechanisms needs further study. Mohammed Al-Hariri Copyright © 2016 Mohammed Al-Hariri. All rights reserved. Short-Term High-Intensity Interval Training on Body Composition and Blood Glucose in Overweight and Obese Young Women Wed, 28 Sep 2016 15:39:38 +0000 This study was to determine the effects of five-week high-intensity interval training (HIIT) on cardiorespiratory fitness, body composition, blood glucose, and relevant systemic hormones when compared to moderate-intensity continuous training (MICT) in overweight and obese young women. Methods. Eighteen subjects completed 20 sessions of HIIT or MICT for five weeks. HIIT involved 60 × 8 s cycling at ~90% of peak oxygen consumption () interspersed with 12 s recovery, whereas MICT involved 40-minute continuous cycling at 65% of . , body composition, blood glucose, and fasting serum hormones, including leptin, growth hormone, testosterone, cortisol, and fibroblast growth factor 21, were measured before and after training. Results. Both exercise groups achieved significant improvements in (+7.9% in HIIT versus +11.7% in MICT) and peak power output (+13.8% in HIIT versus +21.9% in MICT) despite no training effects on body composition or the relevant systemic hormones. Blood glucose tended to be decreased after the intervention (). The rating of perceived exertion in MICT was higher than that in HIIT (). Conclusion. Compared with MICT, short-term HIIT is more time-efficient and is perceived as being easier for improving cardiorespiratory fitness and fasting blood glucose for overweight and obese young women. Zhaowei Kong, Shengyan Sun, Min Liu, and Qingde Shi Copyright © 2016 Zhaowei Kong et al. All rights reserved. The Relationship between Health Literacy and Health Behaviour in People with Diabetes: A Danish Population-Based Study Wed, 28 Sep 2016 14:23:29 +0000 Background. People with diabetes who have poor health behaviours are at greater risk for a range of adverse health outcomes. We aimed to investigate the relationship between health literacy and health behaviour (smoking, alcohol, physical activity, and diet) in people with diabetes. Methods. The study was based on respondents aged 25 years or older from a population-based survey in 2013 who reported having diabetes (). Two dimensions from the Health Literacy Questionnaire were used: “understand health information” and “actively engage with healthcare providers.” We used logistic regression to examine the association between health literacy and health behaviour. Results. After adjustment for sociodemographic factors, individuals with diabetes who found it difficult to understand information about health had higher odds of being physically inactive (OR: 3.43, 95% CI: 2.14–5.51) and having unhealthy dietary habits (OR: 3.01, 95% CI: 1.63–5.58). Similar results were observed for individuals who found it difficult to actively engage with healthcare providers. No associations were found between the two dimensions of health literacy and smoking and alcohol consumption. Conclusion. When developing health services and interventions to improve health behaviour among people with diabetes, our results suggest that they may benefit by including focus on health literacy. Karina Friis, Benedicte Donslund Vind, Rebecca K. Simmons, and Helle Terkildsen Maindal Copyright © 2016 Karina Friis et al. All rights reserved. Diabetic Macular Edema Pathophysiology: Vasogenic versus Inflammatory Wed, 28 Sep 2016 13:24:26 +0000 Diabetic macular edema (DME) can cause blindness in diabetic patients suffering from diabetic retinopathy (DR). DM parameters controls (glycemia, arterial tension, and lipids) are the gold standard for preventing DR and DME. Although the vascular endothelial growth factor (VEGF) is known to play a role in the development of DME, the pathological processes leading to the onset of this disease are highly complex and the exact sequence in which they occur is still not completely understood. Angiogenesis and inflammation have been shown to be involved in the pathogenesis of this disease. However, it