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Introduction: Lifestyle modifications can reduce the risk of type 2 diabetes mellitus (T2DM) and hypertension. Our study investigated whether domain-specific physical activity (such as work, transport and leisure) and sedentary behaviour were associated with T2DM and hypertension, and whether these associations were moderated by sex and age. Method: For this cross-sectional study, data were obtained from a population survey in Singapore (n=2,867) conducted from February 2019 to March 2020. T2DM and hypertension were self-reported. Global physical activity questionnaire was used to assess domain-specific physical activity (in metabolic equivalent of task [MET]-minutes) and sedentary time (in hours). Logistic regression models were generated to examine the abovementioned associations, and adjusted for age, sex, education, ethnicity, personal income, body mass index, diet and hypertension/diabetes. Interaction terms were included individually to investigate whether age and sex moderated the associations. Results: Individuals with >826 MET-minutes of leisure-related physical activity had lower odds of having T2DM (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.24–0.86) and hypertension (OR 0.59, 95% CI 0.37–0.94) than those with no leisure-related physical activity. Individuals with >8 hours of sedentary time had higher odds of having hypertension (OR 1.69, 95% CI 1.06–2.69) than those with 0–5 hours of sedentary time. Logistic regression models including interaction terms showed that the association between leisure-related physical activity and hypertension was significant for those aged 18–34 (OR 0.15, 95% CI 0.03–0.66) and 50–64 years (OR 0.44, 95% CI 0.21–0.91). The association between sedentary time and hypertension was significant for those aged 18–34 years (OR 15.07, 95% CI 1.69–133.92). Conclusion: Our results support the widespread promotion of an active lifestyle to lower the prevalence of diabetes and hypertension in Singapore. Keywords: Active lifestyle, domain-specific physical activity, global physical activity questionnaire

Introduction: Phase angle (PhA), derived from bioelectrical impedance analysis (BIA), is the angle of vector determined by the body’s resistance and reactance. It indicates cellular integrity and hydration status. Though extracellular volume excess was associated with chronic kidney disease (CKD) progression, the association between PhA and CKD progression is unknown. Matrix metalloproteinase-2 (MMP-2) is a member of zinc-dependent endopeptidase family and promotes renal interstitial fibrosis. We investigated association between PhA and CKD progression, and whether the association was through MMP-2 in patients with type 2 diabetes mellitus (T2DM). Method: We conducted a prospective study on 1,078 patients with T2DM (mean age 58.9±9.1 years). PhA was measured using BIA. CKD progression was defined as ≥25% decrease in estimated glomerular filtration rate (eGFR) from baseline with deterioration across eGFR categories. Multiplex immunoassay was used to quantitate MMP-2. We examined association between PhA and CKD progression using Cox proportional hazards model, adjusting for demographics, clinical parameters and medications. Results: Over 8.6 years of follow-up, 43.7% of participants had CKD progression. Compared to tertile 3 PhA (higher level), tertiles 1 and 2 PhA were associated with higher hazards of CKD progression, with corresponding unadjusted hazard ratios (HRs) of 2.27 (95% confidence interval [CI] 1.80–2.87, P

Aims/hypothesis We sought to subtype South East Asian patients with type 2 diabetes by de novo cluster analysis on clinical variables, and to determine whether the novel subgroups carry distinct genetic and lipidomic features as well as differential cardio-renal risks. Methods Analysis by k-means algorithm was performed in 687 participants with recent-onset diabetes in Singapore. Genetic risk for beta cell dysfunction was assessed by polygenic risk score. We used a discovery–validation approach for the lipidomics study. Risks for cardio-renal complications were studied by survival analysis. Results Cluster analysis identified three novel diabetic subgroups, i.e. mild obesity-related diabetes (MOD, 45%), mild age-related diabetes with insulin insufficiency (MARD-II, 36%) and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII, 19%). Compared with the MOD subgroup, MARD-II had a higher polygenic risk score for beta cell dysfunction. The SIRD-RII subgroup had higher levels of sphingolipids (ceramides and sphingomyelins) and glycerophospholipids (phosphatidylethanolamine and phosphatidylcholine), whereas the MARD-II subgroup had lower levels of sphingolipids and glycerophospholipids but higher levels of lysophosphatidylcholines. Over a median of 7.3 years follow-up, the SIRD-RII subgroup had the highest risks for incident heart failure and progressive kidney disease, while the MARD-II subgroup had moderately elevated risk for kidney disease progression. Conclusions/interpretation Cluster analysis on clinical variables identified novel subgroups with distinct genetic, lipidomic signatures and varying cardio-renal risks in South East Asian participants with type 2 diabetes. Our study suggests that this easily actionable approach may be adapted in other ethnic populations to stratify the heterogeneous type 2 diabetes population for precision medicine. Graphical abstract

