Journal of Diabetes Research The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Real Life Cancer Comorbidity in Greek Patients with Diabetes Mellitus Followed Up at a Single Diabetes Center: An Unappreciated New Diabetes Complication Tue, 22 Jul 2014 06:38:00 +0000 We determined cancer comorbidity in patients with diabetes followed up at a single Greek academic clinic and investigated the potential related factors. Cancer comorbidity was prospectively recorded for all patients with type 2 (T2DM, ) or type 1 (T1DM, ) diabetes of at least 10-year duration examined during one year. Patient characteristics, diabetes age of onset, duration, treatment, control, and complication rates were compared between subjects with and without cancer. Moreover, a retrospective collection of data from similar patients examined for the first time during the last 25 years, but lost to follow-up, after at least one-year’s regular visits, was performed. In regularly followed-up T2DM patients cancer comorbidity was 12.6%. Patients with cancer were older and more frequently smokers. Prostate cancer was the most frequent (24.0%) type. In T1DM cancer comorbidity was 3.0%. Similar rates of comorbidity and types of cancer were observed in lost to follow-up patients. In conclusion, our patients with T2DM of at least 10-year’ duration show high cancer comorbidity. No specific characteristics discriminate patients with cancer. Therefore presymptomatic cancer detection and prevention strategies may have to be incorporated into the annual systematic evaluation of our patients. Anastasia Thanopoulou and Demetrios Pectasides Copyright © 2014 Anastasia Thanopoulou and Demetrios Pectasides. All rights reserved. Rectal Sensitivity in Diabetes Patients with Symptoms of Gastroparesis Tue, 22 Jul 2014 00:00:00 +0000 In a clinical setting, diabetic autonomic complications (cardiac, gastrointestinal, urogenital, etc.) are often handled as separate entities. We investigated rectal sensitivity to heat, mechanical distension, and electrical stimulations in 20 patients with diabetes and symptoms of gastroparesis, to evaluate the extent of visceral neuronal damage. Furthermore, to evaluate the relation between the nervous structures we examined gastric emptying and cardiac autonomic function with the hypothesis being an association between these. We found that 60% of patients had delayed gastric empting. Rectal hyposensitivity was a general finding as they tolerated 67% higher thermal, 42% more mechanical, and 33% higher electrical current intensity compared to healthy controls. In patients, most heart rate variability parameters were reduced; they reported significantly more gastrointestinal symptoms and a reduced quality of life in all SF-36 domains. Shortened RR interval correlated with reduced rectal temperature sensitivity, and gastric retention rate was negatively associated with symptoms of nausea and vomiting. To conclude, in these patients with signs and symptoms of diabetic gastroparesis, rectal sensitivity was reduced, and heart rate variability was impaired. Thus, we suggest regarding diabetic autonomic neuropathy as a diffuse disorder. Symptoms of widespread autonomic dysfunction and sensory disorders should be expected and treated in these patients. Eirik Søfteland, Christina Brock, Jens B. Frøkjær, Magnus Simrén, Asbjørn M. Drewes, and Georg Dimcevski Copyright © 2014 Eirik Søfteland et al. All rights reserved. The Effect of Diabetes Self-Management Education on Body Weight, Glycemic Control, and Other Metabolic Markers in Patients with Type 2 Diabetes Mellitus Thu, 17 Jul 2014 08:15:11 +0000 Aims. To comprehensively evaluate the effect of a short-term diabetes self-management education (DSME) on metabolic markers and atherosclerotic parameters in patients with type 2 diabetes. Methods. 76 patients with type 2 diabetes were recruited in this study. They were divided into the intervention group and control group . The patients in the intervention group received a 3-month intervention, including an 8-week education on self-management of diabetes mellitus and subsequent 4 weeks of practice of the self-management guidelines. The patients in the control group received standard advice on medical nutrition therapy. Metabolic markers, carotid intima-media thickness (CIMT), and carotid arterial stiffness (CAS) of the patients in both groups were assessed before and after the 3-month intervention. Results. There was a significant reduction in hemoglobin A1c (HbA1c, % versus %; ) and body weight ( kg versus  kg; ) in the intervention group as compared to the control group. However, no significant improvements were found in other metabolic markers, CIMT and CAS . Conclusions. DSME can improve HbA1c and body weight in patients with type 2 diabetes. Chuang Yuan, Christopher W. K. Lai, Lawrence W. C. Chan, Meyrick Chow, Helen K. W. Law, and Michael Ying Copyright © 2014 Chuang Yuan et al. All rights reserved. Diabetic Retinopathy Treated with Laser Photocoagulation and the Indirect Effect on Glycaemic Control Thu, 17 Jul 2014 08:04:50 +0000 Purpose. To identify any possible relation between glycaemic control and previous laser photocoagulation for diabetic retinopathy. Methods. Seventy-two patients with diabetes were included in the study and were separated into 2 groups according to previous treatment (group A) or