Day 1 :
Keynote Forum
Nir Barzilai
Institute for Aging Research, Albert Einstein College of Medicine, USA
Keynote: Aging as a mechanism for type-2 diabetes mellitus
Time : 09:30-10:05
Biography:
Nir Barzilai is a Chaired Professor of Medicine and Genetics and the director of the Institute for Aging Research at the Albert Einstein College of Medicine, which is currently the biggest center in the world to study the Biology of Aging, and home to 2 Centers of Excellence in the Biology of Aging. He studies healthy life span in rodents by biological interventions, and also families of centenarians and several drugs are developed based, in part, on these studies. He is a recipient of Irving S Wright Award of distinction in aging research and the IPSEN Longevity award. He is the Founder of CohBar Inc. and leading the TAME (Targeting/Taming Aging with Metformin) study multi central study to prove that concept that multi morbidities of aging can be delayed in humans and change the FDA indications to allow for next generation interventions.
Abstract:
Aging is the major risk for type 2 diabetes mellitus and also for cancer, Alzheimer’s and cardiovascular disease. We hypothesize that a progress in preventing these diseases will occur only if we can understand the reason people age at different rates and develop strategy to delay aging. We are intrigued as to why centenarians chronological age does not seem to match their biological age. Studying centenarians taught us that they carry genomic changes compared with people who do not survive so long. For example, they have a mutation that changes the function of the protein involved in cholesterol metabolism. Further, centenarians are also over-represented with genes that do not allow the full function of growth hormones and targeting these pathways in mice increased their health and longevity. Several of these findings have led pharmaceuticals to develop some drugs that can target specific diseases and exemplify an approach of delaying aging and several of its disease, rather than focus on one organ-specific drug at a time. To have proof of concept in humans, we chose metformin, one drug that targets the biology of aging and extends life- and health-span in animals. It is used for the treatment and to delay type 2 diabetes mellitus (T2DM), with over 60 years outstanding safety record. Metformin use is also associated with lower rates of cancer, CVD, all-cause mortality and possibly less cognitive decline. We designed the TAME (Targeting Aging with Metformin) trial, a placebo controlled, multi-center study in ~3000 elderly with a novel primary outcome of delaying the incidence of a composite of multiple age-related diseases. The study was developed in consultation with the FDA to obtain indication that would allow industry to justify the development of next-generation drugs to target aging and will further extend healthy life span in the next decade.
Keynote Forum
Stanley Schwartz
University of Pennsylvania, USA
Keynote: A unified pathophysiologic construct of diabetes and its complications, including malignancies, in the context of the B-cell classification of diabetes
Time : 10:05-10:40
Biography:
Stanley Schwartz is an Emeritus Associate Professor of Medicine at the University of Pennsylvania. He has trained at the University of Chicago and University of Pennsylvania. He actively lectures nationally, as well as internationally, about diabetes and its treatment. He has authored numerous articles in peer-reviewed scientific journals and has been a lead or co-investigator for many clinical trials (DCCT-EDIC, LOOK AHEAD). He has created a call for minimizing hypoglycemia in hospitals using incretins, and minimizing insulin use in ‘Type 2 ‘DM. He has proposed a new classification and unified pathophysiologic construct for all diabetes. He has been elected by his peers for inclusion in Best Doctors in America® from 1996 to 2017. Though he does some research and teaches a great deal, most of his time is spent caring for patients.
Abstract:
We have previously presented a proposal for a new, beta-cell centric classification of diabetes based on a consilience of genetic, metabolic, and clinical research that have accrued since the current classification was instituted. It recognizes that the beta-cell is the core defect in all patients with diabetes. Differences in the genetics, insulin resistance, environment and inflammation/immune characteristics of the damage to the beta-cell in each individual will determine the phenotypic presentation of hyperglycemia and allow for a patient-centric, precision-medicine therapeutic approach, part of which we labeled ‘the Egregious Eleven’. We, now recognize the same pathophysiologic mechanisms that account for damage to the beta-cells govern the susceptibility of the cells involved in the complications of diabetes to damage by the now well-defined abnormal metabolic environment that typifies beta-cell dysfunction. This abnormal metabolic environment is typified by oxidative stress which alters metabolic pathways a la Brownlee’s Hypothesis model, alterations in gene expression, epigenetics and inflammation. This unified pathophysiologic approach to the complications of diabetes in the context of the b-cell– classification of diabetes allows us to understand the varied risk of developing complications of diabetes with similar levels of glycemic control, how non-glycemic effects of some medications for diabetes result in marked complication risk modification and the value treating co-morbidities of diabetes in effecting complication risk. We also believe that the same pathophysiologic mechanism that account for damage to the beta- cells and govern the susceptibility of the cells involved in the complications of diabetes are likely to explain the association of cancer to diabetes and obesity and explains why diabetic medications may affect cancer risk and therapy.
Keynote Forum
Sean Hall
Medlab Clinical Ltd., Australia
Keynote: Mitigating the symptoms of chronic diseases through the administration of probiotics
Biography:
Sean Hall has founded Medlab in August 2012. He has over 20 years’ experience in nutraceutical sales and development, as well as early drug discovery in Australia, Asia and the US. He has led and inspired his teams to author multiple patents, write peer reviewed articles and deliver lectures at global scientific conferences. His passion is leading his researchers into novel areas and strong commercialization opportunities. He is also an Active Member of Medicines Australia, AusBiotech, American Federation of Medical Research (AFMR), The American Academy of Anti-Ageing Medicine (A4M), World Medical Associated (WMA), Special Operations Medical Association (SOMA), and a Board Member of the International Probiotics Association (IPA).