Background: The association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) use and cognitive function in type 2 diabetes remains unclear. Objective: Explore the association between SGLT2i and longitudinal changes in cognitive function in adults with type 2 diabetes (T2DM) and assessed the cognitive domains which were impacted by SGLT2i. Methods: We conducted a prospective cohort study of 476 patients aged 60.6±7.4 years with follow-up period up to 6.4 years. Data on SGLT2i use was derived from questionnaire and verified with clinical database. We used Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess cognition. The association between SGLT2i use and rate of RBANS score change was examined using multiple linear regression. Results: There were 138 patients (29.0%) on SGLT2i, including 84 (17.7%) for

BackgroundRandomized controlled trials have demonstrated the benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2is) in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, real-world data on CKD progression and the development of end-stage kidney disease (ESKD) remains scarce. Our aim was to study renal outcomes of people with diabetic kidney disease (DKD) using SGLT2is in a highly prevalent DKD population.MethodsBetween 2016 and 2019 we recruited T2DM patients in the renal and diabetic clinics in a regional hospital in Singapore. Patients prescribed SGLT2is were compared with those on standard anti-diabetic and renoprotective treatment. The outcome measures were CKD progression [a ≥25% decrease from baseline and worsening of estimated glomerular filtration rate (eGFR) categories according to the Kidney Disease: Improving Global Outcomes guidelines] and ESKD (eGFR ResultsWe analysed a total of 4446 subjects; 1598 were on SGLT2is. There was a significant reduction in CKD progression {hazard ratio [HR] 0.60 [95% confidence interval (CI) 0.49–0.74]} with SGLT2is. The HR for eGFR ≥45 mL/min/1.73 m2 and 15–44 mL/min/1.73 m2 was 0.60 (95% CI 0.47–0.76) and 0.43 (95% CI 0.23–0.66), respectively. There was also a reduction in risk for developing ESKD for the entire cohort [HR 0.33 (95% CI 0.17–0.65)] and eGFR 15–44 mL/min/1.73 m2 [HR 0.24 (95% CI 0.09–0.66)]. Compared with canagliflozin and dapagliflozin, empagliflozin showed a sustained risk reduction of renal outcomes across CKD stages 1–4.ConclusionsThis real-world study demonstrates the benefits of SGLT2is on CKD progression and ESKD. The effect is more pronounced in moderate to advanced CKD patients.

