06

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In the last 12 months, the CUHK Diabetes Care and Research Team continues with its overarching strategy to use large clinical databases and multiomic data, supplemented by experimental studies and interventional programs, to unravel the causes and consequences of diabetes and its complications as well as the genotype-phenotype-treatment-outcome interactions. Supported by the CUHK focused investments, competitive grants, donations, proceedings from educational courses and contract research, we have successfully developed and nurtured a team of young scientists and analysts with complementary skill sets to plan, implement, analyse, interpret, report and publish these findings. Importantly, the support of these infrastructures have led to the graduation of 5 PhD students in 2013 (Xin Liu, ZB Gao, GZ Jiang, Y Zhou, WL Shi) with another 6 PhD students expecting to graduate in the next 24 months. In July 2013, under the stewardship of Professor Ronald Ma and Dr. Wingyee So and in collaboration with researchers from the School of Biomedical Sciences and the School of Life Sciences as well as the Hong Kong University of Science and Technology, our group was awarded the RGC Theme-based Research Scheme (TBRS) to use a transomic approach to discover the genetic regulation of diabetic complications for personalised care. In this project, apart from utilising our existing resources, we will be building a biobank in more than 10 hospitals and setting up collaborations with leading groups

PI:Juliana Chan (Department of Medicine and Therapeutics and Hong Kong Institute of Diabetes and Obesity)

Team:Ronald Ma, Wingyee So, Alice Kong, Risa Ozaki, Andrea Luk, CC Chow, Gang Xu, Heung Man Lee, Ying Wang, Caren He, Ju Luan, Claudia Tam, Guozhi Jiang, Greg Tutino, Yong Hou, Ling-ling Yeung, Amy Wong, Zhou Yue, Alex Ng, Zhan Fang Kang, Mingya Zhou

Research Progress Summary:

95Technical Report on Research Programmes

from the UK, the USA, Asia and Australia for discovery and cross-validation of novel findings. On the other hand, supported by RGC grants and NSFC grants, Professor Alice Kong continued to explore the subjects of sleep disorder and childhood/adolescence/adult obesity and Professor Gang Xu had developed the experimental platform for pancreatic beta-cell/stem cell biology. On a clinical front, supported by the clinical trial centre, led by Dr. Risa Ozaki and Dr. Andrea Luk, the group continues to study the epidemiology of gestational diabetes, obesity and diabetes in the youth as well as develop innovative, holistic and integrated programs to combine research, care and education in pursuit of prevention and control of diabetes and its co-morbidities.

Recognitions:

Awards and Fellowships

Member’s Name Details

RCW Ma • Richard Yu Lecture, Hong Kong College of Physicians (HKCP), 2013

96

1. Tam, C. H., Ho, J. S., Wang, Y., Lam, V. K., Lee, H. M., Jiang, G., Lau, E. S., Kong, A. P., Fan, X., Woo, J., Tsui, S. K., Ng, M. C., So, W. Y., Chan, J. C., & Ma, R. C. (2013). Use of Net Reclassifi cation Improvement (NRI) Method Confirms The Utility of Combined Genetic Risk Score to Predict Type 2 Diabetes. PLoS ONE, 8(12), e83093.

2. Ma, R. C., Hu, C., Tam, C. H., Zhang, R., Kwan, P., Leung, T. F., Thomas, G. N., Go, M. J., Hara, K., Sim, X., Ho, J. S., Wang, C., Li, H., Lu, L., Wang, Y., Li, J. W., Wang, Y., Lam, V. K., Wang, J., Yu, W., Kim, Y. J., Ng, D. P., Fujita, H., Panoutsopoulou, K., Day-Williams, A. G., Lee, H. M., Ng, A. C., Fang, Y. J., Kong, A. P., Jiang, F., Ma, X., Hou, X., Tang, S., Lu, J., Yamauchi, T., Tsui, S. K., Woo, J., Leung, P. C., Zhang, X., Tang, N. L., Sy, H. Y., Liu, J., Wong, T. Y., Lee, J. Y., Maeda, S., Xu, G., Cherny, S. S., Chan, T. F., Ng, M. C., Xiang, K., Morris, A. P., Keildson, S., Hu, R., Ji, L., Lin, X., Cho, Y. S., Kadowaki, T., Tai, E. S., Zeggini, E., McCarthy, M. I., Hon, K. L., Baum, L., Tomlinson, B., So, W. Y., Bao, Y., Chan, J. C., & Jia, W. (2013). Genome-wide association study in a Chinese population identifi es a susceptibility locus for type 2 diabetes at 7q32 near PAX4. Diabetologia, 56(6), 1291-1305.

3. Guan, J., Zhao, H. L., Sui, Y., He, L., Lee, H. M., Lai, F. M., Tong, P. C., & Chan, J. C. (2013). Histopathological correlations of islet amyloidosis with apolipoprotein E polymorphisms in type 2 diabetic Chinese patients. Pancreas, 42(7), 1129-1137.

4. Imai, E., Haneda, M., Chan, J. C., Yamasaki, T., Kobayashi, F., Ito, S., & Makino, H. (2013). Reduction and residual proteinuria are therapeutic targets in type 2 diabetes with overt nephropathy: a post hoc analysis (ORIENT-proteinuria). Nephrology Dialysis Transplantation, 28(10), 2526-2534.

