Day 1 :
Keynote Forum
Toshihide Shima
Kyoto Prefectural University, Japan
Keynote: Hepatocellular carcinoma as a leading cause of cancer-related deaths in Japanese type 2 diabetes mellitus patients
Time : 09:00 - 09:30
Biography:
Toshihide Shima has completed his MD at the age of 24 years from Kyoto Prefectural University of Medicine. He is the vice president of Suita Hospital of Saiseikai, Imperial Gift Foundation, inc. He has published more than 10 papers on nonalcoholic steatohepatitis (NASH) and has been serving as an international member of American Association for the Study of Liver Diseases (AASLD).
Abstract:
We reported a cross-sectional study on causes of liver injury in Japanese type 2 diabetes mellitus (T2D) patients (J of Gastroenterology 48, 2013). We assessed overall and cause-specific mortality risk during follow-up of patients enrolled in JG 2013.
Methods: Of the 5,642 Japanese T2D patients who visited T2D clinics of nine hospitals in the original study, 3,999 patients were followed up for an average of 4.5 years. Expected deaths in T2D patients were estimated using age-speciï¬c mortality rates in the general population (GP) of Japan. Standardized mortality ratios (SMRs) were calculated to compare mortality between T2D patients and GP.
Results: All-cancer mortality was signiï¬cantly higher in T2D patients than in GP [SMR 1.58, 95% confidence interval (CI) 1.21–2.06], whereas all-cause mortality was comparable between the groups (SMR 1.10, 95% CI 0.93–1.32). Among malignancies, hepatocellular carcinoma (HCC) conferred the highest mortality risk in T2D patients (SMR 3.57, 95% CI 1.66–7.67). HCC-associated mortality risk in T2D patients remained significantly high (SMR 2.56, 95% CI 1.15–5.68) after adjusting for high positivity rates of hepatitis B surface antigen (1.7%) and anti-hepatitis C virus (5.3%). In T2D patients with platelet counts < 200 × 103/μl, SMR of HCC increased from 3.57 to 6.58 (95% CI 2.33–18.60).
Conclusions: HCC-associated mortality risk was the highest among all cancers in Japanese T2D patients. Regular follow-up may be important for T2D patients with platelet counts < 200 × 103/μl for early detection of HCC.
Keynote Forum
Sebastian Oltean
University of Exeter,United Kingdom
Keynote: Alternative Splicing in Diabetic Nephropathy and other Chronic Kidney Diseases
Time : 09:30 - 10:00
Biography:
Sebastian studied clinical medicine at “Iuliu Hatieganu” Medical School, Cluj-Napoca, Romania and trained as a junior doctor in Nephrology and Dialysis before moving to USA where he obtained a PhD from the University of Nebraska-Lincoln in 2004.This was followed by postdoctoral training at Duke University Medical Center (North Carolina, USA) where he became interested in studying the connections between alternative splicing and cancer. In 2008 he moved to the University of Bristol where he continued to study alternative splicing in vivo, with focus towards the importance of several genes splice isoforms (e.g VEGF, FGFR2) in cancer as well as kidney diseases and development of splice-based therapeutics. In 2012 he was appointed independent research fellow and principal investigator and developed his own research group in Bristol before moving to University of Exeter Medical School in 2017, where he is now a Senior Lecturer.
Abstract:
Alternative splicing (AS) has emerged in the post-genomic era as one of the main drivers of proteome diversity with at least 94% of multi-exon genes being alternatively spliced in humans. AS is therefore one of the main control mechanisms for cell phenotype, and a process deregulated in disease. Numerous reports describe pathogenic mutations in splice factors, splice sites or regulatory sequences; additionally, in many cases there is an abnormal proportion of splice isoforms (or novel isoforms) in disease compared to the physiological pattern, without an apparent driver mutation. It has therefore become essential to study how AS is regulated in physiology, how it contributes to pathogenesis and whether we can manipulate faulty splicing for therapeutic advantage. While the disease most commonly linked to deregulation of AS in several genes is cancer, there are many in-depth reports of pathogenic splice variants in diseases ranging from neuromuscular disorders to diabetes or cardiomyopathies. In recent years, a plethora of splice variants have been implicated in chronic kidney diseases as well. Examples of these and ideas on how to manipulate them for therapeutic benefit will be presented in this talk.
Keynote Forum
Megan Stevens
University of Exeter, United Kingdom
Keynote: The natural drug DIAVIT is protective in a type II mouse model of diabetic nephropathy
Time : 10:00 - 10:30
Biography:
I am currently working as a Research Fellow at the University of Exeter, UK as part of Dr Sebastian Oltean’s group. I have a background in the alternative splicing of VEGF-A as a therapeutic in chronic kidney disease. I am currently focused on exploring alternative splicing events in diabetic nephropathy, and how DIAVIT and other small molecules can be used to modulate splicing in a therapeutic manner.