Kumari Neelam,1,2,&ast; Khin Chaw Yu Aung,3,&ast; Keven Ang,3 Subramaniam Tavintharan,3,4 Chee Fang Sum,4 Su Chi Lim3– 6 1Department of Ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore; 2Singapore Eye Research Institute, Singapore; 3Clinical Research Unit, Khoo Teck Puat Hospital, Singapore; 4Diabetes Centre, Admiralty Medical Centre, Singapore; 5Saw Swee Hock School of Public Health, National University of Singapore, Singapore; 6Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore&ast;These authors contributed equally to this workCorrespondence: Su Chi Lim, Clinical Research Unit, Khoo Teck Puat Hospital, 90 Yishun Central, 728828, Singapore, Email lim.su.chi@ktph.com.sgObjective: To examine the association of triglyceride glucose (TyG) index (product of fasting triglyceride and glucose) with prevalence and incidence of diabetic retinopathy (DR) in type 2 diabetes.Methods: 1339 patients from an ongoing Singapore Study of Macro-angiopathy and Micro-Vascular Reactivity in Type 2 Diabetes (SMART2D) were included in this study. Fasting triglyceride and glucose levels were quantified and color fundus photographs were assessed for DR presence and severity. Logistic regression models were used to evaluate associations of TyG index with DR prevalence and incidence (median follow-up period = 3.2 years).Results: Mean TyG index was higher in patients with DR than no DR (9.24± 0.7 versus 9.04± 0.6, p< 0.001). TyG index was significantly associated with DR prevalence (OR=1.4, CI 1.1– 1.7, p=0.002) and incidence (OR=1.8, CI 1.04– 2.9, p=0.03), after adjusting for confounders. In a stratified analysis, the association between TyG index and DR prevalence reached significance only in the subgroup with HbA1c levels < 7.0% (OR=2, CI 1.1– 3.8, p=0.03). TyG index significantly predicted DR prevalence and incidence with area under receiver operating curve as 0.77 (CI 0.74– 0.80, p < 0.001) and 0.66 (CI 0.57– 0.76, p value < 0.01), respectively.Conclusion: TyG index is a good predictor for DR prevalence and incidence. It can also be a secondary treatment target for patients with optimally controlled levels of HbA1c.Keywords: triglyceride glucose index, diabetic retinopathy, insulin resistance, prevalence, incidence

Context Elevated levels of plasma leucine-rich α-2-glycoprotein 1 (LRG1), a component of transforming growth factor beta signaling, are associated with development and progression of chronic kidney disease in patients with type 2 diabetes (T2D). However, whether this relationship is causal is uncertain. Objectives To identify genetic variants associated with plasma LRG1 levels and determine whether genetically predicted plasma LRG1 contributes to a rapid decline in kidney function (RDKF) in patients with T2D. Design and participants We performed a genome-wide association study of plasma LRG1 among 3694 T2D individuals [1881 (983 Chinese, 420 Malay, and 478 Indian) discovery from Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes cohort and 1813 (Chinese) validation from Diabetic Nephropathy cohort]. One- sample Mendelian randomization analysis was performed among 1337 T2D Chinese participants with preserved glomerular filtration function [baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2)]. RDKF was defined as an eGFR decline of 3 mL/min/1.73 m2/year or greater. Results We identified rs4806985 variant near LRG1 locus robustly associated with plasma LRG1 levels (meta P = 6.66 × 10−16). Among 1337 participants, 344 (26%) developed RDKF, and the rs4806985 variant was associated with higher odds of RDKF (meta odds ratio = 1.23, P = 0.030 adjusted for age and sex). Mendelian randomization analysis provided evidence for a potential causal effect of plasma LRG1 on kidney function decline in T2D (P Conclusion We demonstrate that genetically influenced plasma LRG1 increases the risk of RDKF in T2D patients, suggesting plasma LRG1 as a potential treatment target. However, further studies are warranted to elucidate underlying pathways to provide insight into diabetic kidney disease prevention.

Background Chronic kidney disease (CKD) is common among people with type 2 diabetes (T2D), and increases the risk of kidney failure and cardiovascular diseases. Shorter leukocyte telomere length (LTL) is associated with CKD in patients with T2D. We previously reported single-nucleotide polymorphisms (SNPs) associated with LTL in an Asian population. In this study, we elucidated the association of these SNPs with CKD in patients with T2D using the Mendelian randomization (MR) approach. Methods The cross-sectional association of 16 LTL SNPs with CKD, defined as an estimated glomerular filtration rate of Results Genetically determined shorter LTL was associated with increased risk of CKD in patients with T2D (meta-IVW adjusted odds ratio = 1.51, 95% confidence interval 1.12–2.12, P = 0.007, Phet = 0.547). Similar results were obtained following sensitivity analysis. MR-Egger analysis (intercept) suggested no evidence of horizontal pleiotropy (β = 0.010, P = 0.751). Conclusions Our findings suggest that genetically determined LTL is associated with CKD in patients with T2D. Further studies are warranted to elucidate the causal role of telomere length in CKD progression.

