Journal of Diabetes Research The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance Tue, 25 Aug 2015 13:35:28 +0000 Nowadays wrong nutritional habits and lack of physical activity give a rich soil for the development of insulin resistance and obesity. Many researches indicate lipids, especially the one from the sphingolipids class, as the group of molecules heavily implicated in the progress of insulin resistance in skeletal muscle. Recently, scientists have focused their scrutiny on myriocin, a potent chemical compound that inhibits ceramide (i.e., central hub of sphingolipids signaling pathway) de novo synthesis. In the present research we evaluated the effects of myriocin application on type 2 diabetes mellitus in three different types of skeletal muscles: (1) slow-oxidative (red gastrocnemius), (2) oxidative-glycolytic (soleus), and (3) glycolytic (white gastrocnemius). For these reasons the animals were randomly divided into four groups: “control” (C), “myriocin” (M), “high fat diet” (HFD), “high fat diet” (HFD), and “high fat diet + myriocin” (HFD + M). Our in vivo study demonstrated that ceramide synthesis inhibition reduces intramuscular ceramide, its precursor sphinganine, and its derivatives sphingosine and sphingosine-1-phosphate concentrations. Moreover, FFA and TG contents were also decreased after myriocin treatment. Thus, myriocin presents potential therapeutic perspectives with respect to the treatment of insulin resistance and its serious consequences in obese patients. Krzysztof Kurek, Agnieszka Mikłosz, Bartłomiej Łukaszuk, Adrian Chabowski, Jan Górski, and Małgorzata Żendzian-Piotrowska Copyright © 2015 Krzysztof Kurek et al. All rights reserved. Urinary Angiotensinogen Could Be a Prognostic Marker of Renoprotective Effects of Alogliptin in Patients with Type 2 Diabetes Tue, 25 Aug 2015 13:28:27 +0000 Background. The aims of this study were (1) to examine the renoprotective effects of alogliptin and (2) to establish urinary angiotensinogen (AGT) as a prognostic marker of renoprotective effects of alogliptin in patients with type 2 diabetes (T2D). Methods. In 43 patients with T2D (18 women, years), 25 mg/day of alogliptin was added to the traditional hypoglycemic agents and/or nondrug treatments. Urinary concentrations of albumin (Alb) and AGT, normalized by urinary concentrations of creatinine (Cr) (UAlbCR and UAGTCR, respectively), were measured before and after the 12-week alogliptin treatment. Results. Alogliptin treatment tended to decrease UAlbCR ( versus  mg/g Cr, ). Based on % change in UAlbCR, patients were divided into two groups, responders () and nonresponders (), and a logistic analysis of UAGTCR before treatment showed cutoff value of 20.8 µg/g Cr. When all patients were redivided into two groups, those with higher values of UAGTCR before the treatment (Group H, ) and those with lower values (Group L), Group H showed significantly decreased UAlbCR in response to alogliptin ( versus , ). Conclusion. Urinary AGT could be a prognostic marker of renoprotective effects of alogliptin in patients with T2D. Tomoko Mizushige, Hiroyuki Kobori, Yoko Nishijima, Yuichiro Yano, Koji Sakata, Manabu Hayakawa, and Akira Nishiyama Copyright © 2015 Tomoko Mizushige et al. All rights reserved. Increased Oxidation as an Additional Mechanism Underlying Reduced Clot Permeability and Impaired Fibrinolysis in Type 2 Diabetes Tue, 18 Aug 2015 12:56:39 +0000 Aims. We sought to investigate whether enhanced oxidation contributes to unfavorable fibrin clot properties in patients with diabetes. Methods. We assessed plasma fibrin clot permeation (, a measure of the pore size in fibrin networks) and clot lysis time induced by recombinant tissue plasminogen activator (CLT) in 163 consecutive type 2 diabetic patients (92 men and 71 women) aged 65 ± 8.8 years with a mean glycated hemoglobin (HbA1c) of 6.8%. We also measured oxidative stress markers, including nitrotyrosine, the soluble form of receptor for advanced glycation end products (sRAGE), 8-iso-prostaglandin F2α (8-iso-PGF2α), oxidized low-density lipoprotein (oxLDL), and advanced glycation end products (AGE). Results. There were inverse correlations between and nitrotyrosine, sRAGE, 8-iso-PGF2α, and oxLDL. CLT showed a positive correlation with oxLDL and nitrotyrosine but not with other oxidation markers. All these associations remained significant for after adjustment for fibrinogen, disease duration, and HbA1c (all ), while oxLDL was the only independent predictor of CLT. Conclusions. Our study shows that enhanced oxidative stress adversely affects plasma fibrin clot properties in type 2 diabetic patients, regardless of disease duration and glycemia control. Anna Lados-Krupa, Malgorzata Konieczynska, Artur Chmiel, and Anetta Undas Copyright © 2015 Anna Lados-Krupa et al. All rights reserved. Psoriasis and Diabetes: A Multicenter Study in 222078 Type 2 Diabetes Patients Reveals High Levels of Depression Tue, 18 Aug 2015 05:59:57 +0000 Objective. This study aimed to investigate the association between psoriasis and disease outcome in type 2 diabetes (T2D). Methods. 222078 T2D patients (≥10 years old) from the prospective, multicenter diabetes patient registry were analyzed. Specific search items were used to identify psoriasis patients. Multiple regression models were fitted and adjusted for demographic confounder. Results. 