Day 2 :
University of Lyon, France
Keynote: Evidences that insulin resistance, core of cardiometabolic diseases, is the primary therapeutic target
Time : 09:30-10:15
Dr Nicolas Wiernsperger is a french physiologist and pharmacologist. He has been head of research department on cerebrovascular accidents at Novartis (Switzerland) until 1984. He established as a world recognized specialist of microcirculation. From 1985 to 2005 he was appointed Head of International Pharmacological Development and Senior Pharmacologist at Merck KgA in Lyon. He was also head of a private/public research unit on diabetes microvascular complications at Lyon University. He is an international recognized expert of cardiometabolic diseases and aging. He has published close to 150 papers as well as 2 books. He has been teaching as Invited Professor at several universities. Since 2005 he deals with the development of new drugs as well as,more recently, nutraceuticals
Cardiometabolic diseases affect about one third of the worldwide population. Recent years revealed that the core of these different pathologies is insulin resistance. Diminished sensitivity to insulin leads to various metabolic and vascular (both macro- and microvascular) disturbances. Epidemiology and clinical observations show that resistance to this hormone can be seen very early, possibly already in early childhood. It has clearcut impacts on adult health and worsens with aging. However also aging-related diseases such as cognitive dysfunction and related dementias are also associated with resistance to insulin.
The presentation will show the poorly recognized importance of microvascular insulin resistance as well as many aspects of this defect in various tissues. It will also be shown how to detect this parameter easily and early in human beings. Finally suggestions will be made about possible new treatment strategies.
Saitama Medical University, Japan
Time : 10:15
Shigehiro Katayama, M.D., Ph.D. has been Director of Saitama Medical University Hospital since 2008 and the Deputy Head from 2002 to 2008. He is currently Director Saitama Medical University Kawagoe Clinic since 2014. He also has been the Professor and the Head of Endocrinology and Diabetes Division at Faculty of Medicine, Saitama Medical University since 1995 and retired to be Emeritus Professor in 2015.
He graduated from Faculty of Medicine, The University of Tokyo and received M.D. degree in 1973 and Ph.D. degree in 1980 from The University of Tokyo. He was Postdoctoral Research Fellow at the Rockfeller University in 1980 and Assitant Professor at the State University of New York at Buffalo from 1981-1983. He moved to Saitama Medical University in 1983.
His research interests are in hypertension in diabetics in relation to effects of hypoglycemic and/or hypotensive agents on insulin resistance and in relation to diabetic nephropathy. He has been the Member of New Drug Approval Advisory Committee at The Department of Health and Welfare since 1993. He was a member of the committee to decide the drug price and the committee to approve a new drug, PMDA. He is now serving as one of the Program Officers in the field of Circulatory Disease and Diabetes Mellitus, Japan Agency fpr Medical Research and Development (AMED). He is a Board Certified Member of Japanese Society of Internal Medicine, Japan Endocrine Society, Japanese Society of Nephrology, Japanese Society of Hypertension, Japanese Society of Diabetes and a Fellow of American Diabetes Association, American Heart Association (High Blood Pressure Council).
He recieved Expert Investigator Award from the Japanese Society of Diabetic Complications in 2012, and Society Award from the Japanese Society of Hypertension in 2013.
In Japan, diabetic nephropathy is the leading cause requiring dialysis since 1998. The number of patients under dialysis is about 320,000, 40% of which are diabetics. Since dialysis costs expensive, prevention of the progression of diabetic nephropathy is an urgent target. We evaluated the incidence of diabetic nephropathy (macroalbuminuria of more than 300 mg/g・Cre) from normo- and low-microalbuminuria (<150 mg/g・Cre) in 1550 type 2 diabetics during 8 years (JDCS; Japan Diabetes Complications Study). The onset of macroalbuminuria was observed in 0.67% of the patients, which was one third of the incidence reported in UKPDS. Moreover, 30% of patients with low-microalbunminuria returned to normoalbuminuria (remission/regression). The higher the initial albuminuria, HbA1c, or systolic blood pressure was, the progression risk to macroalbuminuria was higher. Smoking was also the risk for diabetic nephropathy.
There were many trials which elucidated the effectiveness of ACE inhibitors or ARBs (angiotensin II receptor antagonists) including ours such as Japan IDDM, INNOVATION, ORIENT and ROADMAP study. However, relative risk reduction with these RAS inhibitors was about 20 - 30% in patients with macroalbuminuria and 60% in patients with microalbuminuria. We need more vigorous strategy to prevent the new onset and/or progression of diabetic nephropathy. Recent trials using SGLT2 inhibitors such as empagliflozin or canagliflozin decreased not only cardiovascular outcomes by 14% but also renal outcomes by 30 – 40%. SGLT2 inhibitors may increase sodium delivery to the macula densa and then improve tubuloglomerular (TG) feedback, which may result in constriction of afferent arteriole and hence amelioration of hyperfiltration. DPP-4 inhibitors and GLP-1 receptor antagonists may have such an action as well. These new hypoglycemic agents may have a great potential to protect renal functions, especially diabetics with hyperfiltration. Furthermore, we are waiting new renoprotective drugs such as anti-oxidant Nrf2 stimulator, bardoxolone methyl, or non-steroidal mineralocorticoid receptor antagonist (MRA), finerenone.