OBJECTIVE Leucine-rich α-2 glycoprotein 1 (LRG1) was recently identified as an amplifier of transforming growth factor-β (TGF-β)–induced kidney fibrosis in animal models. We aimed to study whether urine LRG1 is associated with risk of progression to end-stage kidney disease (ESKD) in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 1,837 participants with type 2 diabetes and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 were recruited from a regional hospital and a primary care facility. Association of urine LRG1 with risk of ESKD (progression to sustained eGFR RESULTS During a median follow-up of 8.6 (interquartile range 5.8–9.6) years, 134 incident ESKD events were identified. Compared with those in the lowest tertile, participants with baseline urine LRG1 in the highest tertile had a 1.91-fold (95% CI 1.04–3.50) increased risk of progression to ESKD, after adjustment for cardiorenal risk factors, including eGFR and albuminuria. As a continuous variable, 1 SD increment in urine LRG1 was associated with a 1.53-fold (95% CI 1.19–1.98) adjusted risk of ESKD. Of note, the association of urine LRG1 with ESKD was independent of plasma LRG1. Moreover, urine LRG1 was associated with rapid kidney function decline and progression to macroalbuminuria, two common pathways leading to ESKD. CONCLUSIONS Urine LRG1, a TGF-β signaling modulator, predicts risk of progression to ESKD independently of clinical risk factors in patients with type 2 diabetes, suggesting that it may be a novel factor involved in the pathophysiological pathway leading to kidney disease progression.

The utility of insulin resistance (IR) as a predictor of diabetes remission after metabolic surgery is not well-defined. We assessed the association of baseline surrogate IR indices including triglyceride-glucose (TyG) index and homeostatic model assessment for IR (HOMA-IR) with glycemic control and diabetes remission after metabolic surgery.Patients with type 2 diabetes scheduled for metabolic surgery were recruited at a single-center (n = 149; age: 44 ± 10 years, 47.7% men, body mass index: 41.5 ± 7.5 kg/mElevated TyG index was associated with poor glycemic control cross-sectionally. Compared with non-remitters, lower baseline TyG index levels were observed in individuals with complete diabetes remission after surgery (P = 0.012); whereas HOMA-IR was not significantly different. Consistently, the proportion of diabetes non-remitters (compared to remitters) increased with increasing TyG tertiles from 1 to 3 (P = 0.015). Both TyG index (relative risk = 0.62, 95% CI = 0.42-0.91, P = 0.014) and TyG tertile 1 (relative risk = 1.99, 95% CI = 1.25-3.24, P = 0.003) independently predicted diabetes remission. The TyG index identified diabetes remission with an area under the curve of 0.68. The optimal TyG threshold was 9.41, yielding a sensitivity of 69.6%, specificity of 60.9%, positive predictive value of 64.0%, and negative predictive value of 66.7%.TyG index, previously suggested to predominantly reflect muscle IR, outperforms HOMA-IR as an IR indicator associated with glycemic control and diabetes remission after metabolic surgery.

Arterial stiffness is a risk factor for chronic kidney disease progression (CKD). Pulse pressure is a surrogate marker of arterial stiffness. It is unclear if pulse pressure predicts CKD progression in type 2 diabetes mellitus. This was prospective study involving 1494 patients with estimated glomerular filtration rate (eGFR) ≥ 15 ml/min/1.73 m2. Carotid-femoral pulse wave velocity was measured using applanation tonometry. Pulse pressure was calculated as difference between systolic and diastolic blood pressures. CKD progression was defined as worsening of eGFR categories (stage 1, ≥ 90 ml/min/1.73 m2; stage 2, 60–89 ml/min/1.73 m2; stage 3a, 45–59 ml/min/1.73 m2; stage 3b, 30–44 ml/min/1.73 m2; stage 4; 15–29 ml/min/1.73 m2; and stage 5

