It is clear from clinical studies that periods of good glycaemic control can have long lasting effects on the development of complications in diabetes, potentially even decades after that good control is lost. Equally periods of poor control can cast a long shadow with an increased risk of cardiovascular disease, renal disease, retinopathy and neuropathy, even if adequate glucose control is subsequently restored. This phenomenon has become known as ‘metabolic memory’, ‘the legacy effect’ or ‘metabolic karma’, and has been used to explain many clinical observations surrounding diabetes and its management. For example, the key impediment to benefits in many short and intermediate-term trials of glucose lowering belatedly undertaken in high-risk patients with advanced diabetes may be due to the ‘bad metabolic karma’ from years of poor control prior to enrolment the study. More recently, the idea of ‘good metabolic karma’ has also been used to promote the concept of early intensive diabetes management, as a means to establish a long-term buffer for good vascular health. A number of different factors potentially contribute to ‘metabolic karma’, including increasing power from longer observation, lead-time effects, long-lasting post-translational modification, compositional changes, and the irreversibility of cumulative damage (i.e. once broken, it can’t be mended). However, another key factor may be epigenetic programming induced by periods of hyperglycaemia, obesity or other components of the diabetic milieu which promote persistent activation of pathogenic pathways, even when such risk factors are belatedly treated. This presentation will explore the latest data surrounding the long-lasting benefits of glucose control in diabetes.
Speaker: Professor Merlin Thomas – MBChB, PhD, FRACP
Senior Research Fellow at Baker IDI Heart & Diabetes Institute
Professor Merlin Thomas is a diabetologist, working at the Baker IDI Heart and Diabetes Institute in Melbourne, Australia. He is a consultant physician in endocrinology and nephrology, who also runs a basic science laboratory. His research has been widely published with two hundred and fifty papers in peer-reviewed journals including Diabetes, The Lancet, Diabetes Care and FASEB. He is the author of the best-selling books “Understanding Type 2 diabetes” and “Fast Living, Slow Ageing”. His ongoing research focuses on understanding the mechanisms of vascular damage in diabetes, with a particular focus on renin angiotensin system and metabolic memory.
Abstract
Chronic kidney disease (CKD) is very common among Aboriginal Australians, with increasing rates in poorer more remote communities; endstage kidney disease (ESKD) can occur at up to 30 times the average Australian rate of 1 in a 1000 people. Although late stage CKD is mostly clinically attributed to diabetic nephropathy, risk factors for CKD occur at every stage in Aboriginal life prior to the onset of diabetes: family history, maternal smoking, premature or small-for-dates infants, childhood and lifelong obesity, smoking and low-cost high-protein/high-calorie diets. The chronic stress of family illness and poverty cause hypercortisolism, clinically manifest as insomnia, worsening hunger, central fat distribution, insulin resistance, hypertension, relative hypokalaemia and proximal muscle weakness.
Conventional delivery of medical services can unintentionally worsen patient stress and illness for Aboriginal patients. The stress and cost of an unaccompanied city visit to a specialist clinic can be reduced by outreach services delivered in a local Aboriginal medical service (AMS) in the presence of an Aboriginal health worker. Telehealth sessions for specialists with local GP, bush nurses and patients are a time-efficient way for service delivery. Verbal communication needs to consider poor hearing, English as a second language, and special cultural issues (name avoidance; gender sensitivity). Written correspondence needs to be copied to multiple medical providers, given the frequent family mobility for cultural obligations.
Medication costs can be alleviated through use of generic drugs, Closing The Gap labelling, and the AMS S100 system. Modern anti-diabetic therapies can avoid or reverse the hunger and weight gain of sulfonylureas and insulin. Prioritising BP and lipid control over diabetes and obesity management achieves quicker and greater mortality and morbidity benefits. Using calcium channel blockade as add-on to ACEi/ARB therapy improves cardiac and renal outcomes better than add-on diuretic (if tolerated without oedema).
Holistic diabetic/CKD management for Aboriginal patients from remote areas needs tailoring to optimise their family time and family budgets.
Speaker: Professor Mark Thomas – MBBS, FRACP
Nephrologist at Royal Perth Hospital
Trained in Sydney and London, worked at RPH for last quarter of a century in all aspects of adult nephrology, with special interests in remote area dialysis for Aboriginal Australians, polycystic kidney disease, diabetic nephropathy and Fabry’s disease. Does lots of teaching for allied health, nursing, under- and post-graduate medicine, and has UWA Professorship with Excellence in Clinical Teaching Award (and re-nominated). Likes cycling, sailing, canoeing, travelling … and his home life.
Saturday 7 May 2016
Abstract
Advances in genetic technologies over the last decade have allowed unprecedented discoveries of genetic variants that contribute to the risk of disease. However, the mechanisms by which these variants contribute to disease remain largely unknown. Few of these results have translated into improving clinical treatments for common complex genetic diseases such as diabetes.
We employed novel approaches to identify combinations of genes that can predict disease outcomes. We identified genetic interactions that could define subtypes of disease, and accurately predict an individual’s progression. For example, we defined six disease subtypes of type 1 diabetes (T1D). Affected siblings were highly likely to share the same T1D subtype, consistent with a genetic basis. The subtypes differed significantly in all clinical features examined. Furthermore, we could define genetic signatures for diseases ranging from diabetes to heart disease and melanoma. These signatures could predict disease outcomes years before onset of symptoms.
Definition of genetic risk groups will allow better characterization, prevention and clinical management of people with complex diseases such as diabetes, cardiovascular disease and cancer.
Speaker: Professor Grant Morahan
Scientific Head, Clinical Sciences Division at The Harry Perkins Institute of Medical Research, University of Western Australia
Prof Grant Morahan is Scientific Head of the Clinical Sciences Division of The Harry Perkins Institute of Medical Research, and Professor of Diabetes Research at the University of Western Australia. His research has included discoveries in antibody immunochemistry, immune tolerance, immunogenetics, and genetics of complex genetic diseases, especially type 1 diabetes. Research highlights include identifying IL12B as a susceptibility gene affecting diseases of immune dysregulation including type 1 diabetes, severe childhood asthma and cerebral malaria; conducting the world’s largest genetic linkage study; identifying over 40 genes affecting risk of type 1 diabetes; and establishing the next-generation genetic resource, The Collaborative Cross.
Prof Morahan was on the Steering Committee of the Type 1 Diabetes Genetics Consortium and is a member of the Faculty of 1000. He is the inaugural Professor of Diabetes Research at the University of Western Australia, and is a Visiting Professor at Peking University, Beijing. He has over 200 scientific papers, including in Nature, Science, Lancet, Nature Genetics, Diabetes and PNAS. His work is being commercialized by two companies, Geniad and FitGenes Australia.
