Journal of Diabetes Research The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Chronic Treatment with Ang-(1-7) Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes Tue, 16 Sep 2014 08:46:52 +0000 Angiotensin-(1-7) [Ang-(1-7)] may have beneficial effects in diabetes mellitus-induced erectile dysfunction (DMIED) but its molecular actions in the diabetic corpus cavernosum (CC) are not known. We characterized the effects of diabetes and/or chronic in vivo administration of Ang-(1-7) on vascular reactivity in the rat corpus cavernosum (CC) and on protein expression levels of potential downstream effectors of the renin-angiotensin-aldosterone system (RAAS) such as angiotensin-converting enzyme (ACE), ACE2, Rho kinases 1 and 2 (ROCK1 and ROCK2), and omega-hydroxylase, the cytochrome-P450 enzyme that metabolizes arachidonic acid to form the vasoconstrictor, 20-hydroxyeicosatetraenoic acid. Streptozotocin-treated rats were chronicically administered Ang-(1-7) with or without A779, a Mas receptor antagonist, during weeks 4 to 6 of diabetes. Ang-(1-7) reversed diabetes-induced abnormal reactivity to vasoactive agents (endothelin-1, phenylepherine, and carbachol) in the CC without correcting hyperglycemia. Six weeks of diabetes led to elevated ACE, ROCK1, ROCK 2, and omega-hydroxylase and a concomitant decrease in ACE2 protein expression levels that were normalized by Ang-(1-7) treatment but not upon coadministration of A779. These data are supportive of the notion that the beneficial effects of Ang-(1-7) in DMIED involve counterregulation of diabetes-induced changes in ACE, ACE2, Rho kinases, and omega-hydroxylase proteins in the diabetic CC via a Mas receptor-dependent mechanism. Mariam H. M. Yousif, Batoul Makki, Ahmed Z. El-Hashim, Saghir Akhtar, and Ibrahim F. Benter Copyright © 2014 Mariam H. M. Yousif et al. All rights reserved. Ocular Inflammation in Uveal Tract in Aged Obese Type 2 Diabetic Rats (Spontaneously Diabetic Torii Fatty Rats) Sun, 14 Sep 2014 13:05:14 +0000 We report uveitis observed in an obese type 2 diabetes rat model, Spontaneously Diabetic Torii Leprfa (SDT fatty) rats aged over 50 weeks. The eyes of SDT fatty rats (16 animals: 7 males and 9 females with 50 or 60 weeks of age) were examined histopathologically. Infiltration of inflammatory cells in the uveal tract was observed in 13 of 16 animals. One female showed severe inflammation affecting the entire uveal tract including the iris, ciliary body, and choroid with a variety of inflammatory cells (neutrophils, lymphocytes, and macrophages). Those changes clinically mimic the findings of diabetic iridocyclitis in diabetic patients. Uveitis associated with diabetes can occur in diabetic patients but the pathogenesis still remains unknown. Since increased extramedullary hematopoiesis in the spleen and abscess in the genital and lower urinary tracts were observed in some SDT fatty rats, increased susceptibility to infection, prolongation of inflammatory states, and disorders of the immune system were considered to be possible factors of the uveitis in aged SDT fatty rats. There have been few reports on how diabetes has influence on the development of uveitis associated with bacterial infection. The SDT fatty rat can be an animal model to investigate diabetes-associated uveitis. Yusuke Kemmochi, Katsuhiro Miyajima, Takeshi Ohta, Tomohiko Sasase, Yuzo Yasui, Kaoru Toyoda, Kochi Kakimoto, Toshiyuki Shoda, and Akihiro Kakehashi Copyright © 2014 Yusuke Kemmochi et al. All rights reserved. The Influence of Peripheral Neuropathy, Gender, and Obesity on the Postural Stability of Patients with Type 2 Diabetes Mellitus Tue, 02 Sep 2014 12:04:07 +0000 Aim. To assess the influence of peripheral neuropathy, gender, and obesity on the postural stability of patients with type 2 diabetes mellitus. Methods. 