Fluid imbalance is associated with various clinical conditions, but the association between elevated extracellular-water to total-body-water (ECW/TBW) ratio, an indicator of fluid balance, and cognitive impairment is unknown. We aimed to investigate relationship between ECW/TBW ratio and cognitive function in type 2 diabetes mellitus.This study was a cross-sectional design, comparing 1233 patients aged 61.4 ± 8.0 years from the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D) cohort. ECW/TBW was measured using bioelectrical impedance method. Cognitive function was assessed with Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multiple linear regression was used to examine association between ECW/TBW and RBANS scores, adjusting for demographics, education, clinical covariates, and apolipoprotein E allele.In unadjusted analyses, there was an inverse dose-dependent association between ECW/TBW and RBANS total score. The associations persisted in fully adjusted model with β = -1.18 (95% confidence interval [CI] -2.19 to -0.17; P = 0.022) for slight edema and -2.33 (-3.99 to -0.67; P = 0.006) for edema. Slight edema and edema were significantly associated with reduced cognitive function in delayed memory and attention. There was significant association between edema but not slight edema, with reduced cognitive function in language. Pulse pressure accounted for 16.8% of association between ECW/TBW and RBANS total score.Our novel finding of an independent association between higher ECW/TBW and poorer cognitive function highlights the potential importance of maintaining body fluid balance in the management of cognitive impairment.背景: 体液失衡与多种临床症状有关, 但作为体液平衡指标的细胞外液/全身水比值(ECW/TBW)升高与认知功能损害之间的关系尚不清楚。本研究旨在探讨2型糖尿病患者ECW/TBW比值与认知功能的关系。 方法: 本研究采用横断面设计, 比较了新加坡2型糖尿病大血管病变和微血管反应性研究(SMART2D)队列的1233例患者, 年龄在61.4±8.0岁。采用生物电阻抗法测量ECW/TBW。认知功能采用可重复使用的神经心理状态评定量表(RBANS)进行评定。在校正了人口统计学、教育程度、临床协变量和载脂蛋白E等位基因后, 采用多元线性回归来检验ECW/TBW和RBANS评分之间的相关性。 结果: 在非校正分析中, ECW/TBW与RBANS总分呈剂量负相关。这种关联持续存在于完全校正轻度水肿β=− 1.18(95% 置信区间 [CI] −2.19 to −0.17; P = 0.022)和水肿β= −2.33 (−3.99 to −0.67; P = 0.006) 的模型中。轻度水肿和水肿与延迟记忆和注意力的认知功能降低显著相关。语言认知功能下降与水肿之间有显著的相关性。脉搏压可解释ECW/TBW与RBANS总分相关性的16.8%。 结论: 我们首次发现较高的ECW/TBW和较差的认知功能之间存在独立的关联, 这突出了在认知障碍的管理中保持体液平衡的潜在重要性。.

We aim to examine body composition, and association between SO and cognitive performance in Type 2 Diabetes (T2D) in an Asian population in Singapore.This was a cross-sectional study on 1235 patients with mean age 61.4 ± 8.0 years and T2D primary and secondary care attending diabetes care in Singapore. Body composition was assessed using tetrapolar multi-frequency BIA device analysis. Fat mass to fat-free mass (FM/FFM) ratio was categorized into 3 groups: Group 1, normal,0.40; Group 2, obese and increase of FM is small relative to that in FFM, 0.40 to 0.80; and Group 3, SO,0.80. Cognition was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Mini-Mental State Examination (MMSE).The distribution of body composition based on FM/FFM ratio was: Group 1, 20.2%; Group 2, 60.5%; and Group 3, 19.4%. SO (Group 3) was significantly associated with reduced RBANS total score with β-1.44 (95%CI -2.82 to -0.06; p = 0.041) in multivariable linear regression adjusted for demographics, education, depressive symptom(s) and clinical covariates. SO was significantly associated with reduced index scores for immediate memory and language in fully adjusted models with corresponding βs -2.71 (95%CI -5.06 to -0.36; p = 0.024) and -2.48 (95%CI -4.87 to -0.08; p = 0.043). Association between SO and reduced MMSE score was similarly observed.The prevalence of SO in Asians with T2D is relatively high. There is consistent and independent association of SO with reduced cognitive performance, especially in domains of memory and language, which may impair complex executive function such as adherence to diabetes self-care management.