Abstract:
The human intestines are colonized by a variety of bacterial phyla that with the host co-ordinate numerous metabolic processes in health and disease. As such the intestinal microbiome can positively and adversely affect end organ physiological functions (e.g., liver, skeletal muscle, adipose tissue). Several studies have shown that the gut microbiome can influence metabolic processes, such as signaling pathways, mucus secretion, immune homeostasis, cellular proliferation and maturation, metabolic regulation and stability. The nature of the human microbiome is such that it is largely dependent on dietary practices, physical activity and mode of birth. A diet rich in fermented foods and beverages likely to contain probiotic bacteria has been posited to provide health benefits. The intestinal microbiome can be adversely affected by the administration of pharmaceuticals such as antibiotics, the level of sanitation, as well as lifestyle psychological stressors. The bacteria associated with the gut microbiome undergo a natural selection through inflammatory reactions and only those that tolerate the host immune response survive where a symbiotic or parasitic relationship can be established. Medlab’s research is centered on the therapeutic/pharmacological symbiotic effects of probiotics/gut microbiome with beneficial effects on health and that gut ecology disruptions can lead to adverse outcomes to end organ physiological functions. Numerous clinical studies that have investigated the administration of probiotics and prebiotics on various disease states or conditions including antibiotic or infective diarrhea, pneumonia, various inflammatory intestinal diseases, liver disease, respiratory function, kidney function, skin conditions, allergy, joint diseases, diabetes and obesity. A plausible mechanistic and efficacious pharmacobiotic effect of probiotic bacteria is advanced. This presentation will focus on the adjuvant administration of multi-strain probiotic formulations NAFLD, T2DM and depression, utilizing specific combinations of probiotics to effect therapeutic benefit.
Keynote Forum
James Varani
University of Michigan, USA
Keynote: Western-style diet, calcium supplementation and liver health: Gut microbial and metabolomic signature
Time : 11:40-12:15
Biography:
James Varani has completed his PhD in Microbiology and is a Professor in the Department of Pathology at the University of Michigan. His research interest is epithelial biology and he has focused his studies on gastrointestinal health, and especially on the prevention of chronic diseases with dietary intervention.
Abstract:
Statement of the Problem: The Western-style diet (WSD) is strongly linked with the growing epidemic of obesity and is associated with numerous chronic age-related ailments. In the liver, specifically, non-alcoholic fatty liver disease (NAFLD) is a result. The goal of this work was to determine if dietary calcium supplementation could protect mice fed a WSD from NAFLD, including its down-stream consequences (i.e., liver fibrosis, formation of pre-cirrhotic regenerative nodules and premalignant/ malignant liver tumors).
Methods: Male C56BL/6 mice were maintained for 18-months on a WSD containing dietary calcium at either 0.41gm/Kg or 5.25gm/Kg. Livers were evaluated for steatosis, inflammation, hepatocyte degeneration, fibrosis and necrosis. A metabolomic approach was used to evaluate bile acid composition and other metabolites in bile samples, comparing mice on the WSD with and without calcium supplementation. Cecal and stool microbial communities in mice on the un-supplemented and calciumsupplemented WSD were compared using 16S rRNA gene Illumina sequencing.
Results: Steatosis was observed in most animals, irrespective of dietary calcium level. In contrast, liver inflammation and ballooning degeneration fibrosis, necrosis and incidence of regenerative hyperplastic nodules were less prevalent in mice receiving calcium. Bile acid levels were significantly higher in WSD-fed mice without calcium supplementation than in those with supplementation. Microbial populations were distinctly different on the two diets. Calcium-supplemented mice had more microbial diversity and this reflected the increased levels of several species associated with reduced inflammation and enhanced gastrointestinal barrier function. Of interest, species associated with obesity were more highly represented in mice on the un-supplemented diet, even though mice on both diets had equal weight gain over the course of study.
Conclusion: Dietary calcium supplementation can reduce NAFLD-related consequences in the context of a high-fat diet.Alterations in metabolomic profile and gut microbial populations may contribute to this effect.
Keynote Forum
Magnus S Magnusson
University of Iceland, Iceland
Keynote: T-patterns and self-similarity from protein cities to the only large-brain mass-societies: From naked apes to string-controlled citizens
Time : 12:15-12:50
Biography:
Magnus S Magnusson is a Research Professor in the University of Iceland. He has completed his PhD in 1983 from the University of Copenhagen. He is the Codirector of a DNA analysis project. He has numerous papers and invited talks at international mathematical, neuroscience, proteomics, bioinformatics and science of religion conferences and at leading universities in Europe, USA and Japan. He was the Deputy Director (1983-1988) in the Museum of Mankind, Museum of Natural History, Paris. Then, he was repeatedly invited as temporary Professor in Psychology and Ethology (biology of behavior) at the University of Paris (V, VIII & XIII). He is the Founder and Director of the Human Behavior Laboratory, University of Iceland. He formally collaborated with 32 European and American universities based on “Magnusson’s analytical model” initiated at University René Descartes Paris V, Sorbonne, in 1995.
