Journal of Diabetes Research The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Low Self-Confidence and Diabetes Mismanagement in Youth with Type 1 Diabetes Mediate the Relationship between Behavioral Problems and Elevated HbA1c Mon, 23 Nov 2015 12:22:58 +0000 Introduction. Previous studies indicated an association between behavior problems (internalizing, externalizing) and glycemic control (HbA1c) in youth with type 1 diabetes (T1D). The aim of this study is to examine if this association is mediated by self-confidence and mismanagement of diabetes. Methods. Problem behavior was assessed with the Strengths and Difficulties Questionnaire. Mediating variables were assessed using the Confidence in Diabetes Self-Care-Youth and Diabetes Mismanagement Questionnaire. HbA1c was derived from hospital charts. Bootstrap mediation analysis for multiple mediation was utilized. Results. 88 youths with T1D, age 11–15 y, participated. The relation between both overall problem behavior and externalizing behavior problems and HbA1c was mediated through confidence in diabetes self-care and mismanagement (  path; point estimate = 0.50 BCa CI 95% 0.25–0.85;   path; point estimate = 0.73 BCa CI 95% 0.36–1.25). Conclusions. Increased problem behavior in youth with T1D is associated with elevated HbA1c and mediated by low self-confidence and diabetes mismanagement. Screening for problem behavior and mismanagement and assisting young patients in building confidence seem indicated to optimize glycemic control. Minke M. A. Eilander, Maartje de Wit, Joost Rotteveel, and Frank J. Snoek Copyright © 2016 Minke M. A. Eilander et al. All rights reserved. Metabolic Control and Illness Perceptions in Adolescents with Type 1 Diabetes Sun, 22 Nov 2015 14:21:33 +0000 Background. Disturbed eating behavior and psychosocial variables have been found to influence metabolic control, but little is known about how these variables interact or how they influence metabolic control, separately and combined. Objective. To explore associations between metabolic control (measured by HbA1c) and eating disorder psychopathology, coping strategies, illness perceptions, and insulin beliefs in adolescents with type 1 diabetes. Methods. A total of 105 patients (41.9% males) with type 1 diabetes (12–20 years) were interviewed with the Child Eating Disorder Examination. In addition, self-report psychosocial questionnaires were completed. Clinical data, including HbA1c, was obtained from the Norwegian Childhood Diabetes Registry. Results. Significant gender differences were demonstrated. Among females, HbA1c correlated significantly with eating restriction (.29, p < .05), the illness perception dimensions consequences, personal control, coherence, and concern (ranging from .33 to .48), and the coping strategy ventilating negative feelings (−.26, p < .05). Illness perception personal control contributed significantly to HbA1c in a regression model, explaining 23% of the variance among females (β .48, p < .001). None of the variables were significantly associated with HbA1c among males. Conclusions. Illness perceptions appear to be important contributors to metabolic control in females, but not males, with type 1 diabetes. Line Wisting, Lasse Bang, Henrik Natvig, Torild Skrivarhaug, Knut Dahl-Jørgensen, Bryan Lask, and Øyvind Rø Copyright © 2016 Line Wisting et al. All rights reserved. Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen Sun, 22 Nov 2015 13:39:17 +0000 Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants () but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15–3.20, permuted ); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk. Siew Mei Joyce-Tan, Shamsul Mohd Zain, Munavvar Zubaid Abdul Sattar, and Nor Azizan Abdullah Copyright © 2016 Siew Mei Joyce-Tan et al. All rights reserved. Correlates of Depressive Symptoms in Older Adults with Diabetes Sun, 22 Nov 2015 13:31:09 +0000 Investigators examined correlates of depressive symptoms within a sample of older adults with diabetes. Participants completed a structured telephone interview with measures including depressive symptoms, health conditions, cognitive function, and diabetes distress. Correlations and hierarchical linear regression models were utilized to examine bivariate and covariate-adjusted correlates of depressive symptoms. The sample included 246 community-dwelling adults with diabetes (65 years old). In bivariate analyses, African Americans, individuals with specific health issues (neuropathy, stroke, respiratory issues, arthritis, and cardiac issues), and those with higher levels of diabetes distress reported more depressive symptoms. Older age, higher education, more income, and better cognitive function were inversely associated with depressive symptoms. In the final covariate-adjusted regression model, stroke (B = .22, ), cognitive function (B = −.14, ), and higher levels of diabetes-related distress (B = .49, ) each were uniquely associated with more depressive symptoms. Diabetes distress partially mediated the associations between cardiac issues and depressive symptoms and between cognitive function and depressive symptoms. Findings suggest that interventions targeted at helping older adults manage their diabetes-related distress and reducing the likelihood of experiencing additional health complications may reduce depressive symptoms within this population. LaRita C. Jones, Olivio J. Clay, Fernando Ovalle, Andrea Cherrington, and Michael Crowe Copyright © 2016 LaRita C. Jones et al. All rights reserved. Participant Experiences in the Environmental Determinants of Diabetes in the Young Study: Common Reasons for Withdrawing Sun, 22 Nov 2015 13:29:23 +0000 Background. To characterize participant reasons for withdrawing from a diabetes focused longitudinal clinical observational trial (TEDDY) during the first three study years. Methods. 