not (group B) with argon laser photocoagulation. Glycaemic control was estimated by measuring blood levels of HbA1c in four consecutive measurements. Results. Blood levels of HbA1c in group A were significantly lower 3, 6, and 12 months after laser treatment as compared to blood levels of HbA1c before laser treatment (% versus %, % versus %, and % versus %, resp., all ). Blood levels of HbA1c in group B did not differ significantly in four consecutive measurements. Conclusion. Our results suggest that we should anticipate a better glycaemic control in cases of patients with diabetes previously treated with laser photocoagulation. Anna Praidou, Sofia Androudi, Periklis Brazitikos, George Karakiulakis, Eleni Papakonstantinou, Ioannis Tsinopoulos, and Stavros Dimitrakos Copyright © 2014 Anna Praidou et al. All rights reserved. Compensatory Mechanisms of Pancreatic Beta Cells: Insights into the Therapeutic Perspectives for Diabetes Thu, 17 Jul 2014 00:00:00 +0000 Romano Regazzi, Stephane Dalle, and Amar Abderrahmani Copyright © 2014 Romano Regazzi et al. All rights reserved. Association of Serum Vaspin and Adiponectin Levels with Renal Function in Patients with or without Type 2 Diabetes Mellitus Tue, 15 Jul 2014 09:08:07 +0000 Vaspin and adiponectin are two adipocytokines with antidiabetic effects. Some studies reported that levels of adiponectin and vaspin were correlated with decreased glomerular filtration rate (FGR) and increased albuminuria. We therefore evaluated the vaspin and adiponectin levels in renal insufficiency (RI) patients with or without T2DM. Serum vaspin, adiponectin levels were measured in 416 subjects with or without T2DM. Analysis was made between groups divided by these subjects presence or absence of RI. We found that serum adiponectin level was significantly higher in nondiabetic patients with RI than in nondiabetic subjects without RI; however, there were no statistical differences between the diabetic patients with RI and without RI. In all the subjects, the serum adiponectin level was also higher in 50 individuals with RI than that in 366 subjects without RI. The serum vaspin levels showed no significant differences between the diabetic patients or nondiabetics subjects with RI and without RI. Contrary to adiponectin, the serum vaspin level was lower in 169 patients with T2DM than in 247 individuals without T2DM. Our data suggested that both of T2DM and renal insufficiency were correlated with the serum level of adiponectin. However, the serum vaspin levels showed no significant difference between the individuals with renal insufficiency and without renal insufficiency. Meiyu Yan, Bin Su, Wenhui Peng, Liang Li, Hailing Li, Jianhui Zhuang, Yuyan Lu, Weixia Jian, Yidong Wei, Weiming Li, Shen Qu, and Yawei Xu Copyright © 2014 Meiyu Yan et al. All rights reserved. Chicken Embryos as a Potential New Model for Early Onset Type I Diabetes Sun, 13 Jul 2014 09:54:37 +0000 Diabetic retinopathy (DR) is the leading cause of blindness among the American working population. The purpose of this study is to establish a new diabetic animal model using a cone-dominant avian species to address the distorted color vision and altered cone pathway responses in prediabetic and early diabetic patients. Chicken embryos were injected with either streptozotocin (STZ), high concentration of glucose (high-glucose), or vehicle at embryonic day 11. Cataracts occurred in varying degrees in both STZ- and high glucose-induced diabetic chick embryos at E18. Streptozotocin-diabetic chicken embryos had decreased levels of blood insulin, glucose transporter 4 (Glut4), and phosphorylated protein kinase B (pAKT). In STZ-injected E20 embryos, the ERG amplitudes of both a- and b-waves were significantly decreased, the implicit time of the a-wave was delayed, while that of the b-wave was significantly increased. Photoreceptors cultured from STZ-injected E18 embryos had a significant decrease in L-type voltage-gated calcium channel (L-VGCC) currents, which was reflected in the decreased level of L-VGCCα1D subunit in the STZ-diabetic retinas. Through these independent lines of evidence, STZ-injection was able to induce pathological conditions in the chicken embryonic retina, and it is promising to use chickens as a potential new animal model for type I diabetes. Liheng Shi, Michael L. Ko, Cathy Chia-Yu Huang, So-Young Park, Min-Pyo Hong, Chaodong Wu, and Gladys Y.-P. Ko Copyright © 2014 Liheng Shi et al. All rights reserved. Beneficial Effects of Adiponectin on Periodontal Ligament Cells under Normal and Regenerative Conditions Sun, 13 Jul 2014 00:00:00 +0000 Type 2 diabetes and obesity are increasing worldwide and linked to periodontitis, a chronic disease which is characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium. The mechanisms underlying the association of diabetes mellitus and obesity with periodontal destruction and compromised periodontal healing are not well understood, but decreased plasma levels of adiponectin, as found in diabetic and obese individuals, might be a critical mechanistic link. The aim of this in vitro study was to examine the effects of adiponectin on periodontal ligament (PDL) cells under normal and regenerative conditions, and to study the regulation of adiponectin and its receptors in these cells. Adiponectin stimulated significantly the expression