151 patients with no history of otology, neurology, or orthopaedic or balance disorders accepted to participate in the study. After a clinical interview and neuropathy assessment, postural stability was evaluated by static posturography (eyes open/closed on hard/soft surface) and the “Up & Go” test. Results. During static posturography, on hard surface, the length of sway was related to peripheral neuropathy, gender, age, and obesity; on soft surface, the length of sway was related to peripheral neuropathy, gender, and age, the influence of neuropathy was larger in males than in females, and closing the eyes increased further the difference between genders. The mean time to perform the “Up & Go” test was 11.6 ± 2.2 sec, with influence of peripheral neuropathy, gender, and age. Conclusion. In order to preserve the control of static upright posture during conditions with deficient sensory input, male patients with type 2 diabetes mellitus with no history of balance disorders may be more vulnerable than females, and obesity may decrease the static postural control in both males and females. Aline Herrera-Rangel, Catalina Aranda-Moreno, Teresa Mantilla-Ochoa, Lylia Zainos-Saucedo, and Kathrine Jáuregui-Renaud Copyright © 2014 Aline Herrera-Rangel et al. All rights reserved. The Role of MicroRNAs in Diabetic Nephropathy Mon, 01 Sep 2014 11:24:42 +0000 Diabetic nephropathy (DN), as one of the chronic complications of diabetes, is the major cause of end-stage renal disease. However, the pathogenesis of this disease is not fully understood. In recent years, research on microRNAs (miRNAs) has become a hotspot because of their critical role in regulating posttranscriptional levels of protein-coding genes that may serve as key pathogenic factors in diseases. Several miRNAs were found to participate in the pathogenesis of DN, while others showed renal protective effects. Therefore, targeting miRNAs that are involved in DN may have a good prospect in the treatment of the disease. The aim of this review is to summarize DN-related miRNAs and provide potential targets for diagnostic strategies and therapeutic intervention. Hao Wu, Lili Kong, Shanshan Zhou, Wenpeng Cui, Feng Xu, Manyu Luo, Xiangqi Li, Yi Tan, and Lining Miao Copyright © 2014 Hao Wu et al. All rights reserved. Characteristics and Determinants of Partial Remission in Children with Type 1 Diabetes Using the Insulin-Dose-Adjusted A1C Definition Sun, 31 Aug 2014 09:18:38 +0000 To evaluate the characteristics and determinants of partial remission (PR) in Belgian children with type 1 diabetes (T1D), we analyzed records of 242 children from our center. Clinical and biological features were collected at diagnosis and during follow-up. PR was defined using the insulin-dose-adjusted A1C definition. PR occurred in 56.2% of patients and lasted 9.2 months (0.5 to 56.6). 25.6% of patients entered T1D with DKA, which correlated with lower PR incidence (17.6% versus 82.3% when no DKA). In our population, lower A1C levels at diagnosis were associated with higher PR incidence and in young children (0–4 years) initial A1C levels negatively correlated with longer PR. Early A1C levels were predictive of PR duration since 34% of patients had long PRs (>1 year) when A1C levels were ≤6% after 3 months whereas incidence of long PR decreased with higher A1Cs. C-peptide levels were higher in patients entering PR and remained higher until 3 years after diagnosis. Initial antibody titers did not influence PR except for anti-IA2 titers that correlated with A1C levels after 2 years. Presence of 2 versus 1 anti-islet antibodies correlated with shorter PR. PR duration did not influence occurrence of severe hypoglycemia or diabetes-related complications but was associated with lower A1C levels after 18 months. We show that, at diagnosis of T1D, parameters associated with -cell mass reserve (A1C, C-peptide, and DKA) correlate with the occurrence of PR, which affects post-PR A1C levels. Further research is needed to determine the long-term significance of PR. Aurore Pecheur, Thierry Barrea, Valérie Vandooren, Véronique Beauloye, Annie Robert, and Philippe A. Lysy Copyright © 2014 Aurore Pecheur et al. All rights reserved. Continuous Electrical Current and Zinc Sulphate Administered by Transdermal Iontophoresis Improves Skin Healing in Diabetic Rats Induced by Alloxan: Morphological and Ultrastructural Analysis Thu, 28 Aug 2014 08:44:09 +0000 Purpose. Evaluated the effects of continuous electrical current (CEC) or zinc administrated by transdermal iontophoresis (Zn+TDI). Methods. 