8677 children were recruited into the TEDDY study. At participant withdrawal staff recorded any reason parents provided for withdrawal. Reasons were categorized into (1) family characteristics and (2) protocol reasons. Families who informed staff of their withdrawal were classified as active withdrawals (AW); families without a final contact were considered passive withdrawals (PW). Results. Withdrawal was highest during the first study year . Most families were AW (; 73.4%). PW was more common in the United States (; 37.8%) and among young mothers . The most frequent protocol characteristic was blood draw (55%) and the most common family reason was not having enough time (66%). The blood draw was more common among female participants; being too busy was more common among males. Both reasons were associated with study satisfaction. Conclusions. Results suggest that, for families of children genetically at risk for diabetes, procedures that can be painful/frightening should be used with caution. Study procedures must also be considered for the demands placed on participants. Study satisfaction should be regularly assessed as an indicator of risk for withdrawal. Barbro Lernmark, Kristian Lynch, Judith Baxter, Roswith Roth, Tuula Simell, Laura Smith, Ulrica Swartling, Suzanne Bennett Johnson, and TEDDY Study Group Copyright © 2016 Barbro Lernmark et al. All rights reserved. Demographical, Clinical, and Psychological Characteristics of Users and Nonusers of an Online Platform for T2DM Patients (e-VitaDM-3/ZODIAC-44) Sun, 22 Nov 2015 13:28:26 +0000 Background. Online platforms offer opportunities for support in changing lifestyle and taking responsibility for one’s health, but engaging patients with type 2 diabetes is challenging. Previous studies have shown that patients interested in platforms were more often male, younger, and higher educated. This study aims to investigate differences in clinical and psychological characteristics between users and nonusers of a newly developed platform. Methods. A prospective study started in the Drenthe region of Netherlands. Participants in the study concerning quality of care and quality of life were additionally invited to use the platform. Results. 633 patients were registered after they opted for platform use. Of these patients, 361 (57.0%) never logged on, 184 (29.1%) were labeled “curious” users, and 88 (13.9%) were identified as “active” users. Users had lower HbA1c levels and more often hypertension compared to nonusers, and reported higher quality of life, better well-being, lower diabetes-related distress, and better medication adherence. Discussion. Platform use was associated with more favorable clinical and psychological characteristics relative to nonuse. Those with greater severity of disease, lower mood, and progression of disease used the platform the least. Other approaches need to be developed to reach these patients. Furthermore, improving the platform could also help to reach them. This trial is registered with NCT01570140. Yvonne Roelofsen, Michael van Vugt, Steven H. Hendriks, Kornelis J. J. van Hateren, Klaas H. Groenier, Frank J. Snoek, Nanne Kleefstra, Robbert Huijsman, and Henk J. G. Bilo Copyright © 2016 Yvonne Roelofsen et al. All rights reserved. Health Related Quality of Life among Omani Men and Women with Type 2 Diabetes Sun, 22 Nov 2015 13:18:25 +0000 The aim of this study was to explore predictors of health related quality of life (HRQoL) among men and women with type 2 diabetes. This cross-sectional descriptive study consisted of a random sample of 300 adults with type 2 diabetes in a selected public hospital. Euro-QoL and Revised Summary of Diabetes Self-Care Activities scales were used to collect data between January and June 2010. Schooling and ability to manage positively were highly significant predictors of quality of life (QoL) among women as compared to men. Age, prevention of activities of daily living and knowledge/management of diabetes were significant predictors of Health state among women as compared to men. Findings demonstrate that 30.6% (versus 35.7%) of the variance in the total QoL and 14% (versus 23%) of the variance in health state could be explained by personal and clinical characteristics among women and men, respectively. The study underlines the importance for nurse educators to assess HRQoL among men and women and to develop effective self-care management strategies based on personal and clinical characteristics. Melba Sheila D’Souza, Ramesh Venkatesaperumal, Susan D. Ruppert, Subrahmanya Nairy Karkada, and Devakirubai Jacob Copyright © 2016 Melba Sheila D’Souza et al. All rights reserved. Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways Sun, 22 Nov 2015 13:11:33 +0000 Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) enviroment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients. Hsiao-Ya Tsai, Chih-Pei Lin, Po-Hsun Huang, Szu-Yuan Li, Jia-Shiong Chen, Feng-Yen Lin, Jaw-Wen Chen, and Shing-Jong Lin Copyright © 2016 Hsiao-Ya Tsai et al. All rights reserved. Working Together to Promote Diabetes Control: A Practical Guide for Diabetes Health Care Providers in Establishing a Working Alliance to Achieve Self-Management Support Sun, 22 Nov 2015 13:11:20 +0000 The quality of the “patient-carer” relationship is the foundation of self-management support and has been shown to influence treatment outcome in relation to psychological and somatic illness, including diabetes. It has long been accepted within applied psychology that the quality of the client-therapist relationship—termed the working alliance—is of central importance to treatment outcome and may account for a