of growth factors and extracellular matrix, proliferation, and in vitro wound healing, reduced significantly the constitutive tumor necrosis factor-α expression, and caused a significant upregulation of its own expression. The beneficial actions of enamel matrix derivative on a number of PDL cell functions critical for periodontal regeneration were partially enhanced by adiponectin. The periodontopathogen Porphyromonas gingivalis inhibited the adiponectin expression and stimulated the expression of its receptors. In conclusion, reduced levels of adiponectin, as found in type 2 diabetes and obesity, may compromise periodontal health and healing. Marjan Nokhbehsaim, Sema Keser, Andressa Vilas Boas Nogueira, Joni Augusto Cirelli, Søren Jepsen, Andreas Jäger, Sigrun Eick, and James Deschner Copyright © 2014 Marjan Nokhbehsaim et al. All rights reserved. Acarbose Treatment and the Risk of Cardiovascular Disease in Type 2 Diabetic Patients: A Nationwide Seven-Year Follow-Up Study Mon, 07 Jul 2014 09:42:54 +0000 Objective. To investigate the potential benefits of acarbose treatment on cardiovascular disease (CVD) in patients with type 2 diabetes by using nationwide insurance claim dataset. Research Design and Methods. Among 644,792 newly diagnosed type 2 diabetic patients without preexisting CVD in a nationwide cohort study, 109,139 (16.9%) who had received acarbose treatment were analyzed for CVD risk. Those with CVD followed by acarbose therapy were also subjected to analysis. Result. During 7 years of follow-up, 5,081 patients (4.7%) developed CVD. The crude hazard ratio (HR) and adjusted HR were 0.66 and 0.99, respectively. The adjusted HR of CVD was 1.19, 0.70, and 0.38 when the duration of acarbose use was <12 months, 12–24 months, and >24 months, respectively. Adjusted HR was 1.14, 0.64, and 0.41 with acarbose cumulative doses <54,750 mg, 54,751 to 109,500 mg, and >109,500 mg, respectively. Conclusion. In patients with type 2 diabetes without preexisting CVD, treatment with acarbose showed a transient increase in incidence of CVD in the initial 12 months followed by significant reductions of CVD in prolonged acarbose users. After the first CVD events, continuous use of acarbose revealed neutral effect within the first 12 months. The underlying mechanisms require further investigations. Jui-Ming Chen, Cheng-Wei Chang, Ying-Chieh Lin, Jorng-Tzong Horng, and Wayne H.-H. Sheu Copyright © 2014 Jui-Ming Chen et al. All rights reserved. Gestational Diabetes Mellitus Worsens the Profile of Cardiometabolic Risk Markers and Decrease Indexes of Beta-Cell Function Independently of Insulin Resistance in Nondiabetic Women with a Parental History of Type 2 Diabetes Sun, 06 Jul 2014 08:16:37 +0000 Background. Women with a history of both parental type 2 diabetes (pt2DM) and previous gestational diabetes (pGDM) represent a group at high risk of cardiovascular events. We hypothesized that pGDM changes cardiometabolic risk markers levels as well as theirs associations with glucose indices in nondiabetic pt2DM women. Methods. Anthropometric parameters, glucose regulation (OGTT), insulin resistance (HOMA-IR), beta-cell function, lipid levels, parameters of endothelial dysfunction, and inflammation were evaluated in 55 women with pt2DM, 40 with both pt2DM and pGDM 2–24 months postpartum, and 35 controls. Results. Prediabetes was diagnosed more frequently in women with both pt2DM and pGDM in comparison with women with only pt2DM (10 versus 8, ). The pGDM group had higher LDL-cholesterol, sICAM-1, tPa Ag, fibrinogen, and lower beta-cell function after adjustment for HOMA-IR, in comparison with pt2DM group. In pt2DM group postchallenge glucose correlated independently with hsCRP and in pGDM group fasting glucose with HOMA-IR. Conclusions. pGDM exerts a combined effect on cardiometabolic risk markers in women with pt2DM. In these women higher LDL-cholesterol, fibrinogen, sICAM-1, tPa Ag levels and decreased beta cell function are associated with pGDM independently of HOMA-IR index value. Fasting glucose is an important cardiometabolic risk marker and is independently associated with HOMA-IR. Alina Sokup, Barbara Ruszkowska-Ciastek, Małgorzata Walentowicz-Sadłecka, Marek Grabiec, and Danuta Rość Copyright © 2014 Alina Sokup et al. All rights reserved. Mediation Role of C-Reactive Protein on the Association between Smoking Quantity and Type 2 Diabetes in Current Chinese Smokers Thu, 03 Jul 2014 11:39:08 +0000 Objective. Previous studies have indicated that cigarette smokers are more likely to develop type 2 diabetes and that both smoking and type 2 diabetes are associated with C-reactive protein (CRP). This study examined whether CRP mediates the association between smoking quantity and type 2 diabetes. Methods. Nine hundred and eighty-four current Chinese smokers were selected from a community-based chronic disease survey conducted in Guangzhou and Zhuhai. Type 2 diabetes was defined according to the WHO 1999 criteria. CRP was measured with flow cytometry. Binary logistic regression was performed to assess the mediation. Results. A positive association was observed between smoking quantity and type 2 diabetes (). After controlling for potential confounders, daily cigarette consumption was significantly associated with higher CRP levels. Current smokers with type 2 diabetes had higher CRP levels