Abstract:
Statement of the Problem: There is evidence to suggest that abnormal angiogenesis, inflammation, and fibrosis drive diabetic nephropathy (DN). However, there is no specific treatment to counteract these processes. We aimed to determine whether DIAVIT, a natural Vaccinium myrtillus (blueberry) and Hippophae Rhamnoides (sea buckthorn) extract, is protective in a model of type II DN. Methodology & Theoretical Orientation: Diabetic db/db mice were administered DIAVIT in their drinking water for 14 weeks. We assessed the functional, structural, and ultra-structural phenotype of three experimental groups (lean+vehicle, db/db+vehicle, db/db+DIAVIT), and the angiogenic and fibrotic pathways involved in the DIAVIT mechanism. Findings: Diabetic db/db mice developed hyperglycemia, albuminuria, and an increased glomerular water permeability; the latter two were prevented by DIAVIT. db/db mice developed fibrotic glomeruli, endothelial insult, and glomerular ultra-structural changes, which were absent in DIAVIT-treated mice. VEGF-A splicing was altered in the db/db kidney cortex, increasing pro-angiogenic VEGF-A165 relative to anti-angiogenic VEGF-A165b. This was partially reversed with DIAVIT. TNFα-induced nuclear translocation of p65-NFĸB in cultured glomerular endothelial cells was also prevented by DIAVIT. Conclusion & Significance: In conclusion, DIAVIT alters VEGF-A splicing and p65-NFĸB activation, rescuing the DN phenotype. This study highlights the therapeutic potential of natural drugs in DN through the manipulation of gene splicing and expression.
Keynote Forum
Adil Omar Bahathiq
Um-Alqura University, Saudi Arabia
Keynote: Metabolic Syndrome in young Saudi female
Time : 11:00 - 11:30
Biography:
Adil O. Bahathiq had initial experience of the research tools with Professors Ian Cooke and William Ledger at University of Sheffield, U.K. He found new data the Fallopian tube and epididymis for his Ph.D. Then he conducted a new line of research that helped and improved the health of the community. He has developed this area after years of experience in research, evaluation, teaching and administration both in hospital and educational institutions. This research area was chosen because of the lack of data relating to obesity and the metabolic syndrome in the children and adults of the Makkah community. The findings of this research have been beneficial to the authorities in the fields of education and health in Saudi Arabia.
Abstract:
It is ironic that as people continue to suffer from malnourishment and starvation in some poor parts of the world, others have gone to the other extreme of being overweight or obese particularly in developed, but also in developing countries. The modern world is faced with a terrifying new ‘disease’ that is ‘obesity’. As people get fatter, excess weight is now seen as unhealthy and socially damaging. Obesity can lead to a variety of conditions such as hypertension, hypertriglyceridemia, hypercholesterolemia and high glucose level. These conditions together are called metabolic syndrome.
The syndrome is a cluster of metabolic abnormalities and risk factors that significantly increase the risk of cardiovascular disease and diabetes. It is characterised by a group of metabolic risk factors which include abdominal obesity, atherogenic dyslipidemia, elevated blood pressure and insulin resistance or glucose intolerance. Metabolic syndrome is a state of chronic low-grade inflammation as a consequence of complex interplay between genetic and environmental factors.
The present data were the first to investigate the prevalence of metabolic syndrome among female school children and adolescents in the Makkah area. There were1356 participant’s (6 to 18 years) in this study. Body mass index, waist circumference, blood glucose level, lipid profile, and arterial blood pressure were determined. The Criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) were used to diagnose metabolic syndrome among participants. Among 1356 female participant, 15.2% were overweight and 15.3% were obese. The prevalence of metabolic syndrome was 17.1% overall, 62% in obese and 50% in overweight participants. An enormous population of Saudi children and adolescents, particularly females, have the potential to develop metabolic syndrome. We recommend a national obesity prevention program at to be implemented at community level to promote leaner and consequently healthier communities; lifestyle modification, and screening for risk factors for metabolic syndrome should be given special consideration.
- Track 1: Diabetes, Types and Symptoms
Track 4: Diabetes Chronic Complications
Track 5: Advanced Technologies & Treatments for Diabetes
Track 6: Metabolic Syndrome
Track 10: Current challenges in new therapies to diabetes complications
Track 14: Epidemiology and Public Health
Session Introduction
Yong - Fu Xiao
University of Rutgers, USA
Title: Cardiac, hepatic and renal complications in spontaneously developed diabetic nonhuman primates
Biography:
Yong-Fu Xiao Head of pharmacology at Crown Bioscience, Inc. and adjunct professor of Rutgers University. He has extensive experiences in cardiovascular and metabolic research. Before joining CrownBio, he was principal scientist and worked on gene and protein therapy for heart and metabolic diseases in Medtronic. Before Medtronic, his work focused on cardiovascular physiology and pharmacology and was Assistant Professor of medicine, Harvard University and Associate Biophysicist at Massachusetts General Hospital. He published over 110 peer-reviewed papers, reviews, book chapters and granted over 6 patents.
