Day 2 :
Keynote Forum
Barbara Boucher
Queen Mary University of London, UK
Keynote: The problems of vitamin D and metabolic syndrome: How might varying status affect risks of its component disorders, and at what stage of risk development?
Time : 09:30-10:10
Biography:
Barbara J Boucher worked as a joint NHS and academic physician at the London Hospital, (later Barts & The London) and it's medical school, remaining research active after clinical retirement when she was made an honorary professor. Her main clinical activities were in acute internal medicine, diabetes care, and teaching, with research
carried out on a wide range of clinical metabolic problems, but focused especially on developing systems of diabetes care, the investigation of metabolic disorders, especially in diabetes, and working on vitamin D insufficiency and 'betel-chewing' as potential aetiological factors relevant to the onset of both metabolic syndrome and type 2 diabetes, and she continues to produce peer reviewed publications
Abstract:
Statement of the Problem: Metabolic Syndrome [MetS] and its complications [e.g. T2DM, CVD, NAFDL] are increasingly common at all ages, associated with obesity, and poor life-styles, (both reducing serum 25(OH)D concentrations; vitamin D status). MetS disorders associate inversely with serum 25(OH)D, from childhood, cross-sectionally and prospectively. Known effects of vitamin D capable of reducing MetS risks include effects on adipose tissues, hepatic fat synthesis, lipid profiles, cardiac risk factors, inflammation, insulin secretion and resistance, and hepatic glucose release, but evidence of causality for lack of vitamin D is sparse. However, RCT designs are often inappropriate for nutrients in failing to study correction of deficiency or inadequacy; they may be too short to affect slowly evolving tissue damage, or start after tissue damage is established. Some better designed RCTs have shown MetS disorder improvements.
Methodology & Theoretical Orientation: Discussion of MetS variables for which vitamin D has potentially protective effects is based on peer reviewed literature [e.g. in PubMed in the last >50 years], and includes my own work.
Findings: Beneficial effects of vitamin D on MetS disorders with known mechanisms include: reducing hepatic synthesis of fat and hepatic glucose release, promoting insulin secretion, reducing beta cell damage in hyperglycaemia, suppression of inflammation and tissue-destructive MMP secretion: importantly in early life, they include inhibition of adverse epigenetic changes, and prevention of irreversible adipocyte proliferation.
Statement of the Problem: Metabolic Syndrome [MetS] and its complications [e.g. T2DM, CVD, NAFDL] are increasingly common at all ages, associated with obesity, and poor life-styles, (both reducing serum 25(OH)D concentrations; vitamin D status). MetS disorders associate inversely with serum 25(OH)D, from childhood, cross-sectionally and prospectively. Known effects of vitamin D capable of reducing MetS risks include effects on adipose tissues, hepatic fat synthesis, lipid profiles, cardiac risk factors, inflammation, insulin secretion and resistance, and hepatic glucose release, but evidence of causality for lack of vitamin D is sparse. However, RCT designs are often inappropriate for nutrients in failing to study correction of deficiency or inadequacy; they may be too short to affect slowly evolving tissue damage, or start after tissue damage is established. Some better designed RCTs have shown MetS disorder improvements.
Methodology & Theoretical Orientation: Discussion of MetS variables for which vitamin D has potentially protective effects is based on peer reviewed literature [e.g. in PubMed in the last >50 years], and includes my own work.
Findings: Beneficial effects of vitamin D on MetS disorders with known mechanisms include: reducing hepatic synthesis of fat and hepatic glucose release, promoting insulin secretion, reducing beta cell damage in hyperglycaemia, suppression of inflammation and tissue-destructive MMP secretion: importantly in early life, they include inhibition of adverse epigenetic changes, and prevention of irreversible adipocyte proliferation.
Conclusion & Significance: Maintaining long-term vitamin D repletion from a young enough age to be likely to be able to prevent, slow down or even correct, early MetS pathogenesis, may prove to be a public health bonus if vitamin D inadequacy is eliminated at the population level, as in Finland by food fortification. Maintaining long-term vitamin D repletion from a young enough age to be likely to be able to prevent, slow down or even correct, early MetS pathogenesis, may prove to be a public health bonus if vitamin D inadequacy is eliminated at the population level, as in Finland by food fortification.