120 male Wistar rats were submitted to an incision surgery at the anterior region of abdomen and distributed into 6 experimental groups with 40 animals: 3 diabetic groups and 3 normal groups, untreated and treated with CEC alone or with Zn + TDI. Each group was further divided into 4 subgroups with 10 rats each to be evaluated on the 4th, 7th, 14th, and 21st day after surgery. In each period, clinical and laboratory parameters from the animals were analyzed. Results. The analysis by optical and scanning electron microscopy showed a delay in the phases of wound healing in diabetic rats without treatment in all periods of the experiment; breaking strength (BS) was significantly reduced in skin scars of untreated diabetic rats when compared to other groups. In contrast, BS in skin scars of nondiabetic groups and diabetic rats treated with Zn + TDI showed significant increase in those, besides not presenting delayed healing. Conclusion. Electrical stimulation of surgical wounds used alone or in association with zinc by TDI is able to consistently improve the morphological and ultrastructural changes observed in the healing of diabetic animals. Lucas Langoni Cassettari, Pedro Colli Rocha Dias, Amanda Natália Lucchesi, Maurício Ferraz de Arruda, Érika Veruska Paiva Ortolan, Mariângela Esther A. Marques, and César Tadeu Spadella Copyright © 2014 Lucas Langoni Cassettari et al. All rights reserved. Histone Lysine Methylation in Diabetic Nephropathy Mon, 25 Aug 2014 10:52:46 +0000 Diabetic nephropathy (DN) belongs to debilitating microvascular complications of diabetes and is the leading cause of end-stage renal diseases worldwide. Furthermore, outcomes from the DCCT/EDIC study showed that DN often persists and progresses despite intensive glucose control in many diabetes patients, possibly as a result of prior episode of hyperglycemia, which is called “metabolic memory.” The underlying mechanisms responsible for the development and progression of DN remain poorly understood. Activation of multiple signaling pathways and key transcription factors can lead to aberrant expression of DN-related pathologic genes in target renal cells. Increasing evidence suggests that epigenetic mechanisms in chromatin such as DNA methylation, histone acetylation, and methylation can influence the pathophysiology of DN and metabolic memory. Exciting researches from cell culture and experimental animals have shown that key histone methylation patterns and the related histone methyltransferases and histone demethylases can play important roles in the regulation of inflammatory and profibrotic genes in renal cells under diabetic conditions. Because histone methylation is dynamic and potentially reversible, it can provide a window of opportunity for the development of much-needed novel therapeutic potential for DN in the future. In this minireview, we discuss recent advances in the field of histone methylation and its roles in the pathogenesis and progression of DN. Guang-dong Sun, Wen-peng Cui, Qiao-yan Guo, and Li-ning Miao Copyright © 2014 Guang-dong Sun et al. All rights reserved. Effect of Ranirestat, a New Aldose Reductase Inhibitor, on Diabetic Retinopathy in SDT Rats Mon, 25 Aug 2014 07:51:42 +0000 Purpose. To evaluate the effect of ranirestat, a new aldose reductase inhibitor (ARI), on diabetic retinopathy (DR) in Spontaneously Diabetic Torii (SDT) rats. Methods. The animals were divided into six groups, normal Sprague-Dawley rats , untreated SDT rats , ranirestat-treated SDT rats (0.1, 1.0, and 10 mg/kg/day, , and , resp.), and epalrestat-treated SDT rats (100 mg/kg/day, . Treated rats received oral ranirestat or epalrestat once daily for 40 weeks after the onset of diabetes. After the eyes were enucleated, the retinal thickness and the area of stained glial fibrillary acidic protein (GFAP) were measured. Results. The retinas in the untreated group were significantly thicker than those in the normal and ranirestat-treated (0.1, 1.0, and 10 mg/kg/day) groups. The immunostained area of GFAP in the untreated group was significantly larger than that in the normal and ranirestat-treated (1.0 and 10 mg/kg/day) groups. There were no significant differences between the untreated group and epalrestat-treated group in the retinal thickness and the area of stained GFAP. Conclusion. Ranirestat reduced the retinal thickness and the area of stained GFAP in SDT rats and might suppress DR and have a neuroprotective effect on diabetic retinas. Fumihiko Toyoda, Yoshiaki Tanaka, Ayumi Ota, Machiko Shimmura, Nozomi Kinoshita, Hiroko Takano, Takafumi Matsumoto, Junichi Tsuji, and Akihiro Kakehashi Copyright © 2014 Fumihiko Toyoda et al. All rights reserved. Vitamin D Insufficiency Is Associated with Lower Physical Function in Patients with Heart Failure and Diabetes Mon, 25 Aug 2014 05:48:14 +0000 Vitamin D deficiency is frequent among patients with heart failure (HF) and diabetes, disorders associated with exercise intolerance and