significant degree of the overall treatment effect. Diabetes healthcare providers have recently expressed a need for further training in communication techniques and in the psychological aspects of diabetes. Could we take a page from the psychological treatment manual on working alliance in therapy to guide the diabetes healthcare provider in their role of supporting the person with diabetes achieve and maintain better metabolic control? This paper examines the role of the working alliance in diabetes care and offers a practical guide to the diabetes healthcare provider in establishing a working alliance with the person with diabetes in managing diabetes. Allan Jones, Michael Vallis, Debbie Cooke, and François Pouwer Copyright © 2016 Allan Jones et al. All rights reserved. The Impact of an Internet-Based Self-Management Intervention (HeLP-Diabetes) on the Psychological Well-Being of Adults with Type 2 Diabetes: A Mixed-Method Cohort Study Sun, 22 Nov 2015 13:09:37 +0000 This mixed-method study assessed the impact of an internet-based, self-management intervention (“HeLP-Diabetes”) on the psychological well-being of adults with type 2 diabetes. Nineteen participants were recruited from 3 general practices. Data were collected at baseline and at 6 weeks follow-up. Access to HeLP-Diabetes was associated with a significant decrease in participants’ diabetes-related distress (, , and ). No significant differences were found in emotional distress or self-efficacy. The qualitative data found that participants reported improvements including increased self-efficacy and support, better management of low mood, greater diabetes awareness, and taking the condition more seriously. Participants also reported making improvements to their eating habits, exercise routine, and medical management. Some negative experiences associated with using the intervention were mentioned including feelings of guilt for not using the intervention as suggested or not making any behavioral changes, as well as technical and navigational frustrations with the intervention. Internet-based self-management interventions may have the potential to decrease diabetes-related distress in people with type 2 diabetes. The qualitative data also suggests internet interventions can positively impact both psychological and behavioural outcomes of adults with type 2 diabetes. Megan Hofmann, Charlotte Dack, Chris Barker, and Elizabeth Murray Copyright © 2016 Megan Hofmann et al. All rights reserved. Circulating Levels of Betatrophin and Irisin Are Not Associated with Pancreatic β-Cell Function in Previously Diagnosed Type 2 Diabetes Mellitus Patients Mon, 16 Nov 2015 07:41:26 +0000 Betatrophin and irisin are two recently identified hormones which may participate in regulating pancreatic β-cell function. However, the associations of these two hormones with β-cell function remain unclear. The present study aims to demonstrate the associations of circulating betatrophin and irisin levels with β-cell function, assessed by the area under the curve (AUC) of C-peptide, and the possible correlation between these two hormones in previously diagnosed type 2 diabetes mellitus (T2DM) patients. In total, 20 age-, sex-, and body mass index- (BMI-) matched normal glucose tolerance (NGT) subjects and 120 previously diagnosed T2DM patients were included in this study. Partial correlation analysis was used to evaluate the relationships between these two hormones and indexes of β-cell function and insulin resistance. Our results showed that betatrophin levels were significantly elevated, while irisin levels were significantly decreased, in patients with T2DM compared with NGT subjects. However, partial correlation analysis showed that betatrophin levels did not correlate with β-cell function-related variables or insulin resistance-related variables before or after controlling multiple covariates, while irisin correlated positively with insulin sensitivity but is not associated with β-cell function-related variables. Besides, no correlation was observed between betatrophin and irisin levels. Hence we concluded that betatrophin and irisin were not associated with β-cell function in previously diagnosed T2DM patients. Lingshu Wang, Jun Song, Chuan Wang, Peng Lin, Kai Liang, Yu Sun, Tianyi He, Wenjuan Li, Ruxing Zhao, Jun Qin, Yiran Lu, Jinbo Liu, Fuqiang Liu, Xinguo Hou, and Li Chen Copyright © 2016 Lingshu Wang et al. All rights reserved. HERG Protein Plays a Role in Moxifloxacin-Induced Hypoglycemia Mon, 16 Nov 2015 07:37:13 +0000 The purpose of this study was to investigate the effect of moxifloxacin on HERG channel protein and glucose metabolism. HERG expression was investigated using immunohistochemistry. The whole-cell patch clamp method was used to examine the effect of moxifloxacin on HERG channel currents. A glucose tolerance test was used to analyze the effects of moxifloxacin on blood glucose and insulin concentrations in mice. Results show that HERG protein was expressed in human pancreatic β-cells. Moxifloxacin inhibited HERG time-dependent and tail currents in HEK293 cells in a concentration-dependent manner. The IC50 of moxifloxacin inhibition was 36.65 μmol/L. Moxifloxacin (200 mg/kg) reduced blood glucose levels and increased insulin secretion in wild-type mice at 60 min after the start of the glucose tolerance test. In contrast, moxifloxacin did not significantly alter blood glucose and insulin levels in HERG knockout mice. Serum glucose levels increased and insulin concentrations decreased in HERG knockout mice when compared to wild-type mice. The moxifloxacin-induced decrease in blood glucose and increase in insulin secretion occurred via the HERG protein; thus, HERG protein plays a role in insulin secretion. Hai-Yan Qiu, Sha-Sha