232 T2D patients had comorbid psoriasis. After adjusting psoriasis patients revealed a higher BMI (31.8 [31.0; 32.6] versus 30.6 [30.5; 30.6] kg/m2, ) and HbA1c (64.8 [62.1; 67.6] versus 59.0 [58.9; 59.1] mmol/mol, ). Insulin was used more frequently (62.3 [55.7; 68.5] versus 50.9 [50.7; 51.1] %, ), only OAD/GLP-1 was similar, and nonpharmacological treatment was less common (13.3 [9.5; 18.3] versus 21.9 [21.7; 22.1] %, ). Severe hypoglycemia (0.31 [0.238; 0.399] versus 0.06 [0.057; 0.060] events per patient-year, ), hypertension (86.1 [81.1; 90.0] versus 68.0 [67.8; 68.2] %, ), and thyroid disease (14.0 [10.1; 19.2] versus 4.6 [4.5; 4.7] %, ) were more prevalent. Depression occurred more often (10.5 [7.1; 15.2] versus 2.8 [2.7; 2.8] %, ). Conclusions. Clinical diabetes characteristics in psoriasis T2D patients were clearly worse compared to patients without psoriasis. Comorbid conditions and depression were more prevalent, and more intensive diabetes therapy was required. Anke Schwandt, Dominik Bergis, Albrecht Dapp, Stefan Ebner, Peter M. Jehle, Stefan Köppen, Alexander Risse, Stefan Zimny, and Reinhard W. Holl Copyright © 2015 Anke Schwandt et al. All rights reserved. Effects of E2HSA, a Long-Acting Glucagon Like Peptide-1 Receptor Agonist, on Glycemic Control and Beta Cell Function in Spontaneous Diabetic db/db Mice Mon, 17 Aug 2015 14:09:50 +0000 Glucagon like peptide-1 (GLP-1) receptor agonists such as exendin-4 have been widely used but their short half-life limits their therapeutic value. The recombinant protein, E2HSA, is a novel, long-acting GLP-1 receptor agonist generated by the fusion of exendin-4 with human serum albumin. In mouse pancreatic NIT-1 cells, E2HSA activated GLP-1 receptor with similar efficacy as exendin-4. After single-dose administration in ICR mice, E2HSA showed prolonged glucose lowering effects which lasted up to four days and extended inhibition on gastric emptying for at least 72 hours. Chronic E2HSA treatment in db/db mice significantly improved glucose tolerance, reduced elevated nonfasting and fasting plasma glucose levels, and also decreased HbA1c levels. E2HSA also increased insulin secretion and decreased body weight and appetite. Furthermore, immunofluorescence analysis showed that E2HSA increased -cell area, improved islet morphology, and reduced β-cell apoptosis. In accordance with the promotion of β-cell function and survival, E2HSA upregulated genes such as Irs2, Pdx-1, Nkx6.1, and MafA and downregulated the expression levels of FoxO1 and proapoptotic Bcl-2 family proteins. In conclusion, with prolonged glucose lowering effects and promoting -cell function and survival, the fusion protein, E2HSA, is a promising new therapeutic for once weekly treatment of type 2 diabetes. Shaocong Hou, Caina Li, Yi Huan, Shuainan Liu, Quan Liu, Sujuan Sun, Qian Jiang, Chunming Jia, and Zhufang Shen Copyright © 2015 Shaocong Hou et al. All rights reserved. Corrigendum to “Evacuation after the Fukushima Daiichi Nuclear Power Plant Accident Is a Cause of Diabetes: Results from the Fukushima Health Management Survey” Thu, 13 Aug 2015 12:09:33 +0000 Hiroaki Satoh, Tetsuya Ohira, Mitsuaki Hosoya, Akira Sakai, Tsuyoshi Watanabe, Akira Ohtsuru, Yukihiko Kawasaki, Hitoshi Suzuki, Atsushi Takahashi, Gen Kobashi, Kotaro Ozasa, Seiji Yasumura, Shunichi Yamashita, Kenji Kamiya, and Masafumi Abe Copyright © 2015 Hiroaki Satoh et al. All rights reserved. Tripterygium Glycosides Tablet Ameliorates Renal Tubulointerstitial Fibrosis via the Toll-Like Receptor 4/Nuclear Factor Kappa B Signaling Pathway in High-Fat Diet Fed and Streptozotocin-Induced Diabetic Rats Wed, 12 Aug 2015 06:57:05 +0000 Tripterygium glycosides tablet (TGT) is a Chinese traditional medicine that has been shown to protect podocytes from injury and reduce the proteinuria. The aim of this study was to assess the effect of TGT on renal tubulointerstitial fibrosis and its potential mechanism in high-fat diet fed and STZ-induced diabetic rats. Rats were randomly divided into normal control rats (NC group), diabetic rats without drug treatment (DM group), and diabetic rats treated with TGT (1, 3, or 6 mg/kg/day, respectively) for 8 weeks. The results showed that 24 h proteinuria and urinary N-acetyl-glucosaminidase (NAG) in diabetic rats were decreased by TGT treatment without affecting blood glucose. Masson’s trichrome stains showed that apparent renal tubulointerstitial fibrosis was found in DM group, which was ameliorated by TGT treatment. The expression of -SMA was significantly decreased, accompanied by increased expression of E-cadherin in TGT-treated rats, but not in untreated DM rats. Further studies showed that TGT administration markedly reduced expression of TLR4, NF-B, IL-1, and MCP-1 in TGT-treated diabetic rats. These results showed that TGT could ameliorate renal tubulointerstitial fibrosis, the mechanism which may be at least partly associated with the amelioration of EMT through suppression of the TLR4/NF-B pathway. Ze-jun Ma, Xiao-na Zhang, Li Li, Wei Yang, Shan-shan Wang, Xin Guo, Pei Sun, and Li-ming Chen Copyright © 2015 Ze-jun Ma et al. All rights reserved. The Effects of Probiotic Soymilk Fortified with Omega-3 on Blood Glucose, Lipid Profile, Haematological and Oxidative Stress, and Inflammatory Parameters in Streptozotocin Nicotinamide-Induced Diabetic Rats Tue, 11 Aug 2015 11:27:38 +0000 Objective. The aim of the present study was to evaluate the effects of probiotic soymilk fortified with omega-3 in diabetic rats. Methods. Soymilk (SM), fermented soymilk (FSM), and fermented soymilk fortified with omega-3 (FSM + omega-3) were prepared. Rats were randomly assigned to five groups of 13 animals per group. Diabetes was induced by a single injection of streptozotocin (STZ) 15 min after the intraperitoneal