Diabetes Self-Care Behaviors in Singapore and Their Associations With Patients' Characteristics and Health Literacy.

PURPOSE: The purpose of this study was to examine the relationship between self-management behaviors (eg, healthy eating, being active, medication taking, glucose monitoring, feet check), sociodemographic factors, disease-related characteristics, and health literacy among patients with type 2 diabetes in Singapore. METHODS: Data were analyzed from a nationwide survey conducted between 2019 and 2020 (n = 387). Self-management behaviors were assessed using the Dietary Approaches to Stop Hypertension questionnaire, the Global Physical Activity Questionnaire, and a diabetes care questionnaire. A linear regression model was generated to examine the association of healthy eating with the variables of interest (sociodemographic factors, disease-related characteristics, and health literacy), and logistic regression models were generated to investigate the significant correlates of the remaining self-care behaviors. RESULTS: Regression models showed that the 5 self-care behaviors have different correlates. Nonetheless, compared to individuals aged 50 to 64 years, those aged 65 years and above were less likely to be active, adhere to their medication prescription, and check their feet. Individuals with a higher number of diabetes-related complications were less likely to be sufficiently active but more likely to monitor their glucose level and check their feet. Moreover, individuals with poor health literacy were more likely to eat healthily and be sufficiently active. CONCLUSIONS: Programs related to self-care behaviors can be tailored to specific demographics to improve their uptake in the population. Furthermore, encouraging comprehensive self-care behaviors in those aged 65 years and above is crucial for effective diabetes management.

Association Between Kidney Disease Index and Decline in Cognitive Function with Mediation by Arterial Stiffness in Asians with Type 2 Diabetes.

Background: Decline in renal function impairs systemic clearance of amyloid-ß which characterizes Alzheimer's disease while albuminuria is associated with blood-brain barrier disruption due to endothelial damage. Arterial stiffness adversely affects the brain with high pulsatile flow damaging cerebral micro-vessels. Objective: To examine association between a novel kidney disease index (KDI), which is a composite index of estimated glomerular filtration (eGFR) and urinary albumin-to-creatinine ratio (uACR), and cognitive function with potential mediation by arterial stiffness. Methods: This was a longitudinal multi-center study of participants with type 2 diabetes (T2D) aged 45 years and above. We assessed cognitive function with Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Pulse wave velocity (PWV), an index of arterial stiffness, was measured using applanation tonometry method. KDI was calculated as geometric mean of 1/eGFR and natural logarithmically-transformed (ln)(ACR*100). Results: There were 1,303 participants with mean age 61.3±8.0 years. LnKDI was associated with lower baseline RBANS total score with adjusted coefficient -2.83 (95% CI -4.30 to -1.35; p < 0.001). 590 participants were followed over up to 8.6 years. LnKDI was associated with lower follow-up RBANS score in total, immediate memory, visuo-spatial/construction and attention domains with corresponding adjusted coefficients -2.35 (95% CI -4.50 to -0.20; p = 0.032), -2.93 (95% CI -5.84 to -0.02; p = 0.049), -3.26 (95% CI -6.25 to -0.27; p = 0.033) and -4.88 (95% CI -7.95 to -1.82; p = 0.002). PWV accounted for 19.5% of association between and follow-up RBANS total score. Conclusions: KDI was associated with lower cognitive function globally, and in immediate memory, visuo-spatial/construction and attention domains. Arterial stiffness mediated the association between KDI and cognitive decline in patients with T2D.

Anaphylaxis post-COVID-19 vaccinations in Singapore.