Abstract:
This presentation concerns spatial and temporal self-similarity across >9 orders of magnitude, implicating a particular type of hierarchical self-similar pattern, called T-pattern, a natural (pseudo) fractal, recurring with statistically significant translation symmetry. While the self-similarity in question must have evolved from simpler to more complex, it is presented in the order discovered within a primarily ethological (biology of behavior) project concerning social interaction and organization in social insects and primates, including humans. Beginning in the 1970’s, it was partly inspired by the work of Lorenz, Von Frisch and Tinbergen for which they shared a Nobel Prize in Medicine in 1973. The smallest animals concerned were social insects and there was no implication of self-similarity. The main methodological focus of the present project has been on developing pattern definitions and detection tools. This resulted in the T-pattern, with corresponding detection algorithms and software, and their abundant detection, among others, in different kinds of human (inter-brain) interactions and later in neuronal interactions in living brains, thus showing T-patterned self-similarity of temporal interaction structure within
and between brains. Finally, unexpected spatial T-patterning in the molecular strings of DNA and proteins was noticed and consequently the realization of self-similarity in social organization, based on T-patterned (external memory) strings, more durable than the citizens, in the mass-societies of proteins and of humans – the only large-brain mass-societies. Different from the mass-societies of insects (hives) and of cells (bodies), those of, respectively, protein and human mass-societies relying extensively on external T-patterned strings, respectively, DNA and the very recent strings, called texts, including those thoroughly standardized, copied, distributed, promoted and enforced, called legal or holy texts. With human and protein citizens specialized on the basis of durable external T-patterned strings and with some citizens, for example, moving (even walking) along tracks and doing meaningful work, a new definition of what is alive seems justified. Thus, proteomics may provide new insights and ideas for a bio-social science and vice-versa.
- Analytical Metabolomics | Metabolomics & Biotechnology | Diabetes Complications | Diabetes management | Diabetes Research
Session Introduction
Gerald C Hsu
EclaireMD Foundation, USA
Title: Using signal processing techniques to predict PPG for T2D
Biography:
The author received an honorable PhD in mathematics and majored in engineering at MIT. He attended different universities over 17 years and studied seven academic disciplines. He has spent 20,000 hours in T2D research. First, he studied six metabolic diseases and food nutrition during 2010-2013, then conducted research during 2014-2018. His approach is “math-physics and quantitative medicine” based on mathematics, physics, engineering modeling, signal processing, computer science, big data analytics, statistics, machine learning, and AI. His main focus is on preventive medicine using prediction tools. He believes that the better the prediction, the more control you have.
Abstract:
Background and Aim: The author has collected a complete set of PPG and lifestyle data for a period of 994 days with 2,982 meals (6/11/2015 - 3/1/2018). This paper discusses the methodology and accuracy of his developed PPG prediction model using signal processing techniques for Type 2 Diabetes.
Materials and Method: Due to his academic background in mathematics, physics, and engineering, he views these biomedical and lifestyle data as a collection of nonlinear signal waves. He applied signal processing to decompose this time-series measured PPG signal into multiple (> 10 lifestyle factors) single-sourced composite waveforms, examined each composite signal, and then recombined them into a predicted PPG curve. Finally, he compared this predicted signal against the measured signal to calculate its accuracy and correlation. He further improved his model via a trial-and-error “curve-fitting” method.
Results: The PPG’s major creation source, corresponding glucose, and contribution level are as follows:
Carbs/Sugar: 14.5 mg/dL, 37%
Post-meal Exercise: -15.7 mg/dL, 41%
Weather: 3.8 mg/dL, 10%
Measurement delay: -2.4 mg/dL, 7%
Others: -1.9 mg/dL, 5%
During this period, his average PPG values are:
Predicted: 119.16 mg/dL
Measured: 119.88 mg/dL
with 99.4% linear accuracy and a high correlation of 70%.
Conclusion: The quantitative results from the developed PPG prediction model reflect the accuracy and applicability for Type-2 diabetes control via a guided lifestyle management. The utilization of signal processing from electronics engineering and computer science is also proven quite effective for this investigation.
Jenani Jayakumaran
Rutgers University, USA
Title: Compliance with blood glucose testing and gestational weight gain in patients with gestational diabetes: A secondary analysis
Biography:
Dr. Jenani Jayakumaran’s interest in women’s health began in college during her time at Monmouth University. This led her to pursue graduate studies in reproductive biology at Johns Hopkins Bloomberg School of Public Health. Following her time in Baltimore, she moved to Philadelphia to attend Drexel University College of Medicine. Jenani is currently a second year OB/GYN resident at Rutgers- Robert Wood Johnson Medical School. She plans to pursue a fellowship in Maternal Fetal Medicine. Her interests include preterm labor and gestational diabetes.
Abstract:
Excessive gestational weight gain (GWG) and obesity are associated with increased morbidity. We aimed to compare adverse birth outcomes in obese vs. non-obese women with gestational diabetes mellitus (GDM) and GWG adherence with Institute of Medicine (IOM) recommendations in women compliant vs. non-compliant with blood glucose (BG) testing.
We conducted a secondary analysis of a randomized controlled trial at five tertiary medical centers from 5/2013-5/2016 evaluating the frequency of BG testing (everyday vs. every other day) among women with GDM. Abnormal BG values included fasting ≥ 95 mg/dl or 2-hr postprandial ≥ 120 mg/dl. Women’s weights were categorized based on the international BMI classification. Compliance with BG testing was defined as 90% of expected BG values. GWG was assessed for adherence to IOM recommendations. Primary maternal outcomes included primary cesarean section, labor dystocia, shoulder dystocia, and delivery due to uncontrolled diabetes. Primary neonatal outcomes included NICU admission, neonatal hypoglycemia, macrosomia, hyperbilirubinemia or respiratory distress syndrome. Composite outcomes were evaluated. Fisher exact or chi-square tests were used as appropriate.
287 women were included in this analysis. Maternal and neonatal adverse outcomes did not differ between BG testing groups when stratified by non-obese vs. obese. Pooled BG testing groups demonstrated macrosomia (p=0.0157) and the neonatal outcome composite (p=0.0042) were significantly more common in obese vs. non-obese women. When stratified by obesity class, maternal and neonatal outcomes did not differ between testing groups. GWG was more likely to be within IOM guidelines in compliant vs. noncompliant women (p=0.0283). Pooled BG testing groups stratified by obesity showed no difference in GWG between non-obese vs. obese women in the compliant vs. non-compliant groups.