muscle weakness. This study aims to search for associations between vitamin D sufficiency and physical function indexes in patients with HF and diabetes. A cross-sectional study of 146 HF patients, 39.7% with diabetes, at a Brazilian tertiary outpatient clinic was performed. Patients underwent clinical evaluation, 6-minute walk test (6 MWT), handgrip strength, physical activity level (IPAQ), and biochemical evaluations including serum 25-hydroxyvitamin D. Classification was done according to vitamin D status (≥30 ng/dL, sufficient) and presence/absence of diabetes in vitamin sufficient, no diabetes (DS-C, ), vitamin sufficient, diabetes (DS-DM, ), vitamin deficient, no diabetes (DD-C, ), and vitamin deficient, diabetes (DD-DM, ). Patients age was 55.4 ± 8 yrs; 70.5% had vitamin D deficiency. Clinical characteristics were similar among groups. Total time expended in physical activity was similar among groups . DS-C covered higher distances in the 6 MWT (392 ± 60 m) versus DD-DM (309 ± 116 m); . Handgrip strength was similar among groups but tended to lower levels in DD-DM even after being adjusted to physical activity . Vitamin D deficiency can influence physical function in HF diabetic patients. M. R. Lopes, Paula A. B. Ribeiro, Priscila Ledur, Gabriela C. Souza, Nadine Clausell, and Beatriz D. Schaan Copyright © 2014 M. R. Lopes et al. All rights reserved. Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature Swine Sun, 24 Aug 2014 07:36:19 +0000 Background. Roux-en-Y gastric bypass (RYGB) is the most common bariatric operation; however, the mechanism underlying the profound weight-independent effects on glucose homeostasis remains unclear. Large animal models of naturally occurring insulin resistance (IR), which have been lacking, would provide opportunities to elucidate such mechanisms. Ossabaw miniature swine naturally exhibit many features that may be useful in evaluating the anti diabetic effects of bariatric surgery. Methods. Glucose homeostasis was studied in 53 Ossabaw swine. Thirty-two received an obesogenic diet and were randomized to RYGB, gastrojejunostomy (GJ), gastrojejunostomy with duodenal exclusion (GJD), or Sham operations. Intravenous glucose tolerance tests and standardized meal tolerance tests were performed prior to, 1, 2, and 8 weeks after surgery and at a single time-point for regular diet control pigs. Results. High-calorie-fed Ossabaws weighed more and had greater IR than regular diet controls, though only 70% developed IR. All operations caused weight-loss-independent improvement in IR, though only in pigs with high baseline IR. Only RYGB induced weight loss and decreased IR in the majority of pigs, as well as increasing /. Conclusions. Similar to humans, Ossabaw swine exhibit both obesity-dependent and obesity-independent IR. RYGB promoted weight loss, IR improvement, and increased /, compared to the smaller changes following GJ and GJD, suggesting a combination of upper and lower gut mechanisms in improving glucose homeostasis. Jonathan G. Sham, Vlad V. Simianu, Andrew S. Wright, Skye D. Stewart, Mouhamad Alloosh, Michael Sturek, David E. Cummings, and David R. Flum Copyright © 2014 Jonathan G. Sham et al. All rights reserved. Subjects with Impaired Fasting Glucose: Evolution in a Period of 6 Years Wed, 20 Aug 2014 07:49:03 +0000 Aim. To study the evolution of impaired fasting glucose (IFG), considering glucose and HbA1c levels and risk factors associated, in a period of 6 years. Methods. We studied 94 subjects with impaired fasting glucose (IFG) that were diagnosed in 2005 and followed up to 2012. Glucose and HbA1c levels were determined. A descriptive analysis of contingence charts was performed in order to study the evolution in the development of type-2 diabetes mellitus (T2DM). Results. Twenty-eight of ninety-four subjects became T2DM; 51/94 remained with IFG; and 20/94 presented normal fasting glucose. From the 28 diabetic subjects, 9 had already developed diabetes and were under treatment with oral hypoglycemic agents; 5 were diagnosed with plasma glucose < 126 mg/dL, but with HbA1c over 6.5%. In those who developed diabetes, 15/28 had a family history of T2DM in first relative degree. Also, diabetic subjects had a BMI significantly higher than nodiabetics (t test: P < 0.01). The individuals that in 2005 had the highest BMI are those who currently have diabetes. Conclusion. The IFG constitutes a condition of high risk of developing T2DM in a