INTRODUCTION: Anaphylaxis was the first serious adverse event (AE) of special interest surfaced in Singapore following coronavirus disease 2019 (COVID-19) vaccination. Individuals who developed physician-diagnosed severe allergic reactions to the mRNA vaccines would be medically ineligible for mRNA vaccines and offered non-mRNA alternatives. This paper describes anaphylaxis reports received by the Health Sciences Authority (HSA) and presents a review of individuals who received heterologous COVID-19 vaccination. METHODS: Reports of anaphylaxis associated with the COVID-19 vaccines received till 31 July 2022 were reviewed and adjudicated using the Brighton Collaboration case definition criteria by an HSA-appointed expert panel. Additional review was conducted for cases with heterologous vaccination for any subsequent reactions until administration of third dose of COVID-19 vaccines. RESULTS: Among 112 adjudicated anaphylaxis cases, majority occurred in females, adults and persons with allergy histories, which were consistent with global observations. Most cases (71%) occurred within 30 minutes of vaccination. The reporting incidence rates (IRs) of 0.67 and 0.55 per 100,000 administered doses for Comirnaty and Spikevax vaccines, respectively, were comparable with IRs reported overseas, whereas the IRs for non-mRNA vaccines (Sinovac-CoronaVac and Nuvaxovid) were much higher at 4.14 and 29.82 per 100,000 administered doses, respectively, likely due to selection bias. Review of the 20 cases following heterologous vaccination found varying reactions to subsequent vaccinations. CONCLUSION: Anaphylaxis is a rare but serious AE in which outcomes can be mitigated with timely medical intervention. The case review helped to guide vaccination strategies and added to the cumulative knowledge of safety with heterologous vaccination.

Proteomics profiling and association with cardiorenal complications in type 2 diabetes subtypes in Asian population.

AIM: Among multi-ethnic Asians, type 2 diabetes (T2D) clustered in three subtypes; mild obesity-related diabetes (MOD), mild age-related diabetes with insulin insufficiency (MARD-II) and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII) had differential cardio-renal complication risk. We assessed the proteomic profiles to identify subtype specific biomarkers and its association with diabetes complications. METHODS: 1448 plasma proteins at baseline were measured and compared across the T2D subtypes. Multivariable cox regression was used to assess associations between significant proteomics features and cardio-renal complications. RESULTS: Among 645 T2D participants (SIRD-RII [19%], MOD [45%], MARD-II [36%]), 295 proteins expression differed significantly across the groups. These proteins were enriched in cell adhesion, neurogenesis and inflammatory response processes. In SIRD-RII group, ADH4, ACY1, THOP1, IGFBP2, NEFL, ENTPD2, CALB1, HAO1, CTSV, ITGAV, SCLY, EDA2R, ERBB2 proteins significantly associated with progressive CKD and LILRA5 protein with incident heart failure (HF). In MOD group, TAFA5, RSPO3, EDA2R proteins significantly associated with incident HF. In MARD-II group, FABP4 protein significantly associated with progressive CKD and PTPRN2 protein with major adverse cardiovascular events. Genetically determined NEFL and CALB1 were associated with kidney function decline. CONCLUSIONS: Each T2D subtype has unique proteomics signature and association with clinical outcomes and underlying mechanisms.

Plasma ceramides predict all-cause and cause-specific mortality in individuals with type 2 diabetes.

CONTEXT: The CERT1 (Cardiovascular Event Risk Test) score derived from plasma ceramides has been applied clinically for cardiovascular risk assessment. OBJECTIVE: To study whether plasma ceramides predict risk of mortality in patients with type 2 diabetes. DESIGN, SETTING AND PARTICIPANTS: A prospective study which included 1903 outpatients with type 2 diabetes in a regional hospital and a primary care facility in Singapore. EXPOSURE AND OUTCOME: Plasma ceramides (d18:1/16:0, d18:1/18:0, d18:1/24:0, d18:1/24:1) were measured by mass spectrometry and CERT1 score was calculated accordingly. Main outcomes were all-cause and cause-specific mortality. RESULTS: 252 death events were identified during median of 9.3 years of follow-up. Compared to those with low score (≤ 2), participants with a high CERT1 score (≥ 7) had 1.86 (95% CI 1.30-3.65) fold increased risk for all-cause death after adjustment for cardio-renal risk factors including eGFR and albuminuria. As continuous variable, one- unit increment in CERT1 was associated with 8% increased risk for all-cause death (adjusted HR 1.08 [1.04-1.13]). Adding CERT1 onto RECODe (Risk Equations for Complications Of type 2 Diabetes) mortality risk engine significantly improved prediction of 10- year risk of all-cause death (AUC 0.810 to 0.823, delta 0.013 [0.005-0.022]). The association between CERT1 and non-cardiovascular death remained significant (adjusted HR 2.12 [1.32-3.42]), whereas its association with cardiovascular death became non-significant after adjustment for kidney measurements (adjusted HR 1.41 [0.78-2.56]). CONCLUSION: CERT1 score predicts mortality risk independent of clinical cardio-renal risk factors. Further studies are warranted to elucidate the mechanistic linkage between ceramide and mortality, especially non-cardiovascular mortality.

