Day 1 :
Keynote Forum
Douglas Ishii
Colorado State University, USA
Keynote: Insulin-like Growth Factors (IGFs) Prevent Diabetic Peripheral Neuropathy Despite Unabated Hyperglycemia: Why Hyperglycemia Interventions Fail in Clinical Trials
Time : 9:30-10:00
Biography:
Douglas N. Ishii was born in a concentration camp in California at the onset of W.W.II. He received a B.A. in biochemistry at Univ. Calif. Berkeley, a Ph.D. in pharmacology at Stanford Univ. School of Medicine, and conducted postdoctoral studies in neurobiology at the same institution. He was Assoc. Prof. Pharmacology at Columbia Univ. N.Y.C., and is presently Prof. Biomedical Sciences at Colorado State Univ. He has served on many scientific review panels for N.I.H., N.S.F., and Juvenile Diabetes Found. Internatl. Awards include 20 issued patents for the treatment of neurodegenerative diseases. Dr. Ishii is a founder of Aurogen Inc., a biotechnology company dedicated to developing new treatments for Alzheimer's disease.
Abstract:
Sensory, motor and autonomic neuropathy caused by dying-back axonopathy are common complications in diabetes that may result in limb amputations, impotence, loss of bladder control, increased risk of cardiovascular mortality, and other disturbances. Present therapy is palliative; the development of meaningful treatments requires improved understanding of the pathogenesis of axonopathy. The dominant hypothesis for decades has been that hyperglycemia results in polyol accumulation, protein glycation, accumulation of AGE and subsequent injury to peripheral nerves. rn The alternative hypotheses were tested that a) neuropathy arises mainly as a consequence of a decline in combined neurotrophic insulin and IGF activities, and b) neuropathy can be prevented by restoration of IGF levels irrespective of hyperglycemia (Ishii, 1995; Ishii and Lupien, 2003). IGF levels decline progressively with aging, and more rapidly in obese, T1D and T2D patients. Diabetic rats have reduced IGF gene expression in nerves, spinal cord, brain and livers. Subcutaneous administration of IGF prevented multiple manifestations of sensory, motor and autonomic neuropathy despite unabated hyperglycemia in diabetic rats. IGF blockade in non-diabetic rodents mimics diabetic neuropathy. New results show that insulin provides additive neurotrophic support for the nervous system via pathways separate from glucoregulation. Clinical trial end-points to prevent diabetic neuropathy in T2D should be directed at increasing IGF levels and reducing insulin resistance, whereas hyperglycemia is an unreliable end-point. Indeed, intensive anti-hyperglycemic therapy in T2D, which comprises 90% of diabetic cases, does not prevent microvascular disease (neuropathy, nephropathy and retinopathy). rn
Keynote Forum
Jose Reyes
Center for Research and Advanced Studies of the IPN, Mexico
Keynote: Initial Stages of diabetic nephropathy: The beginning of a catastrophe
Time : 09:00 - 10:00
Biography:
Graduated from the Medical School at the National University of Mexico (1964). Training Infantil de Mexico, sponsored by Dr. Gustavo Gordillo. Graduated as Ph. D. at Centre for Research and Advanced Studies in Physiology and Biophysics (1977). Former Head of the Physiology and Biophysics Department. Currently Full Professor at this same institution. Former President of the National Board of Nephrology (Mexico). Invited professor at the Universities of Paris VI, Nice France, Laussane Switzerland. Postdoctoral training at the Children’s Hospital of Los Angeles, USA. Invited lectures at Department of Pharmacology, Cambridge University, UK, Albert Einstein College of Medicine, USA and New York College of Medicine, USA.
Abstract:
Diabetes is a public health problem worldwide distributed, affecting over 300 million patients. Diabetic nephropathy represents a major complication leading to end stage renal disease (ESRD). Treatment for this condition is dialysis, since frequently these patients are not candidates for transplantation. This evolution is fully recognized, however, initial mechanisms of renal damage in diabetes are not fully established. It is recognized that hyperglycemia provokes oxidative stress, which derives in damage to intercellular tight junctions. Aim of this study is to analyze the functional damage induced by oxidative stress on several segments of the nephron (functional unit of the kidney) and the participation of the tight intercellular junctions (TJs) that are expressed in those segments. We found an extensive oxidative stress at glomeruli (filtration units) and at proximal tubules (site of reabsorption of glucose and sodium). Damage of TJ junctions at endothelial cells explaining proteinuria and at epithelial proximal cells, explaining glucosuria and augmented natriuresis, were observed. Oxidative stress was reduced by administration of All-Trans Retinoic Acid (ATRA), vitamin A active form. As a consequence of reduced oxidative stress by ATRA, proteinuria and abnormalities in sodium renal handling were ameliorated, even in the presence of persistent hyperglycemia. This ATRA beneficial effect was accompanied by improvement of the TJs proteins damage. These data provide evidence of renal TJs as potential therapeutic targets on the evolution and progression of diabetic nephropathy
Keynote Forum
Lixin Li
Central Michigan University,USA
Keynote: Fat fight against fat, a potenital medication in treating obesity
Time : 10:00-10:30
Biography:
Dr.Lixin Li has completed her PhD from Norwegian University of Science and Technology and postdoctoral studies from Departement of Physiology, University of Toronto. She is the assistant professor at Central Michigan University US. She has published more than 20 papers in diabetes, obesity journals, she was the invited speaker of serveal international conferences and has been serving as an editorial board member of serveral jounals
Abstract:
rnObesity is a risk factor for many diseases, including type 2 diabetes. Glucagon like peptide -1 (GLP-1) and analogue are approved by FDA in treating type 2 diabets and has been reported having weight lowering effect in type 2 diabetes patients. Howerver, the underlying mechanisms has not been studied. We aimed to determine the contribution of brown adipose tissue (BAT) thermogenesis to the weight lowering effect induced by liraglutide, a full agonist of the GLP-1 receptor.rn rnMice were fed with either chow diet or high fat high sucrose diet (HFHSD), liraglutide or saline were injected daily for five weeks. Liraglutide significantly attenuated the weight gain along with attenuated epididymal fat mass compare with saline control group. Brown fat specific genes, uncoupling protein-1, were induced in white fat tissue (WAT) after liraglutide treatment, Transcription factor, PR domain–containing protein-16 (PRDM16) binds and coregulates C/EBPα, peroxisome proliferator-activated receptor gamma -α (PPAR-α) during brown fat differentiation, liraglutide significantly induced both genes. Peroxisome proliferator–activated receptor -coactivator-1-α( PGC-1 α), which involved in regulating mitochondrial biogenesis, oxidative metabolism, was also upregulated by liraglutide. In addiction Liraglutide reduced HFHSD induced elevation of BAX-2 ,BCL-2 and Caspases-3 gene expression in fat tissue, which indicated it reduced inflammation induced by obesity. rnrnOur results demonstrated the ability of liraglutide to reduce BW and adiposity, this protective effect on diet induced obesity may act through induction of beige fat (browning in WAT) which lead to elevated energy expenditure. Liraglutide is a potential therapy for obesity and obesity related metabolic disorders.rn
Keynote Forum
Jose Reyes
Associate Professor
Keynote: Initial Stages of diabetic nephropathy: The beginning of a catastrophe
Time : 10:30-11:00
Biography:
Graduated from the Medical School at the National University of Mexico (1964). Training Infantil de Mexico, sponsored by Dr. Gustavo Gordillo. Graduated as Ph. D. at Centre for Research and Advanced Studies in Physiology and Biophysics (1977). Former Head of the Physiology and Biophysics Department. Currently Full Professor at this same institution. Former President of the National Board of Nephrology (Mexico). Invited professor at the Universities of Paris VI, Nice France, Laussane Switzerland. Postdoctoral training at the Children’s Hospital of Los Angeles, USA. Invited lectures at Department of Pharmacology, Cambridge University, UK, Albert Einstein College of Medicine, USA and New York College of Medicine, USA.
