Serena Low

Ethnic disparities in risk of cardiovascular disease, end-stage renal disease and all-cause mortality: a prospective study among Asian people with Type 2 diabetes.

To study prospectively the ethnic‐specific risks of cardiovascular disease, end‐stage renal disease and all‐cause mortality in patients with Type 2 diabetes mellitus among native Asian subpopulations.

Ethnic disparity in central arterial stiffness and its determinants among Asians with type 2 diabetes

OBJECTIVE We previously reported ethnic disparity in adverse outcomes among Asians with type 2 diabetes (T2DM) in Singapore. Central arterial stiffness can aggravate systemic vasculopathy by propagating elevated systolic and pulse pressures forward, thereby accentuating global vascular injury. We aim to study ethnic disparity in central arterial stiffness and its determinants in a multi-ethnic T2DM Asian cohort. METHODS Arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV) and augmentation index (AI) using applanation tonometry method in Chinese (N = 1045), Malays (N = 458) and Indians (N = 468). Linear regression model was used to evaluate predictors of PWV and AI. RESULTS PWV was higher in Malays (10.1 ± 3.0 m/s) than Chinese (9.7 ± 2.8 m/s) and Indians (9.6 ± 3.1 m/s) (P = 0.018). AI was higher in Indians (28.1 ± 10.8%) than Malays (25.9 ± 10.1%) and Chinese (26.1 ± 10.7%) (P < 0.001). Malays remain associated with higher PWV (β = 0.299, P = 0.048) post-adjustment for age, gender, duration of diabetes, hemoglobin A1c, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), soluble receptor for advanced glycation end-products, urinary albumin-to-creatinine ratio, and insulin usage, which were all independent predictors of PWV. Indians remain associated with higher AI (β = 2.776, P < 0.001) post-adjustment for age, gender, BMI, SBP, DBP, and height, which were independent predictors of AI. These variables explained 27.7% and 33.4% of the variance in PWV and AI respectively. CONCLUSIONS Malays and Indians with T2DM have higher central arterial stiffness, which may explain their higher risk for adverse outcomes. Modifying traditional major vascular risk factors may partially alleviate their excess cardiovascular risk through modulating arterial stiffness.

The effect of long‐term glycemic variability on estimated glomerular filtration rate decline among patients with type 2 diabetes mellitus – insights from the Diabetic Nephropathy Cohort in Singapore

In the present study, we examined the association between HbA1c variability and renal disease progression based on estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes mellitus (T2DM) in Singapore.

Arterial stiffness is an independent predictor for albuminuria progression among Asians with type 2 diabetes—A prospective cohort study

AIM Albuminuria progression has been associated with renal deterioration in type 2 diabetes (T2DM). Central arterial stiffness can aggravate systemic vasculopathy by propagating elevated systolic and pulse pressures forward, thereby accentuating global vascular injury. We aim to investigate whether central arterial stiffness is an independent predictor for albuminuria progression in a multi-ethnic T2DM Asian cohort in Singapore. METHODS In a prospective cohort, 1012 T2DM patients were assessed at baseline and after a median follow-up of 3.1years. 880 patients with baseline normo- (urinary albumin-to-creatinine ratio (ACR)<30mg/g, n=579) and microalbuminuria (ACR=30-299mg/g, n=301) were divided into progression and non-progression groups according to ACR changes. Progression was defined as transition from normo- to microalbuminuria, micro- to macroalbuminuria, or normo- to macroalbuminuria. Central arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV) using applanation tonometry method. Stepwise multiple regression analysis was used to determine the predictor(s) for albuminuria progression. RESULTS Albuminuria progression occurred in 178 patients (20.2%). Baseline PWV was higher in progression (10.1±2.9m/s) than non-progression group (9.2±2.4m/s, p<0.001). 1-SD increase in baseline PWV was associated with albuminuria progression (OR=1.457, 95% CI, 1.236-1.718, p<0.001). Stepwise regression analysis identified that baseline PWV (OR=1.241, 95% CI, 1.033-1.490, p=0.021), BMI (OR=1.046, 95% CI, 1.012-1.080, p=0.008), nature log-transformed estimated glomerular filtration rate (LneGFR) (OR=0.320, 95% CI, 0.192-0.530, p=0.010) and LnACR (OR=1.344, 95% CI, 1.187-1.522, p=0.008) are predictors for albuminuria progression. CONCLUSION Increased central arterial stiffness at baseline predicted future progression of albuminuria. Our results suggest the potential benefit of ameliorating central arterial stiffness to retard albuminuria progression in T2DM.