Association of plasma ceramide with decline in kidney function in patients with type 2 diabetes.

Circulating ceramide levels are dysregulated in kidney disease. However, their associations with rapid decline in kidney function (RDKF) and end-stage kidney disease (ESKD) in patients with type 2 diabetes (T2D) are unknown. In this prospective study of 1746 T2D participants, we examined the association of plasma ceramide Cer16:0, Cer18:0, Cer24:0, and Cer24:1 with RDKF, defined as an estimated glomerular filtration rate (eGFR) decline of 5 ml/min/1.73 m2 per year or greater, and ESKD defined as eGFR <15/min/1.73 m2 for at least 3 months, on dialysis or renal death at follow-up. During a median follow-up period of 7.7 years, 197 patients experienced RDKF. Ceramide Cer24:0 (odds ratio [OR] = 0.71, 95% CI 0.56-0.90) and ratios Cer16:0/Cer24:0 (OR = 3.54 [1.70-7.35]), Cer18:0/Cer24:0 (OR = 1.89 [1.10-3.25]), and Cer24:1/Cer24:0 (OR = 4.01 [1.93-8.31]) significantly associated with RDKF in multivariable analysis; 124 patients developed ESKD. The ratios Cer16:0/Cer24:0 (hazard ratio [HR] = 3.10 [1.44-6.64]) and Cer24:1/Cer24:0 (HR = 4.66 [1.93-11.24]) significantly associated with a higher risk of ESKD. The Cer24:1/Cer24:0 ratio improved risk discrimination for ESKD beyond traditional risk factors by small but statistically significant margin (Harrell C-index difference: 0.01; P = 0.022). A high ceramide risk score also associated with RDKF (OR = 2.28 [1.26-4.13]) compared to lower risk score. In conclusion, specific ceramide levels and their ratios are associated with RDKF and conferred an increased risk of ESKD, independently of traditional risk factors, including baseline renal functions in patients with T2D.

Plasma proteomics of diabetic kidney disease among Asians with younger-onset type 2 diabetes.

CONTEXT: Patients with younger onset of type 2 diabetes (YT2D) have increased risk for kidney failure compared to those with late onset. However, the mechanism of diabetic kidney disease (DKD) progression in this high-risk group is poorly understood. OBJECTIVES: To identify novel biomarkers and potential causal proteins associated with DKD progression in patients with YT2D. DESIGN AND PARTICIPANTS: Among YT2D (T2D onset age ≤ 40 years), 144 DKD progressors (cases) were matched for T2D onset age, sex, and ethnicity with 292 non-progressors (controls) and divided into discovery and validation sets. DKD progression was defined as decline of estimated glomerular filtration rate (eGFR) of 3ml/min/1.73m2 or greater or 40% decline in eGFR from baseline. 1472 plasma proteins were measured through a multiplex immunoassay that uses a proximity extension assay technology. Multivariable logistic regression was used to identify proteins associated with DKD progression. Mendelian randomization (MR) was used to evaluate causal relationship between plasma proteins and DKD progression. RESULTS: 42 plasma proteins were associated with DKD progression, independent of traditional cardio-renal risk factors, baseline eGFR and urine albumin-to-creatinine ratio (uACR). The proteins identified were related to inflammatory and remodelling biological processes. Our findings suggested angiogenin as one of the top signals (odds ratio =5.29, 95% CI 2.39-11.73, P = 4.03 × 10-5). Furthermore, genetically determined plasma angiogenin level was associated with increased odds of DKD progression. CONCLUSION: Large-scale proteomic analysis identified novel proteomic biomarkers for DKD progression in YT2D. Genetic evidence suggest a causal role of plasma angiogenin in DKD progression.

