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CLINICAL RESEARCH

The Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D) is funded by the highly competitive National Medical Research Council’s Program Project Grant (PPG) and Clinician Scientist Individual Research Grant (CS-IRG).

The SMART2D study was launched in FY2011 to study the impact of diabetes on blood vessel function and commonly encountered diabetes-related complications among Singaporeans. Funded by a SGD 2-million PPG, Drs Lim Su Chi, Tavintharan Subramaniam, Yeoh Lee Ying and Sum Chee Fang led the study and recruited 2,057 Type 2 Diabetic patients with and without vascular complications.

Upon the completion of the PPG (which is a cross-sectional study) in FY2013, our institution was further awarded a SGD 1.5-million CS-IRG in FY2014 to conduct a follow-up prospective study aimed at recalling all of the initial participants for re-evaluation and to collect new data to study disease progression in relation to changes in risk factors. By exploiting the synergy between clinical and genetic epidemiology, SMART2D will continue as a longitudinal study that investigates the relationship between risk factors (genetic and non-genetic), vascular function (i.e. intermediate phenotype - endothelial reactivity and arterial stiffness) and final phenotypes (diabetic foot syndrome, nephropathy, retinopathy, cognitive dysfunction and mood disorders).

The SMART2D study involves collaboration with prestigious institutions such as the Genome Institute of Singapore (GIS), National University of Singapore (NUS), National Healthcare Group Polyclinics (NHGP) and the Wellcome Trust Centre for Human Genetics at Oxford, UK. In addition, the cohort is part of a nation-wide, multi-institution consortium (DYNAMO: Diabetes study in Nephropathy And other Microvascular complications) devoted to studying diabetic kidney disease and retinopathy. Observations from SMART2D have also been published in several renowned peer-reviewed journals and presented at conferences worldwide and the finding that central obesity is associated with young onset diabetes and increased susceptibility to diabetes-related complications such as chronic kidney disease (CKD) has been reported in Singapore’s national newspaper and in the Singapore Medical Journal.  

We are currently recruiting volunteers to participate in our follow-up prospective study. Various health assessment tests, including blood and urine tests, foot screening, calculation of body composition and cognitive tests may be conducted. The results obtained from these tests can be used to inform the volunteers (and their doctors) of any changes in their health status and blood vessel functions. If you are interested in learning more about the study or would like to join us as a study volunteer, please contact Dr Keven Ang (Project Manager) at 6602-2343 or Ms Amy Ou (Project Lead-Research Nurse) at 8128-9442. Collection, use and disclosure of your personal data shall be in accordance with our privacy policy which is available at https://www.ktph.com.sg/pdpa

 

Publications (Manuscript):

1. Gurung RL, Yiamunaa M, Liu S, Liu JJ, Lim SC, for SMART2D study. Short leukocyte telomere length predicts albuminuria progression in individuals with type 2 diabetes. Kidney International Reports (2018), doi: 10.1016/j.ekir.2017.12.005.

2. Zhang X, Low S, Kumari N, Wang J, Ang K, Yeo D, Tavintharan S, Sum CF, Lim SC. Direct medical cost associated with diabetic retinopathy severity in type 2 diabetes in Singapore. PloS one, 12(7), e0180949.

3. Liu JJ, Pek T, Li S, Ang K, Tavintharan S, Lim SC. Plasma Leucine-rich Alpha-2-glycoprotein 1 Predicts Rapid eGFR Decline and Albuminuria Progression in Type 2 Diabetes. J Clin Endocrinol Metab 102: 3683–3691, 2017

4. Pek SL, Sum CF, Yeoh LY, Lee SB, Tang WE, Lim SC, Tavintharan S. Association of apolipoprotein-CIII (apoC-III), endothelium-dependent vasodilation and peripheral neuropathy in a multi-ethnic population with type 2 diabetes. Metabolism. 2017 Jul 31;72:75-82.

5. Zhang X, Low S, Sum CF, Tavintharan S, Yeoh LY, Liu J, Li N, Ang K, Lee SB, Tang WE, Lim SC. Arterial stiffness is an independent predictor for albuminuria progression among Asians with type 2 diabetes—A prospective cohort study. Journal of Diabetes and its Complications. 2017 Jun 30;31(6):933-8.

6. Moh MC, Sum CF, Tavintharan S, Ang K, Lee SB, Tang WE, Lim SC. Baseline predictors of aortic stiffness progression among multi-ethnic Asians with type 2 diabetes. Atherosclerosis. 2017 May 31;260:102-9.

