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  1. Sabanayagam C, Shankar A, Lee J, Wong TY, Tai ES
    J Hum Hypertens, 2013 Apr;27(4):231-6.
    PMID: 22418747 DOI: 10.1038/jhh.2011.117
    Few previous studies in Western populations have reported an association between C-reactive protein (CRP) and prehypertension. However, no previous study has examined this association in Asians. We examined individuals who were free of hypertension from two independent population-based studies in Singapore: the Singapore Prospective Study Programme (SP2, n=2843 Chinese, Malay and Indians aged 24 years) and the Singapore Malay Eye Study (SiMES, n=957 Malays, aged 40-80 years). Prehypertension was defined as systolic blood pressure (BP) 120-139 mm Hg or diastolic BP 80-89 mm Hg. CRP was analyzed as categories (<1, 1-3, >3 mg l(-1)). The prevalence of prehypertension increased with increasing categories of CRP in both cohorts (P for trend <0.05 in both cohorts). After adjusting for potential confounders including body mass index (BMI), smoking and diabetes, persons with higher levels of CRP were more likely to have prehypertension in both SP2 (compared with CRP <1 mg l(-1), odds ratio (OR) 1.23, 95% confidence interval (CI) 1.03-1.48 for CRP 1-3 and OR 1.67, 95% CI 1.32-2.10 for >3 mg l(-1)) and SiMES (OR 1.45, 95% CI 1.04-2.01 and OR 1.56, 95% CI 1.07-2.27) respectively. In conclusion, data from two population-based Asian cohorts suggest that elevated serum CRP levels are associated with prehypertension.
  2. Chiang PP, Lamoureux EL, Shankar A, Tai ES, Wong TY, Sabanayagam C
    BMC Public Health, 2013;13:730.
    PMID: 23919264 DOI: 10.1186/1471-2458-13-730
    BACKGROUND: Prehypertension has been shown to be an early risk factor of cardiovascular disease (CVD). We investigated the prevalence and pattern of cardiometabolic risk factors in prehypertension in three ethnic Asian populations in Singapore.
    METHODS: We examined data from Chinese (n=1177), Malay (n=774), and Indian (n=985) adults aged 40-80 years who participated in three independent population based studies conducted from 2004-2011 in Singapore who were free of diabetes, hypertension and previous CVD. Prehypertension was defined as systolic blood pressure (BP) 120-139 mm Hg or diastolic BP 80-89 mm Hg. Random blood glucose, glycated haemoglobin (HbA1c), body mass index (BMI), triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were examined as indicators of adverse cardiometabolic profile. The association between metabolic variables and prehypertension was examined using logistic regression models adjusting for potential confounders.
    RESULTS: The prevalence of prehypertension was 59.8% (Chinese), 68.9% (Malays) and 57.7% Indians. Higher levels of blood glucose, HbA1c and BMI were significantly associated with prehypertension in all three ethnic groups, odds ratio (95% confidence interval) of prehypertension in Chinese, Malays and Indians were: 1.42 (1.10, 1.83), 1.53 (1.05, 2.24), 1.49 (1.13, 1.98) for high-glucose; 3.50 (1.01, 12.18), 3.72 (1.29, 10.75), 2.79 (1.31, 5.94) for high-HbA1c; 1.86 (1.34, 2.56), 2.96 (2.10, 4.18), 1.68 (1.28, 2.20) for high-BMI. In addition, higher levels of LDL cholesterol in Chinese and higher levels of triglycerides were significantly associated with prehypertension. These associations persisted when metabolic variables were analysed as continuous variables.
    CONCLUSIONS: Higher levels of blood glucose, HbA1c and BMI were associated with prehypertension in all three ethnic groups in Singapore. Screening for prehypertension and lifestyle modifications could potentially reduce the burden of CVD in otherwise healthy Asian adults living in Singapore.
  3. Sabanayagam C, Teo BW, Tai ES, Jafar TH, Wong TY
    BMC Nephrol, 2013;14:86.
    PMID: 23590421 DOI: 10.1186/1471-2369-14-86
    Chronic kidney disease (CKD) is an emerging public health problem worldwide. Previous studies have shown an association between blood pressure (BP) and CKD. However, it is not clear if there are ethnic differences in this association. We examined the association between BP and CKD in a multi-ethnic Asian population in Singapore.
  4. Sabanayagam C, Shankar A, Lim SC, Tai ES, Wong TY
    Asia Pac J Public Health, 2011 Nov;23(6):936-45.
    PMID: 20460283 DOI: 10.1177/1010539510361637
    Studies conducted in Western populations demonstrate that blood pressure (BP) is a major risk factor for chronic kidney disease (CKD). The authors examined the cross-sectional association between BP and CKD in 3280 adults of Malay ethnicity aged 40 to 80 years living in Singapore. CKD was defined as (1) estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m(2) and (2) presence of microalbuminuria/macroalbuminuria. They observed a dose-dependent positive association between BP and CKD (P trend < .0001). In multivariable-adjusted analysis, compared with participants with normal BP, the odds ratio (OR; 95% confidence interval [CI]) of eGFR < 60 mL/min/1.73 m(2) was 1.85 (0.95-3.62), 2.95 (1.55-5.64), and 4.96 (2.63-9.37) for prehypertension, and stage 1 and stage 2 hypertension, respectively. Similar results were obtained for microalbuminuria/macroalbuminuria. Stage 2 hypertension had the greatest population-attributable risk of CKD (23%). The strong positive association of hypertension with CKD emphasizes the need to control BP in Asian populations to reduce the burden of kidney disease.
  5. Sabanayagam C, Lim SC, Wong TY, Lee J, Shankar A, Tai ES
    Nephrol Dial Transplant, 2010 Aug;25(8):2564-70.
    PMID: 20185856 DOI: 10.1093/ndt/gfq084
    There is substantial heterogeneity in literature regarding the epidemiology for chronic kidney disease (CKD) in different Asian populations. We aimed to assess the prevalence and risk factors of CKD in a multi-ethnic Asian population in Singapore.
  6. Chan JCY, Chee ML, Tan NYQ, Cheng CY, Wong TY, Sabanayagam C
    Nutr Diabetes, 2018 03 07;8(1):16.
    PMID: 29549238 DOI: 10.1038/s41387-018-0018-0
    AIMS: To examine the association of body mass index (BMI) with the incidence of diabetes mellitus (DM) and diabetic retinopathy (DR) in Asians.