Yi-Xin (Jim) Wang senior vice president, Crown Bioscience Inc. Academia in physiology and pharmacology: postdoctoral fellow (Boston University) and assistant professor (Univesity of Tennessee at Memphis). Over 20 years working experience in major pharmaceutical companies (GSK, Roche, Schering/Bayer AG) and biotechnology Inc. (Arete) from preclinical R&D to Phase II. Specialized in cardiometabolic research with ~100 peer-reviewed publications.
Abstract:
Obesity can lead to insulin resistant and Type 2 diabetes mellitus (T2DM). Both obesity and diabetes are serious epidemic issues in developed and some developing countries. T2DM and obesity often complicate each other and escalate patients’ other healthiness. Cardiac, hepatic and renal complications of diabetes and obesity have widely been reported and studied for decades. However, the underlying mechanisms and interactions between obesity and diabetes have yet to be elucidated further. Nonhuman primates (NHPs) can spontaneously develop obesity and diabetes which are the highly valuable models for research to delineate molecular and cellular mechanisms of their pathophysiology. In our housed dysglycemic and dyslipidemic cynomolgus monkeys we evaluated cardiac, hepatic and renal complications. Echocardiography in diabetic NHPs showed left ventricular systolic and diastolic dysfunctions accompanied with left atrial hypertrophic remodeling, the phenotypes similarly to those found in diabetic patients. In addition, dyslipidemic and diabetic monkeys can develop nonalcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH) assembling to the human liver disease. We also evaluated diabetic nephropathy and its molecular mechanisms in diabetic NHPs with significantly high albuminuria. Transcriptome analysis of kidney biopsies showed differentially expressed genes (DEGs) with 75DEGs related to diabetic nephropathy, but only 1 nephropathy specific gene (LCT lactase) and 4 other DEGs were highly altered in diabetic monkeys with albuminuria. Signaling pathway analysis of the relevant DEGs and encoded proteins highlighted the role of a kidney failure, renal and urological diseases, and inflammatory diseases related network, in which the most pivotal gene in this network is Tumor Necrosis Factor, indicating that nephropathy is a disease closely related to inflammation and cell death. Therefore, noninvasive echocardiography and quantitative biomarker measurements in NHP models can be powerful translational tools for evaluation of obesity and diabetes complications and for investigation of potential novel therapies due to the pathophysiological similarity between NHP and humans.
Dragan Nikolic
Dragan Nikolic M, University of Belgrade, School of Medicine, Serbia
Title: Diabetes mellitus and obesity as a result of a disrupted Homeostatic Microbiome. New data on aetiopathogenesis of diabetes mellitus
Biography:
Dragan Nikolic M has his expertise in research of the Diabetes, insulin secretion, transplantation, pancreatic islets culture and influence of microorganisms on the onset of the diabetes, pancreatic infection and on pancreatic islets insulin secretion. Dr. Nikolic has presented new data that could be important factors in pathogenesis of diabetes. It was established that certain bacteria and fungi could penetrate the pancreas thus directly affecting insulin secretion, or indirectly, by secreting certain metabolites which via blood get into pancreas, leading to insulin resistance and glucose intolerance, and finally to obesity and diabetes. He introduced new terms in microbiome research (Homeostatic microbiome, Ring of life). These findings will be important for the future prevention and monitoring of the patients with high risk for developing diabetes. Dr Nikolic is author of many scientific papers dealing with Diabetes and he is Editorial board member and reviewer for many international scientific journals.
Abstract:
The aetiopathology of diabetes mellitus is not fully understood. Recent studies have confirmed that microorganisms can influence insulin secretion directly when present in the pancreas and indirectly by increasing their number in the gastrointestinal tract. In a healthy body, microorganisms are part of the homeostatic microbiome and play a key role in maintaining health, digestion and metabolism. Formation of the Homeostatic Microbiome (Ring of Life) takes place in several stages: pregnancy and childbirth, breastfeeding, contact with family and wider environment, nutrition and sexual contacts. Many internal and environmental factors can lead to disorders of homeostatic microbiome, which leads to certain diseases, including disorder of glucose homeostasis. The present research tests the hypothesis that disruption of the homeostatic microbiome plays an important role in aetiopathogenesis of diabetes mellitus and obesity.
Our research results demonstrated that microorganism can influence on pancreatic islets insulin secretion. Namely, they perform their impact directly (when present in pancreas) and indirectly, by secreting their metabolites which have influence on pancreas islets trough the blood vessels, as a consequence of increase in their number in human body, disorder of HM emerged.