Yuan, Fang-Yuan Yang, Ting-Ting Shi, and Jin-Kui Yang Copyright © 2016 Hai-Yan Qiu et al. All rights reserved. Impact of Real-Time Continuous Glucose Monitoring Use on Glucose Variability and Endothelial Function in Adolescents with Type 1 Diabetes: New Technology—New Possibility to Decrease Cardiovascular Risk? Mon, 16 Nov 2015 07:33:15 +0000 Children with type 1 diabetes (T1DM) are the high-risk group of accelerated atherosclerosis. Real-time continuous glucose monitoring (RT-CGM) provides possibilities for the detection of glycaemic variability, newly recognized cardiovascular risk factor. The aim of the study was to assess the usefulness of RT-CGM as an educational tool to find and reduce glycaemic variability in order to improve endothelial function in T1DM adolescents. Forty patients aged 14.6 years were recruited. The study was based on one-month CGM sensors use. Parameters of glycaemic variability were analyzed during first and last sensor use, together with brachial artery flow-mediated dilatation (FMD) to assess endothelial function. In the whole group, FMD improvement was found (10.9% to 16.6%, ), together with decrease in all studied glycaemic variability parameters. In patients with HbA1c improvement compared to the group without HbA1c improvement, we found greater increase of FMD (12% to 19%, versus 8.2% to 11.3%, ) and greater improvement of glucose variability. RT-CGM can be considered as an additional tool that offers T1DM adolescents the quick reaction to decrease glycaemic variability in short time observation. Whether such approach might influence improvement in endothelial function and reduction of the risk of future cardiovascular disease remains to be elucidated. Milena Jamiołkowska, Izabela Jamiołkowska, Włodzimierz Łuczyński, Joanna Tołwińska, Artur Bossowski, and Barbara Głowińska Olszewska Copyright © 2016 Milena Jamiołkowska et al. All rights reserved. Binding Orientations and Lipid Interactions of Human Amylin at Zwitterionic and Anionic Lipid Bilayers Mon, 16 Nov 2015 06:38:02 +0000 Increasing evidence suggests that the interaction of human islet amyloid polypeptide (hIAPP) with lipids may facilitate hIAPP aggregation and cause the death of pancreatic islet β-cells. However, the detailed hIAPP-membrane interactions and the influences of lipid compositions are unclear. In this study, as a first step to understand the mechanism of membrane-mediated hIAPP aggregation, we investigate the binding behaviors of hIAPP monomer at zwitterionic palmitoyloleoyl-phosphatidylcholine (POPC) bilayer by performing atomistic molecular dynamics simulations. The results are compared with those of hIAPP at anionic palmitoyloleoyl-phosphatidylglycerol (POPG) bilayers. We find that the adsorption of hIAPP to POPC bilayer is mainly initiated from the C-terminal region and the peptide adopts a helical structure with multiple binding orientations, while the adsorption to POPG bilayer is mostly initiated from the N-terminal region and hIAPP displays one preferential binding orientation, with its hydrophobic residues exposed to water. hIAPP monomer inserts into POPC lipid bilayers more readily than into POPG bilayers. Peptide-lipid interaction analyses show that the different binding features of hIAPP at POPC and POPG bilayers are attributed to different magnitudes of electrostatic and hydrogen-bonding interactions with lipids. This study provides mechanistic insights into the different interaction behaviors of hIAPP with zwitterionic and anionic lipid bilayers. Zhenyu Qian, Yan Jia, and Guanghong Wei Copyright © 2016 Zhenyu Qian et al. All rights reserved. Islet Amyloid Polypeptide: Structure, Function, and Pathophysiology Sun, 15 Nov 2015 13:58:40 +0000 The hormone islet amyloid polypeptide (IAPP, or amylin) plays a role in glucose homeostasis but aggregates to form islet amyloid in type-2 diabetes. Islet amyloid formation contributes to β-cell dysfunction and death in the disease and to the failure of islet transplants. Recent work suggests a role for IAPP aggregation in cardiovascular complications of type-2 diabetes and hints at a possible role in type-1 diabetes. The mechanisms of IAPP amyloid formation in vivo or in vitro are not understood and the mechanisms of IAPP induced β-cell death are not fully defined. Activation of the inflammasome, defects in autophagy, ER stress, generation of reactive oxygen species, membrane disruption, and receptor mediated mechanisms have all been proposed to play a role. Open questions in the field include the relative importance of the various mechanisms of β-cell death, the relevance of reductionist biophysical studies to the situation in vivo, the molecular mechanism of amyloid formation in vitro and in vivo, the factors which trigger amyloid formation in type-2 diabetes, the potential role of IAPP in type-1 diabetes, the development of clinically relevant inhibitors of islet amyloidosis toxicity, and the design of soluble, bioactive variants of IAPP for use as adjuncts to insulin therapy. Rehana Akter, Ping Cao, Harris Noor, Zachary Ridgway, Ling-Hsien Tu, Hui Wang, Amy G. Wong, Xiaoxue Zhang, Andisheh Abedini, Ann Marie Schmidt, and Daniel P. Raleigh Copyright © 2016 Rehana Akter et al. All rights reserved. A Multicenter Retrospective Survey regarding Diabetic Ketoacidosis Management in Italian Children with Type 1 Diabetes Sun, 15 Nov 2015 13:44:00 +0000 We conducted a retrospective survey in pediatric centers belonging to the Italian Society for Pediatric Diabetology and Endocrinology. The following data were collected for all new-onset diabetes patients aged 0–18 years: DKA (pH < 7.30), severe DKA (pH < 7.1), DKA in preschool children, DKA treatment according to ISPAD protocol, type of rehydrating solution used, bicarbonates use, and