Abstract:
Diabetes is a public health problem worldwide distributed, affecting over 300 million patients. Diabetic nephropathy represents a major complication leading to end stage renal disease (ESRD). Treatment for this condition is dialysis, since frequently these patients are not candidates for transplantation. This evolution is fully recognized, however, initial mechanisms of renal damage in diabetes are not fully established. It is recognized that hyperglycemia provokes oxidative stress, which derives in damage to intercellular tight junctions. Aim of this study is to analyze the functional damage induced by oxidative stress on several segments of the nephron (functional unit of the kidney) and the participation of the tight intercellular junctions (TJs) that are expressed in those segments. We found an extensive oxidative stress at glomeruli (filtration units) and at proximal tubules (site of reabsorption of glucose and sodium). Damage of TJ junctions at endothelial cells explaining proteinuria and at epithelial proximal cells, explaining glucosuria and augmented natriuresis, were observed. Oxidative stress was reduced by administration of All-Trans Retinoic Acid (ATRA), vitamin A active form. As a consequence of reduced oxidative stress by ATRA, proteinuria and abnormalities in sodium renal handling were ameliorated, even in the presence of persistent hyperglycemia. This ATRA beneficial effect was accompanied by improvement of the TJs proteins damage. These data provide evidence of renal TJs as potential therapeutic targets on the evolution and progression of diabetic nephropathy
Keynote Forum
Yafi Michael
The University of Texas Medical School at Houston,USA
Keynote: Evaluation of Trends in Type 1 Diabetes Mellitus Care in pediatric diabetes
Time : 13:20-13:50
Biography:
Michael Yafi is the director of Pediatric Endrocinology division of University of Texas Medical School. He got the "Best Doctors in Houston" in 2006. Dr. Michael is a member of "Austin Journal of Pediatrics"
Abstract:
Noncompliance with recommended self-care is a principal reason for suboptimal glycemic control and increased morbidity in adolescents with Type 1 Diabetes Mellitus. A number of studies have looked at interventions to improve compliance. The results have been disappointing, but it does appear that approaches which directly address emotional, social, and family dysfunction are more effective than those which reinforce technical education. We selected a population of poorly controlled adolescents in the endocrinology clinics of the University of Texas – Houston and attempted to identify factors leading to noncompliance, and to evaluate the relative effectiveness of two extant interventions, one technical and one psychosocial. Non- compliant adolescents were more often socially disadvantaged, and both the technical and the psychosocial interventions seemed effective for the patients who used them, though neither improvement was statistically significant
- Clinical Diabetes and Diagnostic Approaches, Diabetes and its Complications, Emerging Focus in Diabetes Research
Location: Birmingham, UK
Chair
Rachel Knott
Reader
Co-Chair
Nicolette Houreld
Lecturer
Session Introduction
Rachel Knott
Robert Gordon University, UK
Title: The role of oxygen insufficiency in the onset and development of the vascular complications of diabetes
Biography:
Rachel completed her PhD in 1988 from the University of Aberdeen. She carried out post-doctoral work at the Rowett Research Institute and at the Department of Ophthalmology in the University of Aberdeen. She is currently a reader within the School of Pharmacy & Life Sciences at Robert Gordon Univeristy and is the Graduate School Leader for the Faculty of Health & Social Care. She has published over 50 papers in reputed journals and regulary reviews for journals of international repute.
Abstract:
The ability of oxygen to be delivered to and utilised by cells is of fundamental importance to their ability to survive and function within normal parameters. Regulatory mechanisms within the cell provide a range of tools to facilitate the acquisition and utilisation of oxygen in such a way that the ability of the cell to function within normal parameters is not compromised. The regulation of blood flow, changes in pressure and high, and/or fluctuating concentrations of glucose will affect the ability of cells to metabolise glucose and will be of particular significance if the cell has high energy demands. Endothelial cells form the lining of the vasculature and are influenced by conditions within the diabetic milieu resulting in impaired function leading to the vascular dysfunction. Using isolated endothelial cells and a retinal vascular explant model, results will be presented to demonstrate the key role that oxygen plays in the ability of endothelial cells vessels to proliferate in a wound model. The increase in migration and proliferation resulting from decreased oxygen tension will be contrasted with the detrimental effect that high glucose concentration has on the response. In addition data demonstrating the role of anti-oxidants in the amelioration of glucose-mediated damage will be presented and the role of hyperoxia for the treatment of recalcitrant ulcers will be discussed to highlight the significance of oxygen to the onset, progression and treatment of the vascular complications of diabetes.