Keynote Forum
Albert de Graaf
TNO, Netherlands
Keynote: POWER2DM: Predictive model-based decision support for diabetes patient empowerment
Time : 10:10-10:50
Biography:
Albert de Graaf (Scientific Coordinator of POWER2DM ) joined TNO in 2006 and works as a Senior Scientist coordinating activities on computational modelling for Predictive Health Technolgies. He participated in several recent FP7 projects including MISSION-T2D and NuAge. The main modelling application areas are lipoprotein
metabolism, cholesterol metabolism, gut microbial metabolism, metabolic disease and diagnostics, and systems medicine. Prior to TNO, he worked at Delft University of Technology (biological applications of Nuclear Magnetic Resonance), Philips Medical Systems BV (MRI/MRS techniques), Forschungszentrum Jülich, Germany (modelling and flux analysis of microbial metabolism for Metabolic Engineering purposes), and University of Maastricht (Metabolic pathway modeling and analysis). He was also co-founder and CSO of the French biotech company Metabolic Explorer SA.
Abstract:
Statement of the Problem: There is an urgent need to develop cost-effective intervention strategies for diabetes. Given the enormous scale of the problem, and the fact that such a large percentage of cases arise due to an unhealthy lifestyle, personalized care systems that include innovative self-management support strategies, well-linked to the medical care of patients, are of prime importance.
Methodology & Theoretical Orientation: POWER2DM (started Feb 2016 )will deliver a personalized self-management support system (SMSS) for T1 and T2 diabetes patients. It will offer a guided action plan for self-management by combining decision support based on personalised results of interlinked predictive computer models, e-coaching and e-advice feedback functionalities based on Behavioural Change Theories, and real-time collection, processing and interpretation of personal data (sensors) and self-management activities.
Findings: The user requirements, requirement analysis of the system architecture, and conceptual design of the architecture have been completed. The main software components Personal Data store, Authorization Service, sensor data integration module, Prediction Service, Action Plan Engine, and Communication Engine are nearing completion. A first prototype of the POWER2DM SMSS interlinking these components and providing user interfaces will be operational end of May. A Quantification Campaign to test use of the predictive models in practice currently runs in Netherlands, Germany and Spain.
Conclusion & Significance: POWER2DM is progressing well according to plan. The deliverables of the project will increase selfmanagement capabilities and participation of the patient in the care process, resulting in better self-control and management of the disease. This will lead to better glucose management, thereby preventing severe episodes and long-term complications.
Keynote Forum
Ning Wu
Van Andel Research Institute, USA
Keynote: Regulation of peripheral glucose uptake by regulating GLUT4 endocytosis
Time : 11:10-11:50
Biography:
Ning Wu received her Ph.D. in the Department of Biochemistry from the University of Toronto in 2002. She then served as a research associate at The Scripps Research Institute in the Department of Chemistry. In 2004, She joined the Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School, as a research
fellow where the primary lab focus was to understand the signaling pathways that regulate normal mammalian cell growth and the defects that cause cell transformation. She joined Van Andel Research Institute in 2013 as an assistant professor in the Center for Cancer and Cell Biology.
Abstract:
Statement of the Problem: In diabetes, the body’s response to insulin is impaired, resulting in elevated levels of blood glucose. Peripheral-tissue glucose uptake is an important regulatory point in controlling blood glucose. After a meal, insulin causes most glucose to be quickly taken up by muscle and adipose tissue. This process is carried out by the fusion of storage vesicles containing GLUT4, a glucose transporter, with the cell surface membrane. Failure of this process results in insulin resistance and elevated blood glucose. To prevent hypoglycemia under fasting conditions, GLUT4 on the cell surface is normally kept low by continuous endocytosis. Because AP2- and clathrin-binding sites have been mapped in GLUT4, this basal endocytosis has been thought to be a signaling-independent, passive process. Yet this concept creates a dilemma: how is this process inhibited during insulin stimulation to avoid a futile cycle of endocytosis and cell surface fusion?
Methodology & Findings: We recently identified TXNIP (thioredoxin-interacting protein) as a negative regulator of the class I members of the SLC2 family of glucose transporters, which includes GLUT4. We discovered that TXNIP associates with GLUTs and mediates GLUT endocytosis via the clathrin-dependent pathway, effectively reducing glucose influx. Using TXNIP WT and KO mice, we found that the absence of TXNIP results in higher fasting glucose uptake into muscle and adipose tissue. Using tissue cultures, we found that insulin-induced AKT activation leads to TXNIP phosphorylation that disrupts the TXNIP/GLUT4 interaction, acutely inhibiting GLUT4 endocytosis.