amount of insulin infused. Records of children with newly diagnosed diabetes were collected from 68/77 centers (87%), 39 of which are tertiary referral centers, the majority of whom (, 89.4%) were diagnosed in the tertiary referral centers. DKA was observed in 38.5% and severe DKA in 10.3%. Considering preschool children, DKA was observed in 72%, and severe DKA in 16.7%. Cerebral edema following DKA treatment was observed in 5 (0.5%). DKA treatment according to ISPAD guidelines was adopted in 68% of the centers. In the first 2 hours, rehydration was started with normal saline in all centers, but with different amount. Bicarbonate was quite never been used. Insulin was infused starting from third hour at the rate of 0.05–0.1 U/kg/h in 72% of centers. Despite prevention campaign, DKA is still observed in Italian children at onset, with significant variability in DKA treatment, underlying the need to share guidelines among centers. Stefano Zucchini, Andrea E. Scaramuzza, Riccardo Bonfanti, Pietro Buono, Francesca Cardella, Vittoria Cauvin, Valentino Cherubini, Giovanni Chiari, Giuseppe d’Annunzio, Anna Paola Frongia, Dario Iafusco, Giulio Maltoni, Ippolita Patrizia Patera, Sonia Toni, Stefano Tumini, Ivana Rabbone, and Diabetes Study Group of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED) Copyright © 2016 Stefano Zucchini et al. All rights reserved. Inhibition of IAPP Aggregation and Toxicity by Natural Products and Derivatives Sun, 15 Nov 2015 13:38:17 +0000 Fibrillar aggregates of human islet amyloid polypeptide, hIAPP, a pathological feature seen in some diabetes patients, are a likely causative agent for pancreatic beta-cell toxicity, leading to a transition from a state of insulin resistance to type II diabetes through the loss of insulin producing beta-cells by hIAPP induced toxicity. Because of the probable link between hIAPP and the development of type II diabetes, there has been strong interest in developing reagents to study the aggregation of hIAPP and possible therapeutics to block its toxic effects. Natural products are a class of compounds with interesting pharmacological properties against amyloids which have made them interesting targets to study hIAPP. Specifically, the ability of polyphenolic natural products, EGCG, curcumin, and resveratrol, to modulate the aggregation of hIAPP is discussed. Furthermore, we have outlined possible mechanistic discoveries of the interaction of these small molecules with the peptide and how they may mitigate toxicity associated with peptide aggregation. These abundantly found agents have been long used to combat diseases for many years and may serve as useful templates toward developing therapeutics against hIAPP aggregation and toxicity. Amit Pithadia, Jeffrey R. Brender, Carol A. Fierke, and Ayyalusamy Ramamoorthy Copyright © 2016 Amit Pithadia et al. All rights reserved. Gliptins and Cardiovascular Outcomes: A Comparative and Critical Analysis after TECOS Sun, 15 Nov 2015 13:11:36 +0000 The issue related to macrovascular outcomes and intensive glycemic control was hotly debated after the publication of landmark trials like ACCORD, ADVANCE, and VADT. The only benefits seem to come from intervening early on in the disease process as indicated by the 10-year UKPDS follow-up. To complicate matters USFDA made it mandatory for modern drugs to conduct cardiovascular safety trials in high-risk populations after the 2008 rosiglitazone scare. This led to all the modern group of drugs designing cardiovascular safety trials (gliptins, GLP-1 agonists, and SGLT-2 inhibitors) to meet USFDA regulatory requirements. We saw publication of the first 2 randomized trials with gliptins published a year and a half back. On the face value SAVOR TIMI and EXAMINE satisfied the primary composite CV end-points. However, issues related to significant increase in heart failure and all-cause 7-day on-treatment mortality created a lot of confusion. FDA reanalysis of these data (especially SAVOR) raises a lot of doubts as far as CV safety of these groups of drugs was concerned. Hence, all eyes were on TECOS, which was published this year. We take a microscopic look at these trials trying to understand where we stand as from now on this issue. Samit Ghosal and Binayak Sinha Copyright © 2016 Samit Ghosal and Binayak Sinha. All rights reserved. Psychosocial Predictors of Weight Loss among American Indian and Alaska Native Participants in a Diabetes Prevention Translational Project Sun, 15 Nov 2015 12:43:55 +0000 The association of psychosocial factors (psychological distress, coping skills, family support, trauma exposure, and spirituality) with initial weight and weight loss among American Indians and Alaska Natives (AI/ANs) in a diabetes prevention translational project was investigated. Participants were confirmed as prediabetic and subsequently enrolled in the Special Diabetes Program for Indians Diabetes Prevention (SDPI-DP) demonstration project implemented at 36 Indian health care programs. Measures were obtained at baseline and after completing a 16-session educational curriculum focusing on weight loss through behavioral changes. At baseline, psychological distress and negative family support were linked to greater weight, whereas cultural spirituality was correlated with lower weight. Furthermore, psychological distress and negative family support predicted less weight loss, and positive family support predicted greater weight loss, over the course of the intervention. These bivariate relationships between psychosocial factors and weight remained statistically significant within a multivariate model, after controlling for sociodemographic characteristics. Conversely, coping skills and trauma exposure were not significantly associated with baseline