Haobo Li
The University of Hong Kong, Hong Kong
Title: Diabetes Abolishes Ischemic Postconditioning Cardioprotection by Impairing AdipoR1/Caveolin-3/STAT3 Signaling
Biography:
Haobo Li has completed his Ph.D. from Department of Anaesthesiology, The University of Hong Kong, Hong Kong SAR China, and he is now a research scientist in the same department and honorary assistant professor in Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China. His major focus of research is the mechanism of myocardial ischemia reperfusion injury and ischemic postconditioning cardioprotection against myocardial ischemia reperfusion injury, particularly, of diabetic hearts. He has published more than 20 peer-reviewed papers and services as a reviewer for more than 4 reputed journals and grant.
Abstract:
Ischemic postconditioning (IPo) protects against myocardial ischemia reperfusion injury (MIRI) by activating signal transducer and activator of transcription 3 (STAT3) in non-diabetes, but lost its effectiveness in diabetes in which cardiac STAT3 activation is reduced concomitant with malfunction of adiponectin. Here, we found that IPo increased post-ischemic cardiomyocyte-derived adiponectin and enhanced mitochondrial STAT3 (mitoSTAT3) activation, and improved myocardial mitochondrial biogenesis and reduced oxidative stress, and eventually attenuated MIRI and improved cardiac functional recovery, in wild-type (WT) but not in adiponectin knockout (Adipo-/-) mice. Recombinant globular adiponectin (gAd) reversed the reduction of hypoxic postconditioning (HPo)-induced cardioprotective effects in cardiomyocytes isolated from Adipo-/- mice, but all these effects of adiponectin supplementation were abolished respectively by either specific STAT3 or adiponectin receptor 1(AdipoR1) gene knockdown, or caveolin-3 disruption. Adiponectin overexpression restored IPo cardioprotection by activating STAT3 in 4-week type-1 diabetic where AdipoR1 and Cav3 were functionally interactive, but not in 8-week diabetic rats whose cardiac caveolin-3 was severely reduced and AdipoR1/ caveolin-3 signaling impaired. Together, our data indicated that, under non-diabetic condition, IPo, by increasing cardiac adiponectin, activates mitoSTAT3 through AdipoR1/caveolin-3 to confer cardioprotection, while under diabetic condition, reduced adiponectin and impaired AdipoR1 and caveolin-3 interaction leads to the loss of IPo cardioprotection.
Dongyun Shi
Fudan University, China
Title: MitoPBN prevents reactive oxygen species-mediated mitochondria abnormalities and metabolic reprogram in diabetic mice
Biography:
Dr. Dongyun Shi obtained her PhD degree in Kings College , University of London, in 2007. She is currently an associate professor and a principal investigator at Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University. Her current research interests focus on the relationship of redox regulation and the metabolic diseases, including diabetes and cancer. She has published more than 20 papers in reputed journals and has been serving as committee member of Chinese Free Radical Biology and Medicine, associate deputy director of Shanghai Free Radical Biology and Medicine Committee.
Abstract:
Mitochondrial dysfunction and reactive oxygen species (ROS) have been implicated in the diabetes process, however the underlying mechanisms are still unclear. Our previous results has shown ROS-mediated glucose metabolic reprogram induces insulin resistance in type 2 diabetes. In this study, we using MitoPBN, a mitochondrial targeted free radical scavenger, study the role of mitochondrial-derived ROS in the occurrence of diabetes. By using STZ-induced type 2 diabetic mice, we found that the diabetic mice showed an increased oxidative stress level in parallel with the raised blood glucose and impaired glucose tolerance. Meanwhile, the mitochondria-related protein, such as SIRT3, mitochondria fusion protein MFN-1 and 2, was dysregulated, thus contributing to the impaired respiratory ability and declined adenylate energy charge. In concordance with the mitochondria dysfunction, the glucose metabolism was disordered. MitoPBN treatment reduced NADH:NAD+ ratio, activated the SIRT, PCG-1α and phospho-AMPK, enhanced respiratory ability and increased adenylate energy charge so that alleviated ROS induced-mitochondria dysfunction. MitoPBN also increased glycolysis while decreased gluoconeogenisis, reversing the ROS induced-metabolic reprogram in diabetic mice. Our study suggests mitochondria-derived ROS play an important role in occurrence of diabetes. MitoPBN could be a potential drug to treat diabetes by improving mitochondrial bioenegetis ability and preventing ROS induced metabolic disorder
Shuxing Wang
Guangdong Entomological Institute, China
Title: A Correlative Relationship between Chronic Pain and Insulin Resistance in Zucker Fatty Rats: Role of Downregulation of Insulin Receptors
Time : 12:15-12:35
Biography:
Shuxing Wang completed his PhD from Zhongshan University and postdoctoral studies from Harvard Medical School, Massachusetts General Hospital. He has published more than 45 papers in reputed journals.
Abstract:
Epidemiological studies and meta-analyses report a strong relationship between chronic pain and abnormalities in glucose metabolism, but the exact relationship between chronic pain and insulin resistance in type-2-diabetes (T2D) remains unclear. Using a model of neuropathic thermal and tactile hypersensitivity induced by chronic constriction sciatic nerve injury (CCI) in Zucker diabetic fatty (ZDF) and Zucker lean (ZL) littermates, we compared the recovery period of hypersensitivity and the progression of T2D and studied the possible involvement of insulin receptors (IR) in the comorbidity of these two conditions. We found that besides a lower nociceptive thresholds to thermal and mechanical stimulation in naïve ZDF than in ZL littermates at 6 weeks of age, it took a longer time for CCI-induced nociceptive sensitivity to restore in ZDF rats. Meanwhile, nerve injury accelerated the progression of T2D in ZDF rats, demonstrated by an earlier onset of hyperglycemia, more severe hyperinsulinemia, and a higher concentration of glycosylated hemoglobin (HbAlc) 6 weeks after CCI. IR-immunoreactive cells were located across the central nervous system (CNS) and skeletal muscles. There was a low level of IR expression in skeletal muscles of naïve ZDF rats. In contrast, CCI reduced the IR expression in skeletal muscles as well as the ipsilateral spinal cord, primarily in the dorsal horn. In conclusion, our data suggest that the relationship between insulin resistance and chronic pain in ZDF rats is bidirectional and an impaired IR signaling system may be implicated in this reciprocal relationship.
