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CLINICAL RESEARCH
The Diabetic Nephropathy (DN) cohort at Khoo Teck Puat Hospital (KTPH) (Alexandra Health Pte Ltd) has been initiated since 2002. It includes ~ 5,499 multi-ethnic patients with type 2 diabetes (age 58.3 ± 11.7 years old, duration of diabetes 12.0 ± 8.7 years, Chinese 67.5%, Malays 19.1%, Asian Indians 13.3% and others 0.2%). Blood and urine samples collected at baseline visit have been cryo-preserved. In collaboration with local and overseas institutions, we aim to study biomarkers (both genetic and non-genetic) associated with the development and progression of DN in multi-ethnic Asians with diabetes.
The cohort is enriched by subjects with renal impairment in accordance with the aim of the study (MDRD eGFR 67.8 ± 37.7 ml/min/1.73m2, CKD stage 1- 28.1%, stage 2-31.3%, stage 3-20.8%, stage 4- 9.0% and stage 5-10.7%).  Approximately 30.0% of the subjects are classified as having microalbuminuria (urinary albumin-to-creatinine ratio, .i.e. ACR 30 to 299 mg/g) and 27.7% of them are classified as having macroalbuminuria (ACR >= 300 mg/g). The longitudinal trajectory of eGFR and ACR has also been recorded in a large proportion of the subjects.
The median follow-up duration of this cohort is 5.7 years. Incident diabetes related outcomes can be ascertained by linkage of cohort database with Singapore National Disease registries (Renal Registry, Myocardial Infarct Registry, Death/birth Registry, Stroke Registry and Cancer Registry).

The Diabetic Nephropathy (DN) cohort at Khoo Teck Puat Hospital (KTPH) (Alexandra Health Pte Ltd) has been initiated since 2002. It includes ~ 5,499 multi-ethnic patients with type 2 diabetes (age 58.3 ± 11.7 years old, duration of diabetes 12.0 ± 8.7 years, Chinese 67.5%, Malays 19.1%, Asian Indians 13.3% and others 0.2%). Blood and urine samples collected at baseline visit have been cryo-preserved. In collaboration with local and overseas institutions, we aim to study biomarkers (both genetic and non-genetic) associated with the development and progression of DN in multi-ethnic Asians with diabetes.

The cohort is enriched by subjects with renal impairment in accordance with the aim of the study (MDRD eGFR 67.8 ± 37.7 ml/min/1.73m2, CKD stage 1- 28.1%, stage 2-31.3%, stage 3-20.8%, stage 4- 9.0% and stage 5-10.7%).  Approximately 30.0% of the subjects are classified as having microalbuminuria (urinary albumin-to-creatinine ratio, .i.e. ACR 30 to 299 mg/g) and 27.7% of them are classified as having macroalbuminuria (ACR >= 300 mg/g). The longitudinal trajectory of eGFR and ACR has also been recorded in a large proportion of the subjects.

The median follow-up duration of this cohort is 5.7 years. Incident diabetes related outcomes can be ascertained by linkage of cohort database with Singapore National Disease registries (Renal Registry, Myocardial Infarct Registry, Death/birth Registry, Stroke Registry and Cancer Registry).

 

Publications:

1. Genetic markers for urine haptoglobin is associated with decline in renal function in type 2 diabetes in East Asians. Gurung RL, Dorajoo R, Liu S, M Y, Liu JJ, Wang L, Guo L, Yu X, Liu JJ, Lim SC.
Sci Rep. 2018 Mar 23;8(1):5109. doi: 10.1038/s41598-018-23407-1

2. Ong YH, Koh WCA, Ng ML, Tam ZY, Lim SC, Boehm BO; Adult-Onset Autoimmune Diabetes Mellitus Consortium (ADAMS). Glutamic acid decarboxylase and islet antigen 2 antibody profiles in people with adult-onset diabetes mellitus: a comparison between mixed ethnic populations in Singapore and Germany. Diabet Med. 2017 Aug;34(8):1145-1153. doi: 10.1111/dme.13358.

3. Liu JJ, Ghosh S, Kovalik JP, Ching J, Choi HW, Tavintharan S, Ong CN, Sum CF, Summers SA, Tai ES, Lim SC. Profiling of Plasma Metabolites Suggests Altered Mitochondrial Fuel Usage and Remodeling of Sphingolipid Metabolism in Individuals With Type 2 Diabetes and Kidney Disease. Kidney International Reports. 2017 May 31;2(3):470-80.

4. Low S, Lim SC, Yeoh LY, Liu YL, Liu JJ, Fun S, Su C, Zhang X, Subramaniam T, SUM CF. The effect of long term glycemic variability on estimated glomerular filtration rate decline among patients with type 2 diabetes mellitus–insights from the Diabetic Nephropathy Cohort in Singapore. Journal of Diabetes. 2016 Dec 1.

