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.