- Diabetes and Associated Diseases, Compimentary and Alternative Medicine Therapy
Location: Birmingham, UK
Chair
Belma Turan
Professor
Co-Chair
Omo Ojo
Senior Lecturer
Session Introduction
Nicolette Houreld
University of Johannesburg, South Africa
Title: Photobiomodulation at 660 nm alters the expression of cell adhesion molecules and extracellular matrix proteins in a diabetic wounded fibroblast cell model
Biography:
Dr. Nicolette Nadene Houreld N.Dip (TWR), B.Tech (TWR), M.Tech (TWR), D.Tech (UJ) Biomedical Technology was born in Johannesburg, South Africa. She graduated from the Laser Research Centre, Faculty of Heath Sciences, University of Johannesburg in 2007 with her doctoral degree in Biomedical Technology and became a full time senior researcher and lecturer in the Laser Research Centre in 2009. She received her NRF (National Research Foundation, South Africa) Y2-rating in 2012.Dr Houreld has supervised and co-supervised 8 honours, 8 masters and 4 doctorate students within the Laser Research Centre and other departments within the University of Johannesburg. She has secured external funding towards projects in the Laser Research Centre and has reviewed both National and International grant applications. Over the last 11 years she has published 34 peer-reviewed accredited national and international articles, 17 conference proceedings, 4 book chapters and 1 book, and reviews articles for numerous international journals. Dr Houreld serves on various research-related university and science council committees, and is on the editorial board for the journal Photomedicine and Laser Surgery. She is currently on the executive committee as treasurer for the World Association for Laser Therapy (WALT). She has presented at and been invited to present and give workshops at a number of international conferences
Abstract:
Diabetes was declared a global burden by the International Diabetes Federation, with 382 million cases worldwide in 2013. Diabetic foot ulcers require extensive treatment and impacts heavily on patients quality of life. The ulcer recurrence rate over five years is as high as 70% and often necessitate amputation. The use of lasers and light (photobiomodulation) in medicine has made great strides and today photomedicine is practiced in a wide variety of fields, including the treatment of diabetic foot ulcers. Advances in the area of photobiomodulation continues to revolutionize and transform our world and the medical industry. The use of photobiomodulation at 660 nm with 5 J/cm2 on gene profile of 84 genes was investigated by real-time reverse transcription (RT) quantitative polymerase chain reaction (qPCR) in diabetic wounded skin fibroblast cells (WS1). The expression of various cell adhesion molecules and extracellular matrix proteins was modulated by photobiomodulation; eighteen genes were upregulated, while 31 genes were downregulated. There is a definite need to generate new treatment modalities to improve diabetic wound healing, and photobiomodulation has an unmistakable place in this. It would be ignorant to emasculate a multidisciplinary approach, and photobiomodulation needs to be adequately and critically studied alongside existing treatments in a clinical environment for its benefits to be properly recognized.
Lydiya Thomas
Aberdeen Royal Infirmary, UK
Title: The use of the Problem Areas In Diabetes (PAID) scale amongst patients with Type 2 diabetes
Biography:
Lydiya Thomas has completed her MBChB in 2015 from the University of Aberdeen. She is currently working as a Foundation Year 1 trainee in Aberdeen Royal Infirmary. This project was done as part of her final year medical student elective at the Christian Medical College Vellore, India.
Abstract:
The purpose of this study is to establish the prevalence of Diabetes-Specific Psychological Distress (DSPD) among patients with Type 2 diabetes Mellitus (T2DM) using the "Problem areas in diabetes" (PAID) scale at a tertiary hospital in south India. Other objectives include observing the relationship between socio-demographic factors and DSPD and finally exploring the level of acceptance of the PAID scale by Asian Indian patients.
Malcolm Carruthers
Medical Director of the Centre for Men’s Health, UK
Title: Parallels between Insulin Resistance and Testosterone Resistance: Another Facet of the Metabolic Syndrome?
Biography:
Founder and Chief Medical Consultant to the Centre for Men's Health, Professor Malcolm Carruthers has spent 30 years on research into testosterone treatment. He is adjunct professor at the Alzheimer's and Aging Department, Edith Cowan University, Western Australia
Abstract:
Insulin resistance in type 2 diabetes is a long-established fact and a target for therapeutic intervention. We present the case for there being similar resistance to testosterone causing a relative deficiency in the majority of cases of clinical onset of symptoms of deficiency of this hormone in the adult or comorbid conditions, especially metabolic syndrome. There are many parallels between resistance to the two hormones. This is seen in aetiology, age of onset, genetics, ethnicity, heredity, familial influences, association with obesity, links with viral diseases, and autoimmune conditions. Like diabetes, androgen deficiency can arise before birth, in early life, resulting in early onset, or later on leading to adult onset, with resistance playing a greater role. Similarly treatments such as weight loss and exercise have the effect of reducing resistance to both hormones. Clinical observations suggest that the duration of action of a standard dose of either pellet implants of testosterone, or an injection of testosterone undecanoate, might be a suitable measure of resistance to this hormone. Because of similar causation and co-existence of resistance to these two hormones in metabolic syndrome it is suggested that this may be new facet of the condition which because of its association with the male chromosome could be re-named as Syndrome-Y
Yusuf Ozturk
Anadolu University, Turkey
Title: Experimental Models of Diabetes, Complications, Alternative and Complementary Approaches
Biography:
Professor Yusuf Ozturk has completed his PhD from Ankara University in 1985. He was the former director of Graduate Institute of Health, and is now the head of Department of Pharmacology and the dean of the Faculty of Pharmacy, Anadolu University. He has published more than 160 papers in reputed journals cited around 1800 times and has been serving as an editorial board member of repute. Participating many scientific juries, boards and commissions, he has various national and international awards and prizes, acknowledging top and distguished review service
Abstract:
Diabetes is an important metabolic disease affecting many people worldwide. Current medical problems are the management of long-term complications as well as the management of coexistence of other chronical diseases such as depression, etc. Some of this coexistent diseases may occur as a complication diabetes. Conventional therapies may not be sufficient in the management of such complicated clinical cases of diabetes. On the other hand, some of drugs used for the management of psychiatric drugs may impair glucose metabolism creating diabetic predisposition in patients. So, some alternative and complementary approaches seem to be required. Most of diabetic complications can be observed in experimental models of diabetes. Experimental models of diabetes may be employed not only for the investigation of diabetes and diabetic complications, but also for the study of drug effects on glucose metabolism and diabetic complications. These experimental techniques also allow to investigate alternative and complementary approaches. Therefore, this presentation will focus on experimental models of diabetes in relation to diabetic complications and alternative/complementary approaches discussing data from our laboratories.