administration of nicotinamide (NA). Normal control (NC) and diabetic control (DC) rats received 1 mL/day of distilled water and three groups of diabetic rats were given 1 mL/day of SM, FSM, and FSM + omega-3 products by oral gavage for 28 days. Results. Three products significantly () reduced blood glucose, total cholesterol (TC), triglyceride (TG), and malondialdehyde (MDA) concentrations compared to the DC group, with the maximum reduction seen in the FSM + omega-3 group. Body weight, red blood cells (RBC), haemoglobin (Hb), haematocrit, and superoxide dismutase (SOD) also significantly increased in the FSM + omega-3 group. In the FSM + omega-3 group, MDA level compared with the SM and FSM groups and high sensitivity C-reactive protein (hs-CRP) concentrations compared with the DC and FSM groups were significantly lower (). Conclusion. Fermented soymilk fortified with omega-3 may be beneficial in diabetes. Mohsen Mohammadi Sartang, Seyed Mohammad Mazloomi, Nader Tanideh, and Abbas Rezaian Zadeh Copyright © 2015 Mohsen Mohammadi Sartang et al. All rights reserved. A Family History of Diabetes Modifies the Association between Elevated Urine Albumin Concentration and Hyperglycemia in Nondiabetic Mexican Adolescents Tue, 11 Aug 2015 08:28:20 +0000 We examined the frequency of elevated urine albumin concentration (UAC) and its association with metabolic syndrome (MetS) and metabolic markers in 515 nondiabetic Mexican adolescents stratified by family history of diabetes (FHD). UAC was measured in a first morning urine sample and considered elevated when excretion was ≥20 mg/mL. MetS was defined using International Diabetes Federation criteria. Fasting insulin, insulin resistance, and lipids were evaluated. Multivariate logistic regression was performed. Elevated UAC was present in 12.4% and MetS was present in 8.9% of the adolescents. No association was found between elevated UAC and MetS. Among adolescents with FHD, 18.4% were overweight and 20.7% were obese, whereas, among those without a FHD, 15.9% were overweight and 7.5% were obese. Hyperglycemia was higher in those with elevated UAC than in those without (44.4% versus 5.1%, ). Hyperglycemia (OR = 9.8, 95% CI 1.6–59.4) and number of MetS components (OR = 4.5, 95% CI 1.5–13.3) were independently associated with elevated UAC. Among female participants, abdominal obesity was associated with elevated UAC (OR = 4.5, 95% CI 1.2–16.9). Conclusion. Elevated UAC was associated neither with MetS nor with any metabolic markers in nondiabetic adolescents. However, FHD modified the association of elevated UAC with hyperglycemia and the number of MetS components. Aida Jiménez-Corona, Antonio Ávila-Hermosillo, Robert G. Nelson, and Guadalupe Ramírez-López Copyright © 2015 Aida Jiménez-Corona et al. All rights reserved. Comparison of Glomerular Filtration Rate Estimation from Serum Creatinine and Cystatin C in HNF1A-MODY and Other Types of Diabetes Mon, 10 Aug 2015 13:06:03 +0000 Introduction. We previously showed that in HNF1A-MODY the cystatin C-based glomerular filtration rate (GFR) estimate is higher than the creatinine-based estimate. Currently, we aimed to replicate this finding and verify its clinical significance. Methods. The study included 72 patients with HNF1A-MODY, 72 with GCK-MODY, 53 with type 1 diabetes (T1DM), 70 with type 2 diabetes (T2DM), and 65 controls. Serum creatinine and cystatin C levels were measured. GFR was calculated from creatinine and cystatin C using the CKD-EPI creatinine equation (eGRF-cr) and CKD-EPI cystatin C equation (eGFR-cys), respectively. Results. Cystatin C levels were lower () in the control ( mg/L), HNF1A (), and GCK ( mg/L) groups in comparison to those with either T1DM ( mg/L) or T2DM ( mg/L). Moreover, eGFR-cys was higher than eGRF-cr in HNF1A-MODY, GCK-MODY, and the controls (; ; ). This corresponded to 8.9 mL/min/1.73 m2, 9.7 mL/min/1.73 m2, and 16.9 mL/min/1.73 m2 of difference. Additionally, T1DM patients had higher eGFR-cr than eGFR-cys (11.6 mL/min/1.73 m2; ); no difference occurred in T2DM (). Conclusions. We confirmed that eGFR-cys values in HNF1A-MODY patients are higher compared to eGFR-cr. Some other differences were also described in diabetic groups. However, none of them appears to be clinically relevant. Magdalena Szopa, Maria Kapusta, Bartlomiej Matejko, Tomasz Klupa, Teresa Koblik, Beata Kiec-Wilk, Maciej Borowiec, and Maciej T. Malecki Copyright © 2015 Magdalena Szopa et al. All rights reserved. Polysaccharides from Enteromorpha prolifera Improve Glucose Metabolism in Diabetic Rats Mon, 10 Aug 2015 12:40:38 +0000 This study investigated the effects of polysaccharides from Enteromorpha prolifera (PEP) on glucose metabolism in a rat model of diabetes mellitus (DM). PEP (0, 150, 300, and 600 mg/kg) was administered intragastrically to rats for four weeks. After treatment, fasting blood glucose (FBG) and insulin (INS) levels were measured, and the insulin sensitivity index (ISI) was calculated. The morphopathological changes in the pancreas were observed. Serum samples were collected to measure the oxidant-antioxidant status. The mRNA expression levels of glucokinase (GCK) and insulin receptor (InsR) in liver tissue and glucose transporter type 4 (GLUT-4) and adiponectin (APN) in adipose tissue were determined. Compared with the model group, the FBG and INS levels were lower, the ISI was higher, and the number of islet β-cells was significantly increased in all the PEP groups. In the medium- and high-dose PEP groups, MDA levels decreased, and the enzymatic activities of SOD and GSH-Px increased. The mRNA