few years, especially over 110 mg/dL and in obesity patients. E. Leiva, V. Mujica, R. Orrego, S. Wehinger, A. Soto, G. Icaza, M. Vásquez, L. Díaz, M. Andrews, and M. Arredondo Copyright © 2014 E. Leiva et al. All rights reserved. Vanadyl Sulfate Treatment Stimulates Proliferation and Regeneration of Beta Cells in Pancreatic Islets Tue, 19 Aug 2014 06:18:23 +0000 We examined the effects of vanadium sulfate (VOSO4) treatment at 5 and 10 mg/kg for 30 days on endocrine pancreas activity and histology in nondiabetic and STZ-induced diabetic rats. In diabetic group, blood glucose levels significantly increased while insulinemia level markedly decreased. At the end of treatment, VOSO4 at a dose of 10 mg/Kg normalized blood glucose level in diabetic group, restored insulinemia, and significantly improved insulin sensitivity. VOSO4 also increased in a dose-dependent manner the number of insulin immunopositive beta cells in pancreatic islets of nondiabetic rats. Furthermore, in the STZ-diabetic group, the decrease in the number of insulin immunopositive beta cells was corrected to reach the control level mainly with the higher dose of vanadium. Therefore, VOSO4 treatment normalized plasma glucose and insulin levels and improved insulin sensitivity in STZ-experimental diabetes and induced beta cells proliferation and/or regeneration in normal or diabetic rats. Samira Missaoui, Khémais Ben Rhouma, Mohamed-Tahar Yacoubi, Mohsen Sakly, and Olfa Tebourbi Copyright © 2014 Samira Missaoui et al. All rights reserved. Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats Thu, 14 Aug 2014 08:25:10 +0000 Objective. Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer’s disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies. Jian-Qin Wang, Jie Yin, Yan-Feng Song, Lang Zhang, Ying-Xiang Ren, De-Gui Wang, Li-Ping Gao, and Yu-Hong Jing Copyright © 2014 Jian-Qin Wang et al. All rights reserved. Insulin Detemir Causes Lesser Weight Gain in Comparison to Insulin Glargine: Role on Hypothalamic NPY and Galanin Thu, 14 Aug 2014 00:00:00 +0000 Objective. Compared with other insulin analogues, insulin detemir induces less weight gain. This study investigated whether this effect was achieved by influencing the hypothalamic appetite regulators neuropeptide Y (NPY) and galanin (GAL). Methods. Type  2 diabetic rat models were established with a high-fat diet and intraperitoneal injection of STZ. All rats were divided into NC, DM, DM+DE and DM+GLA groups. Glycemic levels of all study groups were checked at study onset and after 4 weeks of insulin treatment. Food intake and body weight were monitored during treatment. After 4 weeks, the hypothalamus of rats was examined for NPY and GAL mRNA and protein expression. Results. After 4 weeks of treatment, compared with the DM+GLA group, the DM+DE group exhibited less food intake () and less weight gain (), but showed similar glycemic control. The expression of hypothalamic NPY and GAL at both mRNA and protein level were significantly lower () in the DM+DE group. Conclusion. Insulin detemir decreased food intake in type 2 diabetic rats, which led to reduced weight gain when compared to insulin glargine treatment. This effect is likely due to downregulation of hypothalamic NPY and GAL. Mohammad Ishraq Zafar, Cuining Hu, Danfeng Liu, Raja Adeel Shafqat, and Feng Gao Copyright © 2014 Mohammad Ishraq Zafar et al. All rights reserved. Expression of CTRP3, a Novel Adipokine, in Rats at Different Pathogenic Stages of Type 2 Diabetes Mellitus and the Impacts of GLP-1 Receptor Agonist on It Mon, 11 Aug 2014 00:00:00 +0000 This study aimed to investigate the expression of C1q/TNF-related protein-3 (CTRP3) in rats at different pathogenic stages of type 2 diabetes mellitus (T2DM) and the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist on it. Male wistar rats were fed with high-fat diet for 10 weeks to induce insulin resistance (IR) and then were given low-dose streptozotocin (STZ) intraperitoneal injection to induce T2DM. Exendin-4 (Ex-4), a GLP-1 receptor agonist, was subcutaneous injected to the IR rats and T2DM rats for 4 weeks. The expression of CTRP3 mRNA and protein in epididymis adipose tissue of rats at the stage of IR was lower significantly than that of normal control (NC) rats and decreased more when they were at the stage of overt T2DM (all or ). After the treatment with Ex-4, the mRNA and protein expressions of CTRP3 were increased by 15.5% and 14.8% respectively, in