Bacterial agents (Enterobacter spp, Pseudomonas aeruginosa, Staphyloccocus spp) reduce insulin secretion leading to postprandial hyperglycemia.Fungal agents (Candida albicans) increase insulin secretion causing postprandial hypoglycemia and insulin resistance. It is known that increased insulin secretion is frequent in obese persons.Both cases lead to glucose intolerance and insulin resistance and in some cases the development of the type 2 diabetes mellitus and obesity.
Hiroshi Bando
Tokushima University, Japan
Title: Low Carbohydrate Diet research by glucose variability with various medical care such as physiotherapy and music therapy
Biography:
Hiroshi Bando is an unique doctor with 4 main specialties.
1) Physician: specialties are diabetes, primary care medicine, life style-related disease, with the president of Annual Congress of 8th Japanese Primary Care Association (May 2017, Takamatsu Japan, 4700 attendees).
2) Pianist: silver award in 3rd European International Piano Concours in Japan (2012) and registered music therapist, with the president of Annual Congress of 9th Japanese Music Therapy Association (2009),
3) Athlete: speedskater in Japan National Sports Festival (1999-2003), continuing masters’ runner and lecturer in athletics.
1) Physician: specialties are diabetes, primary care medicine, life style-related disease, with the president of Annual Congress of 8th Japanese Primary Care Association (May 2017, Takamatsu Japan, 4700 attendees).
2) Pianist: silver award in 3rd European International Piano Concours in Japan (2012) and registered music therapist, with the president of Annual Congress of 9th Japanese Music Therapy Association (2009),
3) Athlete: speedskater in Japan National Sports Festival (1999-2003), continuing masters’ runner and lecturer in athletics.
4)Essayist: writing books 30<, printed matters 1800<, medical publication and presentation lots, the editors of several medical journals.
Abstract:
Statement of the Problem: There are lots of patients with diabetes and metabolic syndrome worldwide, and nutritional therapy is indispensable. Discussion has continued concerning Calorie Restriction (CR) and Low Carbohydrate Diet (LCD) for years. We have treated thousands of patients with type 2 diabetes mellitus (T2DM) for LCD and investigated clinical research, including ketone bodies and Morbus (M) value.
Methodology & Theoretical Orientation: Subjects were 121 patients with type 2 diabetes mellitus (T2DM), and provided Calorie restriction (CR) on day 1,2 and Low Carbohydrate Diet (LCD) from 3 to 14 days. Basal biomarkers and daily glucose profile on day 2,4 were measured.
Findings: Subjects were classified into 4 groups due to average glucose, with mean HbA1c 6.3%, 6.9%, 7.9%, 9.2%, respectively. Average glucose from day 2 to 4 in each group was significantly decreased. M value considerably decreased in group 2,3,4, indicating useful M value. As for lipids, Triglyceride from day 2 to 14 decreased considerably. RLP-C levels showed significant correlation with Triglyceride, LDL-C, atherogenic index (T-C–HDL/HDL) and TG/HDL value.
Conclusion & Significance: These results would suggest that RLP-C may be involved in the development of arteriosclerosis of T2DM, and may have the role of further research direction in the future. Further Medical Care: Associated with mentioned above, the author have continued several treatment and care for Integrative Medicine (IM) and Complementary and Alternative Medicine (CAM), such as physiotherapy, music therapy with my piano playing. I will show various trials for patient-oriented practice of medicine in the key note lecture.
Biography:
Vivek Kamath founder of heal the world organization is a Reiki Master, Mexican Healer, Melchizedek Healer, Crystal Healer and Past Life Regression Therapy Expert. He has healed many diabetic patients (Type1, Type2, Type 3/1.5/LADA) without any medicines. He has also healed blood pressure (both high and low blood pressure), heart disease (removed the heart blockages), removed kidney stones, ovarian cysts, fibrosis of the breast, fatty liver, lungs disease, cured sinusitis, sever joint pain, lumbar L5 spinal disk pain, neck pain, constipation, rheumatoid arthritis, glaucoma, migraines, headaches, insomnia, stomach related problem, IBS, diabetic gum problems, skin problems( dry skin, eczema) and chronic nasal allergies, nasal blockages without any medicines. Some of the above treatments have been completed within a week to maximum 1month duration.
Abstract:
Statement of the Problem: Diabetes Type1, Type 2 and Type 3 complications.
As most of us are aware Type 2 diabetes can be controlled and cured completely with the diet, workouts (yoga), effective stress management and other healing methods. However, Type 1 and Type 1.5/3/LADA diabetes healing or complete cure is a big challenge because of our body’s immune system issue.