Central arterial stiffness is associated with systemic inflammation among Asians with type 2 diabetes

Objective: To examine the relationship between inflammation and central arterial stiffness in a type 2 diabetes Asian cohort. Method: Central arterial stiffness was estimated by carotid-femoral pulse wave velocity and augmentation index. Linear regression model was used to evaluate the association of high-sensitivity C-reactive protein and soluble receptor for advanced glycation end products with pulse wave velocity and augmentation index. High-sensitivity C-reactive protein was analysed as a continuous variable and categories (<1, 1–3, and >3 mg/L). Results: There is no association between high-sensitivity C-reactive protein and pulse wave velocity. Augmentation index increased with high-sensitivity C-reactive protein as a continuous variable (β = 0.328, p = 0.049) and categories (β = 1.474, p = 0.008 for high-sensitivity C-reactive protein: 1–3 mg/L and β = 1.323, p = 0.019 for high-sensitivity C-reactive protein: >3 mg/L) after multivariable adjustment. No association was observed between augmentation index and soluble receptor for advanced glycation end products. Each unit increase in natural log–transformed soluble receptor for advanced glycation end products was associated with 0.328 m/s decrease in pulse wave velocity after multivariable adjustment (p = 0.007). Conclusion: Elevated high-sensitivity C-reactive protein and decreased soluble receptor for advanced glycation end products are associated with augmentation index and pulse wave velocity, respectively, suggesting the potential role of systemic inflammation in the pathogenesis of central arterial stiffness in type 2 diabetes.

Direct medical cost associated with diabetic retinopathy severity in type 2 diabetes in Singapore

Diabetic retinopathy (DR) is a leading cause of vision-loss globally among type 2 diabetes (T2DM) patients. Information on the economic burden of DR in Singapore is limited. We aim to identify the total annual direct medical costs of DR at different stages, and to examine factors influencing the costs. Four hundreds and seventy T2DM patients who attended the Diabetes Centre in a secondary hospital in Singapore in 2011–2014 were included. Digital color fundus photographs were assessed for DR in a masked fashion. Retinopathy severity was further categorized into non-proliferative DR (NPDR), including mild, moderate and severe NPDR, and proliferative DR (PDR). Medical costs were assessed using hospital administrative data. DR was diagnosed in 172 (39.5%) patients, including 51 mild, 62 moderate and 18 severe NPDR, and 41 PDR. The median cost in DR [2012.0 (1111.2–4192.3)] was significantly higher than that in non-DR patients [1158.1 (724.1–1838.9)] (p<0.001). The corresponding costs for mild, moderate, severe NPDR and PDR were [1167.1 (895.4–2012.0)], [2212.0 (1215.5–3825.5)], [2717.5 (1444.0–6310.7)], and [3594.8.1 (1978.4–8427.7)], respectively. After adjustment, the corresponding cost ratios for mild, moderate, severe NPDR, and PDR relative to non-DR were 1.1 (p = 0.827), 1.8 (p = 0.003), 2.0 (p = 0.031) and 2.3 (p<0.001), respectively. The other factors affecting the total cost include smoking (ratio = 1.7, p = 0.019), neuropathy (ratio = 1.9, p = 0.001) and chronic kidney disease (CKD) (ratio = 1.4, p = 0.019). The presence and severity of DR was associated with increased direct medical costs in T2DM. Our results suggest that preventing progression of DR may reduce the economic burden of DR.

Development and validation of a predictive model for Chronic Kidney Disease progression in Type 2 Diabetes Mellitus based on a 13-year study in Singapore

AIMS This study aims to develop and validate a predictive model for Chronic Kidney Disease (CKD) progression in Type 2 Diabetes Mellitus (T2DM). METHODS We conducted a prospective study on 1582 patients with T2DM from a Diabetes Centre in regional hospital in 2002-2014. CKD progression was defined as deterioration across eGFR categories with ⩾25% drop from baseline. The dataset was randomly split into development (70%) and validation (30%) datasets. Stepwise multivariable logistic regression was used to identify baseline predictors for model development. Model performance in the two datasets was assessed. RESULTS During median follow-up of 5.5years, 679 (42.9%) had CKD progression. Progression occurred in 467 (42.2%) and 212 patients (44.6%) in development and validation datasets respectively. Systolic blood pressure, HbA1c, estimated glomerular filtration rate and urinary albumin-to-creatinine ratio were associated with progression. Areas under receiving-operating-characteristics curve for the training and test datasets were 0.80 (95%CI, 0.77-0.83) and 0.83 (95%CI, 0.79-0.87). Observed and predicted probabilities by quintiles were not statistically different with Hosmer-Lemeshow χ2 0.65 (p=0.986) and 1.36 (p=0.928) in the two datasets. Sensitivity and specificity were 71.4% and 72.2% in development dataset, and 75.6% and 72.3% in the validation dataset. CONCLUSIONS A model using routinely available clinical measurements can accurately predict CKD progression in T2DM.

Medical Costs Associated with Chronic Kidney Disease Progression in an Asian Population with Type 2 Diabetes Mellitus: Chronic Kidney Disease Progression and Medical Costs

We aim to examine difference in incremental direct medical costs between non‐progressive and progressive chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) in Singapore.

Microvascular endothelial function is an independent predictor for albuminuria progression among Asians with type 2 diabetes-A prospective cohort study

We aim to investigate whether microvascular endothelial dysfunction is an independent predictor for future albuminuria progression in T2DM cohort.

Long Term Outcomes of Patients With Type 2 Diabetes Attending a Multidisciplinary Diabetes Kidney Disease Clinic

The best model of care to retard diabetic kidney disease (DKD) in the clinic is underexplored. In this study we investigated the long‐term renal outcomes of a joint endocrinologist–nephrologist clinic.