weight or change in weight. These findings demonstrate the influence of psychosocial factors on weight loss in AI/AN communities and have substantial implications for incorporating adjunctive intervention components. Edward J. Dill, Spero M. Manson, Luohua Jiang, Katherine A. Pratte, Margaret J. Gutilla, Stephanie L. Knepper, Janette Beals, Yvette Roubideaux, and Special Diabetes Program for Indians Diabetes Prevention Demonstration Project Copyright © 2016 Edward J. Dill et al. All rights reserved. Review of Herbal Traditional Chinese Medicine for the Treatment of Diabetic Nephropathy Sun, 15 Nov 2015 12:32:45 +0000 Diabetic nephropathy (DN) is the most serious chronic complications of diabetes; 20–40% of diabetic patients develop into end stage renal disease (ESRD). However, exact pathogenesis of DN is not fully clear and we have great difficulties in curing DN; poor treatment of DN led to high chances of mortality worldwide. A lot of western medicines such as ACEI and ARB have been demonstrated to protect renal function of DN but are not enough to delay or retard the progression of DN; therefore, exploring exact and feasible drug is current research hotspot in medicine. Traditional Chinese medicine (TCM) has been widely used to treat and control diabetes and its complications such as DN in a lot of scientific researches, which will give insights into the mechanism of DN, but they are not enough to reveal all the details. In this paper, we summarize the applications of herbal TCM preparations, single herbal TCM, and/or monomers from herbal TCM in the treatment of DN in the recent 10 years, depicting the renal protective effects and the corresponding mechanism, through which we shed light on the renal protective roles of TCM in DN with a particular focus on the molecular basis of the effect and provide a beneficial supplement to the drug therapy for DN. Guang-dong Sun, Chao-yuan Li, Wen-peng Cui, Qiao-yan Guo, Chang-qing Dong, Hong-bin Zou, Shu-jun Liu, Wen-peng Dong, and Li-ning Miao Copyright © 2016 Guang-dong Sun et al. All rights reserved. Relationship of Hemoglobin A1c with β Cell Function and Insulin Resistance in Newly Diagnosed and Drug Naive Type 2 Diabetes Patients Tue, 10 Nov 2015 12:40:10 +0000 Objective. To investigate changes in the glycated hemoglobin A1c (A1c) level and those in β cell function and insulin resistance in newly diagnosed and drug naive type 2 diabetes patients and to evaluate the relationship between them. Design and Methods. A total of 818 newly diagnosed diabetic individuals who were ≥40 years of age were recruited. The subjects were grouped by A1c values (<6.5%, 6.5–7%, 7-8%, 8-9%, and ≥9%). The homeostasis model assessment (HOMA) was used to evaluate pancreatic β cell function (HOMA-β) and insulin resistance (HOMA-IR). ANOVA, -tests, and binary logistic regression analysis were used for data analysis. Results. Compared with subjects with A1c values <6.5%, individuals with an A1c of 6.5–7% exhibited an increased HOMA-β index. However, the HOMA-β index was significantly decreased at A1c values ≥7% and further decreased by 9.3% and by 23.7%, respectively, at A1c values of 7-8% and 8-9%. As A1c increased to ≥9%, a 62% reduction in β cell function was observed, independently of age, gender, body mass index (BMI), blood pressure (BP), blood lipids, and hepatic enzyme levels. Meanwhile, insulin resistance was significantly increased with an increase in A1c values. Conclusions. Elevated A1c values (≥7%) were associated with substantial reductions in β cell function. Xinguo Hou, Jinbo Liu, Jun Song, Chuan Wang, Kai Liang, Yu Sun, Zeqiang Ma, Weifang Yang, Chengqiao Li, Xiuping Zhang, Peng Lin, Lei Gong, Meijian Wang, Fuqiang Liu, Wenjuan Li, Fei Yan, Jun Qin, Lingshu Wang, Jidong Liu, Ruxing Zhao, Shihong Chen, and Li Chen Copyright © 2016 Xinguo Hou et al. All rights reserved. Effects of Liraglutide Combined with Short-Term Continuous Subcutaneous Insulin Infusion on Glycemic Control and Beta Cell Function in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Pilot Study Tue, 10 Nov 2015 12:26:18 +0000 The objective of this paper is to investigate the effects of liraglutide in combination with short-term continuous subcutaneous insulin infusion (CSII) therapy on glycemic control and beta cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Thirty-nine eligible newly diagnosed T2DM patients were recruited and randomized to receive either of two therapies: short-term CSII alone (CSII alone group) or CSII in combination with liraglutide (CSII + Lira group) for 12 weeks. Blood glucose control, homeostasis model assessment (HOMA) indices, and acute insulin response (AIR) were compared between the two groups. The patients in CSII + Lira group achieved euglycemia with equivalent insulin dosage in shorter time (1 (0) versus 2 (3) days, ). HbA1c at the end of study was comparable between two groups (% versus %, for CSII alone group and CSII + Lira group, resp., ). The increment of AIR was higher in CSII + Lira group (177.58 (351.57) μU·min/mL versus 58.15 (51.30) μU·min/mL, ). However, after stopping liraglutide, its effect on beta cell function disappeared completely. Liraglutide combined with short-term CSII was effective in further improving beta cell function, but the beneficial effects did not sustain after suspension of the therapy. Weijian Ke, Liehua Liu, Juan Liu, Ailing Chen, Wanping Deng, Pengyuan Zhang, Xiaopei Cao, Zhihong Liao, Haipeng Xiao, Jianbin Liu, and Yanbing Li Copyright © 2016 Weijian Ke et al. All rights reserved. The Effect of Tianmai Xiaoke Pian on Insulin Resistance through PI3-K/AKT Signal Pathway Tue, 10 Nov 2015 12:25:58 +0000 In the clinical setting, given the potential adverse effects of thiazolidinediones and biguanides, we