With type 1/1.5 diabetes, the body’s immune system attacks part of its own pancreas. Scientists are not sure why. But our immune system mistakenly sees the insulin-producing cells in the pancreas as foreign, and destroys them. This attack is considered as "autoimmune" disease. These pancreatic cells – called “islets” are the ones that sense glucose in the blood and, in response, produce the necessary amount of insulin to normalize blood sugars.
How do we protect that these “Islets” and how can we ensure that these cells produce enough insulin hormones? Using Reiki Distant Healing and telepathy techniques I have reduced 2 patients glucose level. One was type1 case of a nine-year-old boy with high fasting glucose level (350 mg/dL) and a very high random glucose level (450 to 500 mg/dL) despite of taking high dosage insulin on daily basis for nearly 2 years it was not going down. With the reiki healing techniques, it has come down to normal level within a month or so. The same experiment repeated recently on another young gentleman 38 years old patient who was suffering from Type 1.5/3/LADA disease. His FB glucose level was around 350 to 400 mg/DL from the last 8 years despite of taking strong dose of insulin on daily basis; glucose level was not going down. Within a month after initialing Reiki healing treatment, his FB glucose level came down to 190 mg/DL. He is showing recovery from diabetes. The conclusion from our healing study are that these healing and cure works mainly on 1 ) Energy level of the healer 2) Belief in self for the patients 3) Belief in Reiki Channel and universal energy 4) Intention and thought process/brain wave frequency in alpha state matching between healer and patients. If all of these things are perfect, any disease can be healed. We have made an initial breakthrough in terms of reducing their glucose level. The above study has been followed on other healing such as Lumbar L5 Spine disk pain healing. It worked amazingly and patient has shown drastic improvement in their pain relief. 80% relief on pain has been felt. We are continuing with our research on this healing for various other chronic disease cure not only type1/3 diabetes.
Ibrahim El - Bayoumy
Tanta University, Egypt
Title: Identifying and addressing barriers for insulin use in patients with type 2 diabetes mellitus
Biography:
Dr. Ibrahim El- Bayoumy holds bachelor of medicine and surgery (Tanta faculty of medicine-Egypt,1989),then he earned his master degree in public health, preventive and social medicine (Tanta faculty of medicine-Egypt1996),and MD, PhD in public health ,preventive and social medicine 2003 from Tanta faculty of medicine-Egypt and McGill faculty of medicine –Montreal -Canada in division of clinical epidemiology in Royal Victoria hospital through double channel system as scholarship from ministry of education-Egypt. He is full professor of public health and community medicine in Tanta faculty of medicine-Egypt. Now he is working in ministry of health in Kuwait as consultant of public health and preventive medicine.
Dr. El Bayoumy has published many research works in international journals, he is interested in research in epidemiology of infectious diseases like HIV, tuberculosis, brucellosis and infectious hepatitis, he is interested in epidemiology of chronic diseases like diabetes mellitus and its health economics and pharmacoepidemiology. He is a reviewer of many national and international journals. He has great interest also in childhood obesity and has written a chapter on childhood obesity in a book published by Nova publishers in USA.
Abstract:
Diabetes mellitus type 2 is characterized by gradual decrease in insulin sensitivity in the peripheral tissues and liver(insulin resistance),followed by gradual decline in Beta cell function and insulin secretion. Thus patients with poor glycaemic control require the use of insulin therapy to achieve the target of American Diabetes Association, recommending HbA1c to be less than7%.≥ 8% despite of optimal doses of anti-diabetic drugs
This study aimed to evaluate and addressing the barriers for use of insulin in type 2 diabetes mellitus patients ,where their glycaemic control is poor i.e. HbA1c is .≥ 8% despite of optimal doses of anti-diabetic drugs.
We surveyed 200 patients with type 2 diabetes mellitus i.e. cross sectional quantitative study, patients showed poor glycaemic control HbA1c ≥ 8%,already treated with one or more oral agents, who recently prescribed insulin to control their metabolic status . Data were obtained by patient’s interview using a validated questionnaire The place of the study was in diabetes mellitus clinic in Farwaniyah primary health care center in Kuwait
Patients with type 2 diabetes failing to initiate the prescribed insulin therapy have reported misconception regarding fear of hypoglycaemia in 49% of the total sample ,pain from injections in 68% ,and self blame about need for insulin i.e. sense of failure in 61% of total sample of study. Other factors were addressed like sensation by getting more severity of the disease, weight gain fear and other negative self perceptions and attitudinal barriers were studied.