than smokers without type 2 diabetes. The association between the smoking quantity and type 2 diabetes was mediated by CRP, which accounted for 50.77% of the association. Conclusions. This study provides further evidence that smoking quantity is positively associated with type 2 diabetes and suggests that the association between smoking and type 2 diabetes might be mediated by CRP. Dan Feng, Tao Liu, Hui Wang, Emma Karp, Wenhua Ling, and Wei-Qing Chen Copyright © 2014 Dan Feng et al. All rights reserved. Relationship between HgbA1c and Myocardial Blood Flow Reserve in Patients with Type 2 Diabetes Mellitus: Noninvasive Assessment Using Real-Time Myocardial Perfusion Echocardiography Wed, 02 Jul 2014 07:10:33 +0000 To study the relationship between glycosylated hemoglobin (HgbA1c) and myocardial perfusion in type 2 diabetes mellitus (T2DM) patients, we prospectively enrolled 24 patients with known or suspected coronary artery disease (CAD) who underwent adenosine stress by real-time myocardial perfusion echocardiography (RTMPE). HgbA1c was measured at time of RTMPE. Microbubble velocity (β min−1), myocardial blood flow (MBF, mL/min/g), and myocardial blood flow reserve (MBFR) were quantified. Quantitative MCE analysis was feasible in all patients (272/384 segments, 71%). Those with HgbA1c > 7.1% had significantly lower and MBFR than those with HgbA1c ≤ 7.1% . In patients with suspected CAD, there was a significant inverse correlation between MBFR and HgbA1c (, ); however, in those with known CAD, this relationship was not significant (, ). Using a MBFR cutoff value > 2 as normal, HgbA1c > 7.1% significantly increased the risk for abnormal MBFR, (adjusted odds ratio: 1.92, 95% CI: 1.12–3.35, ). Optimal glycemic control is associated with preservation of MBFR as determined by RTMPE, in T2DM patients at risk for CAD. Runqing Huang, Sahar S. Abdelmoneim, Lara F. Nhola, and Sharon L. Mulvagh Copyright © 2014 Runqing Huang et al. All rights reserved. Decreased Neuronal Bursting and Phase Synchrony in the Hippocampus of Streptozotocin Diabetic Rats Sun, 29 Jun 2014 10:54:04 +0000 Diabetic encephalopathy is one of the complications of diabetes. Cognitive dysfunction is the main consequence. Previous findings from neuroanatomical and in vitro electrophysiological studies showed that the structure and function of the hippocampus is impaired in diabetes, which may underlie the cognitive dysfunction induced by diabetes. However the study of electrophysiological abnormality of hippocampal neurons in intact networks is sparse. In the current study, we recorded the spontaneous firing of neurons in hippocampal CA1 area in anesthetized streptozotozin (STZ)-diabetic and age-matched control rats. Profound reduction in burst activity was found in diabetic rats. Compared to control rats, the intra-burst inter-spike intervals were prolonged significantly in diabetic rats, while the burst ratio and the mean number of spikes within a burst decreased significantly. Treatment with APP 17-mer peptide retarded the effects of diabetes on these parameters. In addition, the average PLV of diabetic rats was lower than that of control rats. These findings provide in vivo electrophysiological evidence for the impairment of hippocampal function in STZ-diabetic rats, and may have some implications in the mechanisms associated with cognitive deficits in diabetes. Zhimei Qiao, Kangning Xie, Kai Liu, and Guoliang Li Copyright © 2014 Zhimei Qiao et al. All rights reserved. Cardiomyopathy in Offspring of Pregestational Diabetic Mouse Pregnancy Thu, 26 Jun 2014 11:30:16 +0000 Purpose. To investigate cardiomyopathy in offspring in a mouse model of pregestational type 1 diabetic pregnancy. Methods. Pregestational diabetes was induced with STZ administration in female C57BL6/J mice that were subsequently mated with healthy C57BL6/J males. Offspring were sacrificed at embryonic day 18.5 and 6-week adolescent and 12-week adult stages. The size and number of cardiomyocyte nuclei and also the extent of collagen deposition within the hearts of diabetic and control offspring were assessed following cardiac tissue staining with either haematoxylin and eosin or Picrosirius red and subsequently quantified using automated digital image analysis. Results. Offspring from diabetic mice at embryonic day 18.5 had a significantly higher number of cardiomyocyte nuclei present compared to controls. These nuclei were also significantly smaller than controls. Collagen deposition was shown to be significantly increased in the hearts of diabetic offspring at the same age. No significant differences were found between the groups at 6 and 12 weeks. Conclusions. Our results from offspring of type 1 diabetic mice show increased myocardial collagen deposition in late gestation and have increased myocardial nuclear counts (hyperplasia) as opposed to increased myocardial nuclear size (hypertrophy) in late gestation. These changes normalize postpartum after removal from the maternal intrauterine environment. Daniel Dowling, Niamh Corrigan, Stephen Horgan, Chris J. Watson, John Baugh, Paul Downey, and Fionnuala M. McAuliffe Copyright © 2014 Daniel Dowling et al. All rights reserved. The Effect of Chromium Picolinate Supplementation on the Pancreas and Macroangiopathy in Type II Diabetes Mellitus Rats Wed, 25 Jun 2014 10:39:46 +0000 Purpose. The