often have difficulty in treatment that no other insulin sensitizers are available for use in type 2 diabetic mellitus (T2DM) patients. Tianmai Xiaoke Pian (TMXKP) is a traditional Chinese medicine tablet, which is comprised of chromium picolinate, Tianhuafen, Maidong, and Wuweizi. To understand its mechanism of action on insulin resistance, TMXKP (50 mg/kg orally) was tested in T2DM rats (induced by a high-fat diet and streptozotocin). Eight weeks later, fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT) were performed. Area under the curve (AUC) and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated, and PI3-K/AKT signal pathway-related genes and proteins were tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis in muscle, adipose, and liver tissues, respectively. TMXKP significantly reduced FBG, OGTT, AUC, and HOMA-IR in diabetic rats . Furthermore, we also observed that TMXKP could significantly decrease IRS-1, IRS-2, PI3-K p85α, and AKT2 gene expression and also IRS-1, IRS-2, PI3-K, AKT2, and p-AKT2 protein expression levels in diabetic rats. These findings confirm that TMXKP can alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Thus TMXKP appears to be a promising insulin sensitizer. Nana Wang, Tiegang Li, and Ping Han Copyright © 2016 Nana Wang et al. All rights reserved. Mannose-Binding Lectin Levels and Carotid Intima-Media Thickness in Type 2 Diabetic Patients Tue, 10 Nov 2015 09:31:27 +0000 Introduction. Mannose-binding lectin (MBL) activates complement system and has been suggested to play a role in vascular complications in diabetics. Carotid intima-media thickness (cIMT) detects subclinical atherosclerosis. We evaluated the association of MBL and IMT in type 2 diabetic (T2DM) patients. Methods. Serum MBL levels and cIMT were measured in a total of 103 diabetics and in 98 age-matched healthy controls. Results. There was no significant difference in MBL level in T2DM versus controls. As expected, IMT was significantly higher in T2DM patients than in controls (). In T2DM, the lowest cIMT was seen in patients with normal MBL level (500–1000) while cIMT continuously increased with both high MBL and absolute MBL deficiency states. This was especially significant in high MBL versus normal MBL T2DM patients (). According to multiple regression analysis the main predictors of IMT in T2DM are age (), ApoA level (), and the MBL (). Conclusions. Our results suggest a dual role of MBL as a risk factor for cIMT in T2DM. MBL may also be used as a marker of macrovascular disease, as both low and high levels indicate the susceptibility for atherosclerosis in T2DM. Miklós Káplár, Shah Sweni, Julianna Kulcsár, Barbara Cogoi, Regina Esze, Sándor Somodi, Mária Papp, László Oláh, Mária Tünde Magyar, Katalin Szabó, Katalin Réka Czuriga-Kovács, Jolán Hársfalvi, and György Paragh Copyright © 2016 Miklós Káplár et al. All rights reserved. Metabolomics and Type 2 Diabetes: Translating Basic Research into Clinical Application Mon, 09 Nov 2015 14:21:31 +0000 Type 2 diabetes (T2D) and its comorbidities have reached epidemic proportions, with more than half a billion cases expected by 2030. Metabolomics is a fairly new approach for studying metabolic changes connected to disease development and progression and for finding predictive biomarkers to enable early interventions, which are most effective against T2D and its comorbidities. In metabolomics, the abundance of a comprehensive set of small biomolecules (metabolites) is measured, thus giving insight into disease-related metabolic alterations. This review shall give an overview of basic metabolomics methods and will highlight current metabolomics research successes in the prediction and diagnosis of T2D. We summarized key metabolites changing in response to T2D. Despite large variations in predictive biomarkers, many studies have replicated elevated plasma levels of branched-chain amino acids and their derivatives, aromatic amino acids and α-hydroxybutyrate ahead of T2D manifestation. In contrast, glycine levels and lysophosphatidylcholine C18:2 are depressed in both predictive studies and with overt disease. The use of metabolomics for predicting T2D comorbidities is gaining momentum, as are our approaches for translating basic metabolomics research into clinical applications. As a result, metabolomics has the potential to enable informed decision-making in the realm of personalized medicine. Matthias S. Klein and Jane Shearer Copyright © 2016 Matthias S. Klein and Jane Shearer. All rights reserved. Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity Mon, 09 Nov 2015 14:19:58 +0000 Chronic intake of saturated free fatty acids is associated with diabetes and may contribute to the impairment of functional beta cell mass. Mitogen activated protein kinase 8 interacting protein 1 also called islet brain 1 (IB1) is a candidate gene for diabetes that is required for beta cell survival and glucose-induced insulin secretion (GSIS). In this study we investigated whether IB1 expression is required for preserving beta cell survival and function in response to palmitate. Chronic exposure of MIN6 and isolated rat islets cells to palmitate led to reduction of the IB1 mRNA and protein content. Diminution of IB1 mRNA and protein level relied on the inducible cAMP early repressor activity and proteasome-mediated degradation, respectively. Suppression of IB1 level mimicked the harmful effects of palmitate on the beta cell survival and GSIS. Conversely, ectopic expression of IB1 counteracted the deleterious effects of palmitate on the beta cell survival and insulin secretion. These findings highlight the importance in preserving the IB1 content for protecting beta cell against lipotoxicity in diabetes. Saška Brajkovic, Mourad Ferdaoussi, Valérie