Our results support obesity as an additional risk factor for adverse pregnancy outcomes in women with GDM and suggest improved adherence with IOM GWG guidelines amongst compliant patients.
Salome Kalandadze
National Institute of Endocrinology, Georgia
Title: Serum leptin levels are strongly associated with body fat mass but not with cardio-metabolic risk factors or insulin resistance with androgen deficiency in Georgian study
Biography:
Salome Kalandadze, MD is an Endocrinologist at National Institute of Endocrinology; Endocrinologists at the Department of Endocrinology and Metabolism of “New Hospitals”; Dietetics at “La Belle Esthetic Center”; She is also a Member of various associations such as Georgian Young Association for the Study Diabetes and Metabolic Disorder, European Association For The Study Of Obesity, Study Group For The Insulin Resistance, European Association For The Study Of Diabetes. She is also a reviewer for Georgian Journal “Aversi Magazine” She has participated and presented at several international conferences. She is a researcher in several clinical trials, author of more than 7 publications & lecturer in Endocrinology and Nutrition
Abstract:
Introduction: Metabolic syndrome and obesity is a chronic disease that concerns over a billion people all over the world. Adipose tissue is a place of synthesis of several metabolically active proteins, called adipokines. One of such adipokines is leptin.
Aim: The aim of present study was to find correlation between leptin and risk factors of cardio-metabolic disease and androgen deficiency.
Materials & Methods: The case-control study was conducted in a group of Georgian people. A total of 186 participants aged 20-70 were included for the study. The subjects who were overweight or obese were enrolled in the study group, whereas the subjects with normal weight were enrolled in the control group. The control group consisted of 20 subjects with normal weight. In both groups, following measurements were done: assessment of height, weight, BMI, waist circumference and blood pressure. Venus blood sample was obtained for plasma leptin, insulin, glucose and lipid profile analysis. The risk of cardiovascular disease was calculated according to the Framingham heart risk calculator. Body fat distribution was measured using Dual Energy X-ray Absorptiometry. Statistical analyses were performed using the SPSS 19.0 software package (SPSS, Inc., Chicago, IL).
Results: Our study revealed that there was a correlation between serum leptin and anthropometric characteristics in the whole study population, but when the population was divided into groups the correlation was lost. The positive correlation was with every region of the body in whole study population and in patients with obesity I and II degree. The correlation was not seen in patients with normal weight, over weight and morbidly obese patients. The correlation between leptin and cardio-metabolic risk factors was not detected.
Conclusion: In our study, serum leptin levels are dependent mostly on body fat percentage and body fat mass. Serum leptin levels did not associate with cardio-metabolic risk factors.
Shalini Verma
Jamia Millia Islamia, India
Title: Oxygen kinetics, oxidative stress, and cardiac autonomic function in type 2 diabetes mellitus: Is nitric oxide the connecting link
Biography:
Shalini Verma is currently a PhD Research Scholar (Exercise Physiology). Her Doctoral work is focused on the compromised oxygen uptake kinetics, elevated oxidative stress, and autonomic dysfunction in patients with type 2 diabetes and the effect of exercise on the same. She has been a part of the Diabetes Research Group exploring the role of physical activity in prevention and management of diabetic complications. With previous research work in exercise-induced muscle damage, and cardiovascular and neuromuscular physiology, she has over 15 papers in reputed journals. Her research interests include metabolic syndrome and physical activity, cardiovascular and pulmonary complications in type 2 diabetes, autonomic dysfunction, and oxygen uptake kinetics in healthy vs. diseased
Abstract:
Background: Type 2 diabetes mellitus (T2DM) is a multi-faceted metabolic disorder associated with a spectrum of complications, such as the commonly overlooked- cardiac autonomic neuropathy. Additionally, oxidative stress is increased in diabetes and may be linked to the development of chronic complications. T2DM is also shown to blunt the oxygen uptake kinetics, implying impairment of the control of oxygen delivery to and/or utilization of oxygen by contracting muscles. Nitric oxide (NO) has been proposed as a common denominator in the molecular mechanisms underlying these manifestations; however its behavior in diabetics is still controversial.
Purpose: The purpose of this study was to examine the correlation between levels of nitric oxide and oxygen uptake kinetics, antioxidant defense, and autonomic function in patients with type 2 diabetes.
Methods: Sixty T2DM patients were assessed for plasma levels of nitric oxide, oxygen uptake kinetics (time constant of steady state), antioxidant enzymes (catalase, superoxide dismutase), and cardiac autonomic function (heart rate variability).
Results: Our results revealed that NO levels were correlated positively with τVO2 (r = 0.503), LFnu (r = 0.334), and LF: HF ratio (r = 0.270), and negatively with CAT (r = -0.456), AvgNN (r = -0.384), RMSSD (r = -0.323), and pRR50 (r = -0.353).
Conclusion: Nitric oxide levels showed a negative correlation with antioxidant enzymes, oxygen uptake kinetics, and vagal indices of heart rate variability. These results are contradictory to the previously proposed protective effects of nitric oxide.
Fatima Zaidi
George Mason University, USA
Title: Metabolomic profiling enables the rapid detection of antimicrobial resistant (AMR) human pathogenic bacteria
Biography:
Fatima Zaidi is a Pharmacist by training. She has completed her Master of Molecular Biology from George Mason University, USA. She is currently pursuing her Doctoral degree (Cell and Molecular Biology) at George Mason University and is affiliated with Mason Metabolomics facility operated in the Couch Lab at Chemistry and Biochemistry Department, GMU. She has completed her Biosafety level 3 (BSL-3) and Animal Biosafety level 3 (ABSL-3) training. She has been awarded Elaine Joyce Outstanding Graduate Teaching Assistant Award by GMU in May 2017. Her research interests include but not limited to understanding general health and well-being, including metabolic and infectious diseases. To this end, her research focuses on the development and application of metabolomics-based in vitro diagnostics (IVDs).