Conclusion & Significance: Our results indicate that GLUT4 endocytosis is actually a regulatable process, both in fasting and insulin-stimulated states. Together with our previous finding that cellular energy stress stimulates glucose uptake via AMPK phosphorylation of TXNIP, it points to TXNIP as a key node of regulation of blood glucose by both exercise and insulin.
- Computerised Applications in Diabetes | Diabetes Education and its Risk Factors | Emerging Focus in the Treatment of Diabetes | Gestational Diabetes
Location: Bleriot 2
Chair
Vithian Karunakaran
Colchester Hospital University NHS Foundation Trust|, UK
Co-Chair
Bandar Manawer Alharbi
Prince Sultan Military Medical City, Saudi Arabia
Session Introduction
Jana Votapkova
Charles University, Czech Republic
Title: Type 2 diabetes mellitus in the Czech Republic: Prediction of prevalence and costs
Biography:
Jana Votapkova specializes in healthcare economics and economic modelling. She cooperates with the Observatory for Health systems and policies and other
international institutions on economic expertise. Her research concentrates on technical and economic efficiency in the healthcare sector, economic analyses of
healthcare reforms or analyses of determinants affecting long-term sustainability of healthcare finances.
Abstract:
Statement of the Problem: Costs associated with the treatment of type 2 diabetes mellitus represent a large share of healthcare costs of developed societies. Being diagnosed with type 2 diabetes mellitus is associated with increased healthcare costs compared to the population not suffering from diabetes. As opposed to published research which analyzes small samples or
survey data, we use population-based individual data to predict the number of Czechs that will suffer from diabetes and their healthcare costs.
Methodology & Theoretical Orientation: Individual-level data on healthcare costs and drug consumption for the whole Czech population over 30 years of age for the period 2010- 2015 are used to identify patients with diabetes. Observations are divided into age and sex groups to identify how costs of different age cohorts of diabetics change over time using a GLM model. The share of diabetics in age cohorts and sex groups is predicted using linear regression. Absolute numbers of diabetics are calculated based on the official demographic prediction of the Czech Republic. Future healthcare costs of diabetes reflect different percentiles of distribution and inflation expectations.
Findings: The strongest association between increased healthcare costs and the presence of diabetes was found for 55-69 year olds Czechs. The highest share of diabetics is among 75-year-olds reaching 21.4 % (22.3 % males; 20.8 % females] in 2015. In the observed period, costs of a 75-old-diabetic increase by 2.7 % on average (3 % males; 2.4 % females] annually. Future costs of diabetes are expected to rise and so is the share of diabetics.
Conclusion & Significance: Given escalating costs and increasing prevalence boosted by population ageing, ceteris paribus, diabetes will represent a significant burden for the Czech healthcare system. The methodology is applicable to other chronic diseases too.
Gauri Billa
Abbott Healthcare Pvt. Ltd, India
Title: A retrospective study to determine the prevalence of hyperuricemia in Indian subjects attending hyperuricemia screening camps
Biography:
Gauri Billa is an experienced senior medical advisor with a demonstrated history of working in the hospital & health care industry. She is skilled in clinical research, pharmacology, clinical trials, healthcare, and clinical pharmacology. She has a strong healthcare services professional with a Doctor of Medicine (M.D.) focused in Pharmacology from King Edward Memorial Hsopital.
Abstract:
Statement of the Problem: The prevalence of type-2 diabetes mellitus (T2DM) and hypertension (HTN) has been rapidly rising in India, over the past few decades. Elevated levels of serum uric acid (SUA) have been shown to be associated with both T2DM and HTN. About two-thirds of hyperuricemics remain asymptomatic, without any signs and symptoms of urate crystal deposition/gout. Hence screening for hyperuricemia may play a significant role in early detection, prevention, and management of complications associated with T2DM and HTN. However, limited information is available regarding the
burden of hyperuricemia in Indian population. The objective of this study was to determine the prevalence of hyperuricemia in subjects with HTN and T2DM, in Indian setting.
Methodology & Theoretical Orientation: A retrospective analysis of patients undergoing screening for hyperuricemia in health clinics across India between April to May 2017 was carried out. Data regarding demographics, history of T2DM and HTN and uric acid levels (easy touch uric acid monitoring system) were recorded during the camps.
Findings: Data from 3044 screening camps was analyzed. The mean age of the study population was 47.92 years; about two-thirds of the subjects were men. Of the 29,391 subjects screened, 25.79% were found to have hyperuricemia (uric acid >7mg/dl). The percentage of diabetics, hypertensives and Diabetic hypertensives who had hyperuricemia was 33.62%, 35.11%, and 34.39% respectively. A trend towards increased prevalence of hyperuricemia was seen with increasing age and increased duration of diseases like HTN and diabetes.