aim was to explore the effect of the chromium picolinate (CrPic) administration on the pancreas and macroangiopathy of type II diabetes mellitus rats. Methods. The type II diabetes mellitus (T2DM) rat model was induced by low-dose streptozotocin (STZ). The rats were randomly divided into 5 groups (ten rats in each group). After supplementing CrPic for 15 weeks, the histopathological examination was performed by hematoxylin-eosin (HE) staining. Serum insulin and NO level were determined by radioimmunoassay and colorimetry, respectively. Serum glycosylated hemoglobin (HbA1C), adiponectin (APN), advanced glycation end products (AGES), and apelin were measured by ELISA. Real-time reverse transcription polymerase chain reaction (RT-PCR) was applied for detecting the mRNA expression of APN and apelin. Results. After CrPic treatment, compared with the T2DM control group (group 2), pancreas sections stained with HE showed the completed pancreatic cells structure and no inflammatory infiltration in groups 4 and 5. In addition, the levels of serum NO and insulin were significantly increased and the serum levels of HbA1C, AGES, APN, and apelin were significantly decreased in groups 4 and 5 compared with group 2. The mRNA expression of APN and apelin in groups 4 and 5 was also recovered to the normal level. Conclusion. CrPic can recover the function of Β-cells and alleviate macroangiopathy in STZ-induced T2DM rats. Shan Huang, Wenfang Peng, Xiaohong Jiang, Kan Shao, Lili Xia, Yubin Tang, and Jiayin Qiu Copyright © 2014 Shan Huang et al. All rights reserved. The Experimental and Clinical Aspects of Beta Cell Function and Its Underlying Mechanism Wed, 18 Jun 2014 00:00:00 +0000 Yanbing Li, Li Chen, Chen Wang, and Dongqi Tang Copyright © 2014 Yanbing Li et al. All rights reserved. JNK3 Is Required for the Cytoprotective Effect of Exendin 4 Mon, 16 Jun 2014 09:31:29 +0000 Preservation of beta cell against apoptosis is one of the therapeutic benefits of the glucagon-like peptide-1 (GLP1) antidiabetic mimetics for preserving the functional beta cell mass exposed to diabetogenic condition including proinflammatory cytokines. The mitogen activated protein kinase 10 also called c-jun amino-terminal kinase 3 (JNK3) plays a protective role in insulin-secreting cells against death caused by cytokines. In this study, we investigated whether the JNK3 expression is associated with the protective effect elicited by the GLP1 mimetic exendin 4. We found an increase in the abundance of JNK3 in isolated human islets and INS-1E cells cultured with exendin 4. Induction of JNK3 by exendin 4 was associated with an increased survival of INS-1E cells. Silencing of JNK3 prevented the cytoprotective effect of exendin 4 against apoptosis elicited by culture condition and cytokines. These results emphasize the requirement of JNK3 in the antiapoptotic effects of exendin 4. Hélène Ezanno, Valérie Pawlowski, Saida Abdelli, Raphael Boutry, Valery Gmyr, Julie Kerr-Conte, Christophe Bonny, François Pattou, and Amar Abderrahmani Copyright © 2014 Hélène Ezanno et al. All rights reserved. Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress Mon, 16 Jun 2014 00:00:00 +0000 Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS) and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH), respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome. Liang-Jun Yan Copyright © 2014 Liang-Jun Yan. All rights reserved. Ethanol at Low Concentration Attenuates Diabetes Induced Lung Injury in Rats Model Thu, 12 Jun 2014 09:23:31 +0000 To observe the changes of lung injury when diabetic rats were treated with low concentration of ethanol (EtOH) and analyze the related mechanisms, male Sprague-Dawley (SD) rats were divided into control, diabetic (DM), and EtOH+DM groups. Diabetic rat was mimicked by injection of streptozotocin intraperitoneally. Fasting blood glucose (FBG) level, lung weight (LW), body weight (BW), and LW/BW were measured. The changes of lung tissue and Type II alveolar cell were detected. Pulmonary malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured; meanwhile, ALDH2 mRNA and protein expressions were detected by RT-PCR and western blotting, respectively. Compared with control group, in DM group, SOD activity was decreased; FBG level, LW/BW, MDA content, ALDH2 mRNA, and protein expressions were decreased. Compared with DM group, in EtOH+DM group, SOD activity, ALDH2 mRNA, and protein expressions were increased; LW/BW and MDA content were decreased. The structures of lung tissue and lamellar bodies were collapsed in DM group; the injury was attenuated in EtOH+DM group. Our findings suggested that, in diabetic rat, pulmonary ALDH2 expression was decreased accompanying lung injury. EtOH at low concentration decreased diabetes induced lung injury through activating ALDH2 expression. Jun-Feng Hu, Guan-Jun Zhang, Lei Wang, Pin-Fang Kang, Jun Li, Hong-Ju Wang, Qin Gao, and Yu-Qing Chen Copyright © 2014 Jun-Feng Hu et al. All rights reserved. Ventral Prostate Fibrosis in the Akita Mouse Is Associated with Macrophage and Fibrocyte Infiltration Wed, 11 Jun 2014 12:31:07 +0000 A higher incidence of lower urinary tract symptoms (LUTS) among diabetic men is unexplained. Recently, prostate inflammation and fibrosis have been implicated as major contributing factors to bladder outlet obstruction and LUTS. We