Abstract:
Statement of the Problem: Rapid diagnosis of AMR strains of human pathogenic bacteria enables informed decisions regarding therapeutic options and can be critical to the effectiveness of clinical treatment. Techniques such as Polymerase Chain Reaction (PCR), Microbial Culturing, and/or Enzyme-Linked Immunosorbent Assays (ELISA) are well established, however can be time consuming, laborious, and costly. The purpose of this study was to develop a very rapid detection method for the identification of AMR strains of pathogenic bacteria, using Yersinia pestis (the causative agent of the plague) as a model organism.
Methodology & Theoretical Orientation: Microbial volatile organic compounds (mVOCs) are a family of structurally diverse, microbial-derived metabolites, generally related by their volatility at room temperature. Here, we employed headspace solid phase microextraction (hSPME), coupled with gas chromatography (GC), for the extraction and analysis of mVOCs emanating
from bacterial cultures of wild type and kanamycin resistant strains of Yersinia pestis. To ensure broad chemical diversity in the derived mVOC profiles, while still enabling a rapid analysis time, we employed a technique referred to as simultaneous multi-headspace SPME (simulti-hSPME).
Findings: Using simulti-hSPME with diverse sorbent types, we generated mVOC profiles that serve as metabolomic fingerprints that readily differentiate wild type (kanamycin sensitive) and kanamycin resistant strains of Yersinia pestis. The complete analysis can be completed within 15 minutes.
Conclusion & Significance: Rapid diagnosis of AMR strains of human bacterial pathogens is crucial for effective therapeutic intervention. Our mVOC metabolomics profiling approach quickly and effectively differentiates wild type (kanamycin sensitive) and kanamycin resistant strains of Yersinia pestis. Application of this method to other bacteria and other types of AMR is ongoing and holds promise as an effective clinical diagnostic technique.
Arjun Sengupta
University of Pennsylvania, USA
Title: Could not win thee sleep: Metabolic cost of sleep debt
Biography:
Arjun Sengupta is a Chemist who has received his PhD training in the fields of Metabolomics of Infectious Diseases and NMR Spectroscopy. Currently, he is working in the Laboratory of Aalim M Weljie in University of Pennsylvania. His research interest involves deciphering the link between metabolism, sleep and circadian rhythm and how such links can be exploited for translational and clinical purpose. He uses high resolution NMR spectroscopy and mass spectrometry to profile tissues and biofluids from sleep restricted animals and human recruits to explore the connection between sleep, metabolism and other phenotypes related to disease and aging. His research in the field of Metabolomics of insomnia and sleep restriction unraveled crucial changes in metabolic pathways that may explain some of the clinical manifestation of sleep curtailment.
Abstract:
This presentation will discuss recent translational discoveries from our group that demonstrate metabolic profiling using cutting edge NMR spectroscopy and mass spectrometry are instrumental in understanding the biology of sleep and chronobiology. Sleep or sleep like behavior is conserved in almost all animal species across the evolutionary timescale. The physiological role of sleep to increased quality of life is known but not well understood. It is believed that sleep serves as a compensating mechanism for the systemic tax related to the activities during wakefulness. In spite of clear health benefits, sleep curtailment is an overwhelming and prevalent burden across the globe. Decreased sleep and sleep disorders are associated to life threatening diseases including cardiometabolic ailments and cancer. Using metabolomics technologies, we have shown in a rat model that sleep restriction imparts significant changes in hepatic metabolic profiles. Similar changes are also heavily manifested in circulatory peripheral metabolites and lipids. Together, these observations demonstrate a shift in oxidative metabolism. In humans, sleep restriction leads to global metabolic shift associated to alteration in energy metabolism. We have further demonstrated that metabolic changes are manifested in chronic diseases such as insomnia associated with decreased quality and quantity of sleep. These studies reveal that insomnia rewires the metabolic network to induce night-time catabolic activities and significantly affects the metabolic oscillation during the diurnal day. Some of the changes are associated to altered metabolic networks preceding type 2 diabetes hence reaffirming the notion that altered sleep leads to metabolic diseases. Finally, we posit that these types of studies will be critical in clinics for unraveling sleep deprivation related disorders and their treatment.
Mohamed A Elrayess
Anti Doping Lab, Qatar
Title: Metabolic profiling of elite athletes with different cardiovascular demand
Biography:
Mohamed A Elrayess has completed his PhD at University College London (UCL) in Cardiovascular Genetics in 2002, and then studied the therapeutic utilization of hematopoietic stem cells in cardiovascular disease at the Department of Medicine at UCL for one year. He then spent over seven years working as a Stem Cell Scientist in Eisai Ltd., a major international pharmaceutical company, leading projects focusing on stem cell therapy in various neurodegenerative diseases. He is currently a Senior Scientist at Anti-Doping Lab Qatar, where he leads projects focusing on the role of stem cells in diabetes and genetics and metabolomics of elite athletes and holds an Honorary Senior Lectureship at UCL.
Abstract:
Background: Intensive exercise of elite athletes leads to physiological changes in response to increased cardiovascular demand. This study aims to profile metabolic changes in elite athletes from different sport disciplines.
Methods: Metabolic profiling of serum samples from 500 elite athletes from different sports disciplines who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between athletes with varying cardiovascular demands were assessed by univariate linear models.
Results: Out of 743 analyzed metabolites, 112 novel metabolites that changed significantly with increased cardiovascular demand were detected. These included markers of fatty acid beta oxidation, oxidative stress and energy-related metabolites. GGM sub-networks identified 6 subnetworks that captured the major metabolic pathways perturbed in relation to cardiovascular demand including fatty acids beta oxidation.