Urine tricarboxylic acid cycle metabolites and risk of end stage kidney disease in patients with type 2 diabetes.

CONTEXT: Metabolites in tricarboxylic acid (TCA) pathway have pleiotropic functions. OBJECTIVE: To study the association between urine TCA cycle metabolites and the risk for chronic kidney disease (CKD) progression in individuals with type 2 diabetes. DESIGN, SETTING AND PARTICIPANTS: A prospective study in a discovery (n = 1826) and a validation (n = 1235) cohort of type 2 diabetes in a regional hospital and a primary care facility. EXPOSURE AND OUTCOME: Urine lactate, pyruvate, citrate, alpha-ketoglutarate, succinate, fumarate and malate were measured by mass spectrometry. CKD progression was defined as a composite of sustained eGFR below 15 ml/min/1.73 m2 , dialysis, renal death or doubling of serum creatinine. RESULTS: During a median of 9.2 (IQR 8.1-9.7) and 4.0 (3.2-5.1) years of follow-up, 213 and 107 renal events were identified. Cox regression suggested that urine lactate, fumarate and malate were associated with an increased risk (adjusted hazard ratio, aHR [95% CI] 1.63 [1.16-2.28], 1.82 [1.17-2.82] and 1.49 [1.05-2.11], per SD), while citrate was associated with a low risk (aHR 0.83 [0.72-0.96] per SD) for the renal outcome after adjustment for cardio-renal risk factors. These findings were reproducible in the validation cohort. Noteworthy, fumarate and citrate were independently associated with the renal outcome after additional adjustment for other metabolites. CONCLUSION: Urine fumarate and citrate predict the risk for progression to ESKD independent of clinical risk factors and other urine metabolites. These two metabolites in TCA cycle pathway may play important roles in the pathophysiological network underpinning progressive loss of kidney function in patients with type 2 diabetes.

Association of plasma angiogenin with risk of major cardiovascular events in type 2 diabetes.

BACKGROUND: Angiogenin, an enzyme belonging to the ribonucleases A superfamily, plays an important role in vascular biology. Here, we sought to study the association of plasma angiogenin and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes (T2D). METHODS: This prospective study included 1083 T2D individuals recruited from a secondary hospital and a primary care facility. The primary outcome was a composite of four-point MACE (nonfatal myocardial infarction, stroke, unstable angina pectoris leading to hospitalization and cardiovascular death). Circulating angiogenin was measured by a proximity extension assay. Cox regression models were used to evaluate the association of baseline plasma angiogenin with the risk of MACE. RESULTS: During a median follow-up of 9.3 years, 109 (10%) MACE were identified. Plasma angiogenin was significantly higher in participants with MACE than in those without MACE (P < 0.001). Doubling of plasma angiogenin concentration was associated with a 3.10-fold (95% CI 1.84-5.22) increased risk for MACE. The association was only moderately attenuated after adjustment for demographic and cardiometabolic risk factors (adjusted HR 2.38, 95% CI 1.34-4.23) and remained statistically significant after additional adjustment for estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (uACR) (adjusted HR 1.90, 95% CI 1.02-3.53). A consistent outcome was obtained when plasma angiogenin was analysed as a categorical variable in tertiles. CONCLUSIONS: Plasma angiogenin was associated with the risk of future cardiovascular events in patients with T2D and may be a promising novel biomarker for identifying high-risk T2D patients for early management.