characterized the inflammatory cell infiltrate and collagen content of the anterior, dorsal, and ventral lobes of 18-week-old DBA2J.Ins2-Akita mice (Akita) and age-matched control mice. We performed hematoxylin and eosin staining to score tissue injury and inflammation, picrosirius red staining to quantitate collagen content, and immunostaining to identify monocytes/macrophages and infiltrating fibrocytes. We observed significantly greater numbers of monocytes/macrophages and fibrocytes specifically in the ventral prostate of the Akita mice and found that this was associated with significant greater collagen content specifically in the ventral prostate of the Akita mice. These observations support the inference that diabetes elicits monocyte/macrophage infiltration and collagen accumulation in the prostate and suggest that further study of Akita mice may inform translational studies of diabetes in the genesis prostatic inflammation, prostatic fibrosis, and LUTS. Sanghee Lee, Guang Yang, William Mulligan, Jerry Gipp, and Wade Bushman Copyright © 2014 Sanghee Lee et al. All rights reserved. Vitamin Status as a Determinant of Serum Homocysteine Concentration in Type 2 Diabetic Retinopathy Tue, 10 Jun 2014 05:45:17 +0000 We investigated the association of serum homocysteine levels and vitamin status with type 2 diabetic retinopathy. This study included 65 patients with and 75 patients without diabetic retinopathy. Patients with diabetic retinopathy had significantly higher serum homocysteine levels , higher prevalence of hyperhomocysteinemia , lower serum folic acid , and vitamin B12 () levels than those without diabetic retinopathy. Regression analysis revealed that homocysteine was an independent risk factor for diabetic retinopathy and there was a threshold in its serum level (13.7 μmol/L), above which the risk of diabetic retinopathy greatly increases (, ). Folic acid was associated with decreased odds for diabetic retinopathy (, ). There was a threshold in serum vitamin B12 level (248.4 pg/mL), below which serum homocysteine concentration significantly increases with decreasing serum vitamin B12 (). Our findings suggest that hyperhomocysteinemia is an independent risk factor for the development and progression of diabetic retinopathy. Decreased serum levels of folic acid and vitamin B12, through raising serum homocysteine concentrations, may also affect the diabetic retinopathy risk. Pandelis Fotiou, Athanasios Raptis, George Apergis, George Dimitriadis, Ioannis Vergados, and Panagiotis Theodossiadis Copyright © 2014 Pandelis Fotiou et al. All rights reserved. No Evidence of Viral Transmission following Long-Term Implantation of Agarose Encapsulated Porcine Islets in Diabetic Dogs Thu, 05 Jun 2014 11:32:08 +0000 We have previously described the use of a double coated agarose-agarose porcine islet macrobead for the treatment of type I diabetes mellitus. In the current study, the long-term viral safety of macrobead implantation into pancreatectomized diabetic dogs treated with pravastatin () was assessed while 2 dogs served as nonimplanted controls. A more gradual return to preimplant insulin requirements occurred after a 2nd implant procedure (days 148, 189, and >652) when compared to a first macrobead implantation (days 9, 21, and 21) in all macrobead implanted animals. In all three implanted dogs, porcine C-peptide was detected in the blood for at least 10 days following the first implant and for at least 26 days following the second implant. C-peptide was also present in the peritoneal fluid of all three implanted dogs at 6 months after 2nd implant and in 2 of 3 dogs at necropsy. Prescreening results of islet macrobeads and culture media prior to transplantation were negative for 13 viruses. No evidence of PERV or other viral transmission was found throughout the study. This study demonstrates that the long-term (2.4 years) implantation of agarose-agarose encapsulated porcine islets is a safe procedure in a large animal model of type I diabetes mellitus. Lawrence S. Gazda, Horatiu V. Vinerean, Melissa A. Laramore, Richard D. Hall, Joseph W. Carraway, and Barry H. Smith Copyright © 2014 Lawrence S. Gazda et al. All rights reserved. Effects of Simvastatin on Glucose Metabolism in Mouse MIN6 Cells Wed, 04 Jun 2014 11:19:57 +0000 The aim of this study was to investigate the effects of simvastatin on insulin secretion in mouse MIN6 cells and the possible mechanism. MIN6 cells were, respectively, treated with 0 μM, 2 μM, 5 μM, and 10 μM simvastatin for 48 h. Radio immunoassay was performed to measure the effect of simvastatin on insulin secretion in MIN6 cells. Luciferase method was used to examine the content of ATP in MIN6 cells. Real-time PCR and western blotting were performed to measure the mRNA and protein levels of inward rectifier potassium channel 6.2 (Kir6.2), voltage-dependent calcium channel 1.2 , and glucose transporter-2 (GLUT2), respectively. ATP-sensitive potassium current and L-type calcium current were recorded by whole-cell patch-clamp technique. The results showed that high concentrations of simvastatin (5 μM and 10 μM) significantly reduced the synthesis and secretion of insulin compared to control groups in MIN6 cells . ATP content in simvastatin-treated cells was lower than in control cells . Compared with control group, the mRNA and protein expression