Background: Type 2 diabetes mellitus (T2DM) has been shown to increase the risks of cognitive decline and dementia. Paired box gene 4 (PAX4), a transcription factor for beta cell development and function, has recently been implicated in pathways intersecting Alzheimer’s disease and T2DM. Objective: In this report, we evaluated the association of the ethnic-specific PAX4 R192H variant, a T2DM risk factor for East Asians which contributes to earlier diabetes onset, and cognitive function of Chinese T2DM patients. Methods: 590 Chinese patients aged 45–86 from the SMART2D study were genotyped for PAX4 R192H variation using Illumina OmniExpress-24 Array. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) which had been validated in the Singapore population was administered to assess five cognitive domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Multiple linear regression was used to assess the association of the R192H risk allele and cognitive domains. Results: Patients with two PAX4 R192H risk alleles showed significantly lower attention index score (β= –8.46, 95% CI [–13.71, –3.21], p = 0.002) than patients with wild-type alleles after adjusting for age, gender, diabetes onset age, HbA1c, body-mass index, renal function, lipid profiles, systolic blood pressure, metformin usage, smoking history, education level, Geriatric Depression Scale score, and presence of APOE ɛ4 allele. Conclusion: Ethnic-specific R192H variation in PAX4 is associated with attention-specific cognitive impairment in Chinese with T2DM. Pending further validation studies, determining PAX4 R192H genotype may be helpful for early risk assessment of early-onset T2DM and cognitive impairment to improve diabetes care.

Type 2 diabetes mellitus (T2DM) has been shown to be associated with cognitive decline and dementia. As earlier onset of diabetes implies a longer disease duration and an increased risk to complications, we sought to investigate the effect of T2DM onset on cognitive function of our patients.We administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to T2DM patients aged 45-85 from our SMART2D cohort. We assessed the association of the T2DM onset age (both continuous and stratified into 3 groups: early-onset ≤40 (n = 326), middle-aged onset 41-64 (n = 703) and late-onset ≥65 years old (n = 38)) and RBANS cognitive indices in 1067 patients. Potential mediation of this association by vascular compliance using mediation analysis was investigated.T2DM onset associates significantly with RBANS total score. Patients with early T2DM onset have lower RBANS total score as compared to patients with middle-aged onset (β = -2.01, p = 0.0102) and those with late-onset (β = -5.80, p = 0.005). This association was partially mediated by pulse pressure index (25.8%), with indirect effect of 0.028 (Bootstrapped-CI: 0.008-0.047).Association of early-onset T2DM with cognitive impairment is partly mediated by diminished vascular compliance. Appropriate screening and assessment of cognitive function is important for early intervention and management of cognitive impairment.

Background Chronic conditions are a leading cause of death and disability worldwide and respective data on dietary patterns remain scant. The present study aimed to investigate dietary patterns and identify sociodemographic factors associated with Dietary Approaches to Stop Hypertension (DASH) scores within a multi-ethnic population with various chronic conditions. Methods The present study utilised data from the 2019-2020 Knowledge, Attitudes, and Practices study on diabetes in Singapore – a nationwide survey conducted to track the knowledge, attitudes, and practices pertaining to diabetes. The study analysed data collected from a sample of 2,895 Singapore residents, with information from the sociodemographic section, DASH diet screener, and the modified version of the World Mental Health Composite International Diagnostic Interview (CIDI) version 3.0 checklist of chronic physical conditions. Results Respondents with no chronic condition had a mean DASH score of 18.5 (±4.6), those with one chronic condition had a mean DASH score of 19.2 (±4.8), and those with two or more chronic conditions had a mean DASH score of 19.8 (±5.2). Overall, the older age groups [35– 49 years (B = 1.78, 95% CI: 1.23 – 2.33, p p p p p Conclusion Overall, respondents with two or more chronic conditions reported better quality of diet while the sociodemographic factors of age, gender and ethnicity demonstrated a consistent pattern in correlating with diet quality, consistent with the extant literature. Results provide further insights for policymakers to refine ongoing efforts in relation to healthy dietary practices for Singapore.