Conclusion: Data provide evidence that athletes with high cardiovascular demand exhibit a distinct metabolic profile that may reflect a unique life style characterized by a strict exercise and a special diet. Metabolic signatures associated with elite athletes could potentially be used as biomarkers for their overall health and response to their strict environment
- Therapeutic Metabolomics | Metabolomics in Precision Medicine | Cellular and Molecular Endocrinology
Session Introduction
Maria E Peña
Icahn School of Medicine, USA
Title: Diabetes and nutritional screening in post-bariatric patients
Biography:
Maria E Peña is an Assistant Professor at the Icahn School of Medicine and Director of Endocrine Services at Mount Sinai Doctors Forest Hills. She is board certified in Internal Medicine, Endocrinology, and Obesity Medicine. She proceeded to finish the last two years of her clinical training at their affiliate school, New York Medical College, where she obtained her MD degree in 2008. Dr. Peña completed her residency and fellowship training at North Shore University Hospital/LIJ. Dr. Peña is a member of numerous Medical Societies including: The Endocrine Society, the American Association of Clinical Endocrinologists, the American Diabetes Association and the Obesity Society. She also served as a member of the American Board of Obesity Medicine exam questions writing committee. She has given presentations at medical grand rounds, published in medical journals, including a chapter in Current Diabetes Reviews and has presented her work at National Conferences. Furthermore, Dr. Peña is actively involved in coordinating medical missions in Latin America, volunteering in mentoring programs for minority students interested in health care and health education in the community.
Abstract:
With the rise of obesity there has been a concomitant increase in the incidence of type 2 diabetes (T2DM). As a result, the term “diabesity” has become a popular disease entity in the past several years. When lifestyle modification and pharmacotherapy fail to achieve successful weight loss and diabetes control, bariatric surgery is a recommended treatment option. Bariatric surgery has been shown to promote sustained T2DM remission in 30–63% of patients and improve other components of metabolic syndrome; thus a preferred term has been “metabolic surgery”. As the practice of bariatric surgery for the treatment of T2DM increases, so will the number of patients with T2DM not achieving remission or with T2DM recurrence. There are currently no clear evidence-based guidelines delineating the proper management of T2DM in post-bariatric surgery patients. The focus of this review is to discuss current data on the efficacy of bariatric surgery in promoting T2DM remission, factors that predict T2DM remission and recurrence, and current treatment options for persistent hyperglycemia in postbariatric surgery patients. To increase long-term T2DM remission and prevent or delay recurrence, post-bariatric surgery patients need close follow up to encourage adherence to healthy nutrition and lifestyle practices that will lead to sustained weight loss. In addition to this, patients need adequate nutritional supplementation and periodic screening for vitamin, mineral and protein deficiencies. Therefore, we will conclude with a brief review of current recommendations for nutritional deficiency screening and supplementation.
Keti Zeka
The University of Cambridge, UK
Title: Use of natural products in prevention and management of type 2 diabetes
Biography:
Keti Zeka has completed her MSc from The University of L’Aquila, Italy in Medical Biotechnology and finished her PhD degree in Chemical Engineering and Biotechnology Innovation in 2015. She has been serving as a Lecturer and Tutor at the School of Medicine in L’Aquila and at the Faculty of Pharmacy in Leicester (UK). She is now a Postdoc at the University of Cambridge (UK) with an AIRC Fellowship. Her areas of expertise include the Chemistry of Medicinal Natural Products and their role in diseases prevention. Her current research interests cover the performance of diet and natural products in the revention of degenerative diseases, focusing in optimization of metabolomics and proteomics tools in cancer and development of novel druggable agents.
Abstract:
Metabolic syndrome is an umbrella term for a group of disorders related to imbalance of energy utilization and storage. It includes obesity, hypertension, increased triglyceride levels, aberrant cholesterol levels, insulin resistance with the resulting elevated fasting blood glucose levels. Metabolic syndrome is associated with chronic low-grade local tissue inflammation and increased susceptibility to a variety of degenerative diseases. Lifestyle changes, e.g. more physical exercise, a diet rich in fruit and vegetables, can help prevent or delay metabolic syndrome related problems. In addition, certain food supplements or herbal extracts are commonly believed to make an important contribution to a healthy life style. Whereas, there is a consensus that a vegetable-rich diet contributes to a lower occurrence of metabolic syndrome related disorders, the exact nature of the compounds in the diet that contribute to prevention of degenerative diseases is still a matter of debate. Our work sets out to evaluate several models that are currently considered to play a role in the prevention or management of type 2 diabetes. Phytochemicals with antioxidant activity were long believed to be a major contributing factor in the suppression of chronic inflammation. However, all antioxidant compounds do not always have anti-inflammatory properties. Further, the peroxisome proliferator-activated receptor gamma (PPARγ)-activating potential of a wide range of natural products has been explored in great detail and resulted in a credible model. A third model considers the potential role of phytoestrogens on human physiology. These compounds are known to interact with oestrogen receptors and can modulate a range of cell signaling pathways, either as agonists or as antagonists. The efficacy of several of the identified pharmaceutically active compounds and plant extracts, either as supplements or as dietary factors as part of a healthy life style, may be underpinned by laboratory results. However, caution is justified when considering food supplements in doses that greatly exceed the amounts that would be obtained through a regular diet.