expression of InsR and GCK increased in all the PEP groups; APN mRNA expression increased in the high-dose PEP group, and GLUT-4 mRNA expression increased in adipose tissue. These findings suggest that PEP is a potential therapeutic agent that can be utilized to treat DM. Wenting Lin, Wenxiang Wang, Dongdong Liao, Damiao Chen, Pingping Zhu, Guoxi Cai, and Aoyagi Kiyoshi Copyright © 2015 Wenting Lin et al. All rights reserved. Can the Onset of Type 2 Diabetes Be Delayed by a Group-Based Lifestyle Intervention in Women with Prediabetes following Gestational Diabetes Mellitus (GDM)? Findings from a Randomized Control Mixed Methods Trial Mon, 10 Aug 2015 09:29:56 +0000 Objective. To evaluate a 12-week group-based lifestyle intervention programme for women with prediabetes following gestational diabetes (GDM). Design. A two-group, mixed methods randomized controlled trial in which 50 women with a history of GDM and abnormal glucose tolerance postpartum were randomly assigned to intervention () or wait control () and postintervention qualitative interviews with participants. Main Outcome Measures. Modifiable biochemical, anthropometric, behavioural, and psychosocial risk factors associated with the development of type 2 diabetes. The primary outcome variable was the change in fasting plasma glucose (FPG) from study entry to one-year follow-up. Results. At one-year follow-up, the intervention group showed significant improvements over the wait control group on stress, diet self-efficacy, and quality of life. There was no evidence of an effect of the intervention on measures of biochemistry or anthropometry; the effect on one health behaviour, diet adherence, was close to significance. Conclusions. Prevention programmes must tackle the barriers to participation faced by this population; home-based interventions should be investigated. Strategies for promoting long-term health self-management need to be developed and tested. Angela O’Dea, Marie Tierney, Brian E. McGuire, John Newell, Liam G. Glynn, Irene Gibson, Eoin Noctor, Andrii Danyliv, Susan B. Connolly, and Fidelma P. Dunne Copyright © 2015 Angela O’Dea et al. All rights reserved. Detecting Prediabetes and Diabetes: Agreement between Fasting Plasma Glucose and Oral Glucose Tolerance Test in Thai Adults Thu, 06 Aug 2015 13:16:22 +0000 Aim. To evaluate an agreement in identifying dysglycemia between fasting plasma glucose (FPG) and the 2 hr postprandial glucose tolerance test (OGTT) in a population with high risk of diabetes. Methods. A total of 6,884 individuals aged 35–65 years recruited for a community-based diabetes prevention program were tested for prediabetes including impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and diabetes. The agreement was assessed by Kappa statistics. Logistic regression was used to examine factors associated with missed prediabetes and diabetes by FPG. Results. A total of 2671 (38.8%) individuals with prediabetes were identified. The prevalence of prediabetes identified by FPG and OGTT was 32.2% and 22.3%, respectively. The proportions of diabetes classified by OGTT were two times higher than those identified by FPG (11.0% versus 5.4%, resp.). The Kappa statistics for agreement of both tests was 0.55. Overall, FPG missed 46.3% of all prediabetes and 54.7% of all diabetes cases. Prediabetes was more likely to be missed by FPG among female, people aged <45 yrs, and those without family history of diabetes. Conclusion. The detection of prediabetes and diabetes using FPG only may miss half of the cases. Benefit of adding OGTT to FPG in some specific groups should be confirmed. Wichai Aekplakorn, Valla Tantayotai, Sakawduan Numsangkul, Wilarwan Sripho, Nutchanat Tatsato, Tuanjai Burapasiriwat, Rachada Pipatsart, Premsuree Sansom, Pranee Luckanajantachote, Pongpat Chawarokorn, Anek Thanonghan, Watchira Lakhamkaew, Aungsumalin Mungkung, Rungnapa Boonkean, Chanidsa Chantapoon, Mayuree Kungsri, Kasetsak Luanseng, and Kornsinun Chaiyajit Copyright © 2015 Wichai Aekplakorn et al. All rights reserved. Roles of Commensal Microbiota in Pancreas Homeostasis and Pancreatic Pathologies Thu, 06 Aug 2015 12:11:17 +0000 The pancreas plays a central role in metabolism, allowing ingested food to be converted and used as fuel by the cells throughout the body. On the other hand, the pancreas may be affected by devastating diseases, such as pancreatitis, pancreatic adenocarcinoma (PAC), and diabetes mellitus (DM), which generally results in a wide metabolic imbalance. The causes for the development and progression of these diseases are still controversial; therefore it is essential to better understand the underlying mechanisms which compromise the pancreatic homeostasis. The interest in the study of the commensal microbiome increased extensively in recent years, when many discoveries have illustrated its central role in both human physiology and maintenance of homeostasis. Further understanding of the involvement of the microbiome during the development of pathological conditions is critical for the improvement of new diagnostic and therapeutic approaches. In the present review, we discuss recent findings on the behavior and functions played by the microbiota in major pancreatic diseases and provide further insights into its potential roles in the maintenance of pancreatic steady-state activities. Camila Leal-Lopes, Fernando J. Velloso, Julia C. Campopiano, Mari C. Sogayar, and Ricardo G. Correa Copyright © 2015 Camila Leal-Lopes et al. All rights reserved. Differential Telomere Shortening in Blood versus Arteries in an Animal Model