Public awareness of war on diabetes campaign and its association with behavioural outcomes.

The War on Diabetes campaign was launched in 2016, encouraging Singapore residents to engage in regular exercise, adopt healthy dietary habits and screen for early detection of diabetes. This study aims to examine campaign awareness and its associations with sedentary behaviour, dietary habits and identifying diabetes. Data were obtained from the nationwide Knowledge, Attitudes and Practices study on diabetes in Singapore. A total of 2895 participants responded to a single question assessing campaign awareness. The Dietary Approaches to Stop Hypertension (DASH) diet screener assessed dietary habits, and the Global Physical Activity Questionnaire (GPAQ) measured sedentary behaviour. Recognition of diabetes was established using a vignette depicting a person with diabetes mellitus. Logistic and linear regression models were used to measure the associations. Most participants were 18- to 34-years old (29.9%) and females (51.6%). About 57.4% identified the campaign. Campaign awareness exhibited positive associations with identifying diabetes based on the vignette [odds ratio (OR): 1.5; 95% confidence interval (CI): 1.1-2.2; P = 0.022], lower odds of sedentary behaviour ≥7 h/day (OR: 0.7; CI: 0.5-0.9; P = 0.018) and higher DASH scores (ß = 1.3; P < 0.001). The study recognized early significant associations between the behavioural outcomes and the campaign, emphasizing the need for ongoing campaign sustainability and evaluation of its long-term impact on population health.

Association Between Plasma LRG1 and Lower Cognitive Function in Asians With Type 2 Diabetes Mellitus.

CONTEXT: Leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in the pathogenesis of diabetic complications, but its association with cognitive function remains unclear. OBJECTIVE: Our primary objective is to investigate the longitudinal association between LRG1 and cognitive function in patients with type 2 diabetes mellitus (T2DM). Secondarily, we determine the causal relationship using Mendelian randomization (MR) and the role of arterial stiffness as a potential mediator. METHODS: T2DM patients (n = 1039; age = 64.1 ± 6.4 years) were followed-up for 5.3 ± 1.2 years. Plasma LRG1 was measured at baseline using enzyme-linked immunosorbent assay. Baseline and follow-up cognitive function was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). One-sample MR was performed with rs4806985 as plasma LRG1-associated single-nucleotide polymorphism. Mediation analysis was performed to examine if pulse wave velocity (PWV), an arterial stiffness index, mediated the association between plasma LRG1 and follow-up cognitive function. RESULTS: Elevated baseline natural log (Ln)-transformed LRG1 was inversely associated with baseline and follow-up RBANS total score with adjusted coefficients -1.38 (95% CI -2.55 to -.21; P = .021) and -1.38 (95% CI -2.70 to -.07; P = .039), respectively. Genetically predicted higher levels of plasma LRG1 was associated with lower follow-up RBANS total score with coefficient -7.44 (95% CI -14.14 to -.74; P = .030) per unit increase in LnLRG1. Higher PWV accounted for 27.7% of the association between LnLRG1 and follow-up RBANS total score. CONCLUSION: Baseline plasma LRG1 was associated with lower cognitive function at follow-up in patients with T2DM, mediated by PWV. MR analysis provided evidence of an association between genetically influenced plasma LRG1 and lower cognitive function at follow-up.

Reduced skeletal muscle mass to visceral fat area ratio is independently associated with reduced cognitive function in type 2 diabetes mellitus.