    METHODS: We analysed data from 4101 adults (Malay, n = 1901 and Indian, n = 2200) who participated in the baseline (2004-2009) and 6-year follow-up (2011-2015) of two independent population-based studies with similar methodology in Singapore. BMI was categorised into normal (<25 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). DM was diagnosed as random plasma glucose ≥200 mg/dL, HbA1c ≥6.5% or self-reported physician diagnosed DM. DR was assessed from retinal photographs graded using a standard protocol. The associations of baseline BMI with incident DM and DR was examined using multivariable poisson regression models adjusting for potential confounders including duration of DM, family history of DM and HbA1c.

    RESULTS: The incidence of DM was 12.8% and among 1586 participants with DM, the incidence of DR was 17.6% over a median follow-up period of 6.2 years. Compared to those with BMI 

  7. Jeganathan VS, Sabanayagam C, Tai ES, Lee J, Sun C, Kawasaki R, et al.
    Hypertens Res, 2009 Nov;32(11):975-82.
    PMID: 19713968 DOI: 10.1038/hr.2009.130
    Blood pressure has a significant effect on retinal arterioles. There are few data on whether this effect varies by race/ethnicity. We examined the relationship of blood pressure and retinal vascular caliber in a multi-ethnic Asian population. The study is population-based and cross sectional in design. A total of 3749 Chinese, Malay and Indian participants aged > or =24 years residing in Singapore were included in the study. Retinal vascular caliber was measured using a computer program from digital retinal photographs. The associations of retinal vascular caliber with blood pressure and hypertension in each racial/ethnic group were analyzed. The main outcome measures are retinal arteriolar caliber and venular caliber. The results show that retinal arterioles were narrower in persons with uncontrolled/untreated hypertension (140.0 microm) as compared with persons with controlled hypertension (142.1 microm, P=0.0001) and those with no hypertension (146.0 microm, P<0.0001). On controlling for age, gender, body mass index, lipids and smoking, each 10 mm Hg increase in mean arterial blood pressure was associated with a 3.1 microm decrease in arteriolar caliber (P<0.0001), with a similar magnitude seen in all three racial/ethnic groups: 3.1 microm in Chinese, 2.8 microm in Malays and 3.2 microm in Indians (P<0.0001 for all). Each 10 mm Hg increase in mean arterial blood pressure was associated with a 1.8 microm increase in venular caliber (P<0.0001); furthermore, the magnitude of this effect was similar across the three racial/ethnic groups. The effect of blood pressure on the retinal vasculature was similar across three major racial/ethnic groups in Asia.
  8. Tan AG, Tham YC, Chee ML, Mitchell P, Cumming RG, Sabanayagam C, et al.
    Clin Exp Ophthalmol, 2020 07;48(5):580-592.
    PMID: 32255547 DOI: 10.1111/ceo.13757
    IMPORTANCE: Long-term data on age-related cataract, a leading cause of blindness and visual impairment, is scarce in Asian populations.