IR rats and increased by 20.6% and 16.5% respectively, in T2DM rats. Overall, this study found that the expression of CTRP3 in visceral adipose tissue was progressively decreased in a T2DM rat model from the pathogenic stage of IR to overt diabetes, while Ex-4 treatment increased its expression in such animals. Xin Li, Li Jiang, Miao Yang, Yu-wen Wu, Su-xin Sun, and Jia-zhong Sun Copyright © 2014 Xin Li et al. All rights reserved. Effects of Unilateral Nephrectomy on Renal Function in Male Spontaneously Diabetic Torii Fatty Rats: A Novel Obese Type 2 Diabetic Model Sun, 10 Aug 2014 12:41:54 +0000 The Spontaneously Diabetic Torii (SDT) fatty rat is a new model for obese type 2 diabetes. The aim of the present study was to investigate the effect of 1/2 nephrectomy (Nx) on renal function and morphology and on blood pressure in SDT fatty rats. Male SDT fatty rats underwent 1/2 Nx or a sham operation (Sham). Subsequently, animals were studied with respect to renal function and histological alterations. Induction of 1/2 Nx in SDT fatty rats led to functional and morphological damage to the remnant kidney and to hypertension, which are considered main characteristics of chronic kidney disease, at a younger age compared with the sham group. In conclusion, the SDT fatty rat is useful in investigations to elucidate the pathogenesis of human diabetic nephropathy and in new drug discovery. Yoshiaki Katsuda, Yusuke Kemmochi, Mimi Maki, Ryuhei Sano, Yasufumi Toriniwa, Yukihito Ishii, Katsuhiro Miyajima, Kochi Kakimoto, and Takeshi Ohta Copyright © 2014 Yoshiaki Katsuda et al. All rights reserved. Peripheral Neuropathy and Tear Film Dysfunction in Type 1 Diabetes Mellitus Thu, 07 Aug 2014 11:37:23 +0000 Purpose. To compare tear film metrics in patients with type 1 diabetes mellitus (DM) and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality. Methods. Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy assessment. Results. Neither mean age nor dry eye symptom scores differed significantly between the DM and control groups ( and , resp.). Tear lipid thickness (), stability (), and quantity () were significantly lower in the DM group. Corneal sensitivity was also reduced in the DM group () and tear film stability was inversely associated with total neuropathy score (, ). Conclusion. The DM group exhibited significantly reduced tear film stability, secretion, and lipid layer quality relative to the age-matched control group. The negative correlation between tear film parameters and total neuropathy score suggests that ocular surface abnormalities occur in parallel with diabetic peripheral neuropathy. Stuti L. Misra, Dipika V. Patel, Charles N. J. McGhee, Monika Pradhan, Dean Kilfoyle, Geoffrey D. Braatvedt, and Jennifer P. Craig Copyright © 2014 Stuti L. Misra et al. All rights reserved. Early Detection of Atrophy of Foot Muscles in Chinese Patients of Type 2 Diabetes Mellitus by High-Frequency Ultrasonography Wed, 06 Aug 2014 11:42:14 +0000 The aim of this study was to evaluate the diagnostic value of high-frequency ultrasonography in detecting atrophy of foot muscles in Chinese patients of type 2 diabetes mellitus (T2DM). Chinese patients of T2DM with () or without () diabetic peripheral neuropathy (DPN) and the control subjects () were enrolled. The nondominant foot of all subjects was examined with high-frequency ultrasonography. The transverse diameter, thickness, and cross-sectional area of the extensor digitorum brevis muscle (EDB) and the thickness of the muscles of the first interstitium (MILs) were measured. The results showed that the ultrasonographic transverse diameter, thickness, and cross-sectional area of EDB and the thickness of MILs in patients of T2DM with DPN were significantly smaller than those in patients of T2DM without DPN (all ) and those in the control subjects (all ). The transverse diameter and cross-sectional area of the EDB and thickness of MILs in patients of T2DM without DPN were significantly smaller than those of the control subjects (all ). In conclusion, the atrophy of foot muscle in Chinese T2DM patients can be detected by high-frequency ultrasonography. Notably, ultrasonography may detect early atrophy of foot muscles in patients without DPN. Xiaohui Wang, Liang Chen, Weiwei Liu, Benli Su, and Yuhong Zhang Copyright © 2014 Xiaohui Wang et al. All rights reserved. Study of Postprandial Lipaemia in Type 2 Diabetes Mellitus: Exenatide versus