of Kir6.2 increased with treatment of simvastatin , and mRNA and protein expression of and GLUT2 decreased in response to simvastatin . Moreover, simvastatin increased the ATP-sensitive potassium current and reduced the L-type calcium current. These results suggest that simvastatin inhibits the synthesis and secretion of insulin through a reduction in saccharometabolism in MIN6 cells. Jieqiong Zhou, Weihua Li, Qiang Xie, Yuxi Hou, Shaopeng Zhan, Xi Yang, Xiaofeng Xu, Jun Cai, and Zhengrong Huang Copyright © 2014 Jieqiong Zhou et al. All rights reserved. Decreased Plasma Nesfatin-1 Level Is Related to the Thyroid Dysfunction in Patients with Type 2 Diabetes Mellitus Wed, 04 Jun 2014 11:15:30 +0000 Aims. Thyroid dysfunction is frequently observed in patients with type 2 diabetes mellitus (T2DM), but the underlying mechanism is still poorly understood. The present study aimed to investigate whether nesfatin-1 played a role in the thyroid dysfunction in patients with T2DM. Methods. 55 euthyroid patients were enrolled in this study including 30 patients with T2DM and 25 patients with impaired glucose regulation (IGR). 30 age-matched healthy people were also included as the control. The plasma levels of nesfatin-1, thyrotropin (TSH), and glycosylated hemoglobin (HbA1c) as well as the body mass index (BMI) were comparatively analyzed among the three groups. Results. The nesfatin-1 was significantly lower in patients with T2DM than in patients with IGR and in the control. On the contrary, the TSH level was significantly higher in patients with T2DM than in patients with IGR and in the control. Simple regression analysis showed that the plasma nesfatin-1 was negatively correlated with the TSH and HbA1c levels and positively correlated with the BMI. With multiple stepwise regression analysis, the nesfatin-1 remained to be independently correlated with the TSH, BMI, and HbA1c. Conclusions. The study was suggesting a role of nesfatin-1 in thyroid dysfunction in patients with T2DM. Fupeng Liu, Qing Yang, Ning Gao, Fangfang Liu, and Shaohua Chen Copyright © 2014 Fupeng Liu et al. All rights reserved. Pharmacological Effects of JTT-551, a Novel Protein Tyrosine Phosphatase 1B Inhibitor, in Diet-Induced Obesity Mice Thu, 29 May 2014 13:24:12 +0000 Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin signaling as well as insulin signaling. JTT-551 is a new PTP1B inhibitor, which is reported to improve glucose metabolism by enhancement of insulin signaling. We have evaluated an antiobesity effect of JTT-551 using diet-induced obesity (DIO) mice. A single administration of JTT-551 was provided to DIO mice with or without leptin, and DIO mice were given food containing JTT-551 for six weeks. A single administration of JTT-551 with leptin treatment enhanced the food inhibition and the signal transducer and activator of transcription 3 (STAT3) phosphorylation in hypothalamus. Moreover, chronic administration of JTT-551 showed an antiobesity effect and an improvement of glucose and lipid metabolism in DIO mice. JTT-551 shows an antiobesity effect possibly by enhancement of leptin signaling and could be useful in the treatment of type 2 diabetes and obesity. Makoto Ito, Sumiaki Fukuda, Shohei Sakata, Hisayo Morinaga, and Takeshi Ohta Copyright © 2014 Makoto Ito et al. All rights reserved. Association of Pulse Pressure with Serum TNF-α and Neutrophil Count in the Elderly Tue, 27 May 2014 12:30:02 +0000 Aims. Elevated pulse pressure (PP) has been reported to be a risk factor for type 2 diabetes in elderly patients with hypertension. Methods. Cross-sectional relationships of PP with known risk factors for type 2 diabetes and inflammatory markers were examined in 150 elderly community-dwelling women, 79 women (52.7%) of whom had hypertension. Results. Systolic blood pressure (standardized β, 0.775), log tumor necrosis factor-α (TNF-α, standardized β, 0.110), age (standardized β, 0.140), and neutrophil count (standardized β, 0.114) emerged as determinants of PP independent of high-sensitivity C-reactive protein, interleukin-6, monocyte count, plasminogen activator inhibitor-1, homeostasis model assessment of insulin resistance, HDL-cholesterol, and adiponectin (2 = 0.772). Conclusions. The present studies have demonstrated an independent association of higher PP with higher TNF-α, a marker of insulin resistance, and neutrophil count in community-living elderly women and suggest that insulin resistance and chronic low-grade inflammation may in part be responsible for the association between high PP and incident type 2 diabetes found in elderly patients with hypertension. Eriko Yamada, Mika Takeuchi, Miki Kurata, Tsutomu Kazumi, and Keisuke Fukuo Copyright © 2014 Eriko Yamada et al. All rights reserved. The Association between Serum Uric Acid and Residual β-Cell Function in Type 2 Diabetes Mon, 26 May 2014 13:28:30 +0000 The aim of this study was to investigate the relationship of serum uric acid (sUA) with residual β-cell function in type 2 diabetes. Oral glucose tolerance tests (OGTT) were performed on 1021 type 2 diabetes patients. The ratio of area under curve of insulin to glucose during 0 to 30 min and 0 to 120 min of the OGTT was calculated as indices of insulin secretion function. The products of insulin secretion indices multiplied by Matsuda insulin sensitivity index were used as disposition