Reducing the negative influence of psychological insulin resistance (PIR) on treatment outcomes should be a clinical priority. Approaching and understanding the multifaceted and complex nature of PIR and discussing the etiology of every patient's PIR is the first important step. The incorporation of well-validated clinical measures assessing these barriers, as well as further research should be conducted on the impact of interventions to overcome such barriers. Clinicians should prescribe simple insulin regimen to decrease their patients' fear from dependency of insulin, and the use of modern insulin analogs and insulin pen services, may greatly reduce PIR by mitigating the fear of life style changes and side effects, as well as social stigma associated with using insulin in a vial and syringe
- Track 2: Complications in Diabetes
Track 3: Trends in Diabetic Complications
Track 7:Genetics of Diabetes
Track 9: Diabetes Nursing
Track 12: Antibiotics for Diabetes
Session Introduction
Seriho Nagafuchi
Kyushu University, Japan
Title: Virus-induced Diabetes: Diabetogenic Viruses and Host Susceptibility Genes
Biography:
Seiho Nagafuchi has graduated from Medical School of Kyushu University, Japan. He was the Resident in Department of Medicine, Kyushu University Hospital (1975) and the Visiting Fellow (1978) National Institute of Health, USA. He was the Chief Internist, Internal Medicine, Fukuoka-Teishin Hospital (1983). He was the Associate Professor (1998), Department of Health Sciences, Kyushu University; presently, a Visiting Research Scientist, Department of Hepatology, Faculty of Medicine, Saga University and a Professor Emeritus, Kyushu University, Japan since 2016.
Abstract:
Explosive increase of patients with diabetes in the world must be, at least in part, due to environmental factors, especially viruses. Experimental evidence had shown that even diabetogenic encephalomyocarditis strain D (EMC-D) virus-induced diabetes is inducible only in limited strains of mice such as SJL, DBA/2 and SWR backgrounds. We could show that natural mutation of Tyrosine kinase 2 (Tyk2) gene: Interferon (IFN) receptor-associated signaling molecule is responsible for susceptibility to murine EMC-D virus-induced diabetes, with deteriorated IFN dependent anti-viral response in pancreatic beta-cells. Moreover, a human Tyk2 gene haplotype with multiple genetic polymorphisms at promoter region in complete linkage disequilibrium, named Tyk2 promoter variant (NCBI ClinVar, variation ID: 440728), is associated with an increased risk for type-1 diabetes (T1D), particularly for anti-glutamic acid decarboxylase antibody (GADAb) negative T1D associated with flu-like syndrome at onset (Odds ratio: 3.6). Surprisingly, the risk is high in non-obese patients with type-2 diabetes (T2D) (Odds ratio: 2.4). We also found that patients with T1D had increased serum IgE levels, however, those with flu-like syndrome at the onset showed no relation to increased IgE nor anti-GAD, but with Tyk2 promoter variant. These experimental and clinical evidences taken together indicated that Tyk2 gene serves a virus-induced diabetes susceptibility gene, common to mice and humans. Conversely, these findings suggested that latent diabetogenic viruses may induce diabetes only in small fraction of people possessing virus-induced susceptibility gene. Moreover, the concept could extend to other infectious diseases such as Zika virus infection complicated with microcephalic infants among a few pregnant women. Thus, these observations should enhance the research for the identification of latently diabetogenic viruses using rodents with multiple virus-induced diabetes susceptibility genes in high sensitivity. Those studies will convincingly lead to the development of anti-diabetogenic virus vaccine not only to prevent T1D but also to reduce the risk of T2D, among patients due to viral infection.
Joseph F. Ndisang
University of Saskatchewan College of Medicine, Canada
Title: Heme oxygenase ameliorates cardio-renal complications in diabetic animals
Biography:
Dr. Joseph Fomusi Ndisang is an Associate Professor in the University of Saskatchewan College of Medicine, Department of Physiology. He received postdoctoral training in Physiology at the University of Saskatchewan College of Medicine from 2000-2005. He obtained a PhD in Pharmacology & Toxicology from the University of Florence, Italy, 2000. He obtained a Doctor of Pharmacy degree from University of Florence, Italy in 1995. He has received several distinguished awards and distinctions including: (i) Fellow of the Canadian Cardiovascular Society (FCCS) in 2016, (ii) Fellow of the American Heart Association (FAHA) in 2011; (iii) Fellow of the International College of Angiology (FICA) in 2007; (iv) Young Investigator Award by International College of Angiology (2007); (v) Young Investigator Award by the American Society of Pharmacology & Experimental Therapeutics-Division for Drug Discovery, Development & Regulatory Affairs (2005); (vi) Young Investigator Award by the Society of Experimental Biology and Medicine (2005); (vii) Caroline tum Suden/Frances A Hellebrandt Professional Opportunity Award for Meritorious Research by the American Physiological Society (2005); and (viii) Recognition Award for Meritorious Research by a Young Investigator by the American Physiological Society (2004). Top 5% of cited authors in journals of Biology and Biochemistry in 2011, by Thomson-Reuters. Currently, Dr. Ndisang is an Editor for Frontiers in Bioscience (impact factor 3.8) and Executive Guest Editor for Current Medicinal Chemistry (impact factor 3.7) He has published more than 64-full length manuscripts in peerreviewed journals and more than 80 abstracts. Dr. Ndisang has served as external PhD examiner for several universities in Canada, has given more than 30-invited talks, and has also served as peer-reviewer for several reputed journals and granting agencies in United States, United Kingdom, Canada, New Zealand and Poland. Research Interest: His research is mainly focused on investigating the role of the heme oxygenase system in hypertension, diabetes (types-1 and -2), and obesity.