Background: Chronic conditions are a leading cause of death and disability worldwide and respective data on dietary patterns remain scant. The present study aimed to investigate dietary patterns and identify sociodemographic factors associated with Dietary Approach to Stop Hypertension (DASH) scores within a multi-ethnic population with various chronic conditions. Method: The present study utilised data from the Knowledge, Attitudes, and Practices on diabetes study in Singapore – a nationwide survey conducted to track the knowledge, attitudes, and practices pertaining to diabetes. The study analysed data collected from a sample of 2,895 Singapore residents, with information from the sociodemographic section, DASH diet screener, and the modified version of the World Mental Health Composite International Diagnostic Interview (CIDI) version 3.0 checklist of chronic medical conditions.Results: Respondents with no chronic condition had a mean DASH score of 18.5 (±4.6), those with one chronic condition had a mean DASH score of 19.2 (±4.8), and those with two or more chronic conditions had a mean DASH score of 19.8 (±5.2). Overall, the older age groups [35– 49 years (B = 1.78, 95% CI: 1.23 – 2.33, p p p p p Conclusion: Overall, respondents with two or more chronic conditions reported better quality of diet while the sociodemographic factors of age, gender and ethnicity demonstrated a consistent pattern in correlating with diet quality, consistent with the extant literature. Results provide further insights for policymakers to refine ongoing efforts in relation to healthy dietary practices for Singapore.

AIMS This real-world observational clinical programme evaluated short and medium-term effects of intermittent flash glucose monitoring on HbA1c, glycaemic variability and lifestyle behavioural changes. METHODS Two first-generation Libre flash glucose monitoring sensors were provided 3-4 months apart with a food, activity diary, user evaluation survey and treatment modification after each sensor wear. T-tests were used to compare glucose variables within each sensor (week 1 vs. week 2) and between sensors (1st sensor vs. 2nd sensor). EasyGV software was used to calculate glycaemic variability. RESULTS From 42 type 1 diabetes and 120 type 2 diabetes participants, there was no statistically significant change in mean HbA1c for participants with type 1 diabetes at 3-4 months after the 1st sensor but there was a statistically significant HbA1c reduction for participants with type 2 diabetes [-4 mmol/mol (-0.4%), p = 0.008], despite no statistically significant differences in carbohydrate intake, exercise frequency and duration. Greater reduction was seen in those with baseline HbA1c> 86 mmol/mol (10%) in both type 1 [-12 mmol/mol (-1.1%), p = 0.009] and type 2 diabetes [-11 mmol/mol (-1.0%), p = 0.001). Both type 1 and type 2 diabetes showed improvements in Glucose Management Indicator and percentage time-above-range when comparing week 1 versus week 2 of the same sensor. Higher scan frequency resulted in improved glycaemic parameters and certain measures of glycaemic variability. The majority of participants (85%) agreed that flash glucose monitoring is a useful device but only 60% were keen to use it for daily monitoring. CONCLUSION Constant feedback from flash glucose monitoring improves glycaemic parameters within the first week of wear. Intermittent use 3-4 months apart resulted in greater improvements for those with higher baseline HbA1c.

Abstract Purpose Sodium-glucose co-transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors are increasingly used as second-line therapies in patients with type 2 diabetes. The aim of this study was to assess the real-world effects of SGLT2 inhibitors in a multi-ethnic population in Singapore. Methods This retrospective cohort study examined patients diagnosed with and treated for diabetes from the Ministry of Health’s administrative database. Differences in outcomes between treatment groups were assessed using Poisson regression. Demographics, clinical characteristics, previous diagnoses and hospitalisations, and diabetes medication history were used for propensity score matching. Subgroup analyses by ethnicity were performed. Effect size was estimated using risk ratios (RRs) with 95% confidence intervals (CIs). Results Patients initiating SGLT2 inhibitors were more likely to achieve glycaemic control target than DPP4 inhibitor-treated patients (RR 1.09; 95% CI 1.04, 1.14). This was observed only in patients of Chinese ethnicity. A higher risk of diabetic ketoacidosis in SGLT2 inhibitor initiators was not observed. SGLT2 inhibitors were associated with reduced risk of hypoglycaemia (RR 0.69; 95% CI 0.59, 0.82) and urinary tract infection (RR 0.52; 95% CI 0.43, 0.63) but was not statistically significant for hypoglycaemia in Malay patients. Compared to DPP4 inhibitors, SGLT2 inhibitors were associated with 12% and 34% reduction in any-cause hospitalisation and all-cause mortality, respectively, potentially resulting in more than $50 million savings over 10 years. Conclusion SGLT2 inhibitors were associated with improvements in glycaemic control, reduced risk of complications, and was well tolerated. Ethnicity also plays a role and should be considered in future studies.