of Type 2 Diabetes Thu, 06 Aug 2015 11:21:43 +0000 Vascular dysfunction is an early feature of diabetic vascular disease, due to increased oxidative stress and reduced nitric oxide (NO) bioavailability. This can lead to endothelial cell senescence and clinical complications such as stroke. Cells can become senescent by shortened telomeres and oxidative stress is known to accelerate telomere attrition. Sirtuin 1 (SIRT1) has been linked to vascular health by upregulating endothelial nitric oxide synthase (eNOS), suppressing oxidative stress, and attenuating telomere shortening. Accelerated leukocyte telomere attrition appears to be a feature of clinical type 2 diabetes (T2D) and therefore the telomere system may be a potential therapeutic target in preventing vascular complications of T2D. However the effect of T2D on vascular telomere length is currently unknown. We hypothesized that T2D gives rise to shortened leukocyte and vascular telomeres alongside reduced vascular SIRT1 expression and increased oxidative stress. Accelerated telomere attrition was observed in circulating leukocytes, but not arteries, in T2D compared to control rats. T2D rats had blunted arterial SIRT1 and eNOS protein expression levels which were associated with reduced antioxidant defense capacity. Our findings suggest that hyperglycemia and a deficit in vascular SIRT1 per se are not sufficient to prematurely shorten vascular telomeres. Samira Tajbakhsh, Kamelya Aliakbari, Damian J. Hussey, Karen M. Lower, Anthony J. Donato, and Elke M. Sokoya Copyright © 2015 Samira Tajbakhsh et al. All rights reserved. Moderate Intensity Training Impact on the Inflammatory Status and Glycemic Profiles in NOD Mice Wed, 05 Aug 2015 10:22:02 +0000 The nonobese diabetic (NOD) mouse represents a well-established experimental model analogous to human type 1 diabetes mellitus (T1D) as it is characterized by progressive autoimmune destruction of pancreatic β-cells. Experiments were designed to investigate the impact of moderate-intensity training on T1D immunomodulation and inflammation. Under a chronic exercise regime, NOD mice were trained on a treadmill for 12 weeks (12 m/min for 30 min, 5 d/wk) while age-matched, control animals were left untrained. Prior to and upon completion of the training period, fed plasma glucose and immunological soluble factors were monitored. Both groups showed deteriorated glycemic profiles throughout the study although trained mice tended to be more compensated than controls after 10 weeks of training. An exercise-induced weight loss was detected in the trained mice with respect to the controls from week 6. After 12 weeks, IL-6 and MIP-1β were decreased in the trained animals compared to their baseline values and versus controls, although not significantly. Morphometric analysis of pancreata revealed the presence of larger infiltrates along with decreased α-cells areas in the control mice compared to trained mice. Exercise may exert positive immunomodulation of systemic functions with respect to both T1D and inflammation, but only in a stringent therapeutic window. Roberto Codella, Giacomo Lanzoni, Alessia Zoso, Andrea Caumo, Anna Montesano, Ileana M. Terruzzi, Camillo Ricordi, Livio Luzi, and Luca Inverardi Copyright © 2015 Roberto Codella et al. All rights reserved. Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading Tue, 04 Aug 2015 12:43:28 +0000 Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA) over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid) for 4 weeks (phase 1). Subsequently, responders were randomized to receive ALA (600 mg qd; ) or to ALA withdrawal () for 16 weeks (phase 2). During phase 1, the Total Symptom Score (TSS) decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group () and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (). In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid) administration of ALA, subsequent treatment with ALA (600 mg qd) over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with Identifier: NCT02439879. Hector Garcia-Alcala, Celia Isabel Santos Vichido, Silverio Islas Macedo, Christelle Nathalie Genestier-Tamborero, Marissa Minutti-Palacios, Omara Hirales Tamez, Carlos García, and Dan Ziegler Copyright © 2015 Hector Garcia-Alcala et al. All rights reserved. Influence of Melatonin on the Proliferative and Apoptotic Responses of the Prostate under Normal and Hyperglycemic Conditions Thu, 30 Jul 2015 12:12:35 +0000 The antitumor properties of melatonin (MLT) are known for prostate cancer cells. This study investigated whether MLT affects prostate maturation and interferes with tissue injuries induced by diabetes. MLT was administered to Wistar rats from 5 weeks of age in the drinking water (10 μg/kg b.w.), and diabetes was induced at the 13th week by streptozotocin (4.5 mg/100g b.w., i.p.). The animals were euthanized in the 14th and 21st weeks. MLT reduced the immunostained cells for androgen receptor (AR) by 10% in younger rats. Diabetes decreased cell proliferation and increased apoptosis. MLT treatment impeded apoptosis and augmented proliferation and PCNA content in prostate following long-term diabetes due to restoration of testosterone levels and expression of melatonin receptor type 1B. The effect of MLT (500 µM, 5 mM, and 10 mM) on androgen-dependent (22Rv1) and androgen-independent (PC3) cancer cells and human prostate epithelial cells (PNTA1) under normal and hyperglycemic conditions (HG, 450 mg/dL) was analyzed. Contrary to PNTA1 and 22Rv1 cells, MLT improved the proliferation of PC3 cells in hyperglycemic medium. The combined data indicated that MLT had proliferative and antiapoptotic effects in prostate cells subjected to HG levels and it seems to involve specific MLT pathways rather than AR. Marina G. Gobbo, Nishtman Dizeyi, Per-Anders Abrahamsson, Per-Anders Bertilsson, Viviane Sanches Masitéli, Eloisa Zanin Pytlowanciv, Sebastião R. Taboga, and Rejane M. Góes Copyright © 2015 Marina G. Gobbo et al. All rights reserved. Cross Talk between Lipid Metabolism and Inflammatory Markers in Patients with Diabetic Retinopathy Wed, 29 Jul 2015 07:12:59 +0000 Purpose. The purpose of this study was to examine the relationship between metabolic and inflammatory markers in patients with diabetic retinopathy (DR). Methods. 