    BACKGROUND: We report the 6-year incidence and progression of age-related cataract and associated risk factors in Malay adults living in Singapore.

    DESIGN: Population-based cohort study.

    PARTICIPANTS: A total of 3280 Malays aged 40+ years participated in baseline examinations of the Singapore Malay Eye Study (2004-2006). Six years later, 1901 (72.1% of eligible) baseline participants were re-examined.

    METHODS: Cataract was assessed using lens photos, taken during eye examinations, following the Wisconsin Cataract Grading System.

    MAIN OUTCOMES AND MEASURES: Incidence and progression of cortical, nuclear and posterior subcapsular (PSC) cataract. Poisson regression models and generalized estimating equations models (with Poisson link) were used to assess factors associated with cataract incidence and progression, respectively, adjusting for age, sex and other risk factors.

    RESULTS: Age-adjusted 6-year incidence of cortical, nuclear and PSC cataract was 14.1%, 13.6% and 8.7%, respectively, and was strongly age-related (P for trend

  9. Lim EWL, Chee ML, Sabanayagam C, Majithia S, Tao Y, Wong TY, et al.
    Invest Ophthalmol Vis Sci, 2019 05 01;60(6):1889-1897.
    PMID: 31042796 DOI: 10.1167/iovs.19-26810
    Purpose: The purpose of this study was to investigate the association between sleep (duration and quality) and symptoms of dry eye in Singapore Malay and Indian adults.

    Methods: This was a prospective cross-sectional study. A total of 3303 subjects aged 40 years and above from two large population-based cohorts, the Singapore Malay Eye Study-2 (n = 1191, 2011-2013) and the Singapore Indian Eye Study-2 (n = 2112, 2013-2015), were included. The presence of symptoms of dry eye was defined as having at least one of six symptoms often or all the time. Sleep questionnaires included the Epworth Sleepiness Scale, Berlin Questionnaire, STOP-bang questionnaire, and Insomnia Severity Index. Poor sleep quality was defined as meeting the respective questionnaire thresholds. General health questionnaires (including sleep duration) and standardized ocular and systemic tests were also used.

    Results: Of 3303 participants, 6.4% had excessive sleepiness, 20.5% had high risk for sleep apnea, 2.7% had clinical insomnia, and 7.8% had <5 hours of sleep. These sleep factors were associated with symptoms of dry eye. After adjusting for relevant demographic, medical, and social factors, the following were associated with higher odds of symptoms of dry eye: excessive sleepiness (Epworth Sleepiness Scale: odds ratio [OR] = 1.77 [1.15-2.71]), high risk of sleep apnea (Berlin Questionnaire: OR = 1.55 [1.17-2.07], STOP-Bang Questionnaire: OR = 2.66 [1.53-4.61]), clinical insomnia (Insomnia Severity Index: OR = 3.68 [2.17-6.26]) and <5 hours of sleep (OR = 1.73 [1.17-2.57], reference sleep duration 5-9 hours). Sleep apnea, insomnia, and sleep duration were each shown to be independently associated with symptoms of dry eye.

    Conclusion: Short sleep duration and poor quality are both significantly and independently associated with symptoms of dry eye.

