Keven Ang

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

AIMnAlbuminuria 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.nnnMETHODSnIn 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.nnnRESULTSnAlbuminuria 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.nnnCONCLUSIONnIncreased 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.

Discovery and validation of serum creatinine variability as novel biomarker for predicting onset of albuminuria in Type 2 diabetes mellitus

AIMnWe aim to study association serum creatinine(cr) variability and albuminuria progression.nnnMETHODSnWe conducted a retrospective cohort study on patients with Type 2 Diabetes Mellitus at a Diabetes Centre in Singapore (discovery cohort). Outcome is worsening of urinary albumin-to-creatinine(ACR) across stages. Cr variability was expressed as adjusted cr-intrapersonal standard deviation(SD) and coefficient-of-variation(cr-CV). A separate cohort was used for validating association between cr variability and albuminuria progression (validation cohort).nnnRESULTSnOver median follow-up of 4.2u202fyears, 38.4% of 636 patients had albuminuria progression in the discovery cohort. Increasing log-transformed adjusted cr-intrapersonal SD and cr-CV were significantly associated with albuminuria progression: HRs 1.43 (95%CI 1.11-1.85) and 1.44 (1.11-1.87) respectively in the discovery cohort, and HRs 1.94 (1.09-3.45) and 1.91 (1.05-3.45) respectively in the validation cohort. When stratified by baseline urinary ACR, higher cr variability was significantly associated with albuminuria progression in patients with normoalbuminuria but not microalbuminuria.nnnCONCLUSIONSnCr variability independently predicts albuminuria onset. This is evident in patients with normoalbuminuria, suggesting that higher cr variability could herald albuminuria onset.

Baseline predictors of aortic stiffness progression among multi-ethnic Asians with type 2 diabetes

BACKGROUND AND AIMSnThis 3-year prospective study aimed to identify baseline parameters that predicted the progression of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness, among Singapores multi-ethnic Asians with type 2 diabetes (T2DM).nnnMETHODSnThe cf-PWV was measured by the gold-standard tonometry method in 994 T2DM subjects at baseline and follow-up. The annual rate of cf-PWV change was calculated, and individuals above the 90th percentile with rate≥1.42xa0m/s per year were regarded as rapid progressors (nxa0=xa0104). In a subgroup analysis of subjects with normal cf-PWV at 1st visit (nxa0=xa0611), incident aortic stiffness was defined as follow-up cf-PWV≥10xa0m/s (nxa0=xa0188).nnnRESULTSnThe total cohort (mean age:57xa0±xa010 years; 53.4% Chinese, 20.4% Malay, 22.9% Indian, 3.2% Others) displayed a median annual cf-PWV progression rate of 0.2xa0m/s. Adjusted multivariate regression analyses showed that baseline age, cf-PWV and body mass index (BMI) constantly predicted follow-up cf-PWV, annual cf-PWV progression rate, rapid cf-PWV progression, and incident aortic stiffness. Paradoxically, lower baseline cf-PWV was associated with elevated annual cf-PWV progression rate and rapid progressors. This inverse relationship remained significant across ethnicities after ethnic stratification. Higher BMI independently predicted cf-PWV progression in Chinese and Indians, but not in Malay and Others ethnic groups. Increased age was a significant predictor in Chinese and Others ethnicities.nnnCONCLUSIONSnWe demonstrated that baseline BMI is a modifiable independent risk factor of cf-PWV progression and incident aortic stiffness. Therefore, better obesity management may impede aortic stiffness in Singapores T2DM patients, especially in the Chinese and Indians.

Ethnic disparities in relationship of obesity indices and telomere length in Asians with type 2 diabetes

Obesity and shorter telomeres increase the risk for diabetes complications and mortality. However, the relationship between obesity and telomere length in diverse Asian populations with type 2 diabetes (T2D) is not well understood. This study examined the association of baseline and changes in obesity indices with telomere length in multiethnic Asian populations with T2D.

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.

Risk of progressive chronic kidney disease in individuals with early-onset type 2 diabetes: a prospective cohort study