Nuray Yazihan
Ankara University, Turkey
Title: Macrophage polarization and hypoxia in obesity
Time : 14:30-14:50
Biography:
Prof. Dr. Nuray Yazihan (MD) is physiologist and pathophysiologist and currently works in Ankara University,Faculty of Medicine, Internal Medicine Division, Pathophysiology Department. Her current research areas are inflammatory aspects of ischemia, hypoxia, cancer and metabolic diseases. She has projects about novel inflammatory molecules in cell/organ defense systems and special interest in erythropoietin and midkine. She has extensive experience in developing animal and in vitro/ex vivo organ and cell culture models and molecular tecniques. She has also studies in mathematical modelling , risk analysis and health economics. She has been leading national and international projects, and being as advisor in different projects of national and international public sector.
Abstract:
Obesity is a complex disorder which also predisposes subjects to other diseases including type 2 diabetes. Inflammation is the common key feature in both diseases. Evidence exists that the inflammation could be induced by hypoxia or vice versa. A hypoxic and inflammatory phenotype has been reported in adipose tissue during obesity. The cellular response to hypoxia is principally regulated by hypoxia-inducible factors (HIFs). Therefore, the present part focuses HIFs-mediated effects of hypoxia in adipocyte inflammation and macrophage polarization associated with obesity pathogenesis.
Mehtap Kacar
Yeditepe University, Turkey
Title: The roles of macrophages polarization in the pathophysiology of diabetic atherosclerosis
Biography:
Dr. Mehtap KAÇAR (MD) completed her PhD at the Ankara University, Faculty of Medicine in pathophysiology in 2002. She was recruited to the position of Associate Professor in the pathophysiology in 2014. Currently she works at Yeditepe University, Faculty of Medicine, in Physiology Department. Her researchs usually focus inflammatory aspects of heavy metal toxicity, ischemia, hypoxia and trace elements. She is responsible for coordination of phase II academic education at Yeditepe University Faculty of Medicine. She is assistant manager in Experimental Research Center at Yeditepe University
Abstract:
Diabetes is associated with increased risk for atherosclerosis. Atherosclerosis is a chronic inflammatory disease. The increased inflammation and accelerated atherosclerosis are observed in diabetic patients. The inflammatory response in the pathogenesis of atherosclerosis is generated by interactions between plasma lipoproteins, monocytes/macrophages, T lymphocytes, endothelial cells, and smooth muscle cells as well as the extracellular matrix of the arteries. Macrophages are the most important cells in pathogenesis of atherosclerosis, and play main roles in generation of foam cells which produce inflammatory mediators. M1 and M2 macrophages present in the atherosclerotic plaques. M1 macrophages play an important roles in the development of plaque, on the other hand M2 macrophages help to regression of inflammation. Hyperglycemia and advanced glycation end products (AGEs) effect macrophages polarization.
Julieta Palomeque
University of La Plata, Argentina
Title: The heart with impaired glucose tolerance: a time bomb
Biography:
Julieta Palomeque is working as an assistant professor in National University of La Plata. She is a member of International Society for Heart Research (ISHR). Her PHD work focus on the study of excitation contraction coupling (ECC) through measuring intracellular ions by epifluorescence and confocal microscopy. During her postdoctoral residency at Dr. R. Hajjar´s laboratory (Massachusetts General Hospital & Harvard Medical School, Boston, USA) she gained expertise in heart failure models, gene transfer, fluorescence techniques and intracellular ions measurements. Currently she is studying the basis of diabetic cardiomyopathy in a prediabetic model.
Abstract:
Heart failure and arrhythmias occur more frequently in patients with type 2 diabetes (T2DM) than in the general population. T2DM is preceded by a prediabetic condition, characterized by impaired glucose tolerance or impaired fasting glucose, marked by elevated reactive oxygen species (ROS) and subclinical cardiovascular defects. Moreover, multifunctional Ca2+ calmodulin-dependent protein kinase II (CaMKII) is ROS-activated and CaMKII hyperactivity promotes heart disorders. However, a link between prediabetes and CaMKII in the heart is unprecedented. The aim of the present study was to prove the hypothesis that increased ROS and
contribute to the initial events in the development of heart failure and arrhythmogenic mechanisms, life-threatening in the overt T2DM
Alla Ovsyannikova
Institution of Internal and Preventive medicine, Russia
Title: MODY 2 diabetes in Siberia: 3 years of follow up
Biography:
Ovsyannikova Alla finished Novosibirsk Medical University, Russia with honors, had two certificates of specialists: internal medicine and endocrinologist. She is PhD since 2013 year (dissertation work was "Diabetes mellitus in young people: some clinical and molecular genetic aspects "). Now she is working endocrinologist and scientist in Scientific - Research Institute of Therapy and Preventive Medicine. Research work is about monogenic types of diabetes mellitus (especially MODY diabetes) in young patients. This researcher work was supported by 3 grants and 2 awards. She published more than ten abstracts in national refereed journals, 15 abstracts in conference with international participation
Abstract:
We observed 11 patients (8 families). We diagnosed MODY 2 diabetes during the molecular genetic testing (direct automatic sequencing) of glucokinase gene. Follow-up was of 3 years. All patients had once a year a full clinical examination, blood samples for biochemical research, determination of C-peptide and TSH, antibodies to b- cells, microalbuminuria, abdominal ultrasound, heart and thyroid ultrasound, examination of ophthalmologist.
