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  1. Low SK, Khoo JK, Tavintharan S, Lim SC, Sum CF
    Ann Acad Med Singap, 2016 Jan;45(1):1-5.
    PMID: 27118222
  2. Liu JJ, Sum CF, Tavintharan S, Yeoh LY, Ng XW, Moh AM, et al.
    Atherosclerosis, 2014 Oct;236(2):286-91.
    PMID: 25112799 DOI: 10.1016/j.atherosclerosis.2014.07.017
    OBJECTIVE: Type 2 diabetes (T2DM) among the young population has become a serious concern globally, presumably due to the rising trend of obesity. Compared to other forms of diabetes, young-onset T2DM experiences more cardiovascular events and other vascular complications although the underlying mechanisms remain largely unknown. Increased arterial stiffness is a hallmark of vasculopathy. We aim to study the clinical and metabolic determinants of arterial stiffness in a cohort of multi-ethnic Asians with young-onset T2DM.
    METHODS: 179 subjects with T2DM onset age below 30 years old were selected in this cross sectional study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV).
    RESULTS: PWV was correlated with age, duration of diabetes, systolic blood pressure, alanine aminotransferase, urinary albumin-to-creatinine ratio (ACR) and eGFR in bivariate correlation analysis. However, PWV was only significantly correlated with body mass index (BMI), waist circumference, urinary ACR and eGFR after adjustment for age. Overweight individuals with young-onset T2DM had significantly higher PWV levels compared to their lean counterparts (7.3 ± 2.4 m/s vs 6.4 ± 2.3 m/s, p = 0.072 and p < 0.0001 without and with adjustment for age, respectively). Multivariable regression models revealed that age, BMI, eGFR and usage of insulin were independently associated with PWV. These 4 variables explained 35.5% variance in PWV levels.
    CONCLUSION: Age, BMI, renal function and insulin usage are the main determinants of PWV levels in Asians with young-onset T2DM. Notably, obesity is a modifiable determinant of arterial stiffness independent of high blood pressure, dyslipidemia and hyperglycemia in this population.
  3. Liu S, Liu JJ, Gurung RL, Chan C, Yeo D, Ang K, et al.
    Ann Acad Med Singap, 2019 Jul;48(7):217-223.
    PMID: 31495867
    INTRODUCTION: The risk for diabetes progression varies greatly in individuals with type 2 diabetes mellitus (T2DM). We aimed to study the clinical determinants of diabetes progression in multiethnic Asians with T2DM.

    MATERIALS AND METHODS: A total of 2057 outpatients with T2DM from a secondary-level Singapore hospital were recruited for the study. Diabetes progression was defined as transition from non-insulin use to requiring sustained insulin treatment or glycated haemoglobin (HbA1c) ≥8.5% when treated with 2 or more oral hypoglycaemic medications. Multivariable logistic regression (LR) was used to study the clinical and biochemical variables that were independently associated with diabetes progression. Forward LR was then used to select variables for a parsimonious model.

    RESULTS: A total of 940 participants with no insulin use or indication for insulin treatment were analysed. In 3.2 ± 0.4 (mean ± SD) years' follow-up, 163 (17%) participants experienced diabetes progression. Multivariable LR revealed that age at T2DM diagnosis (odds ratio [95% confidence interval], 0.96 [0.94-0.98]), Malay ethnicity (1.94 [1.19-3.19]), baseline HbA1c (2.22 [1.80-2.72]), body mass index (0.96 [0.92-1.00]) and number of oral glucose-lowering medications (1.87 [1.39-2.51]) were independently associated with diabetes progression. Area under receiver operating characteristic curve of the parsimonious model selected by forward LR (age at T2DM diagnosis, Malay ethnicity, HbA1c and number of glucose-lowering medication) was 0.76 (95% CI, 0.72-0.80).

    CONCLUSION: Young age at T2DM diagnosis, high baseline HbA1c and Malay ethnicity are independent determinants of diabetes progression in Asians with T2DM. Further mechanistic studies are needed to elucidate the pathophysiology underpinning progressive loss of glycaemic control in patients with T2DM.
  4. Zhang X, Liu JJ, Sum CF, Ying YL, Tavintharan S, Ng XW, et al.
    Atherosclerosis, 2015 Sep;242(1):22-8.
    PMID: 26162317 DOI: 10.1016/j.atherosclerosis.2015.06.019
    OBJECTIVE: We previously reported ethnic disparity in adverse outcomes among Asians with type 2 diabetes (T2DM) in Singapore. Central arterial stiffness can aggravate systemic vasculopathy by propagating elevated systolic and pulse pressures forward, thereby accentuating global vascular injury. We aim to study ethnic disparity in central arterial stiffness and its determinants in a multi-ethnic T2DM Asian cohort.
    METHODS: Arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV) and augmentation index (AI) using applanation tonometry method in Chinese (N = 1045), Malays (N = 458) and Indians (N = 468). Linear regression model was used to evaluate predictors of PWV and AI.
    RESULTS: PWV was higher in Malays (10.1 ± 3.0 m/s) than Chinese (9.7 ± 2.8 m/s) and Indians (9.6 ± 3.1 m/s) (P = 0.018). AI was higher in Indians (28.1 ± 10.8%) than Malays (25.9 ± 10.1%) and Chinese (26.1 ± 10.7%) (P < 0.001). Malays remain associated with higher PWV (β = 0.299, P = 0.048) post-adjustment for age, gender, duration of diabetes, hemoglobin A1c, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), soluble receptor for advanced glycation end-products, urinary albumin-to-creatinine ratio, and insulin usage, which were all independent predictors of PWV. Indians remain associated with higher AI (β = 2.776, P < 0.001) post-adjustment for age, gender, BMI, SBP, DBP, and height, which were independent predictors of AI. These variables explained 27.7% and 33.4% of the variance in PWV and AI respectively.
    CONCLUSIONS: Malays and Indians with T2DM have higher central arterial stiffness, which may explain their higher risk for adverse outcomes. Modifying traditional major vascular risk factors may partially alleviate their excess cardiovascular risk through modulating arterial stiffness.
    KEYWORDS: Arterial stiffness; Augmentation index; Pulse wave velocity; Type 2 diabetes
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