208 adult patients with type 2 diabetes participated in this study and were categorized into (1) mild nonproliferative diabetic retinopathy (NPDR) without clinically significant macular edema (CSME), (2) NPDR with CSME, (3) proliferative diabetic retinopathy (PDR) without CSME, and (4) PDR with CSME. Variable serum metabolic markers were assessed using immunoassays. Multinomial logistic regression analysis was performed. Results. Diabetes duration and hypertension are the most significant risk factors for DR. Serum Apo-B and Apo-B/Apo-A ratio were the most significant metabolic risk factors for PDR and CSME. For every 0.1 g/L increase in Apo-B concentration, the risk of PDR and CSME increased by about 1.20 times. We also found that 10 pg/mL increase in serum TNF-α was associated with approximately 2-fold risk of PDR/CSME while an increase by 100 pg/mL in serum VEGF concentration correlated with CSME. Conclusions. In conclusion, it seems that there is a link between metabolic and inflammatory markers. Apo-B/Apo-A ratio should be evaluated as a reliable risk factor for PDR and CSME, while the role of increased systemic TNF-α and VEGF should be explored in CSME. Roxanne Crosby-Nwaobi, Irini Chatziralli, Theodoros Sergentanis, Tracy Dew, Angus Forbes, and Sobha Sivaprasad Copyright © 2015 Roxanne Crosby-Nwaobi et al. All rights reserved. Association Analysis of Genetic Variants with Type 2 Diabetes in a Mongolian Population in China Tue, 28 Jul 2015 14:04:04 +0000 The large scale genome wide association studies (GWAS) have identified approximately 80 single nucleotide polymorphisms (SNPs) conferring susceptibility to type 2 diabetes (T2D). However, most of these loci have not been replicated in diverse populations and much genetic heterogeneity has been observed across ethnic groups. We tested 28 SNPs previously found to be associated with T2D by GWAS in a Mongolian sample of Northern China (497 diagnosed with T2D and 469 controls) for association with T2D and diabetes related quantitative traits. We replicated T2D association of 11 SNPs, namely, rs7578326 (IRS1), rs1531343 (HMGA2), rs8042680 (PRC1), rs7578597 (THADA), rs1333051 (CDKN2), rs6723108 (TMEM163), rs163182 and rs2237897 (KCNQ1), rs1387153 (MTNR1B), rs243021 (BCL11A), and rs10229583 (PAX4) in our sample. Further, we showed that risk allele of the strongest T2D associated SNP in our sample, rs757832 (IRS1), is associated with increased level of TG. We observed substantial difference of T2D risk allele frequency between the Mongolian sample and the 1000G Caucasian sample for a few SNPs, including rs6723108 (TMEM163) whose risk allele reaches near fixation in the Mongolian sample. Further study of genetic architecture of these variants in susceptibility of T2D is needed to understand the role of these variants in heterogeneous populations. Haihua Bai, Haiping Liu, Suyalatu Suyalatu, Xiaosen Guo, Shandan Chu, Ying Chen, Tianming Lan, Burenbatu Borjigin, Yuriy L. Orlov, Olga L. Posukh, Xiuqin Yang, Guilan Guilan, Ludmila P. Osipova, Qizhu Wu, and Narisu Narisu Copyright © 2015 Haihua Bai et al. All rights reserved. Insulin Resistance, Type 1 and Type 2 Diabetes, and Related Complications 2015 Tue, 28 Jul 2015 07:44:54 +0000 Joseph Fomusi Ndisang, Sharad Rastogi, and Alfredo Vannacci Copyright © 2015 Joseph Fomusi Ndisang et al. All rights reserved. Healthy Chilean Adolescents with HOMA-IR ≥ 2.6 Have Increased Cardiometabolic Risk: Association with Genetic, Biological, and Environmental Factors Mon, 27 Jul 2015 13:14:44 +0000 Objective. To determine the optimal cutoff of the homeostasis model assessment-insulin resistance (HOMA-IR) for diagnosis of the metabolic syndrome (MetS) in adolescents and examine whether insulin resistance (IR), determined by this method, was related to genetic, biological, and environmental factors. Methods. In 667 adolescents (16.8 ± 0.3 y), BMI, waist circumference, glucose, insulin, adiponectin, diet, and physical activity were measured. Fat and fat-free mass were assessed by dual-energy X-ray absorptiometry. Family history of type 2 diabetes (FHDM) was reported. We determined the optimal cutoff of HOMA-IR to diagnose MetS (IDF criteria) using ROC analysis. IR was defined as HOMA-IR values above the cutoff. We tested the influence of genetic, biological, and environmental factors on IR using logistic regression analyses. Results. Of the participants, 16% were obese and 9.4 % met criteria for MetS. The optimal cutoff for MetS diagnosis was a HOMA-IR value of 2.6. Based on this value, 16.3% of participants had IR. Adolescents with IR had a significantly higher prevalence of obesity, abdominal obesity, fasting hyperglycemia, and MetS compared to those who were not IR. FHDM, sarcopenia, obesity, and low adiponectin significantly increased the risk of IR. Conclusions. In adolescents, HOMA-IR ≥ 2.6 was associated with greater cardiometabolic