AIM: Skeletal muscle mass to visceral fat area ratio (SVR) has been recognised as an index of sarcopenic obesity. SVR is associated with type 2 diabetes mellitus (T2DM), metabolic syndrome and arterial stiffness which are known risk factors for cognitive dysfunction. We aimed to investigate association between SVR and cognitive function in patients with T2DM. METHODS: This was a cross-sectional study of 1326 patients with T2DM and mean age 61.3 ± 8.0 years. SVR was assessed based on bioelectrical impedance measurements of muscle mass and visceral fat area (VFA). Cognitive function was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Linear regression was used to examine the association between SVR in quartiles and RBANS score, adjusting for demographics, education, presence of depressive symptoms, clinical covariates and medications. RESULTS: The lower SVR quartiles were negatively associated with RBANS total score in the unadjusted analysis. The corresponding coefficients for Quartiles 1 and 2 SVR were -3.79 (95 % CI -5.39 to -2.19; p < 0.001) and -1.47 (95 % CI -2.86 to -0.07; p = 0.039) in fully adjusted analysis. The negative association between Quartile 1 SVR and RBANS score was evident in immediate memory, delayed memory, visuo-spatial construction, language and attention domains. Muscle mass and VFA alone had weaker associations with RBANS scores. CONCLUSION: Our study demonstrated, for the first time, an independent association between reduced SVR and lower cognitive function. This is evident in global and multiple cognitive domains. The synergistic effects of reduced muscle mass and visceral obesity may be more pronounced than their independent effects on cognitive function.

Longitudinal profiling and tracking stability in the Singapore study of macro-angiopathy and microvascular reactivity in type 2 diabetes cohort.

INTRODUCTION: The Singapore Study of Macro-Angiopathy and microvascular Reactivity in Type 2 Diabetes (SMART2D) is a prospective cohort study which was started in 2011 to investigate the effect of risk factors on vascular function and diabetes-related complications in Asians. We aimed to compare the longitudinal change in risk factors by accounting for batch effect and assess the tracking stability of risk factors over time in patients recruited for SMART2D. In this study, we (1) described batch effect and its extent across a heterogenous range of longitudinal data parameters; (2) mitigated batch effect through statistical approach; and (3) assessed the tracking stability of the risk factors over time. METHODS: A total of 2258 patients with type 2 diabetes mellitus (T2DM) were recruited at baseline. The study adopted a three-wave longitudinal design with intervals of 3 years between consecutive waves. The changes in a few selected risk factors were assessed after calibration, assuming patients with similar demographic and anthropometry profile had similar physiology. The tracking pattern of the risk factors was determined with stability coefficients derived from generalised estimating equations. RESULTS: The medians of the longitudinal differences in risk factors between the waves were mostly modest at <10%. Larger increases in augmentation index (AI), aortic systolic blood pressure (BP) and aortic mean BP were consistently observed after calibration. The medians of the longitudinal differences in AI, aortic systolic BP and aortic mean BP between the waves were <2% before calibration, but increased slightly to <5% after calibration. Most of the risk factors had moderate to high tracking stability. Muscle mass and serum creatinine were among those with relatively high tracking stability. CONCLUSIONS: The longitudinal differences in parameters between the waves were overall modest after calibration, suggesting that calibration may attenuate longitudinal differences inflated by non-biological factors such as systematic drift due to batch effect. Changes of the hemodynamic parameters are robust over time and not entirely attributable to age. Our study also demonstrated moderate to high tracking stability for most of the parameters.

Plasma Tryptophan-Kynurenine Pathway Metabolites and Risk for Progression to End-Stage Kidney Disease in Patients With Type 2 Diabetes.