still remains to be clarified whether angiogenesis following VEGF overexpression is a cause or a consequence of inflammation. This paper provides a review of the data currently available, focusing on VEGF, angiogenesis, and inflammation. Our analysis suggests that angiogenesis and inflammation act interdependently during the development of DME. Knowledge of DME etiology seems to be important in treatments with anti-VEGF or anti-inflammatory drugs. Current diagnostic techniques do not permit us to differentiate between both etiologies. In the future, diagnosing the physiopathology of each patient with DME will help us to select the most effective drug. Pedro Romero-Aroca, Marc Baget-Bernaldiz, Alicia Pareja-Rios, Maribel Lopez-Galvez, Raul Navarro-Gil, and Raquel Verges Copyright © 2016 Pedro Romero-Aroca et al. All rights reserved. Effect of Alkaloids from Nelumbinis Plumula against Insulin Resistance of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Mice Wed, 28 Sep 2016 11:41:34 +0000 This study aimed to investigate the effects of total alkaloids from Nelumbinis Plumula (NPA) on insulin resistance (IR) of high-fat diet- (HFD-) induced nonalcoholic fatty liver disease (NAFLD). Rats were fed with HFD for 8 weeks to induce NAFLD. Then, the effect of NPA on ameliorating IR in HFD-induced NAFLD was evaluated. Fasting serum insulin was determined using an enzyme-linked immunosorbent assay (ELISA) kit for insulin following the manufacturer’s protocol. Some inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were determined using ELISA kits to assess the inflammatory burden in rats. The results showed that HFD could induce a significant increase in blood glucose and IR in rats. However, rats treated with NPA (400 or 600 mg/kg) showed improved IR and reduction in serum inflammatory cytokines TNF-α and IL-6. Further investigation indicated that NPA could inhibit IR by restoring the insulin receptor substrate-1 (IRS-1) and suppressing the expression of c-Jun N-terminal kinase (JNK) phosphorylation. The present results supported the view that the pathogenesis of NAFLD was complex with inflammation, together with increasing serum glucose and IR. Also, JNK and IRS phosphorylation were suggested for their involvement in the modulating of IR during NAFLD progression. Therefore, NPA may serve as a potential natural remedy against IR in NAFLD. Yong Xie, Yi Zhang, Zebin Guo, Hongliang Zeng, and Baodong Zheng Copyright © 2016 Yong Xie et al. All rights reserved. Rapid Acting Insulin Use and Persistence among Elderly Type 2 Diabetes Patients Adding RAI to Oral Antidiabetes Drug Regimens Wed, 28 Sep 2016 11:13:43 +0000 We examined the real-world utilization and persistence of rapid acting insulin (RAI) in elderly patients with type 2 diabetes who added RAI to their drug (OAD) regimen. Insulin-naïve patients aged ≥65 years, with ≥1 OAD prescription during the baseline period, who were continuously enrolled in the US Humana Medicare Advantage insurance plan for 18 months and initiated RAI were included. Among patients with ≥2 RAI prescriptions (RAIp), persistence during the 12-month follow-up was assessed. Multivariate logistic regression analyses identified factors affecting RAI use and persistence. Of 3734 patients adding RAI to their OAD regimen, 2334 (62.5%) had a RAIp during follow-up. Factors associated with RAIp included using ≤2 OADs; cognitive impairment, basal insulin use during follow-up; and higher RAI out-of-pocket costs (36 to <56 versus 0 to 6.30). Patients were less likely to persist with RAI when on ≤2 OADs versus ≥3 OADs and when having higher RAI out-of-pocket costs (36 to <56 versus 0 to 6.30) and more likely to persist when they had cognitive impairment and basal insulin use during follow-up. Real-world persistence of RAI in insulin-naïve elderly patients with type 2 diabetes was very poor when RAI was added to an OAD regimen. Usha Sambamoorthi, Arijita Deb, Steve Zhou, Rahul Garg, Tao Fan, and Anders Boss Copyright © 2016 Usha Sambamoorthi et al. All rights reserved. Metformin