risk. R. Burrows, P. Correa-Burrows, M. Reyes, E. Blanco, C. Albala, and S. Gahagan Copyright © 2015 R. Burrows et al. All rights reserved. Dysglycaemia and Other Predictors for Progression or Regression from Impaired Fasting Glucose to Diabetes or Normoglycaemia Mon, 27 Jul 2015 12:52:13 +0000 Aims. Diabetes mellitus is a growing health problem worldwide. This study aimed to describe dysglycaemia and determine the impact of body composition and clinical and lifestyle factors on the risk of progression or regression from impaired fasting glucose (IFG) to diabetes or normoglycaemia in Australian women. Methods. This study included 1167 women, aged 20–94 years, enrolled in the Geelong Osteoporosis Study. Multivariable logistic regression was used to identify predictors for progression to diabetes or regression to normoglycaemia (from IFG), over 10 years of follow-up. Results. At baseline the proportion of women with IFG was 33.8% and 6.5% had diabetes. Those with fasting dysglycaemia had higher obesity-related factors, lower serum HDL cholesterol, and lower physical activity. Over a decade, the incidence of progression from IFG to diabetes was 18.1 per 1,000 person-years (95% CI, 10.7–28.2). Fasting plasma glucose and serum triglycerides were important factors in both progression to diabetes and regression to normoglycaemia. Conclusions. Our results show a transitional process; those with IFG had risk factors intermediate to normoglycaemics and those with diabetes. This investigation may help target interventions to those with IFG at high risk of progression to diabetes and thereby prevent cases of diabetes. L. de Abreu, Kara L. Holloway, Mark A. Kotowicz, and Julie A. Pasco Copyright © 2015 L. de Abreu et al. All rights reserved. Association of the Genetic Polymorphisms in Transcription Factor 7-Like 2 and Peroxisome Proliferator-Activated Receptors-γ2 with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status in Emirati Population Mon, 27 Jul 2015 12:48:28 +0000 Background. Transcription factor 7-like 2 gene (TCF7L2) and peroxisome proliferator-activated receptors-γ2 (PPAR-γ2) have a profound effect on the incidence of type 2 diabetes mellitus (T2DM) and had previously been found to be associated with T2DM risk in various ppopulations. However, studies in the Arab population are inconsistent. We conducted a case control study to confirm the association of variants rs10885409 of TCF7L2 and Pro12Ala (rs1801282) of PPAR-γ2 with risk of T2DM and related complications in Emirati population of Arab origin. We also investigated the interaction of these associations with obesity status. Methods. DNA was extracted from the saliva samples of 272 T2DM patients and 216 nondiabetic Emiratis. Genotyping for rs10885409 (TCF7L2) and rs1801282 (PPAR-γ2 P12A) variants was accomplished with a TaqMan assay. The subgroups were constituted according to obesity status. Results. In the nonobese group, the rs10885409 C allele in the recessive model was significantly associated with the incidence of T2DM (OR 1.975 [95% CI 1.127–3.461], ), but this association was not observed in the obese group or when BMI was not considered. PPAR-γ2 risk allele Pro12 frequency (0.96) was similar in the groups tested and more than 90% population was homozygous for this allele. Conclusions. Our case-control study is the first of its kind in Emiratis which establishes TCF7L2 rs10885409 C allele as a T2DM risk factor in Emiratis and this association is modulated by obesity status. We also confirmed that Pro12Ala mutation in PPAR-γ2 is not associated with T2DM risk in this population. Habiba Al-Safar, Ahmed Hassoun, Shaikha Almazrouei, Wala Kamal, Bachar Afandi, and Naushad Rais Copyright © 2015 Habiba Al-Safar et al. All rights reserved. Edible Bird’s Nest Prevents High Fat Diet-Induced Insulin Resistance in Rats Mon, 27 Jul 2015 12:09:03 +0000 Edible bird’s nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance. Zhang Yida, Mustapha Umar Imam, Maznah Ismail, Der-Jiun Ooi, Nadarajan Sarega, Nur Hanisah Azmi, Norsharina Ismail, Kim Wei Chan, Zhiping Hou, and Norhayati Binti Yusuf Copyright © 2015 Zhang Yida et al. All rights reserved. Effect of Rosiglitazone and Insulin Combination Therapy on Inflammation Parameters and Adipocytokine Levels in Patients with Type 1 DM Mon, 27 Jul 2015 12:06:55 +0000 Aim. To investigate the efficacy of combined therapy of insulin and rosiglitazone on metabolic and inflammatory parameters, insulin sensitivity, and adipocytokine levels in patients with type 1 diabetes mellitus (type 1 DM). Material and Methods. A total of 61 adults with type 1 DM were randomly and prospectively assigned in open-label fashion to take insulin and rosiglitazone 4 mg/day () or insulin alone () for a period of 18 weeks while undergoing insulin therapy without acute metabolic complications. Results. Combination therapy did not significantly improve metabolic and inflammatory parameters, insulin sensitivity, and adiponectin levels. While leptin and resistin levels decreased in both groups (group 1: resistin 6.96 ± 3.06 to 4.99 ± 2.64, ; leptin 25.8 ± 17.6 to 20.1 ± 12.55, ; group 2: resistin 7.16 ± 2.30 to , ; leptin 16.72 ± 16.1 to 14.0 ± 13.4, ) Hgb and fibrinogen levels decreased only in group 1 (Hgb 13.72 ± 1.98 to 13.16 ± 1.98, , and fibrinogen 4.00 ± 1.08 to 3.46 ± 0.90, ). Patients in both groups showed weight gain and the incidence of hypoglycemia was not lower. Discussion. The diverse favorable effects of TZDs were not fully experienced in patients with type 1 DM. These results are suggesting that insulin sensitizing