indices. After correlation and multiple linear regression analysis, sUA was significantly associated with insulin secretion and disposition indices in male, female, and total groups adjusted for confounding factors (including metabolic indicators like sex, age, course of the disease, blood glucose, blood pressure, serum lipids, and so on). Superficially steeper time-dependent decline of insulin secretion function was found in patients with sUA above the median than those below it. In conclusion, our results suggest an independent positive association between sUA and residual β-cell function in type 2 diabetes. Patients with higher sUA have greater insulin secretion ability than those with lower sUA at the early stage of disease, but their residual β-cell function seems to decay more rapidly. Wei Tang, Qi Fu, Qingqing Zhang, Min Sun, Yuan Gao, Xuan Liu, Li Qian, Shan Shan, and Tao Yang Copyright © 2014 Wei Tang et al. All rights reserved. Effect of Metformin Intervention during Pregnancy on the Gestational Diabetes Mellitus in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis Wed, 21 May 2014 00:00:00 +0000 Metformin is an effective insulin sensitizer treating type 2 diabetes mellitus. However, the functional consequences of metformin administration throughout pregnancy on gestational diabetes mellitus (GDM) with polycystic ovary syndrome (PCOS) have not been assessed. We therefore performed a meta-analysis and system review to determine the effect of metformin on GDM in PCOS. A meta-analysis was performed on the published studies before December, 2013. Meta-analysis examined whether metformin could reduce GDM occurrence in PCOS with a fixed effect model. The odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of association. A total of 13 studies including 5 RCTs and 8 non-RCTs were enrolled. Ultimately, effectiveness analysis demonstrated that, in total, there was no significant availability of metformin on GDM in PCOS in contrast to placebo (OR = 1.07, 95% CI 0.60–1.92) in RCTs and significant availability of metformin on GDM (OR = 0.19, 95% CI 0.13–0.27) was indicated in non-RCTs. In summary, according to the results of our meta-analysis, strictly, metformin did not significantly effect on GDM with PCOS, though more multicenters RCTs still need to be investigated. Zhihong Zhuo, Aiming Wang, and Huimin Yu Copyright © 2014 Zhihong Zhuo et al. All rights reserved. Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors Mon, 19 May 2014 08:54:06 +0000 The neogenesis of insulin-producing cells (IPCs) from non-beta-cells has emerged as a potential method for treating diabetes mellitus (DM). Many groups have documented that activation of pancreatic transcription factor(s) in hepatocytes can improve the hyperglycemia in diabetic mice. In the present study, we explored a novel protocol that reprogrammed primary hepatocytes into functional IPCs by using multicistronic vectors carrying pancreatic and duodenal homeobox-1 (Pdx1), neurogenin 3 (Ngn3), and v-musculoaponeurotic fibrosarcoma oncogene homolog A (MafA). These triple-transfected cells activated multiple beta-cell genes, synthesized and stored considerable amounts of insulin, and released the hormone in a glucose-regulated manner in vitro. Furthermore, when transplanted into streptozotocin-induced diabetic mice, the cells markedly ameliorated glucose tolerance. Our results indicated that ectopic expression of Pdx1, Ngn3, and MafA facilitated hepatocytes-to-IPCs reprogramming. This approach may offer opportunities for treatment of DM. Haizhao Luo, Rongping Chen, Rui Yang, Yan Liu, Youping Chen, Yi Shu, and Hong Chen Copyright © 2014 Haizhao Luo et al. All rights reserved. Pravastatin Improves Glucose Regulation and Biocompatibility of Agarose Encapsulated Porcine Islets following Transplantation into Pancreatectomized Dogs Mon, 19 May 2014 07:40:51 +0000 The encapsulation of porcine islets is an attractive methodology for the treatment of Type I diabetes. In the current study, the use of pravastatin as a mild anti-inflammatory agent was investigated in pancreatectomized diabetic canines transplanted with porcine islets encapsulated in agarose-agarose macrobeads and given 80 mg/day of pravastatin () while control animals did not receive pravastatin (). Control animals reached preimplant insulin requirements on days 18, 19, and 32. Pravastatin-treated animals reached preimplant insulin requirements on days 22, 27, and 50. Two animals from each group received a second macrobead implant: control animals remained insulin-free for 15 and 21 days (AUC = 3003 and 5078 mg/dL/24 hr days 1 to 15) and reached preimplant insulin requirements on days 62 and 131. Pravastatin treated animals remained insulin-free for 21 and 34 days (AUC = 1559 and 1903 mg/dL/24 hr days 1 to 15) and reached preimplant insulin requirements on days 38 and 192. Total incidence (83.3% versus 64.3%) and total severity (22.7 versus 18.3) of inflammation on tissue surfaces were higher in the control group at necropsy. These findings support pravastatin therapy in conjunction with the transplantation of encapsulated xenogeneic islets for the treatment of diabetes mellitus. Lawrence S. Gazda, Horatiu V. Vinerean, Melissa A. Laramore, Richard D. Hall, Joseph W. Carraway, and Barry H. Smith Copyright © 2014 Lawrence S. Gazda et al. All rights reserved.