Conclusion and Significance: High prevalence of hyperuricemia was observed in T2DM and HTN and in patients with both co-morbidities. Age-wise analysis revealed an increasing trend of hyperuricemia with age. Further, the prevalence of hyperuricemia also increased with increasing duration of T2DM and HTN.
Eleni Andreou
University of Nicosia, Cyprus
Title: Type 2 diabetes and obesity and its correlates in a first nationwide study among Cypriot adults
Biography:
Eleni Andreou is currently working as Assistant Professor, at the University of Nicosia , Cyprus. She received her Doctoral degree on Clinical Dietetics, Health Education and Behavioral Studies from the University of Middlesex, UK. Dr Andreou completed her Masters/CPD Nutrition and Clinical Dietetics from the University of Youngstown, USA. She then worked in Cyprus as clinical dietitian, elected as president of the Cyprus Dietetic and Nutrition Association, served as Assistant Professor at the University of Nicosia in Cyprus. Dr Andreou has authored several publications in various journals and books. Her publications reflect her research interests in diabetes, obesity, weight management, eating disorders, nutrition behavioral modification. She is also an Associate Editor of the Journal PANR. Dr. Andreou is serving as the president of the Cyprus Dietetic and Nutrition Association, vise president of the Cyprus Registration Board for Food Scientists and Dietitians and a member in American Academy of Nutrition and Dietetics. She is currently in charge of ongoing scholarly project of epidemiological study of obesity and nutritional habits of Cypriots in Cyprus. She is awarded by the American Dietetic Association (ADA)/AODA.
Abstract:
Obesity rates in Cyprus are very high and epidemiological information on type 2 Diabetes mellitus is limited. The correlates of type 2 diabetes among adults remain unknown in the Cypriot population. Thus, the purpose of this study is to provide the first national estimate of the prevalence of type 2 diabetes and investigate its correlates. A randomly stratified nationally sample of 1001 adults aged 18-80 participated in the study. Only 950 subjects completed the study. All subjects were free of any diseases (known diabetes, kidney, liver), medication and supplementation. The overall prevalence of diabetes and pre-diabetes based on WHO criteria was 9.2% and 16.3%, respectively. After adjusting for age, energy intake, smoking and physical activity participants with obesity (BMI) (OR=2.00, P<0.001), waist circumference (WC) OR=2.08, P<0.001), hypertension (HT) (OR=1.99, P<0.001) and hypercholesterolemia (HC) (OR=2.07, P<0.007) were most likely to develop T2DM compared with the normal ones. The odds of having Diabetes was also found significant between subjects with high levels of Triglycerides (TG) (OR=1.49, P<0.007), compared with the normal ones and between subjects with low levels of HDL (OR=1.44, P<0.008) compared with the ones with high levels of HDL. The prevalence of type 2 diabetes in Cyprus is relatively medium- high. However, the pre-diabetes rates are very high showing a promising increase towards total rates of type 2 Diabetes. Obesity, HT, WC, TG, HC and low HDL are all strong correlates of type 2 Diabetes. Healthy education programs should be initiated for young and Elderly people and those with described abnormal risk factors.
Armin Ezzati
University of Leeds, UK
Title: Does the olive-derived polyphenol oleuropein affect postprandial glycaemic response following a short term high fat intake: Randomised, double-blinded, placebocontrolled, crossover trial
Time : 14:40-15:10
Biography:
Armin Ezzati is a MSc student in Nutrition at University of Leeds, conducting human research on the health effects of functional foods under supervision of Prof. Gary Williamson, professor of functional food.
Abstract:
Polyphenol-rich foods have the potential to improve post-prandial glycaemic response by decreasing glucose absorption thus lowering the risk of Type 2 Diabetes. A randomised, double-blinded, placebo-controlled, cross-over study was conducted on 10 healthy volunteers (5women, 5 men) to investigate whether supplementation with oleuropein extracted from olive leaves extract (Oleaeuropea L.) could attenuate post-prandial blood glucose levels following a 3-day high/normal fat diet. The participants randomised to receive a 3-day high fat diet(~43%fat from daily energy intake) or normal fat diet (~23%fat from daily energy intake) and were given oleuropein(100mg) or placebo capsules for three days before each visits. The participants were fasted and attended four sessions: two control visits and two test visits(after 3-day high fat with or without oleuropein). Blood samples were collected following eating a 109g of white bread at 0(fasted), 15, 30, 45, 60, 90, 120, 150, 180 min. High fat diet with oleuropein, high fat diet with placebo, normal diet with and without oleuropein trials were compared together. There were no significant differences between the tests and controls. Change in mean incremental areas under the glucose curves (IAUC) was calculated and no significant difference were observed. Further studies with a larger sample size with more fat percentage from energy is essential to obtain more accurate results.