  10. Lim CC, Teo BW, Ong PG, Cheung CY, Lim SC, Chow KY, et al.
    Eur J Prev Cardiol, 2015 Aug;22(8):1018-26.
    PMID: 24857889 DOI: 10.1177/2047487314536873
    BACKGROUND: Few studies have examined the impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes and deaths in Asian populations. We evaluated the associations of CKD with cardiovascular disease (CVD) and all-cause mortality in a multi-ethnic Asian population.
    DESIGN: Prospective cohort study of 7098 individuals who participated in two independent population-based studies involving Malay adults (n = 3148) and a multi-ethnic cohort of Chinese, Malay and Indian adults (n = 3950).
    METHODS: CKD was assessed from CKD-EPI estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Incident CVD (myocardial infarction, stroke and CVD mortality) and all-cause mortality were identified by linkage with national disease/death registries.
    RESULTS: Over a median follow-up of 4.3 years, 4.6% developed CVD and 6.1% died. Risks of both CVD and all-cause mortality increased with decreasing eGFR and increasing albuminuria (all p-trend <0.05). Adjusted hazard ratios (HR (95% confidence interval)) of CVD and all-cause mortality were: 1.54 (1.05-2.27) and 2.21 (1.67-2.92) comparing eGFR <45 vs ≥60; 2.81 (1.49-5.29) and 2.34 (1.28-4.28) comparing UACR ≥300 vs <30. The association between eGFR <60 and all-cause mortality was stronger among those with diabetes (p-interaction = 0.02). PAR of incident CVD was greater among those with UACR ≥300 (12.9%) and that of all-cause mortality greater among those with eGFR <45 (16.5%).
    CONCLUSIONS: In multi-ethnic Asian adults, lower eGFR and higher albuminuria were independently associated with incident CVD and all-cause mortality. These findings extend previously reported similar associations in Western populations to Asians and emphasize the need for early detection of CKD and intervention to prevent adverse outcomes.
  11. Gupta P, Majithia S, Fenwick EK, Gan ATL, Tham YC, Poh S, et al.
    Transl Vis Sci Technol, 2020 04;9(5):11.
    PMID: 32821483 DOI: 10.1167/tvst.9.5.11
    Purpose: The purpose of this study was to determine the rates of, and factors associated with, eyecare utilization and spectacle affordability among Singaporeans with vision impairment (VI).

    Methods: We included adults with VI from their second visit of the Singapore Epidemiology of Eye Disease Study. Data on eyecare utilization and spectacle affordability were collected. Low eyecare utilization was defined as no eye check ever or eye checks not even once per year in reference to at least once per year. Difficulty affording glasses was defined as glasses being rated as expensive in reference to not expensive.

    Results: There were 985 adults (14.5%; 415 Malays, 260 Indian, and 310 Chinese; mean age [SD]: 69.5 [10.2] years; 55.4% women) with VI who answered the above questions, were included. Of these, 624 (63.4%) wore glasses. The rates of low eyecare utilization and difficulty affording eyeglasses were 31% and 63%, respectively. Compared to Chinese (23.8%) and Indians (18.8%), Malays (57.4%) had the highest rates of low eyecare utilization (P < 0.001), and most difficulty affording eyeglasses (47.2% vs. 26.1% and 26.6% in Chinese and Indians, respectively; P < 0.001). Younger age, low socioeconomic status, absence of diabetes, absence of self-reported eye conditions, and poor vision were independently associated with low eyecare utilization, whereas older age and female sex was associated with difficulty affording glasses.

    Conclusions: In this multi-ethnic population with VI, almost one-third had low eyecare utilization and nearly two-thirds reported difficulty affording eyeglasses.

    Translational Relevance: This will inform strategies, such as tailored eyecare utilization awareness campaigns and awareness of available subsidy schemes for at-risk Singaporeans, such as Malays.

  12. Man REK, Veerappan AR, Tan SP, Fenwick EK, Sabanayagam C, Chua J, et al.
    Ocul Surf, 2017 Oct;15(4):742-748.
    PMID: 28442380 DOI: 10.1016/j.jtos.2017.04.004
    PURPOSE: To evaluate the incidence of symptomatic dry eye disease (SDED) and associated risk factors in a well-characterized cohort of ethnic Malays in Singapore.

    METHODS: We included 1682 participants (mean age [SD]: 57 [10]years; 55.4% female) without SDED from the Singapore Malay Eye Study (SiMES), a population-based longitudinal study with baseline examination (SiMES-1) conducted between 2004 and 2006, and follow-up examination (SiMES-2) conducted between 2010 and 2013. SDED was considered to be present if a participant answered "often" or "all the time" to any of the six questions from the Salisbury Eye Evaluation Study dry eye questionnaire. Age-standardized incidence of SDED was calculated as the crude 6-year cumulative incidence standardized to Singapore's population census. Gender-stratified multivariable log-binomial regression models were utilized to determine the independent risk factors of incident SDED.

    RESULTS: At the 6-year follow-up, 86 of 1682 participants had developed SDED, which was equivalent to an age-standardized 6-year incidence of 5.1% (95% CI 4.1-6.4%). There were no differences in the incidence of SDED between men and women (P = 0.9). Multivariable models revealed that presence of glaucoma and poorer self-rated health were independently associated with incident SDED in men (P = 0.003 and 0.03, respectively), while contact lens wear (P = 0.002), history of thyroid disease (P = 0.03), and having had cataract surgery (P = 0.02) were predictive of incident SDED in women.