OBJECTIVE: We sought to study the associations between plasma metabolites in the tryptophan-kynurenine pathway and the risk of progression to end-stage kidney disease (ESKD) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Plasma tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid, and xanthurenic acid concentrations were measured in discovery (n = 1,915) and replication (n = 346) cohorts. External validation was performed in Chronic Renal Insufficiency Cohort (CRIC) participants with diabetes (n = 1,312). The primary outcome was a composite of incident ESKD (progression to estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2, sustained dialysis, or renal death). The secondary outcome was annual eGFR decline. RESULTS: In the discovery cohort, tryptophan was inversely associated with risk for ESKD, and kynurenine-to-tryptophan ratio (KTR) was positively associated with risk for ESKD after adjustment for clinical risk factors, including baseline eGFR and albuminuria (adjusted hazard ratios [HRs] 0.62 [95% CI 0.51, 0.75] and 1.48 [1.20, 1.84] per 1 SD). High levels of kynurenic acid and xanthurenic acid were associated with low risks of ESKD (0.74 [0.60, 0.91] and 0.74 [0.60, 0.91]). Consistently, high levels of tryptophan, kynurenic acid, and xanthurenic acid were independently associated with a slower eGFR decline, while a high KTR was predictive of a faster eGFR decline. Similar outcomes were obtained in the replication cohort. Furthermore, the inverse association between kynurenic acid and risk of ESKD was externally validated in CRIC participants with diabetes (adjusted HR 0.78 [0.65, 0.93]). CONCLUSIONS: Accelerated catabolism of tryptophan in the kynurenine pathway may be involved in progressive loss of kidney function. However, shunting the kynurenine pathway toward the kynurenic acid branch may potentially slow renal progression.

The Role of Triglyceride-Glucose Index in the Prediction of the Development of Hypertension - Findings from a Community Cohort in Singapore.

Objectives: Triglyceride-glucose index (TyGI) is an emerging surrogate marker of insulin resistance. We aim to explore the role of triglyceride-glucose index in the prediction of the development of hypertension. Methodology: We conducted a retrospective cohort study that included 3,183 study participants identified from a community health screening programme who had no baseline hypertension and were then followed up after an average of 1.7 years. Cox proportional-hazard model was used to assess the association between risk of incident hypertension and TyGI in quartiles, while adjusting for demographics and clinical characteristics. Results: Hypertension occurred in 363 study participants (11.4%). Those who developed hypertension had higher TyGI [8.6 (IQR 8.2-9.0)] than those who did not [8.2 (IQR 8.0-8.7)] (p<0.001). Significant association between TyGI and hypertension was observed in both the unadjusted and proportional hazard model [Quartile (Q)2, p=0.010; Q3, p<0.001 and Q4, p<0.001] and the model that adjusted for demographics (Q2, p=0.016; Q3, p=0.003; Q4, p<0.001). In the model adjusted for clinical covariates, the hazard of developing hypertension remained higher in TyGI Q4 compared to TyGI Q1(Hazard Ratio=2.57; 95% Confidence Interval: 1.71, 3.87). Increasing triglyceride-glucose index accounted for 16.4% of the association between increasing BMI and incident hypertension, after adjusting for age, gender, ethnicity and baseline HDL cholesterol (p<0.001). Conclusion: Triglyceride-glucose index was an independent predictor of the development of hypertension. It may potentially be used as an inexpensive indicator to predict the development of hypertension and risk-stratify individuals to aid management in clinical practice.

Measuring social desirability bias in a multi-ethnic cohort sample: its relationship with self-reported physical activity, dietary habits, and factor structure.

BACKGROUND: Social desirability bias is one of the oldest forms of response bias studied in social sciences. While individuals may feel the need to fake good or bad answers in response to sensitive or intrusive questions, it remains unclear how rampant such a bias is in epidemiological research pertaining to self-reported lifestyle indicators in a multicultural Asian context. The main purpose of the current study is, therefore, to examine the sociodemographic correlates and impact of social desirability responding on self-reported physical activity and dietary habits at an epidemiological scale in a non-western multi-cultural Asian setting. METHODS: Prior to the main analyses, confirmatory and exploratory factor analyses were conducted to determine the factorial validity of a western derived concept of social desirability. Multiple regression analyses were conducted on cross-sectional data (n = 2995) extracted from a nationwide survey conducted between 2019 and 2020. RESULTS: A unique factor structure of social desirability was found and was therefore used for subsequent analyses. Multiple regression analyses revealed older age groups, the Indian ethnic group, those with past or present marriages, and having no income, had a significantly greater tendency to act on the bias. CONCLUSION: The construct of social desirability bias was fundamentally different in a multicultural context than previously understood. Only a small proportion of variance of self-report lifestyle scores was explained by social desirability, thus providing support for data integrity.