Carina Proença
University of Porto, Portugal
Title: Structure-related inhibition of Protein Tyrosine Phosphatase 1B (PTP1B) by flavonoids
Time : 15:30-16:00
Biography:
Carina Proença is a PhD student of Pharmaceutical Sciences at UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy of University of Porto. Her actual domain of study involves the in vitro and in silico evaluation of the inhibitory effect of flavonoids against several enzymes intrinsically related with the type 2 diabetes mellitus.
Abstract:
Type 2 diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia resulting from inadequate insulin secretion and/or resistance to insulin action. Protein tyrosine phosphatase 1B (PTP1B) is considered a major
negative regulator in the insulin signaling pathway, contributing to insulin resistance. Thus, the discovery and development of selective and effective PTP1B inhibitors is a potential therapeutic target for the management of type 2 DM. Some flavonoids have already been shown to inhibit this enzyme, but the literature still lacks in depth structure-activity relationship studies. The main aim of the present work was to test a diversified panel of known and new flavonoids, with different types of substituents (-OH, -OMe and/or -OBn) in different positions, against the PTP1B inhibitory activity. The evaluation of PTP1B activity was performed in vitro by monitoring PTP1B-catalyzed hydrolysis of the substrate p-nitrophenyl phosphate (pNPP) into the product p-nitrophenolate at 405 nm in a microplate reader. The study of the inhibition type of the most active flavonoid was made using the nonlinear regression Michaelis-Menten enzymatic kinetics and the corresponding Lineweaver-Burk plot. Our results suggest that that the presence of -OMe groups at positions 7 and 8 in A ring, together with the presence of -OBn groups at 3’ and 4’ positions in B ring and a OH group at 3 position in C ring, increases the flavonoids’ ability to inhibit PTP1B. The most active flavonoid was 3’,4’-dimethoxy-7,8-dibenzoxyflavonol, presenting a mixed type inhibition. In conclusion, some of the tested flavonoids seem to be promising PTP1B inhibitors and potential effective drugs in the management of type 2 DM, increasing insulin sensitivity.
Ugochukwu Offor
University of KwaZulu-Natal, South Africa
Title: Possible attenuating influence of M. Charantia in diabetic nephropathy following triplavar: Any glimmer of hope?
Time : 16:00-16:30
Biography:
Ugochukwu Offor is a PhD researcher in the department of clinical anatomy, University of KwaZulu-Natal Durban, South Africa. He is a member of Morphology and Andrology Group (MAG) UKZN which philosophical ethos is geared towards addressing core health issues, particularly complications arising from diabetes using sophisticated techniques for medical investigations while promoting indigenous knowledge system (IKS) that is of cutting edge significance in the Republic of South Africa. He is also a Member of Golden Key International Honours Society, an organization that recognizes specifically top 15% academic achievers globally. He was recently nominated for the International Scholars Laureate Program in Australia and China.
Abstract:
Diabetic nephropathy (DN) has become a primary cause of end-stage kidney disease. Several complex dynamics converge together to accelerate the advancement of DN. The study was carried out to explore the mechanism of reno-protective nature of Momordica Charantia (MC) in streptozotocin (STZ) - induced diabetes rats following treatment with triplavar in adult male Sprague-Dawley rats. 78 male Sprague-Dawley rats (n=78) weighing 200±250 were used for the study. The study comprised of two groups i.e. a non-diabetic (A-F) comprising of six animals per group and a diabetic group (G-L) comprising
of seven animals per group. Diabetes was induced in the overnight fasted rats by intraperitoneal injection of STZ (45 mg/kg body weight). The animals were euthanized on the tenth week and the kidneys were removed and prepared for examination. M. charantia illustrates significant improvement in blood glucose levels. Urinary parametric indices displayed positive outputs and enhanced protection of M. charantia. Consequently, histological observations restored kidney tissues from hyperglycemia mediated oxidative damage and efficient protection from apoptotic index.