Abstract:
Impaired glucose metabolism and dysfunctional insulin signaling are forerunners of cardio-renal complications. Upregulating heme-oxygenase (HO) with HO-inducers potentiates insulin signaling and improved glucose metabolism in type-1 and type-2 diabetic models. Particularly, pro-inflammatory/oxidative mediators including: (i) cytokines (TNF-α, IL-6, IL-1β), (ii) chemokines (MCP-1, MIP-1α), (iii) macrophage-M1 infiltration, (iv) NF-κB, AP-1, AP-2, cJNk and 8-isoprostane were suppressed by the HO-inducer, hemin whereas components of insulinsignaling such as IRS-1, GLUT4, PI3K and PKB were robustly enhanced. Furthermore, hemin reduced insulin/glucose intolerance. These were associated with the amelioration of cardiac lesions (hypertrophy, collagen deposition in cardiomyocytes and left ventricular longitudinal muscle-fiber thickness) and the improvement of renal lesions (glomerulosclerosis, tubular necrosis, tubular vacuolization, interstitial macrophage infiltration). In addition, the HO-inducer, hemin and abrogated pro-fibrotic/extracellular-matrix proteins like collagen and fibronectin that deplete nephrin, a protein which forms the scaffolding of the podocyte slit-diaphragm for filtration. Correspondingly, improved cardiac hemodynamics and reduced albuminuria/proteinuria and enhanced creatinine clearance was observed suggesting improved cardiac and renal functions. Collectively, these data suggest that HO-inducers may be explored in the search for novel and effective remedies against cardio-renal complications.
Achaiah Garlapati
Kakatiya University, India
Title: New thiazolidine-4-ones: Synthesis and evaluation for antidiabetic activity
Biography:
Achaiah Garlapati has been working as Professor at Pharmacy institute in Kakatiya university and associated with design, synthesis and screening of various heterocyclic compounds for different biological potencies viz anticancer, anti-inflammatory, antihistaminic, antidiabetic and antimicrobial activities. He guided several PhD students and project work as number of post-graduate students. Some of the compounds synthesized were found to more potent than the existing drug molecules. The results are published in several peer reviewed journals.
Abstract:
1,3-Thiazolidindiones (TZDs) are important class of antidiabetic agents which enhance insulin sensitivity of the target cells via activation of Peroxisome Proliferator-Activated Receptor gamma (PPAR-γ), a nuclear receptor involved primarily in glucose homeostasis, adipogenesis, inflammatory diseases and certain types of cancers.1,3-Thiazolidindiones are associated with various untoward effects, restricting their usage in the treatment of Type 2 diabetes. The main side effects of all TZDs are water retention, heart failure. Therefore, TZDs should be prescribed with both caution and patient warnings about the potential for water retention/weight gain, especially in patients with decreased ventricular function. The two TZDs, pioglitazone and rosiglitazone, are PPAR-γ agonists, do not cause serious liver damage, but do induce weight gain, fluid retention and heart failure and they have been associated with an increase in peripheral fractures in postmenopausal women, particularly in the humerus, hands and feet. Furthermore, it has been established that selective activation of PPAR-γ sub-type is primarily responsible for the observed undesirable effects. Therefore, partial agonists are considered a safer alternative to currently used thiazolidinediones (TZDs).
The attempt to develop such molecules, several modifications have been attempted in the tail and head groups of the TZDs to result in thiazolidin-4-ones and a few of them have been identified to possess potential antihyperglycemic activity. The purpose of this study is to synthesize and screen new derivatives (General Structure) obtained by the incorporation of pyridine/pyrimidine in the tail and thiazolidine-4-one with cyclopropyl, alkyl, aryl groups etc. In place of R group and methyl and hydrogen in place of R1. Methodology: 4-[2-(Methyl-pyrimidin/pyridin-2-yl-amino)-ethoxy]-benzaldehyde (2) was prepared from 2-(methyl-pyrimidin/pyridin-2-yl-amino)-ethanol (1) and 4-fluorobenzaldehyde. The compound 2 in turn treated with appropriate amine and thioglycolic acid/ thiolactic acid to get the thiazolidine-4-ones. Findings: All the seven target molecules showed significant reduction in blood glucose levels in the streptozotocin induced diabetic rats at 4th and 6th Hrs after administration. Among the series, the compound with cyclopropyl group and pyridine moiety (IIg) showed comparable potency to that of the standard piogliazone at 6th hour (~55% reduction). Further, the activity increased with % reduction in blood glucose levels reaching 65.75 at 10th Hrs compared to 3% shown by standard indicating prolonged activity by the test compound. Conclusion & Significance: The findings suggest that compound (IIg) could be further modified to improve the potency and tested for toxicity to identify safer molecules for further pre-clinical evaluation.