7. Zhang X, Liu JJ, Sum CF, Ying YL, Tavintharan S, Li N, Su C, Low S, Lee SB, Tang WE, Lim SC. Ethnic Disparity in Inter-Arm Systolic Blood Pressure Difference and its Determinants among Asians with Type 2 Diabetes: A Cross-Sectional Study. Journal of the ASEAN Federation of Endocrine Societies. 2016 Nov 4;31(2):81.

8. Lim SC, Dorajoo R, Zhang X, Wang L, Ang SF, Tan CS, Yeoh LY, Ng XW, Li N, Su C, Liu S. 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. Nephrology Dialysis Transplantation. 2016 Jul 21:gfw263.

9. Moh MC, Sum CF, Tavintharan S, Pek SL, Yeoh LY, Ng X, Lee SB, Tang WE, Lim SC. Association of the anti-angiogenic factor secreted protein and rich in cysteine (SPARC) with vascular complications among Chinese type 2 diabetic patients in Singapore. Journal of Diabetes and its Complications. 2016 Mar 31.

10. Zhang X, Liu JJ, Fang Sum C, Ying YL, Tavintharan S, Ng XW, Su C, Low S, Lee SB, Tang WE, Lim SC. Central arterial stiffness is associated with systemic inflammation among Asians with type 2 diabetes. Diabetes and Vascular Disease Research. 2016 Jul;13(4):303-6.

11. Zhang X, Liu JJ, Sum CF, Ying YL, Tavintharan S, Ng XW, Low S, Lee SB, Tang WE, Lim SC. Ethnic disparity in central arterial stiffness and its determinants among Asians with type 2 diabetes. Atherosclerosis. 2015 Sep 30;242(1):22-8.

12.  Pek SL, Tavintharan S, Wang X, Lim SC, Woon K, Yeoh LY, Ng X, Liu J, Sum CF. Elevation of a Novel Angiogenic Factor, Leucine-Rich-α2-Glycoprotein (LRG1), Is Associated With Arterial Stiffness, Endothelial Dysfunction, and Peripheral Arterial Disease in Patients With Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism. 2015 Jan 30;100(4):1586-93. 

13.  Liu JJ, Yeoh LY, Sum CF, Tavintharan S, Ng XW, Liu S, Lee SB, Tang WE, Lim SC. Vascular cell adhesion molecule-1, but not intercellular adhesion molecule-1, is associated with diabetic kidney disease in Asians with type 2 diabetes. Journal of diabetes and its complications. 2015 Jul 31;29(5):707-12. 

14.  Low KMS, Sum CF, Yeoh LY, Tavintharan S, Ng X, Lee SBM, Tang WE, Lim SC. Prevalence of Chronic Kidney Disease in Singaporean Adults with Type 2 Diabetes Mellitus. ANNALS Academy of Medicine Singapore. 2015;44:164-171. 

15.   Moh MC, Sum CF, Lam BCC, Ng X, Su C, Tavintharan S, Yeoh LY, Wong MDS, Lee SBM, Tang WE, Lim SC. Evaluation of body adiposity index as a predictor of aortic stiffness in multi-ethnic Asian population with type 2 diabetes. Diabetes & Vascular Disease Research. 2014;12(2):111-118.

16.    Yeoh CKE, Sum CF, Su C, Low KMS, Lim SC, Yeoh LY, Ng X, Tang WE, Lee SBM, Tavintharan S. Low-density Lipoprotein Cholesterol levels in adults with Type 2 Diabetes: an alternative equation for accurate estimation and improved cardiovascular risk classification. Diabetes & Vascular Disease Research. 2014 Nov;11(6):431–439.

17.   Liu JJ, Sum CF, Tavintharan S, Yeoh LY, Ng XW, Moh AM, Lee S, Tang WE, Lim SC. Obesity is a determinant of arterial stiffness independent of traditional risk factors in Asians with young-onset type 2 diabetes. Atherosclerosis. 2014 Oct 31;236(2):286-91.

18.   Liu JJ, Tavintharan S, Yeoh LY, Sum CF, Ng XW, Pek SL, Lee SB, Tang WE, Lim SC. High normal albuminuria is independently associated with aortic stiffness in patients with type 2 diabetes. Diabetic Medicine. 2014 Oct 1;31(10):1199-204.

19.   Tavintharan S, Pek LT, Liu JJ, Ng XW, Yeoh LY, Su Chi L, Chee Fang S. Osteoprotegerin is independently associated with metabolic syndrome and microvascular complications in type 2 diabetes mellitus. Diabetes and Vascular Disease Research. 2014 Sep;11(5):359-62.

 

Publications (Abstracts):

1. Gurung RL, Y. M, Liu S, Liu JJ, Lim SC. Short leukocyte telomere length is associated with increased risk for albuminuria progression in type 2 diabetes in Asians. Diabetologia 60(Suppl 1):S94 .