    CONCLUSION: One in twenty adult Malays developed SDED over a 6-year period. Risk factors for incident SDED were different between men and women. Future studies and public health interventions should consider this gender-specific difference in risk factors.
  13. Cheung CMG, Ong PG, Neelam K, Tan PC, Shi Y, Mitchell P, et al.
    Ophthalmology, 2017 09;124(9):1305-1313.
    PMID: 28501376 DOI: 10.1016/j.ophtha.2017.03.056
    PURPOSE: To determine the 6-year incidence of early and late age-related macular degeneration (AMD) in a Singaporean Malay population and to validate the Age-Related Eye Disease Study (AREDS) simplified severity scale in Asians.

    DESIGN: Prospective, population cohort study.

    PARTICIPANTS: The Singapore Malay Eye Study baseline participants (age, ≥40 years; 2006-2008) were followed up in 2011 through 2013, and 1901 of 3280 of eligible participants (72.1%) took part.

    METHODS: Fundus photographs were graded using the Wisconsin AMD grading system.

    MAIN OUTCOME MEASURES: Incidence of early and late AMD.

    RESULTS: Gradable fundus photographs were available for 1809 participants who attended both baseline and 6-year follow-up examinations. The age-standardized incidences of early and late AMD were 5.89% (95% confidence interval [CI], 4.81-7.16) and 0.76% (95% CI, 0.42-1.29), respectively. The 5-year age-standardized incidence of early AMD (calculated based on the 6-year incidence) was lower in our population (5.58%; 95% CI, 4.43-7.01) compared with the Beaver Dam Eye Study population (8.19%). The incidence of late AMD in our population was similar to that of the Beaver Dam Eye Study population (0.98% [95% CI, 0.49-1.86] vs. 0.91%), the Blue Mountains Eye Study population (1.10% [95% CI, 0.52-9.56] vs. 1.10%), and the Hisayama Study population (1.09% [95% CI, 0.54-4.25] vs. 0.84%). The incidence of late AMD increased markedly with increasing baseline AREDS score (step 0, 0.23%; step 4, 9.09%).

    CONCLUSIONS: This study documented the incidence of early and late AMD in a Malay population. The AREDS simplified severity scale is useful in predicting the risk of late AMD development in Asians.

  14. Chai JF, Kao SL, Wang C, Lim VJ, Khor IW, Dou J, et al.
    J Clin Endocrinol Metab, 2020 Dec 01;105(12).
    PMID: 32936915 DOI: 10.1210/clinem/dgaa658
    CONTEXT: Glycated hemoglobin A1c (HbA1c) level is used to screen and diagnose diabetes. Genetic determinants of HbA1c can vary across populations and many of the genetic variants influencing HbA1c level were specific to populations.

    OBJECTIVE: To discover genetic variants associated with HbA1c level in nondiabetic Malay individuals.

    DESIGN AND PARTICIPANTS: We conducted a genome-wide association study (GWAS) analysis for HbA1c using 2 Malay studies, the Singapore Malay Eye Study (SiMES, N = 1721 on GWAS array) and the Living Biobank study (N = 983 on GWAS array and whole-exome sequenced). We built a Malay-specific reference panel to impute ethnic-specific variants and validate the associations with HbA1c at ethnic-specific variants.

    RESULTS: Meta-analysis of the 1000 Genomes imputed array data identified 4 loci at genome-wide significance (P 

  15. Sheng B, Pushpanathan K, Guan Z, Lim QH, Lim ZW, Yew SME, et al.
    Lancet Diabetes Endocrinol, 2024 Aug;12(8):569-595.
    PMID: 39054035 DOI: 10.1016/S2213-8587(24)00154-2
    Artificial intelligence (AI) use in diabetes care is increasingly being explored to personalise care for people with diabetes and adapt treatments for complex presentations. However, the rapid advancement of AI also introduces challenges such as potential biases, ethical considerations, and implementation challenges in ensuring that its deployment is equitable. Ensuring inclusive and ethical developments of AI technology can empower both health-care providers and people with diabetes in managing the condition. In this Review, we explore and summarise the current and future prospects of AI across the diabetes care continuum, from enhancing screening and diagnosis to optimising treatment and predicting and managing complications.
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