President's lecture

Abstract

Prof. Karen Lam is Chair Professor in Medicine, Director of the Research Centre in Heart, Brain, Hormone & Healthy Aging, Clinical Director of the State Key Lab of Pharmaceutical & Biotechnology and Chairman of the Clinical Trial Centre at the University of Hong Kong. She is also the Department Head and Chief of Endocrinology at the University Department of Medicine, Queen Mary Hospital. Prof. Lam was the Founding President of Diabetes Hong Kong (Honorary President since 2014), a past president of the Hong Kong Society of Endocrine, Metabolism and Reproduction, and past Chairman of two specialty boards of the HK College of Physicians - Advanced Internal Medicine and Endocrinology, Diabetes & Metabolism. She is currently the associate editor/editorial board member of several international peer-reviewed journals in diabetes and endocrinology. Prof. Lam has published extensively on clinical, basic and translational research in diabetes and endocrinology, including publications in Diabetes, Diabetes Care, Diabetologia, JCEM, Hypertension, ATVB, Circulation, Annals of Internal Medicine, Endocrinology, JBC, PNAS, JCI and Lancet. Her current research focuses on the role of adipokines and hepatokines in diabetes and other obesity-related cardiometabolic disorders. Her team has established two large cohorts, the CRISPS and HKW Diabetes Registry, for the study of genetic and environmental determinants of diabetes and its related medical problems. INSIGHTS ON THE ROLES OF ADIPOKINES IN CLINICAL DIABETES: The adipose tissue, previously considered as an inert energy store, is now recognized as an important endocrine organ that secretes a variety of bioactive peptides, known as adipokines or adipocytokines. Since the identification of leptin as a fat-derived hormone, an increasing number of adipokines have been identified through gene expression profiling and proteomic techniques, and shown to impact on glucose and lipid metabolism, energy homeostasis and inflammation. Dysregulated secretion of various adipokines has been demonstrated in the obese state, leading to chronic low-grade systemic inflammation and insulin resistance which, at least in part, explain why obesity is responsible for 58% of the cases of diabetes and 21% of ischemic heart disease worldwide. Of the known adipokines, adiponectin and adipocyte fatty acid binding protein (A-FABP) have the highest circulating levels in humans and are biomarkers predictive of type 2 diabetes, with increased risk being conferred by low adiponectin or high A-FABP levels. On the other hand, we have shown that, in obese individuals, the adipose tissue becomes one of the major sources of fibroblast growth factor 21 (FGF21), a hormone generally held to be a hepatokine. Beneficial metabolic effects of FGF21 have been demonstrated in animal studies and more recently, in humans, in part mediated through inducing the secretion of adiponectin. Paradoxically, high levels of FGF21 are found in obesity and type 2 diabetes, suggesting the presence of FGF21 resistance, analogous to leptin resistance in obesity. Recent studies have attributed this FGF21 resistance to adipose tissue inflammation and changes in microRNA expression, demonstrated in animal and human studies. High FGF21 levels have been found to predict the development of type 2 diabetes and diabetic nephropathy, whereas reduced FGF21 levels are found in autoimmune diabetes. The methodological difficulties that limit the clinical use of some adipokines, such as RBP-4 and angiopoietin-like-protein 4, as biomarkers in clinical diabetes and diabetic complications, will be reviewed. The relative contribution of the adipokines which have been implicated in glucose metabolism, with regard to the prediction and treatment of clinical diabetes, will be discussed.