Inhibits Advanced Glycation End Products-Induced Inflammatory Response in Murine Macrophages Partly through AMPK Activation and RAGE/NFκB Pathway Suppression Wed, 28 Sep 2016 11:11:06 +0000 Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects. In conclusion, metformin inhibits AGEs-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFκB pathway suppression. Zhong’e Zhou, Yong Tang, Xian Jin, Chengjun Chen, Yi Lu, Liang Liu, and Chengxing Shen Copyright © 2016 Zhong’e Zhou et al. All rights reserved. Exercise Therapy for Management of Type 2 Diabetes Mellitus: Superior Efficacy of Activity Monitors over Pedometers Wed, 28 Sep 2016 10:49:24 +0000 We compared the efficacy of activity monitor (which displays exercise intensity and number of steps) versus that of pedometer in exercise therapy for patients with type 2 diabetes. The study subjects were divided into the activity monitor group () and pedometer group (). The primary goal was improvement in hemoglobin A1c (HbA1c). The exercise target was set at 8,000 steps/day and 20 minutes of moderate-intensity exercise (≥3.5 metabolic equivalents). The activity monitor is equipped with a triple-axis accelerometer sensor capable of measuring medium-intensity walking duration, number of steps, walking distance, calorie consumption, and total calorie consumption. The pedometer counts the number of steps. Blood samples for laboratory tests were obtained during the visits. The first examination was conducted at the start of the study and repeated at 2 and 6 months. A significant difference in the decrease in HbA1c level was observed between the two groups at 2 months. The results suggest that the use of activity level monitor that displays information on exercise intensity, in addition to the number of steps, is useful in exercise therapy as it enhances the concept of exercise therapy and promotes lowering of HbA1c in diabetic patients. Masaaki Miyauchi, Masao Toyoda, Noriko Kaneyama, Han Miyatake, Eitaro Tanaka, Moritsugu Kimura, Tomoya Umezono, and Masafumi Fukagawa Copyright © 2016 Masaaki Miyauchi et al. All rights reserved. Hyperglycemia Induced by Glucokinase Deficiency Accelerates Atherosclerosis Development and Impairs Lesion Regression in Combined Heterozygous Glucokinase and the Apolipoprotein E-Knockout Mice Wed, 28 Sep 2016 07:50:44 +0000 Aim. Models combining diabetes and atherosclerosis are important in evaluating the cardiovascular (CV) effects and safety of antidiabetes drugs in the development of treatments targeting CV complications. Our aim was to evaluate if crossing the heterozygous glucokinase knockout mouse (GK+/−) and hyperlipidemic mouse deficient in apolipoprotein E (ApoE−/−) will generate a disease model exhibiting a diabetic and macrovascular phenotype. Methods. The effects of defective glucokinase on the glucose metabolism and on the progression and regression of atherosclerosis on high-fat diets were studied in both genders of GK+/−ApoE−/− and ApoE−/− mice. Coronary vascular function of the female GK+/−ApoE−/− and ApoE−/− mice was also investigated. Results. GK+/−ApoE−/− mice show a stable hyperglycemia which was increased on Western diet. In oral glucose tolerance test, GK+/−ApoE−/− mice showed significant glucose intolerance and impaired glucose-stimulated insulin secretion. Plasma lipids were comparable with ApoE−/− mice; nevertheless the GK+/−ApoE−/− mice showed slightly increased atherosclerosis development. Conclusions. The GK+/−ApoE−/− mice showed a stable and reproducible hyperglycemia, accelerated atherosclerotic lesion progression, and no lesion regression after lipid lowering. This novel model provides a promising tool for drug discovery, enabling the evaluation of compound effects against both diabetic and cardiovascular endpoints simultaneously in one animal model. Damilola D. Adingupu, Suvi E. Heinonen, Anne-Christine Andréasson, Mikael Brusberg, Andrea Ahnmark, Margareta Behrendt, Brendan Leighton, and Ann-Cathrine Jönsson-Rylander Copyright © 2016 Damilola D. Adingupu et al. All rights reserved.