Kashif Rizvi
New Mowasat Hospital Diabetes & Medical Centre, Kuwait
Title: Diabetes current perspectives and lessons learnt from the epicenter, the Persian Gulf
Biography:
Kashif Rizvi is a Consultant Endocrinologist at Mazaya Clover Centre, Jabriya, Kuwai, Director of New Mowasat Hospital Diabetes & Medical Centre, Kuwait and Former Head of Department of Endocrinology and Diabetes - Kettering, UK. He earned Certificate of Completion of Specialist Training UK and served as Accredited Physician, Endocrinologist & Diabetologist and Teaching Faculty at University of Leicester/Wales, UK. He is the Editor of Journal of Endocrinology & Human metabolism, California USA. He is a Member of Royal College of Physicians (London - UK), British Diabetes Association, British Endocrine Society and Association of British Clinical Diabetologists, author of several peer reviewed research papers and Tutor of Royal College of Physicians.
Abstract:
Given the upsurge in type 2 diabetes of epidemic proportions especially within the Persian Gulf region, it is of utmost importance to realize that no health care system in the world could deal with it just through therapeutic interventions or management of its complications. Given its myriad affects type 2 diabetes has the potential to pass the threshold of sustainable spending in the health care sector of even the wealthiest economies of the world. This talk aims to run through lifestyle habits of a sedentary obesogenic society as the root cause of the epidemic and addresses the current dearth of knowledge
amongst health care providers and their ‘glucocentric’ approach which often results in missed diagnosis of warning signs of this syndrome or suboptimal care once diagnosed. In the industrial and automation age there has been a paradigm shift in the metabolic syndrome’s prevalence and unless a holistic, multifaceted and multifactorial approach is adopted we run the risk of not only cutting short the productive years of life but also add to the enormous burden of morbidity and mortality spanning virtually all age groups . Kuwait features amongst the top countries of the world in this regard and has a unique cohort where an indigenous population compares expats in the disease prevalence indicating a strong environmental factor. This talk runs through type 2 diabetes in a holistic manner covering all aspects of it within Kuwaiti society and sets guidelines for the rest of the affluent world.
Saeed Akhter
Pak Diabetes Center, Pakistan
Title: Beat the diabetes with novel and future therapies for T1DM
Biography:
Completed MBBS from Pakistan at the age of 26 years. And MSc applied Envi. Sci. from University of Punjab, Pakistan and MSc Diabetes Care and Management from the Glasgow Caledonian University, Scotland United Kingdom. Presently working as Director PAK DIABETES CENTER in Pakistan
Abstract:
Type 1 diabetes (T1D) still remains a big mystery disease of the 21st century. It has posed a big challenge for all the stakeholders in its management. As the incidence and prevalence of diabetes is increasing worldwide so the complications and cost related to diabetes are increasing. Researchers are still unable to completely understand the aetiopathological nature of this disease. Treatment of T1D was revolutionized after the discovery of Insulin. Exogenous insulin replacement therapy is being used effectively since then, but it does not provide a cure. There are many other treatment options, which are being investigated extensively all over the world in an effort to find a cure. Limitations of insulin therapy have led to search for strategies targeting beta cell replacement therapies. Plasticity towards beta cells has been revealed in clinical trials. Stem cells (SC) are colonogenic cells and have been found capable of both self-renewal and multilineage differentiation. SCs are unspecialized cell but has a potential to differentiate into specialized cells. In SC engineering, exploring the potential of embryonic and adult stem cells or induced pluripotent stem cells to differentiate into insulin producing beta cells, if given the specific growth factors, signaling molecules and transcription factors has demonstrated encouraging results in rodent models. Reprogramming or genetic modification of other cell types such as gut and liver cells in the production of insulin producing beta cells are one of the possibility which could be utilized in human beings after the encouraging results obtained in rodent models These properties now offer a great scope and potential for their clinical use and are being explored further. Vaccine for T1D based on the rationale that reestablishment of immune tolerance to diabetes specific self-antigens has been seen as a step forward in finding the cure. Artificial pancreas which will work just like a normal functioning pancreas by using automatic techniques is another option and is seen as a mechanical cure by many researchers is being tested in many research centers and is in its final stages of developments. Studies on diabetic animals have proved useful and have helped to understand the molecular and pathophysiological events leading to the underlying causes of the T1D, with an emphasis on the current, novel and future techniques and their potential for clinical use in future.
Biography:
Zelalem Kiros Bitsue has completed his PhD in Immunology, MBBS Degree in Medicine and Surgery, a Bachelor’s degree in Nursing and Health Administration, a Bachelor’s degree in Theology and Leadership and a Diploma in advanced research proposal writing, research report writing, methods and grant proposal writing. He is an Assistant Professor at the Addis Ababa Institute of Technology. He is the Owner, Founder and General Director of the African Health Organization “USAHO”. He has made 120+ publications, is corresponding/first author of 112+ Publications as well as over 44,000 citations.
Abstract:
Hypothesis: Estrogen and leptin independently regulate neuroendocrine, leukocytes, and mitochondrial, along with cytokine function. I hypothesis that depending on the concentration of estrogen and leptin has synergetic effect in regulating hormonal signaling, and transcription factors and maintaining metabolic disorders.
Objective: The objective of this study was to determine the effective potential of estrogen in combination with leptin in T4, NADPH dependent cytochrome P450 monooxygenase (mixed function oxidases, MFO), glutathione-S-transferase, epoxide hydrolase, APCs (gilial, DC, Mθ), CD4 T cell subsets (Th1, Th17, Treg), CD8+ Sub sets (CD25+ (for Treg cells) response in animal models of lipoprotein disorders.