Associations of non-invasive indices of liver steatosis and fibrosis with progressive kidney impairment in adults with type 2 diabetes.

AIMS: Longitudinal data linking non-alcoholic fatty liver disease to kidney dysfunction in type 2 diabetes (T2D) are limited. This study evaluated the associations of non-invasive indices of liver steatosis and liver fibrosis with kidney impairment, and the mediatory role of the pro-angiogenic factor leucine-rich α-2 glycoprotein 1 (LRG1). METHODS: T2D adults (n = 2057) were followed for a mean period of 6.1 ± 1.6 years. Baseline liver steatosis [(hepatic steatosis index (HSI) and Zhejiang University index (ZJU)] and liver fibrosis [aspartate transaminase/alanine transaminase ratio (AAR) and BARD] indices derived from composite scoring systems were calculated. Plasma LRG1 levels were quantified using immunoassay. The study outcomes were progressive kidney function decline defined as estimated glomerular filtration rate (eGFR) decline of ≥ 40% and albuminuria progression defined as an increase in albuminuria category. RESULTS: Cross-sectionally, liver steatosis and liver fibrosis indices were associated with increased albuminuria (urinary albumin/creatinine ratio ≥ 30 µg/mg) and reduced renal function (eGFR < 60 mL/min/1.73 m2) after covariate adjustment, respectively. Approximately 32% of the participants experienced progressive kidney function decline, while 38% had albuminuria worsening over time. Longitudinal analysis revealed that baseline AAR (hazard ratio: 1.56; 95% CI 1.15-2.11) and BARD (hazard ratio: 1.16, 95% CI 1.04-1.28) predicted progressive kidney function decline, partly mediated by LRG1. In contrast, liver steatosis (HSI and ZJU) but not liver fibrosis (AAR and BARD) indices were independently associated with albuminuria progression. CONCLUSIONS: Increased liver steatosis scores were associated with albuminuria deterioration. Conversely, liver fibrosis indices may be associated with progressive kidney function decline, potentially driven by increased inflammation and angiogenesis.

Association between neutrophil/lymphocyte ratio and kidney impairment in type 2 diabetes mellitus: A role of extracellular water/total body water ratio.

AIMS: We explored the predictive utility of baseline neutrophil/lymphocyte ratio (NLR), which reflects a systemic inflammatory tone, in kidney impairment in type 2 diabetes mellitus (T2DM); and investigated the effect of extracellular water/total body water (ECW/TBW) ratio on the relationship. METHODS: This longitudinal study included 1,224 T2DM adults recruited from a single centre. Cox regression analyses examined the association between NLR and progressive kidney function decline or albuminuria progression. Improvements in risk discrimination were assessed using Harrell's concordance-statistics. The mediatory role of ECW/TBW ratio estimated by bioelectrical impedance was evaluated. RESULTS: Higher baseline NLR levels were observed in cases with kidney function decline or albuminuria progression over a median 2-year follow-up. NLR independently predicted progressive kidney function decline (hazard ratio:1.39, 95% CI:1.21-1.60, P < 0.001) or albuminuria progression (hazard ratio:1.34, 95% CI:1.08-1.68, P = 0.009). Addition of NLR to a base model comprising demographics, T2DM duration, metabolic and renal parameters, and medications significantly improved the risk discrimination of kidney function decline (P = 0.022) but not albuminuria progression. ECW/TBW ratio accounted for 19.7% of the total effect between NLR and kidney function loss. CONCLUSIONS: Increased NLR reflecting systemic inflammation is associated with progressive kidney function decline in T2DM, partially explained by dysregulated body fluid balance.

Association of Triglyceride Glucose Index with Prevalence and Incidence of Diabetic Retinopathy in a Singaporean Population.

Objective: 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.