Pawlowski, Hélène Ezanno, Valérie Plaisance, Erik Zmuda, Tsonwin Hai, Jean-Sébastien Annicotte, Gérard Waeber, and Amar Abderrahmani Copyright © 2016 Saška Brajkovic et al. All rights reserved. Cardiac Resynchronization Therapy Outcomes in Type 2 Diabetic Patients: Role of MicroRNA Changes Mon, 09 Nov 2015 14:15:32 +0000 Heart failure (HF) and type 2 diabetes mellitus (T2DM) are two growing and related diseases in general population and particularly in elderly people. In selected patients affected by HF and severe dysfunction of left ventricle ejection fraction (LVEF), with left bundle brunch block, the cardiac resynchronization therapy with a defibrillator (CRT) is the treatment of choice to improve symptoms, NYHA class, and quality of life. CRT effects are related to alterations in genes and microRNAs (miRs) expression, which regulate cardiac processes involved in cardiac apoptosis, cardiac fibrosis, cardiac hypertrophy and angiogenesis, and membrane channel ionic currents. Different studies have shown a different prognosis in T2DM patients and T2DM elderly patients treated by CRT-D. We reviewed the literature data on CRT-D effect on adult and elderly patients with T2DM as compared with nondiabetic patients. Celestino Sardu, Michelangela Barbieri, Maria Rosaria Rizzo, Pasquale Paolisso, Giuseppe Paolisso, and Raffaele Marfella Copyright © 2016 Celestino Sardu et al. All rights reserved. Development of Diagnostic Biomarkers for Detecting Diabetic Retinopathy at Early Stages Using Quantitative Proteomics Mon, 09 Nov 2015 13:58:32 +0000 Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults. Here, we performed a comprehensive proteomic analysis to discover biomarkers for DR. First, to identify biomarker candidates that are specifically expressed in human vitreous, we performed data-mining on both previously published DR-related studies and our experimental data; 96 proteins were then selected. To confirm and validate the selected biomarker candidates, candidates were selected, confirmed, and validated using plasma from diabetic patients without DR (No DR) and diabetics with mild or moderate nonproliferative diabetic retinopathy (Mi or Mo NPDR) using semiquantitative multiple reaction monitoring (SQ-MRM) and stable-isotope dilution multiple reaction monitoring (SID-MRM). Additionally, we performed a multiplex assay using 15 biomarker candidates identified in the SID-MRM analysis, which resulted in merged AUC values of 0.99 (No DR versus Mo NPDR) and 0.93 (No DR versus Mi and Mo NPDR). Although further validation with a larger sample size is needed, the 4-protein marker panel (APO4, C7, CLU, and ITIH2) could represent a useful multibiomarker model for detecting the early stages of DR. Jonghwa Jin, Hophil Min, Sang Jin Kim, Sohee Oh, Kyunggon Kim, Hyeong Gon Yu, Taesung Park, and Youngsoo Kim Copyright © 2016 Jonghwa Jin et al. All rights reserved. Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes Mellitus Mon, 09 Nov 2015 13:29:29 +0000 Human islet amyloid polypeptide (hIAPP) is the major component of the amyloid deposits found in the pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Mature hIAPP, a 37-aa peptide, is natively unfolded in its monomeric state but forms islet amyloid in T2DM. In common with other misfolded and aggregated proteins, amyloid formation involves aggregation of monomers of hIAPP into oligomers, fibrils, and ultimately mature amyloid deposits. hIAPP is coproduced and stored with insulin by the pancreatic islet β-cells and is released in response to the stimuli that lead to insulin secretion. Accumulating evidence suggests that hIAPP amyloid deposits that accompany T2DM are not just an insignificant phenomenon derived from the disease progression but that hIAPP aggregation induces processes that impair the functionality and the viability of β-cells. In this review, we particularly focus on hIAPP structure, hIAPP aggregation, and hIAPP-membrane interactions. We will also discuss recent findings on the mechanism of hIAPP-membrane damage and on hIAPP-induced cell death. Finally, the development of successful antiamyloidogenic agents that prevent hIAPP fibril formation will be examined. Lucie Caillon, Anais R. F. Hoffmann, Alexandra Botz, and Lucie Khemtemourian Copyright © 2016 Lucie Caillon et al. All rights reserved. New Methods in Exploring Old Topics: Case Studying Brittle Diabetes in the Family Context Sun, 08 Nov 2015 19:16:50 +0000 Background. In questing for a more refined quantitative research approach, we revisited vector autoregressive (VAR) modeling for the analysis of time series data in the context of the so far poorly explored concept of family dynamics surrounding instable diabetes type 1 (or brittle diabetes). Method. We adopted a new approach to VAR analysis from econometrics referred to as the optimized multivariate lag selection process and applied it to a set of raw data previously analyzed through standard approaches. Results. We illustrated recurring psychosomatic circles of cause and effect relationships between emotional and somatic parameters surrounding glycemic control of the child’s diabetes and the affective states of all family members. Conclusion. The optimized multivariate lag selection process allowed for more specific, dynamic, and statistically reliable results (increasing R2 tenfold in explaining glycemic variability), which were derived from a larger window of past explanatory variables (lags). Such highly quantitative versus historic more qualitative approaches to case study analysis of psychosomatics surrounding diabetes in adolescents were reflected critically. Moritz Philipp Günther, Peter Winker, Stefan A. Wudy, and Burkhard Brosig Copyright © 2016 Moritz Philipp Günther et al. All rights reserved.