Qunli Wu
Peking Union Medical College Hospital, China
Title: Jinmaitong capsule: An effective traditional Chinese medicine for the treatment of diabetic peripheral neuropathy
Biography:
Xiaochun Liang is Director and Doctorate tutor of the Department of TCM in Peking Union Medical College Hospital. She is engaged in the study of diabetes and its complications and developed Jinmaitong capsule for the treatment of diabetic peripheral neuropathy. Prof. Liang presides over 18 scientific research projects such as the National Natural Science Foundation of China and published more than 200 papers. Furthermore, she has written or edited more than 20 academic books. Prof. Liang was awarded 11 scientific research awards such as Beijing Scientific and Technological Progress. Besides, she was entitled “Beijing 2nd Award of General Higher School Achievement” for her outstanding contribution to the reform of TCM teaching. She is a member of the academic committee of the Chinese Academy of Medical Sciences and the executive director of the China Society of Integrated Traditional Chinese and Western medicine.
Abstract:
Statement of the Problem: Up to 50% of patients with diabetes mellitus develop peripheral neuropathy. Painful peripheral neuropathy has a profound negative impact on quality of life and is one of the leading causes of non-traumatic lower limb amputations. The pathogenesis of diabetic peripheral neuropathy (DPN) remains unclear and there are no drugs known to halt or reverse the progression of DPN. The purpose of this study is to seek effective methods for the treatment of DPN from the traditional Chinese Medicine. Methodology & Theoretical Orientation: Guided by the thought of integrated traditional and western medicine, a long term study on the etiology, pathogenesis and syndrome characteristics of DPN is carried out. Then we developed the compound traditional Chinese medicine Jinmaitong capsule, and its clinical efficacy was verified. Findings: The syndrome of Yin-Yang deficiency with blood stasis is the most common syndrome differentiation type of DPN. The scores of neurological symptoms and signs were positively correlated with the scores of yin deficiency, Yang deficiency and blood stasis. The more severe Yang deficiency and blood stasis, the slower the conduction velocity of nerve. After treatment by Jinmaitong capsule, the scores of TCM symptoms and neurological function were obviously decreased, and the neurological symptoms and signs were improved. Furthermore, the abnormal parameters of nerve conduction velocity and sympathetic skin response test were also improved. JMT capsule can also reduce fasting and postprandial blood glucose, total cholesterol, triglyceride, whole blood viscosity and plasma viscosity, improve erythrocyte deformability, and reduce the activity of aldose reductase and the concentration of sorbitol, increase the activity of Na+/K+ -ATPase. The patients treated with Jinmaitong capsule had no definite adverse reactions during the medication. Conclusion & Significance: Chinese medicine Jinmaitong capsule is an effective and safe medicine for the treatment of DPN.
Grzegorz Onik
Medical University of Silesia in Katowice, Poland
Title: Treatment of diabetic foot ulcers with physical medicine modalities.
Biography:
Grzegorz Onik is physiotherapist trying to promote application of physical medicine modalities
in internal diseases. He is a lecturer at Medical University of Silesia in Katowice in Department
of Physical Medicine.
Abstract:
Diabetic foot ulcers treatment requires multidisciplinary approach. To reduce the lower limbs amputations rate various procedures are applied. Physical medicine modalities may complement standard treatment. Variable magnetic fields, low-level laser therapy and local hyperbaric oxygen therapy are frequently applied modalities in Poland to promote diabetic foot ulcers. These procedures are proved to stimulate epithelization, new blood vessels creation and reduce pain. The study aims were assessment of rheological properties of blood in people with diabetic foot ulcers and the influence of local hyperbaric oxygen therapy on rheological properties of blood in people with diabetic foot ulcers.
Study included 36 people divided into two group. Study group constituted 16 people with diabetic foot ulcerations: 2 females and 14 males with mean age: 66,66±9,39 years. Control group constituted 20 healthy people: 14 females and 6 males with mean age: 52,6±7,24 years. In study group rheological properties of blood were assessed twice: before and after treatment with local hyperbaric oxygen therapy. In diabetic patients, in comparison with healthy subjects, increased blood and plasma viscosity were obtained. Erythrocytes’ aggregation parameters were altered also. Application of local hyperbaric oxygen therapy resulted in blood viscosity decrease at shear velocity equal 150 s-1. The influence of local hyperbaric oxygen therapy requires further research. However, obtained results may encourage for usage of this modality as wounds healing was enhanced.