and anti-inflammatory characteristics of TZDs were likely to be more pronounced in patients who were not totally devoid of endogenous insulin secretion. Metin Guclu, Ozen Oz Gul, Soner Cander, Oguzkaan Unal, Guven Ozkaya, Emre Sarandol, and Canan Ersoy Copyright © 2015 Metin Guclu et al. All rights reserved. GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective Mon, 27 Jul 2015 11:58:20 +0000 Growth differentiation factor-15 (GDF-15) is a stress responsive cytokine. It is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells in normal and pathological condition. GDF-15 increases during tissue injury and inflammatory states and is associated with cardiometabolic risk. Increased GDF-15 levels are associated with cardiovascular diseases such as hypertrophy, heart failure, atherosclerosis, endothelial dysfunction, obesity, insulin resistance, diabetes, and chronic kidney diseases in diabetes. Increased GDF-15 level is linked with the progression and prognosis of the disease condition. Age, smoking, and environmental factors are other risk factors that may increase GDF-15 level. Most of the scientific studies reported that GDF-15 plays a protective role in different tissues. However, few reports show that the deficiency of GDF-15 is beneficial against vascular injury and inflammation. GDF-15 protects heart, adipose tissue, and endothelial cells by inhibiting JNK (c-Jun N-terminal kinase), Bad (Bcl-2-associated death promoter), and EGFR (epidermal growth factor receptor) and activating Smad, eNOS, PI3K, and AKT signaling pathways. The present review describes the different animal and clinical studies and patent updates of GDF-15 in diabetes and cardiovascular diseases. It is a challenge for the scientific community to use GDF-15 information for patient monitoring, clinical decision-making, and replacement of current treatment strategies for diabetic and cardiovascular diseases. Ramu Adela and Sanjay K. Banerjee Copyright © 2015 Ramu Adela and Sanjay K. Banerjee. All rights reserved. NLRP3 Inflammasome Polymorphism and Macrovascular Complications in Type 2 Diabetes Patients Mon, 27 Jul 2015 11:42:26 +0000 Background. It is generally accepted that poor glycemic control, arterial hypertension and/or hyperlipidemia, and the associated oxidative stress may contribute to the development of macro- and microvascular complications in type 2 diabetes (T2D). Such metabolic damage signals may activate inflammasome and trigger chronic inflammation. We investigated common polymorphisms in inflammasome coding genes and the risk for macro- and microvascular complications in T2D. Methods. In total 181 clinically well-characterised T2D patients were genotyped for NLRP3 rs35829419 and CARD8 rs2043211. Risk for diabetic complications was assessed using logistic regression. Results. Patients with median duration of T2D 11 (6–17) years had relatively well controlled blood glucose and lipid levels and blood pressure on the prescribed treatment regimen. Duration of T2D and plasma cholesterol levels were the most important clinical risk factors for macrovascular complications ( and ). NLRP3 rs35829419 was associated with increased risk for macrovascular complications (), with myocardial infarction in particular (). No association was observed between CARD8 polymorphism and any of T2D complications. Conclusions. Our preliminary data suggest the role of NLRP3 polymorphism in diabetic macrovascular complications, especially in myocardial infarction. Jasna Klen, Katja Goričar, Andrej Janež, and Vita Dolžan Copyright © 2015 Jasna Klen et al. All rights reserved. Study of Protein Biomarkers of Diabetes Mellitus Type 2 and Therapy with Vitamin B1 Mon, 27 Jul 2015 11:40:09 +0000 In the present research work, the levels of protein biomarkers specific to diabetes mellitus type 2 in the Pakistani population using proteomic technology have been identified and characterized and effect of high dose thiamine has been seen on the levels of these marker proteins. Diabetic patients and normal healthy controls were recruited from the Sheikh Zayed Hospital, Lahore, Pakistan. Total biochemical assays and proteins were estimated by modern proteomic techniques. Some proteins were up- and downregulated in diabetic samples as compared to control and decreased after thiamine therapy, while other protein markers did not show a significant change after the thiamine therapy. The effect of high dose thiamine on the levels of these identified protein biomarkers in the human urine has also been observed. Assessment of the levels of these biomarkers will be helpful in not only early diagnosis but also prognosis of diabetes mellitus type 2. Samreen Riaz Copyright © 2015 Samreen Riaz. All rights reserved. Inflammatory Cytokine Profile Associated with Metabolic Syndrome in Adult Patients with Type 1 Diabetes Mon, 27 Jul 2015 11:10:26 +0000 Objective. To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cut-off point of the estimated glucose disposal rate that accurately differentiated these groups. Design. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. Methods. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. Results. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (), 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. Conclusion. We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance. Aldo Ferreira-Hermosillo, Mario Molina-Ayala, Claudia Ramírez-Rentería, Guadalupe Vargas, Baldomero Gonzalez, Armando Isibasi, Irma Archundia-Riveros, and Victoria Mendoza Copyright © 2015 Aldo Ferreira-Hermosillo et al. All rights reserved.