2. Zhang X, Neelam K, Low SM, Li N, Ying YL, Lee S, Tang WE, Tavintharan S, Sum CF, Lim SC. Central arterial stiffness is associated with the presence and severity of diabetic retinopathy among Asians with type 2 diabetes mellitus. Singapore Med J. 2016;57(1 Suppl):S50.

3. Wong DSM, Moh MC, Sum CF, Tavintharan S, Lim SC. Association of Fractalkine and Overt Albumin Excretion in Type 2 Diabetes. Singapore Med J. 2016;57(1 Suppl):S49.

4. Gurung RL, Liu S, Yeo SJ, Jeevith B, Li N, Sum CF, Lim SC. Novel association of NPAT variant and gastrointestinal side effects of metformin in patients with type 2 diabetes mellitus. Singapore Med J. 2016;57(1 Suppl):S36. (Top Poster Abstract Awards: Basic Science Research)

5. Goenadi CJ, Zhang X, Pek S, Tavintharan S, Sum CF, Lim SC, Yip CC, Neelam K. Elevated plasma leucine-rich alpha-2-glycoprotein 1 is associated with diabetic retinopathy in Asians with type 2 diabetes mellitus. Singapore Med J. 2016;57(1 Suppl):S29. (Top Oral Abstract Awards: Basic Science Research)

6. Pek SLT, Moh AMC, Yeoh LY, Lim SC, Sum CF, Tavintharan S. Prevalence of peripheral arterial disease and peripheral neuropathy in early-onset diabetes in a cohort of multiethnic patients with Type 2 Diabetes. AAMS. 2016;45(9 Suppl):S27. (Silver - Singapore Young Investigators Award)

7. Lim SC, Zhang X, Li N, Liu JJ, Moh MC, Su C, Low S, Tavintharan S, Yeoh LY, Sum CF. Prospective cohort study suggests that central arterial stiffness is an independent predictor of albuminuria progression among Asians with type 2 diabetes. JAFES. 2015;30(2):52 (Oral Abstract). Winner of Best Overall Oral Presentation & Best Section Oral Presentation.

8. Pek SLT, Yeoh LY, Lim SC, Sum CF, Tavintharan S. Plasma apoCIII is independently associated with peripheral neuropathy in patients with Type 2 Diabetes (T2D). AAMS. 2015;44(10 Suppl):S175.

9. Sandhya D, Woon K, Pek S, Lin M, Lee YY, Lim SC, Sum CF, Tavintharan S. Effects of Fenofibrate on Pigment Epithelium-Derived Factor (PEDF) in clinical human subjects and ARPE-19 eye cells. AAMS. 2015;44(10 Suppl):S51. (Winner of Gold Award)

10.   Zhang X, Liu JJ, Sum CF, Ying YL, Tavintharan S, Ng XW, Low S, Lee SB, Tang WE, Lim SC. Central arterial stiffness is associated with systemic inflammation among Asians with type 2 diabetes. AAMS. 2015;44(10 Suppl):S333.

11.   Wong MDS, Moh MC, Yeoh LY, Sum CF, Tavintharan S, Ng X, Lee SBM, Tang WE, Lim SC. Association between visceral adiposity and microalbuminuria in type 2 diabetes - potential role of inflammation and insulin resistance. Diabetes Research and Clinical Practice. 2014;106(1 Suppl):S241.

12.   Liu S, Liu JJ, Sum CF, Tavintharan S, Ng X, Yeoh LY, Lee SBM, Tang WE, Lim SC. Plasma adiponectin is independently associated with soluble VCAM-1 but not ICAM-1 in patients with type 2 diabetes mellitus. Diabetes Research and Clinical Practice. 2014;106(1 Suppl):S47.

13.   Liu JJ, Sum CF, Tavintharan S, Yeoh LY, Lee SBM, Tang WE, Ng X, Lim SC. Ethnic disparity in arterial stiffness among Asians with Type 2 Diabetes. Diabetes Research and Clinical Practice. 2014;106(1 Suppl):S57.

14.   Moh MC, Sum CF, Ng X, Tavintharan S, Yeoh LY, Wong MDS, Lee SBM, Tang WE, Lim SC. Insulin resistance mediates association of elevated liver alanine aminotransferase and endothelial dysfunction among Type 2 Diabetes Chinese male patients in Singapore. Diabetes Research and Clinical Practice. 2014;106(1 Suppl):S44.