Biography:
He is an assistant professor in Ahwaz University of Medical Sciences, Iran holding PhD in nutrition sciences graduated in Newcastle University, UK. His research interests are mainly “Nutrition and Oral health” and “Diabetes and periodontal disease”. He has some undergoing researches in these fields. He is also as a lecturer in Ahvaz University and teaching some nutritional modules (advanced nutrition, nutrition counseling and education, nutrition physiology, nutrition and oral health, advanced English,…) for PhD, Msc and Bsc students. He is also supervising some PhD, MSc and BSc students in their thesis.
Abstract:
Diabetes mellitus and periodontitis are two chronic and common diseases with close relationship together affecting public health and quality of life. The aim of this study was to investigate the effect of resveratrol supplementation on blood glucose, triglyceride, periodontal status and inflammatory markers in type 2 diabetic patients with periodontal disease. This double-blind clinical trial study was conducted on 43 diabetic patients with periodontitis referred to the Endocrinology Clinic in Ahvaz, Iran. All subjects were randomly assigned into two groups of intervention and control and received either 480 mg/d resveratrol or placebo capsules (2 PCs) for four weeks. All subjects underwent non-surgical periodontal therapy during the intervention period. Anthropometric parameters, 24-hour dietary recall, fasting blood sugar, insulin, insulin resistance (HOMA-IR), triglycerides, pocket depth (PD), IL6 and TNFα were evaluated in all subjects pre- and post-intervention.The mean serum levels of fasting insulin and insulin resistance (HOMA-IR) were significantly (P=0.02, P=0.045, respectively) lower in intervention group compared with control group (10.42 ± 0.28 and 10.92 ± 0.9; 3.66 ± 0.97 and 4.49 ± 1.56, respectively). Moreover, significant difference (P < 0.001) was obtained in the mean pocket depth (PD) between intervention and control groups (2.35 ± 0.6 and 3.38 ± 0.5, respectively) post-intervention. In intervention group, the mean serum level of IL6 was reduced significantly (P= 0.039) post-intervention (1.58 ± 1.06 and 2.19± 1.09). No significant differences were seen in the mean levels of fasting blood sugar, triglycerides, IL6 and TNFα between two groups post-intervention. It is suggested that resveratrol may be recommended as adjuvant therapy along with non-surgical periodontal treatment in diabetic patients with periodontal disease
Fransiska Rungkat Zakaria
Bogor Agricultural University , Indonesia
Title: R-CBSTIMSDS- Consumption of Black Soybean Tofu Improved Metabolic Syndromes of Diabetic Subjects
Biography:
Prof Fransiska Rungkat Zakaria has completed his PhD at the age of 41 years from University of Lorraine, France. She is a teaching and research staff in the Department of Food Sciece and Technology Bogor Agricultural University Bogor Indonesia. He has published several papers in reputed journals and has been serving as an editorial board member of reputed journal.
Abstract:
Normal and easy to find food item for diabetics should be available and accesible. Tofu has important role in providing perfect food for the diet of diabetics but in general made of yellow soybean. Black soybean is widely used to produce soysauce in Asian countries. Its use for tofu is still limited inspite of its excellent nutrient, prebiotic and bioactive compound but trace digestible carbohydrate content. In this research, black soybean tofu productions were optimized in the university production laboratory. The tofu product has purple color and were given in form of general simple soup containing 85 grams tofu to 15 diabetic subjects. There were 11 diabetic subjects participating in control group. The participating subjects were patients of a local neighbourhood clinic and all signed the informed consents. The tofu soup were disributed for 30 days daily while observing the subjects acceptance and general condition. Blood collections were done before and after intervention by certified nurses for analysis in the department laboratory. Consumption of black soy tofu resulted in declining of fasting glucose level (P=0.23), reduced HbA1c level and increase in plasma antioxidant status (P=0.19). SGOT / SGPT tests showed a decrement (p < 0.05), from 14.27 ± 3.81 / 21.07 ± 6.73 (U/L) to 12.73 ± 2.34 / 18.60 ± 4.29 (U/L). There were no changes in blood DNA-adduct level. We concluded that consumption of black soybean tofu contribute to improvement in overall health of diabetic subjects and may serve as important preventive food.
Mohsen Khalid
Egyptian National Institute of Diabetes and Endocrinology, Egypt
Title: Study of metabolic and some hormonal aspects among pubertal type 1 diabetic girls
Biography:
Prof. Dr. Mohsen Khalid has graduated from faculty of medicine Cairo University in November 1980. He has completed his Master degree in Internal Medicine May 1986, and then he completed his Medical Doctorate in Internal Medicine November 2003. He is a consultant of Diabetes and Endocrinology in the Egyptian National Institute of Diabetes and Endocrinology. He has published more than 20 papers in reputed journals. The research interest of Prof. Dr. Mohsen Khalid is Genetics of Diabetes, diabetic complications and how to assist diabetic patients to live a good life with life style modification and medical treatment
Abstract:
The onset of type 1 diabetes before menarche was a risk factor for the subsequent development of hyperandrogenic disorders. It has been also suggested that the use of exogenous insulin to treat type 1 diabetes mellitus in those patients may contribute to the development of PCOS. Abnormal lipid levels were also reported in children with type 1 diabetes mellitus during pubertal years. Aim of Work: This study was designed to investigate metabolic and some hormonal changes in relation to puberty among type 1 diabetic girls. Subjects and Methods: The study was carried out on 60 girls, 40 of them were type 1 diabetic patients (the diabetic group), subdivided into 2 groups (according to age and Tanner breast staging) ,and 20 of them were normal healthy girls (the control group), also subdivided into 2 groups ( according to age and Tanner breast staging). All girls were subjected to full history taking, thorough clinical examination, estimation of fasting blood glucose and HbA1c (as an estimation for glycemic control), lipid profile, hormonal profile (FSH, LH and free testosterone) in addition to pelvic ultrasound
- Genetics and Transplantation of Diabetes, Therapy for Diabetes
Location: Birmingham, UK
Chair
Lixin Li
Central Michigan University, USA
Co-Chair
Haobo Li
The University of Hong Kong, Hong Kon
Session Introduction
Jae Woong Sull
Eulji University School of Health Science, South Korea
Title: Effects of fasting glucose levels on the association between CDH13 (rs4783244) and adiponectin among Korean population
Biography:
Dr. Jae Woong Sull (MHS, Ph.D.) is an Assistant Professor at Eulji University. He obtained both his Ph.D. degree in the Genetic Epidemiology and Master of Health Science degree in Epidemiology from Yonsei University in Korea. He was also trained as a postdoctoral fellow in genetic epidemiology at Johns Hopkins Univiersity in USA. He has published over 50 papers in peer-reviewed journals.