Methods: After encephalomyocarditis virus induction was done using 40 C57BL/6 mice; for experimental animal models of lipoprotein disorders in the presence of estrogen in combination with leptin on the 10 weeks old female mice, we analyzed the culture supernatant or serum levels to determining the level of NADPH dependent cytochrome P450 monooxygenase (mixed function oxidases, MFO), glutathione-S-transferase, epoxide hydrolase, IFN-γ, IL-6, IL-1β, IL-10, IL-17 and TGFβ. ELISA method is performed according to the manufacturer's instructions. Tbet, RORÒ¯t, FOXP3, IFN γ, IL-17, IL-10, IL-1β, TGFβ, TNFα, IL-12, IL-6 and HPRT1, gene expressions analysis was done using Real time PCR method and perform according to the protocol of the manufacturer ERα and ERβ, Ca++ influx, ATP, cytochromeoxidase subunits I, II, III, techniques such as immunohistochemistry, immunocytochemistry, and immunoblots using a wide range of antibodies
Result/Conclusions: Estrogen in combination with leptin exerts a dual effect (inhibition versus enhancement) in regulation and prevention of lipoprotein disorders; moreover, maintaining tolerance and balance modifying in B cells, APCs, CD4+T cell subsets (Th1, Th17 and Treg), and CD8+ Sub sets. Which are implicated in the immune-pathogenesis, molecular mechanism, and cytokine pathways, suggest that Estrogen in combination with leptin both prevention and therapeutically relevant in lipoprotein disorders and autoimmunity. However, while exciting discoveries have been made, further work is required to understand the diverse effect of Estrogen in combination with leptin in in regulation and prevention of lipoprotein disorders; moreover, maintaining tolerance and balance modifying in B cells, APCs, CD4+T cell subsets (Th1, Th17 and Treg), and CD8+ Sub sets.
Kenneth K Wu
China Medical University, Taiwan
Title: Cell-specific 5-hydroxytryptophan (5-HTP) metabolism and its relevance to cell function
Biography:
Kenneth K Wu is Professor Emeritus at University of Texas Health Science Center in Houston, Distinguished Investigator and President emeritus at National Health Research Institutes (NHRI) in Taiwan. He is currently a Distinguished Professor and the Director in the Metabolomics Medicine Research Center at China Medical University (CMU) in Taichung, Taiwan. He also holds Hou Jindui Chair at National Tsing-Hua University in Hsin-Chu, Taiwan and Distinguished Chair Professorship at National Taiwan University in Taipei, Taiwan. His research experiences and expertise are in the areas of hematology, vascular biology and prostaglandin cellular and molecular biology.
Abstract:
5-HTP is derived from L-tryptophan via the catalysis by tryptophan hydroxylase (TPH). It is a common precursor of several bioactive molecules including serotonin (5-hydroxytryptamine), melatonin (N-acetyl- 5-methoxytryptamine) and cytoguardin (5-methoxytryptophan). Enzymes catalyzing serotonin and melatonin synthesis are well characterized. In serotonergic neurons, 5-HTP is converted to serotonin by aromatic amino acid decarboxylase (AADC) while its conversion to melatonin in pineal cells is catalyzed sequentially by AADC, alkylamine N-acetyltransferase (AANAT) and N-acetylserotonin methyltransferase (ASMT also known as hydroxyindole O-methyltransferase or HIOMT). 5-HTP catabolism in non-neuron, non-pineal cells are less clear. We have shown that human fibroblasts and endothelial cells (EC) possess enzymatic machinery to convert 5-HTP to 5-methoxytryptophan (5-MTP). Neither cell type expresses AADC and hence is unable to synthesize serotonin or melatonin. 5-MTP suppresses pro-inflammatory mediator-induced COX-2 and cytokine expressions and plays a
fundamental role in defending against inflammatory tissue damage and tumorigenesis. Thus, there is cell-specific utilization of 5-HTP to generate distinct bioactive metabolites to carry out anti-inflammatory, neurotransmission and circadian rhythm regulatory functions. Our preliminary results show that A549 cancer cells express AADC to convert 5-HTP to serotonin. Metabolomic analysis detected miniscule quantities of 5-MTP or melatonin which is correlated with low level of HIOMT. Stable transfection of HIOMT reprogrammed 5-HTP catabolism resulting in a switch from serotonin to 5-MTP synthesis. HIOMT overexpressed A549 cells had slow growth and low metastasis when compared to vector controls. In contrast with production of CNS bioactive metabolites, i.e. serotonin and melatonin by neurons and pineal cells, peripheral cells such as fibroblasts, EC and epithelial cells convert 5-HTP to 5-MTP to defend against inflammation. Cancer cells have an aberrant transcription program which can be corrected by HIOMT gene transfer.
Biography:
Zelalem Kiros Bitsue has completed his PhD in Immunology, MBBS Degree in Medicine and Surgery, a Bachelor’s degree in Nursing and Health Administration, a Bachelor’s degree in Theology and Leadership and a Diploma in advanced research proposal writing, research report writing, methods and grant proposal writing. He is an Assistant Professor at the Addis Ababa Institute of Technology. He is the Owner, Founder and General Director of the African Health Organization “USAHO”. He has made 120+ publications, is corresponding/first author of 112+ Publications as well as over 44,000 citations.
Abstract:
Background: Modern biomedical, space science research and health care are provided by multidisciplinary teams in which biomedical engineers contribute to the advancement of knowledge equally as medical professions. Biomedical engineering represents one of the most rapidly growing branches of industry in the developed world.
Objective: The objective of this study was to develop software, hardware, and bioelectronics devices (machine) and identify and determine the effective potential in biomedical and space science researches.
Methods: The software development methods to be use formal, informal, approaches, and various forms of prototyping methods, are of interest in this work.
Result & Discussion: Having a cross-disciplinary approach, the project will have the potential to discover whole new softwares, hard wares, and bioelectronics devices openings in the area of the biomedical and space science research. This research project enhances the prospects of the economy as a whole as it improves the capabilities and competitive advantage of the soft wares, hard wares, and bioelectronics devices development at university.