5. Low S, Lim SC, Zhang X, Zhou S, Yeoh LY, Liu YL, Tavintharan S, Sum CF. Development and validation of a predictive model for Chronic Kidney Disease progression in Type 2 Diabetes Mellitus based on a 13-year study in Singapore. Diabetes Research & Clinical Practice 2016; 123:49-54

6. Liu JJ*, Liu S*, Wong MDS, Gurung RL and Lim SC. Urinary haptoglobin predicts rapid renal function decline in Asians with type 2 diabetes and early kidney disease. J Clin Endo Metab 2016; 101(10):3794-3802 (* equal contributors)

7. SC Lim*, R Dorajoo*, X Zhang, L Wang, SF Ang, C Tan, Yeoh LY, XW Ng, Na Li, Chang Su, S Liu, M Wong, S Low, AY Ou, Jeevith B, S Fun, SY Zhou, Simon BM Lee, WE Tang, Subramaniam T, CF Sum, JJ Liu. Genetic variants in the receptor for advanced glycation end products (RAGE) gene were associated with circulating soluble RAGE level (sRAGE), but not with renal function among Asians with type 2 diabetes: a genome-wide association study. Neph Dial Transplant 2016; Jul 21. pii: gfw263. [Epub ahead of print]

8. Liu JJ, Lim SC, Yeoh LY, Su C, Tai BC, Low S, Fun S, Tavintharan S, Chia KS, Tai ES and Sum CF. Ethnic disparities in risk of cardiovascular disease, end stage renal disease and all-cause mortality- a prospective study among South East Asians with type 2 diabetes. Diabetic Medicine 2016; 33(3):332-9

9. Low S, Lim SC, Yeoh LY, Su C, Zhang X, Subramaniam T, Sum CF. Long-term diabetes outcomes in multi-ethnic Asians living in Singapore. Diabetes Res Clin Pract 2016; 111: 83-92. 

10. Low S, Tai ES, Yeoh LY, Liu YL, Liu JJ, Tan KH, Fun S, Su C, Zhang X, Subramaniam T, Sum CF, Lim SC. Onset and progression of kidney disease in type 2 diabetes among multi-ethnic Asian population. J Diabetes Complications 2016; 30(7): 1248-54.

11. Liu JJ, Liu S, Morgenthaler NG, Wong MDS, Tavintharan S, Sum CF, Lim SC. Association of soluble α-klotho with endothelin-1 in type 2 Diabetes. Atherosclerosis 2014;233(2):415-418

12. Lim SC*, Liu JJ*, Tavintharan S and Sum CF.  Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients. Journal of renin-angiotensin-aldosterone system. 2014;15(4):487-90 

13. Liu JJ, Liu S, Wong MDS, Tan CS, Tavintharan S, Sum CF and Lim SC. Relationship between circulating irisin, renal function and body composition in type 2 diabetes. J Diabetes Complications 2013;28(2):208-213

14. Liu JJ, Wong MDS, Toy WC, Tan CSH, Liu S, Ng XW, Tavintharan S, Sum CF and Lim SC. Lower circulating irisin is associated with type 2 diabetes mellitus. J Diabetes Complications (with editorial comments) 2013;27(4):365-369

15. JJ Liu, WC Toy, Melvin DS Wong, Clara SH Tan, Subramaniam T; MS Wong, CF Sum and SC Lim. Elevated undercarboxylated and reduced carboxylated osteocalcin are associated with metabolic syndrome in middle age Asian females. Exp Clin Endocrinol Diabetes. 2013;121:329-33. doi: 10.1055/s-0033-1334883.

16. Lim SC, Phua E J, Sharon F Nne, Amizah B Asrap, Wong DS Melvin, Tan SH Clara, Liu J Jun, Toy W Ching, Ng X Wei, Lau PX Dawn, Pek LT Sharon, Woon Kaing, Lin LF Bernice, S Tavintharan, Sum C Fang. Modifiable risk factors associated with arterial stiffness in diabetic nephropathy in an Asian Population Cohort. Journal of ASEAN Federal Endocrine Societies (JAFES) 2011; 26:163-167

17. SC Lim, Dollyn Quek L, WC Toy, Melvin Wong DS, Lee Ying Yeoh, C Tan MF, D Lau, C Tan, T Subramaniam, C F Sum. Adipocytokine zinc alpha-2 glycoprotein (ZAG) as novel urinary biomarker for normo-albuminuric diabetic nephropathy. Diabetic Medicine 2012;29:1-5 

18. Toy W C, Liu JJ, Anton Cheng KS, C Tan, D Lau, M Wong, T Subramaniam, Sum C F, Lim SC. Adiponectin Gene Polymorphisms and Type 2 Diabetes among Singaporean Chinese Adults. J Diabetes Metab 2011, 2:8

19. S.C. Lim, J. J. Liu, H. Q. Low, N. G. Morgenthaler, Y. Li, L. Y. Yeoh, Y. S. Wu, S.K. Goh, C. Y. Chionh, S. H. Tan, Y. C. Kon, P. C. Soon, Y. M. Bee, T. Subramaniam, C. F. Sum, K. S. Chia. Microarray analysis of multiple candidate genes and associated plasma proteins for nephropathy secondary to type 2 diabetes among Chinese. Diabetologia 2009 52:1343-51

20. Lim, Su-Chi; Morgenthaler, Nils; Subramaniam, Tavintharan; Wu, Yew-Seng; Goh, Siew-Kheng; Sum, Chee-Fang. The relationship between adrenomedullin, metabolic factors and vascular function in individuals with type 2 diabetes mellitus. Diabetes Care 2007;30:1513-1519

21. SC Lim, H H Tan, SK Goh, T Subramaniam, CF Sum, I K Tan, B L Lee, C N Ong. Oxidative Burden in Pre-diabetic and Diabetic Individuals: Evidence from Plasma Coenzyme Q10. Diabetic Med 2006 23: 1344-1349

22. SC Lim, T Goh, YR Lai, WW Tee, Angela Koh, XH Xu, YS Wu, Eric Yap, T Subramaniam, C F Sum. Relationship between common functional polymorphisms of the p22phox gene (-930A>G & +242 C>T) and nephropathy due to type 2 diabetes among Chinese. Diabetic Medicine 2006 23:1037-1041