Abstract:
Adiponectin is associated with obesity and insulin resistance. Several genome-wide association studies of adiponectin levels have identified candidate genes, including the CDH13 gene. The study objective was to examine the association of serum adiponectin levels (or hypoadiponectinemia) with SNP rs4783244 in CDH13 gene considering fasting blood glucose levels. This study included 2,005 subjects. Hypoadiponectinemia was defined as the lowest quartile of adiponectin. The CDH13 gene SNPs were genotyped via the TaqMan reaction. The multivariate linear regression models and multiple logistic regression analysis were performed. The majority of individuals were middle-aged. Subjects with the GG genotype had a 2.44-fold (range 1.97–3.03-fold) higher risk of hypoadiponectinemia than subjects with the TG/TT genotype. When analyzed by fasting blood glucose levels, the CDH13 association was much stronger in male subjects with pre-diabetes (odds ratio, 10.96; 95% confidence interval, 4.31–27.88; P < 0.0001). Our results suggested that the association between CDH13 and adiponectin can be modified by fasting blood glucose levels.
Hande Ozge Altunkaynak
Baskent University School of Medicine, Turkey
Title: The Impact of adipose tissue hypoxia on insulin sensitivity
Biography:
Hande Ozge Altunkaynak (PhD) is pharmacologist and currently works in Baskent University, Faculty of Medicine, Department of Medical Pharmacology. Her research work involves the cardioprotective mechanisms on the response of hearts against ischemia reperfusion injury, particularly, of diabetic hearts.
Abstract:
A growing body of evidence indicates that adipose tissue could become hypoxic in the obese state. The response to hypoxia is mainly regulated by oxygen-sensitive transcription factors also known as hypoxia-inducible factors (HIFs). Among these, three members of the family are described as HIF-1, HIF-2 and HIF-3. Despite HIF-1α and HIF-2α target many common gene expression, HIF-1α is rather associated with glycolytic gene expression and hence participates different roles in the regulation of insulin sensitivity and glucose tolerance. In addition, it is clear from recent studies by using genetically modified mice that HIF-1α is also involved in the insulin signalling pathway and insulin secretion.Therefore, the present part focuses the impact of hypoxic signalling pathway driven by HIFs in adipose tissue on insulin sensitivity and glucose tolerance.
Sunita Singh
Banaras Hindu University, India
Title: KCNJ11 gene polymorphism E23K (rs5219): An Association study in Type 2 diabetes mellitus in Indian population of eastern Uttar Pradesh
Biography:
Sunita Singh, Ph.D. is Associate Professor in Banaras Hindu University, India. She did her Ph.D. in Biochemical and Evolutionary Genetics and postdoctoral studies in Population Genetics from Banaras Hindu University. Dr. Singh’s current research work involves genetics of complex diseases, including genetics of Type 2 Diabetes and molecular pathology of multiple cancers. Dr. Singh has authored/co-authored 23 papers in the field of Molecular evolution, Type 2 Diabetes and Carcinogenesis.
Abstract:
Despite a very large burden of type 2 diabetes in India, insight into the genetic architecture of Type 2 Diabetes (T2D) in Indian population of eastern Uttar Pradesh is currently lacking. Genome-wide association scan studies (GWASs) have led to the discovery of several novel genetic markers associated to Type 2 diabetes (T2D). Multiple studies have demonstrated reproducible association of several genetic markers (SNPs) with T2D risk, each making a modest contribution to the overall risk mainly in European populations. Only a few investigations for T2D susceptibility genes have been reported in South Asians. Recent studies suggest that the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-sensitive potassium (KATP) channel, may also be a candidate diabetogenic gene. The E23K KATP channel polymorphism has received much attention recently due to its higher frequency in the Caucasian type-2 diabetic population. The variant E23K (rs5219) of KCNJ11 has been demonstrated to have modest association with T2D in European, Japanese and North Indian populations. In the present investigation, we have studied the association of KCNJ11 (E23K) (rs5219) gene polymorphism to T2D in the Indian population of eastern Uttar Pradesh in 240 cases and 229 ethnically matched control subjects. Our data show weak association to T2D with odds ratio 1.086 (95% CI 0.832-1.416; P = 0.544). Our data also show association to T2D under co-dominant model only.
Zipeng Liu
The University of Hong Kong, Hong Kong
Title: Combining genomic and genetic knowledge to discover the underlying mechanism of diabetic cardiac dysfunction
Biography:
Zipeng LIU, MSc and PhD in Bioinformatics and Pharmacogy at the University of Hong Kong. His research interest lies in the application of bioinformatic approaches to study diabetic cardioprotection. He has published related research as either first author or co-authors on peer-reviewed journals such as Nucleic Acids Research, Diabetes and Cardiovascular Diabetology.
Abstract:
Myocardial infarction (MI) is a major cause of sudden death and one of the most common perioperative complications prevalent in diabetes mellitus. The underlying biological process is different from that in non-diabetes partially due to increased oxidative stress in diabetes. Cardioprotective interventions that are effective in non-diabetic patients loss their effectiveness in diabetic patients, which exacerbates the susceptibility of diabetic hearts to myocardial ischemia reperfusion injury (IRI). However, the mechanism is still largely unclear. The rapid evolution of genomic and genetic approaches, such as microarray and genome-wide association study (GWAS), provides additional insights into complex disease studies. Here, by combining gene co-expression network analysis from a set of microarray profiling and MI/type 2 diabetes (T2D) associated gene sets from GWAS, we built a transcription factor (TF) based regulatory network to explore the pathological behavior. The resulting network using this combination method was validated by high enrichment in several well-documented pathways of diabetic cardiac pathology (e.g. PI3K/Akt and Jak/Stat3 signaling pathway) and was also significantly improved than that using only genomic or genetic data individually. This TF-based network also revealed numbers of previously unreported protein interactions linking distinct pathways, among which we verified a relation between Stat3 and Hif-1α in diabetic myocardial IRI models. Thus, our study showed potency of combining knowledge from genomic and genetic studies in discovering the hidden mechanism in diabetic cardiac dysfunction.