To evaluate the effects of Roux-en-Y gastric bypass (RYGB) versus best medical treatment in Asians with type 2 diabetes mellitus (T2DM) and class I obesity.In this 5-year single-centre, open-label randomized controlled trial, participants were randomized to RYGB or medical treatment including newer classes of diabetes medications (ClinicalTrials.gov:NCT02041234). The primary endpoint was diabetes remission defined as HbA1c ≤ 6% (≤42 mmol/mol) and discontinuation of glucose-lowering medication at 12 months post-intervention and beyond. Glycaemia and weight changes were assessed. Continuous glucose monitoring was performed.Of 28 subjects randomized, 26 were analyzed in the final cohort (14 medical, 12 RYGB; age:44 ± 10 years, 34.6% males, BMI:29.4 ± 1.6 kg/mOver 5 years, RYGB outperforms best medical treatment in glycemia and weight improvements for Asians with T2DM and class I obesity.

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. Key words: Glucose-lowering medications, Glycaemic control, High-density lipoprotein

Objective: Arterial stiffness has been associated with diabetic retinopathy; however, the information is limited in Asians. We aim to examine the association of central arterial stiffness with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients in Singapore. Methods: Arterial stiffness was estimated by carotid-femoral pulse wave velocity and augmentation index using applanation tonometry method. Digital colour fundus photographs from 1,203 patients were assessed for diabetic retinopathy. Diabetic retinopathy severity was categorized into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. Logistic regression model was used to evaluate the associations of diabetic retinopathy with pulse wave velocity and augmentation index. Results: Diabetic retinopathy was diagnosed in 391 (32.5%) patients, including 271 non-proliferative diabetic retinopathy and 108 proliferative diabetic retinopathy. Diabetic retinopathy have higher pulse wave velocity (11.2 ± 3.3 vs 9.5 ± 2.6 m/s, p Conclusion: Central arterial stiffness was associated with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients, suggesting its etiologic implication in diabetic retinopathy.

To examine the longitudinal association between skeletal muscle mass (SMM) loss and cognitive decline over time in type 2 diabetes mellitus (T2DM).We conducted a prospective cohort study of 453 patients from SMART2D cohort with follow-up intervals of 1.6 to 6.4 years. Baseline and follow-up measurements included bio-impedance analysis (BIA) measure of skeletal muscle mass index (SMI) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measure of cognitive function. We examined the association between annual rate of SMI and RBANS scores using linear regression, adjusting for demographics, education, depression, clinical co-variables and presence of apolipoprotein E4 (APOE)The mean age of participants was 60.3 ± 7.4 years. Compared to patients with Tertile 1 SMI change, the group with greater SMI decline (Tertile 3 SMI change) experienced 0.30 decline in RBANS total score (95%CI -0.57 to -0.03; p = 0.030) in the adjusted analysis. RBANS scores for subdomains in immediate memory and visuo-spatial/construction were lower in Tertile 3 SMI change group with corresponding coefficients -0.54 (95%CI -1.01 to -0.06; p = 0.026), and -0.71 (95%CI -1.30 to -0.12; p = 0.019) respectively.In patients with T2DM, BIA measure of muscle mass loss over time was independently associated with cognitive decline globally and in the domains of memory and visuo-spatial/construction.