15.   Wong MDS, Moh MC, Yeoh LY, Sum CF, Ng X, Tavintharan S, Lee SBM, Tang WE, Lim SC. Determinants of elevated high-sensitivity C-reactive protein in a type 2 diabetic multi-ethnic Asian population. Singapore Med J. 2014;55(1 Suppl):S60.

16.   Pek SLT, Ng X, Yeoh LY, Lim SC, Sum CF, Tavintharan S. Alternative ankle branchial index predicts arterial compliance in patients with type 2 diabetes mellitus. Singapore Med J. 2014;55(1 Suppl):S62.

17.   Woon K, Ong YC, Pek SLT, Ng X, Yeoh LY, Lim SC, Sum CF, Tavintharan S. Fenofibrate treatment is associated with increased expression of pigment epithelium-derived factor in patients with type 2 diabetes mellitus and HepG2 cells. Singapore Med J. 2014;55(1 Suppl):S28.

18.  Moh MC, Yeoh LY, Sum CF, Ng X, Tavintharan S, Wong MDS, Lee SBM, Tang WE, Lim SC. Association of central obesity with renal function in early-onset type 2 diabetes. Singapore Med J. 2014;55(1 Suppl):S29.

19.  Tavintharan S, Pek SLT, Wang X, Lim SC, Yeoh LY, Sum CF. Leucine-Rich-Alpha2-Glycoprotein1 (LRG1) Is Reduced in Males with Type 2 Diabetes Complicated with Peripheral Arterial Disease. Diabetes. 2014;63(1 Suppl):A109.

20.  Moh MC, Tavintharan S, Sum CF, Yeoh LY, Ng X, Lee SBM, Tang WE, Lim SC. Relationship between Anthropometric Measurements of Adiposity and Arterial Stiffness in Subjects with Type 2 Diabetes. Diabetes. 2014;63(1 Suppl):A528.

21.  Tavintharan S, Lim SC, Yeoh LY, Ng X, Tang WE, Lee SBM, Sum CF. The Impact of Ethnicity on Risk of Complications in Patients with Type 2 Diabetes— findings from Multiethnic Asian Population. Diabetes. 2014;63(1 Suppl):A372.

22.  Moh MC, Sum CF, Ng X, Tavintharan S, Yeoh LY, Wong MDS, Lee SBM, Tang WE, Lim SC. Ethnic disparity in the relationship of insulin resistance and body mass index with serum alanine aminotransferase among a multi-ethnic Asian population with type 2 diabetes. AAMS. 2014;43(9 Suppl):S328.

23.  Wong MDS, Moh MC, Sum CF, Ng X, Tavintharan S, Yeoh LY, Lee SBM, Tang WE, Lim SC. Association between visceral adiposity, inflammation (C-reactive protein), micro-vascular endothelial dysfunction and nephropathy in multi-ethnic Asians with type 2 diabetes (SMART2D cohort). AAMS. 2014;43(9 Suppl):S47.

24.  Liu S, Liu JJ, Ng X, Sum CF, Tavintharan S, Yeoh LY, Lee SBM, Tang WE, Lim SC. Circulating vascular cell adhesion molecule 1, but not intercellular adhesion molecule 1, is associated with renal impairment in patients with type 2 diabetes mellitus. AAMS. 2014;43(9 Suppl):S296.

25.  Ng X, Lim SC, Tavintharan S, Yeoh LY, Asrap A, Cheok J, Ou Y, Arof M, Lum NJ, Riffin N, Sum CF. Clinical Predictors of Established Diabetic Nephropathy in a Large Asian Population. Singapore Med J. 2012;53(1 Suppl):S25 (Also orally presented in AH Health Forum 2012).

26.  Liu JJ, Lim SC, Tavintharan S, Yeoh LY, Ng X, Sum CF. Multiple Predictors of Arterial Stiffness in Type 2 Diabetes. AAMS. 2012;41(9 Suppl):S93.

27.  Ng X, Lim SC, Tavintharan S, Yeoh LY, Asrap A, Arof M, Ou Y, Cheok J, Riffin N, Liew YT. Arterial Stiffness in Diabetic Nephropathy is Associated with Endothelial Dysfunction. AAMS. 2012;41(9 Suppl):S106.

28.  Arof M, Asrap A, Ou Y, Cheok J, Riffin N, Ng X, Lum NJ, Tavintharan S, Yeoh LY, Sum CF. Validation of the Accuracy of Bio-impedence Body Composition Analyzer (InBody S20) in Estimating Waist Circumference among Subjects with Type 2 Diabetes. AAMS. 2012;41(9 Suppl):S39.


Media:

1.  Short leukocyte telomere length is associated with increased risk for albuminuria progression in type 2 diabetes in Asians (Oral Presentation)



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