BackgroundnThe progression trajectory of renal filtration function has not been well characterized in patients with early-onset type 2 diabetes mellitus (T2DM) although albuminuria is often reported in this population. We aim to study the risk of progressive chronic kidney disease (CKD) in individuals with early-onset T2DM.nnnMethodsnIn total, 1189 T2DM participants were followed for 3.9 (interquartile range 3.2-4.7) years. Progressive CKD was defined as estimated glomerular filtration rate (eGFR) decline of ≥5u2009mL/min/1.73u2009m2 per year. Early-onset T2DM was defined as age at T2DM diagnosis between 18 and 30u2009years.nnnResultsnCompared with later-onset counterparts (Nu2009=u20091032), participants with early-onset T2DM (Nu2009=u2009157) were more obese and had poorer glycaemic control at baseline. In the follow-up, 24.2% and 15.6% experienced progressive CKD in early-onset and later-onset participants, respectively (Pu2009=u20090.007). Logistic regression suggested that participants with early-onset T2DM had 2.63-fold [95% confidence interval (CI) 1.46-4.75] higher risk of progressive CKD after accounting for multiple traditional risk factors. Furthermore, the excess risk of progressive CKD associated with early-onset T2DM mainly occurred in participants with preserved renal function [eGFR ≥60u2009mL/min/1.73u2009m2, odds ratio (OR) 2.85, 95% CI 1.50-5.42] and was more pronounced in those with diabetes duration <10u2009years (OR 3.67, 95% CI 1.51-8.90).nnnConclusionsnIndividuals with early-onset T2DM have a higher risk of progressive CKD. The excess risk mainly exhibits in early stage of CKD and cannot be solely attributed to traditional risk factors and a longer diabetes duration.

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.

PAX4 R192H is associated with younger onset of Type 2 diabetes in East Asians in Singapore

AIMSnYoung-onset T2D (YT2D) is associated with a more fulminant course and greater propensity for diabetic complications. The association of PAX4 R192H (rs2233580) variation with YT2D was inconsistent partly because of its Asian-specificity and under-representation of Asians in international consortiums. Interestingly, in our preliminary YT2D (meanu202f=u202f25u202fyears old) cohort, the prevalence of PAX4 R192H variant was remarkably higher (21.4%) than the general population. Therefore, we sought to determine whether PAX4 R192H is associated with younger onset of T2D in our East Asian (Chinese) population.nnnMETHODSnGenotyping of PAX4 R192H was carried out using Illumina OmniExpress BeadChips as part of a genome-wide association study. Data analysis was performed using SPSS Ver. 22.nnnRESULTSnPAX4 R192H genotype was associated with younger onset age (CC: 47.1, CT: 46.0, TT: 42.6) after adjusting for gender, Fu202f=u202f5.402, pu202f=u202f0.005. Independently, onset of diabetes was younger among males by 2.52u202fyears, 95% CI [-3.45, -1.59], pu202f<u202f0.0001. HOMA-IR and HOMA-%B were not significantly different across genotypes for a subset (nu202f=u202f1045) of the cohort.nnnCONCLUSIONSnMinor allele (T) of PAX4 R192H is associated with younger onset diabetes among Chinese in Singapore. Determining this genotype is important for identifying at-risk individuals for earlier onset diabetes and diabetic complications.

Gain in adiposity over 3 years is associated with progressive renal decline in multi-ethnic South-east Asians with type 2 diabetes

This study evaluated the association between gain in adiposity and renal decline in a large prospective multiethnic South‐east Asian cohort with type 2 diabetes mellitus (T2DM).

Excess visceral adiposity is associated with diabetic retinopathy in a multiethnic Asian cohort with longstanding type 2 diabetes

ABSTRACT Purpose/Aim: Diabetic retinopathy (DR) is the most common diabetic microvascular complication, and it typically develops after 10 years of diabetes diagnosis. The primary aim of this study was to evaluate the association between adiposity and DR susceptibility among individuals with longstanding type 2 diabetes mellitus (T2D). Materials and Methods: In this cross-sectional study, DR was assessed by fundus photography in 953 T2D subjects. DR prevalence by categories of T2D duration was evaluated. In a sub-cohort analysis, subjects having T2D for ≥10 years were divided into DR (N = 241) and non-DR (N = 377) groups. Measures of adiposity including body mass index (BMI), waist circumference (WC), and visceral fat area (VFA) were analyzed. Urinary albumin:creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measured. Results: DR prevalence markedly increased 10 years after T2D diagnosis (p < 0.001). Among subjects with T2D duration ≥10 years, BMI, WC, and VFA were elevated in DR compared with non-DR (all p < 0.05). Contrasting with BMI and WC, the association between VFA and DR sustained adjustment for demographics, metabolic factors, and insulin treatment (OR: 1.060, 95% CI: 1.004–1.119, p = 0.035). However, the association became insignificant after controlling for ACR and eGFR. Mediation analysis revealed that ACR and eGFR explained 47.3% of the relationship between VFA and DR. Conclusions: The findings suggest that visceral adiposity is associated with DR in individuals with longstanding T2D. This relationship may be attributable to generalized vascular injury as reflected by coexisting renal burden. Therefore, effective management of visceral adiposity and ameliorating renal burden may ameliorate susceptibility to DR.