Liraglutide Mon, 04 Aug 2014 11:36:34 +0000 Therapeutic approaches based on the actions of the incretin hormone GLP-1 have been widely established in the management of T2DM. Nevertheless, much less research has been aimed at elucidating the role of GLP-1 in lipid metabolism and in particular postprandial dyslipidemia. Exenatide and liraglutide are two GLP-1 receptor agonists which are currently available as subcutaneously administered treatment for T2DM but their chronic effects on postprandial lipaemia have not been well investigated. The aim of this study is to examine the effect of treatment with either liraglutide or exenatide for two weeks on postprandial lipaemia in obese subjects with T2DM. This study was a single-center, two-armed, randomized, controlled 2-week prospective intervention trial in 20 subjects with T2DM. Patients were randomized to receive either liraglutide or exenatide treatment and underwent a standardized meal tolerance test early in the morning after 10 h fast at baseline (visit 1, beginning of treatment) and after a two-week treatment period (visit 2). Exenatide and liraglutide both appear to be equally effective in lowering postprandial lipaemia after the first administration and after a two-week treatment. The mechanisms which lead to this phenomenon, which seem to be independent of gastric emptying, are yet to be studied. Maria Voukali, Irene Kastrinelli, Sapfo Stragalinou, Dimitra Tasiopoulou, Pinelopi Paraskevopoulou, Nicholas Katsilambros, Alexandros Kokkinos, Nicholas Tentolouris, and Ioannis Ioannidis Copyright © 2014 Maria Voukali et al. All rights reserved. Remodeling Intestinal Flora with Sleeve Gastrectomy in Diabetic Rats Mon, 04 Aug 2014 06:09:34 +0000 Objective. As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats. Methods. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them underwent sham operation. Meanwhile 10 male normal rats underwent sleeve gastrectomy as control. The animals’ weight and FBG had been measured. The composition changes of intestinal flora were detected by 16S rDNA sequence analysis. Results. In diabetic rats, weight and fasting blood glucose decreased significantly after sleeve gastrectomy. However, there was no significant change for weight and blood glucose in normal rats after operation. The intestinal flora of diabetic rats reduced in the proportion of Firmicutes and increased in the proportion of Bacteroidetes after sleeve gastrectomy. Conclusion. The change of dominant microorganisms in intestinal flora might play an important role in the glucose metabolism. Xiaofei Huang, Pan Weng, Huixin Zhang, and Yingli Lu Copyright © 2014 Xiaofei Huang et al. All rights reserved. Relationship between Autonomic Nervous System Function and Continuous Interstitial Glucose Measurement in Patients with Type 2 Diabetes Sun, 03 Aug 2014 11:33:29 +0000 Aims. The Aim of the present study was to examine whether there is a relationship between autonomic nervous system function and glycemic variability (GV) in patients with type 2 diabetes (T2D). Methods. A total of 50 (29 males) patients with T2D (mean age 58.4 ± 9.9 years, median diabetes duration 5.5 [IQR 2.0–9.25] years), on oral antidiabetic agents, underwent ECG recording and subcutaneous glucose monitoring, simultaneously and continuously, for 24 hours. Results. After adjustment for HbA1c and diabetes duration, total power of heart rate variability (HRV) was inversely associated with the standard deviation of the mean interstitial tissue glucose (MITG) and with the -value during the entire recording (: −0.29, ; : −0.30, , resp.) and during the night (: −0.29, ; : −0.31, , resp.). Most of the HRV time-domain indices were significantly correlated with standard deviation of the MITG and the -value. These correlations were stronger for the HRV recordings during the night. No significant association was found between HRV parameters and MAGE. Conclusions. HRV is inversely associated with GV in patients with T2D, which might be a sign of causation between GV and autonomic dysfunction. Prospective studies are needed to further investigate the importance of GV in the pathogenesis of long-term complications of diabetes. Stavroula Kalopita, Stavros Liatis, Petros Thomakos, Ioannis Vlahodimitris, Chryssoula Stathi, Nicholas Katsilambros, Nicholaos Tentolouris, and Konstantinos Makrilakis Copyright © 2014 Stavroula Kalopita et al. 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.