Biography:
Gopeshwar Narayan has completed his Ph.D. from Banaras Hindu University in 1994; and postdoctoral studies from Institute of Human Genetics, Frei University, Berlin, Germany and Columbia University, New York, USA. Currently he is working as Professor in the Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India. He has published more than 50 papers in reputed journals in the fields of Animal Genetics, Cancer Genetics and Type 2 Diabetes.
Abstract:
Type 2 diabetes (T2D) has become a major health problem throughout the world. Compared with European populations, Asians develop diabetes at younger age, at lower degrees of obesity, and at much higher incidence rates given the same amount of weight gain. Recent Genome Wide Association studies (GWAS) in populations of European descent have identified several single nucleotide polymorphisms (SNPs) associated with T2D. The variants have been identified to be differentially associated with T2D in different ethnic groups. The reasons for these ethnic variations towards the risk of T2D have to be understood in order to delineate the role of ethnicity in the background of same genetic elements. We have investigated the association of TCF7L2 rs12255372 (G/T) and PPARγ rs1801282 (C/G) gene polymorphism (SNPs) with T2D in Indian population of eastern Uttar Pradesh. Genomic DNA was extracted from peripheral blood of 434 cases and 292 controls for TCF7L2 (rs12255372) and PPARγ (rs1801282) genes. Gene polymorphisms were analyzed by PCR-RFLP. We compared the genotype distributions and allelic frequencies of each variant in the studied population between cases and controls. Odds ratio (OR) at 95% confidence interval (CI) was determined to describe the strength of association by 2x2 and 2x3contingency table. We report that while allele frequency distribution for TCF7L2 polymorphism is statistically significant (OR = 1.33, 95% CI 1.029- 1.738, P=0.03), it is not significantly different for PPARγ (OR-0.98, 95% CI 0.7O59-1.366, P=0.98) between Type2 diabetic patient and the control groups. Our findings suggest that while TCF7L2 gene polymorphism increases susceptibility to T2D, the PPARγ polymorphism does not show significant association with T2D in the Indian population of eastern Uttar Pradesh. To our knowledge this is the first report in this population and provides valuable information for comparison with other ethnic groups as well as in determining disease susceptibility in this population.
Khalid K Alharbi
King Saud University, Saudi Arabia
Title: Obesity and the incidence of apolipoprotein E polymorphisms in an assorted population from Saudi Arabia population
Biography:
Khalid K Alharbi has completed his PhD in 2004 from University of Southampton. He is a professor and chairman of Saudi society for clinical labaoratory sciences in college of Applied Medical Sciences at King Saud University. He has published more than 50 papers in reputed journals and has been serving as an editorial board member of repute. He is actively involved in Deanship of Scientific Research and National Plan for Scince and Technology projects. His area of interest was type 2 diabetes, obesity, familial hypercholesterolemia and consanguineous problems.
Abstract:
Obesity is known to be a complex disorder caused by both genetic and environmental factors. Patients with obesity tend to develop cardiovascular disease and type 2 diabetes. Earlier studies have revealed that obesity is associated with genetic variations like those found in apolipoprotein E (APOE), a genetic determinant of obesity-related factors and lipid profiles. Hence, in the present study we aimed to perform a molecular characterization of APOE gene polymorphisms found in obese patients within a Saudi population. A case-control study was performed on 198 cases and 198 controls, selected from participants at the King Saud University. TaqMan genotyping was performed to investigate polymorphisms in the APOE gene. The present study identified that APOE polymorphisms were significantly associated with obesity in a Saudi population with the ɛ4 allele (p=0.0001). We found a statistically significant difference in the genotype distribution between cases and controls [for E3/E4: OR, 2.16 (95% CI: 1.19-3.91); p=0.009]. A significant difference was observed in the lipid profile parameters like triglycerides, low-density lipoprotein, and APOE alleles (p<0.001). Our results confirm that APOE variants are associated with obesity in a Saudi population.
Yuliia Klitsunova
Zaporizhia Medical Academy, Ukraine
Title: Sitagliptin as combination therapy in the treatment of inadequately controlled type 2 diabetes
Biography:
Klitsunova Yuliia, PhD is assistant professor of State Institution “Zaporizhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine”, Zaporizhzhia, Ukraine, where she covers endocrinology and cardiology projects. She holds B.S. and M.S. degrees in medicine from the Zaporizhzhia State Medical University. She is a member of EASD (reg.# 360234) and she has more than 9 years of experience in medicine. She is the author of more than 35 scientific articles and 1 guidelines for daily monitoring of blood pressure.
Abstract:
The purpose of this study was to evaluate the effects of sitagliptin 100 mg in the treatment of participants with type 2 diabetes mellitus who have inadequate glycemic control on metformin ≥1500mg/day. Materials and methods: Outpatients aged 52-72 years with type 2 diabetes. Patients were on metformin monotherapy (>=1500 mg/day) for >=8 weeks with a A1C >=7.5% and <=11.0% before treatment with sitagliptin. Glycemic efficacy endpoints were included the changes from baseline in A1C and FPG at week 26 and also Percentage of Participants Achieving a HbA1c of <7%. Other efficacy endpoints that were assessed include changes from baseline at week 26 in body weight, and some safety endpoints such as hepatic safety tests ALT and AST, total and direct bilirubin, renal failure tests - serum creatinite calculated using the CKD-EPI formula, urinary albumin/creatinine ratio. The efficacy and safety were retrospectively evaluated by comparison of laboratory values before and after the administration of sitagliptin and by review of adverse events after treatment.