5. Imai, E., Haneda, M., Yamasaki, T., Kobayashi, F., Harada, A., Ito, S., Chan, J. C., & Makino, H. (2013). Effects of dual blockade of the renin-angiotensin system on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy and hypertension in the ORIENT: a post-hoc analysis (ORIENT-Hypertension). Hypertension Research, 36(12), 1051-1059.

6. Raz, I., Riddle, M. C., Rosenstock, J., Buse, J. B., Inzucchi, S. E., Home, P. D., Del Prato, S., Ferrannini, E., Chan, J. C., Leiter, L. A., Leroith, D., Defronzo, R., & Cefalu, W. T. (2013). Personalized management of hyperglycemia in type 2 diabetes: refl ections from a Diabetes Care Editors' Expert Forum. Diabetes Care, 36(6), 1779-1788.

7. Kang, Z. F., Deng, Y., Zhou, Y., Fan, R. R., Chan, J. C., Laybutt, D. R., Luzuriaga, J., & Xu, G. (2013) Pharmacological reduction of NEFA restores the effi cacy of incretin-based therapies through GLP-1 receptor signalling in the beta cell in mouse models of diabetes. Diabetologia, 56, 423-433.

8. Kong, A. P., Choi, K. C., Ho, C. S., Chan, M. H., Ozaki, R., Chan, C. W., & Chan, J. C. (2013). A s s o c i a t i o n s o f u r i c a c i d a n d g a m m a -glutamyltransferase (GGT) with obesity and components of metabolic syndrome in children and adolescents. Pediatric Obesity, 8(5), 351-357.

9. Kong, A. P., Xu, G., Brown, N., So, W. Y., Ma, R. C., & Chan, J. C. (2013). Diabetes and its comorbidities - where East meets West . Nature Rev iews Endocrinology, 9(9), 537-547.

10. Lam, V. K., Ma, R. C., Lee, H. M., Hu, C., Park, K. S., Furuta, H., Wang, Y., Tam, C. H., Sim, X., Ng, D. P., Liu, J., Wong, T. Y., Tai, E. S., Morris, A. P., Tang, N. L., Woo, J., Leung, P. C., Kong, A. P., Ozaki, R., Jia, W. P., Lee, H. K., Nanjo, K., Xu, G., Ng, M. C., So, W. Y., & Chan, J. C. (2013). Genetic associations of type 2 diabetes with islet amyloid polypeptide processing and degrading pathways in Asian populations. PLoS ONE, 8(6), e62378.

11. Leung, R. K., Wang, Y., Ma, R. C., Luk, A. O., Lam, V., Ng, M., So, W. Y., Tsui, S. K., & Chan, J. C. (2013). Using a multi-staged strategy based on machine learning and mathematical modeling to predict genotype-phenotype risk patterns in diabetic kidney disease: a prospective case-control cohort analysis. BMC Nephrology, 14, 162.

12. Liu, L. Z., Cheung, S. C., Lan, L. L., Ho, S. K., Chan, J. C., & Tong, P. C. (2013). Microtubule network is required for insulin-induced signal transduction and actin remodeling. Molecular and Cellular Endocrinology, 365(1), 64-74.

13. Luk, A. O., Ma, R. C., Lau, E. S., Yang, X., Lau, W. W., Yu, L. W., Chow, F. C., Chan, J. C., & So, W. Y. (2013). Risk association of HbA1c variability with chronic kidney disease and cardiovascular disease in type 2 diabetes: prospective analysis of the Hong Kong Diabetes Registry. Diabetes/Metabolism Research and Reviews, 29(5), 384-390.

14. Yang, X., Wang, Y., Luk, A. O., So, W. Y., Ma, R. C., Kong, A. P., Xu, G., & Chan, J. C. (2013). Enhancers and attenuators of risk associations of chronic hepatitis B virus infection with hepatocellular carcinoma in type 2 diabetes. Endocrine-Related Cancer, 20(2), 161-171.

Publications:

97Technical Report on Research Programmes

15. Xu, H., Tsang, K. S., Chan, J. C., Yuan, P., Fan, R., Kaneto, H., & Xu, G. (2013). The combined expression of Pdx1 and MafA with either Ngn3 or NeuroD improves the differentiation efficiency of mouse embryonic stem cells into insulin-producing cells. Cell Transplantation, 22(1), 147-158.

16. Ma, R. C., & Chan, J. C. (2013). Type 2 diabetes in East Asians: similarities and differences with populations in Europe and the United States. Annals of the New York Academy of Sciences, 1281, 64-91.

17. Ting, R. Z., Lau, E. S., Ozaki, R., Lau, W. W., Kong, A. P., Luk, A. O., Chow, C. C., Ma, R. C., Wing, Y. K., Chan, J. C., & So, W. Y. (2013). High risk for cardiovascular disease in Chinese type 2 diabetic patients with major depression--a 7-year prospective analysis of the Hong Kong Diabetes Registry. Journal of Affective Disorders, 149(1-3), 129-135.

Discovery of a genetic variant in the PAX4 loci in Chinese type 2 diabetes – a joint collaboration between the Chinese University of Hong Kong and Jiaotung University, Shanghai, China.

This fi gure was published in Diabetologia 2013.

Copyright © 2013 Springer