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

Neelam, Kumari / Aung, Khin Chaw Yu / Ang, Keven / Tavintharan, Subramaniam / Sum, Chee Fang / Lim, Su Chi

Clinical ophthalmology (Auckland, N.Z.)

2023 Volume 17, Page(s) 445–454

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2023-02-02
Publishing country	New Zealand
Document type	Journal Article
ISSN	1177-5467
ISSN	1177-5467
DOI	10.2147/OPTH.S382336
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Article ; Online: Association of plasma angiogenin with risk of major cardiovascular events in type 2 diabetes.

Gurung, Resham L / Liu, Sylvia / Liu, Jian-Jun / M, Yiamunaa / Zheng, Huili / Chan, Clara / Ang, Keven / Subramaniam, Tavintharan / Sum, Chee Fang / Lim, Su Chi

Cardiovascular diabetology

2024 Volume 23, Issue 1, Page(s) 70

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/complications ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/diagnosis ; Myocardial Infarction/complications ; Prospective Studies ; Ribonuclease, Pancreatic ; Risk Factors
Chemical Substances	angiogenin (EC 3.1.27.-) ; Ribonuclease, Pancreatic (EC 3.1.27.5)
Language	English
Publishing date	2024-02-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2093769-6
ISSN	1475-2840 ; 1475-2840
ISSN (online)	1475-2840
ISSN	1475-2840
DOI	10.1186/s12933-024-02156-8
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Article ; Online: Association between Plasma LRG1 and Lower Cognitive Function in Asians with Type 2 Diabetes Mellitus.

Low, Serena / Moh, Angela / Pandian, Bhuvaneswari / Tan, Xin Li / Pek, Sharon / Zheng, Huili / Ang, Keven / Tang, Wern Ee / Lim, Ziliang / Subramaniam, Tavintharan / Sum, Chee Fang / Lim, Su Chi

The Journal of clinical endocrinology and metabolism

2024

Abstract: 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 ... ...

Abstract	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 (SNP). 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 -0.21; p = 0.021) and -1.38 (95%CI -2.70 to -0.07; p = 0.039), 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 -0.74; p = 0.030) per unit increase in LnLRG1. Higher PWV accounted for 27.7% of the association between LnLRG1 and follow-up RBANS total score. Conclusions: 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.
Language	English
Publishing date	2024-01-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad768
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Article ; Online: Plasma proteomics of diabetic kidney disease among Asians with younger-onset type 2 diabetes.

Gurung, Resham Lal / Zheng, Huili / Koh, Hiromi Wai Ling / Yiamunaa, M / Liu, Jian-Jun / Liu, Sylvia / Chan, Clara / Ang, Keven / Tan, Clara Si Hua / Sobota, Radoslaw Mikolaj / Subramaniam, Tavintharan / Sum, Chee Fang / Lim, Su Chi

The Journal of clinical endocrinology and metabolism

2024

Abstract: 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.: ...

Abstract	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.
Language	English
Publishing date	2024-04-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgae266
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Article ; Online: Association of plasma ceramide with decline in kidney function in patients with type 2 diabetes.

Gurung, Resham L / M, Yiamunaa / Tham, Wai Kin / Liu, Sylvia / Zheng, Huili / Lee, Janus / Ang, Keven / Wenk, Markus / Subramaniam, Tavintharan / Sum, Chee Fang / Torta, Federico / Liu, Jian-Jun / Lim, Su Chi

Journal of lipid research

2024 , Page(s) 100552

Abstract: 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 ... ...

Abstract	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 5ml/min/1.73m
Language	English
Publishing date	2024-05-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	80154-9
ISSN	1539-7262 ; 0022-2275
ISSN (online)	1539-7262
ISSN	0022-2275
DOI	10.1016/j.jlr.2024.100552
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Article ; Online: Reduced skeletal muscle mass to visceral fat area ratio is independently associated with reduced cognitive function in type 2 diabetes mellitus.

Low, Serena / Ng, Tze Pin / Goh, Kiat Sern / Moh, Angela / Khoo, Jonathon / Ang, Keven / Yap, Philip / Cheong, Chin Yee / Tang, Wern Ee / Lim, Ziliang / Subramaniam, Tavintharan / Sum, Chee Fang / Lim, Su Chi

Journal of diabetes and its complications

2024 Volume 38, Issue 2, Page(s) 108672

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Middle Aged ; Aged ; Diabetes Mellitus, Type 2/diagnosis ; Intra-Abdominal Fat ; Cross-Sectional Studies ; Cognition ; Cognitive Dysfunction/complications ; Cognitive Dysfunction/epidemiology ; Muscle, Skeletal
Language	English
Publishing date	2024-01-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1105840-7
ISSN	1873-460X ; 1056-8727
ISSN (online)	1873-460X
ISSN	1056-8727
DOI	10.1016/j.jdiacomp.2023.108672
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Article ; Online: Urine tricarboxylic acid cycle metabolites and risk of end stage kidney disease in patients with type 2 diabetes.

Liu, Jian-Jun / Liu, Sylvia / Zheng, Huili / Lee, Janus / Gurung, Resham L / Chan, Clara / Lee, Lye Siang / Ang, Keven / Ching, Jianhong / Kovalik, Jean-Paul / Tavintharan, Subramaniam / Sum, Chee Fang / Sharma, Kumar / Coffman, Thomas M / Lim, Su Chi

The Journal of clinical endocrinology and metabolism

2024

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgae199
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Article: The torments of the cohesin ring

Chavda, Alap P / Ang, Keven / Ivanov, Dmitri

Nucleus. 2017 May 4, v. 8, no. 3

2017

Abstract: Cohesin is a ring-shaped protein complex which comprises the Smc1, Smc3 and Scc1 subunits. It topologically embraces chromosomal DNA to connect sister chromatids and stabilize chromatin loops. It is required for proper chromosomal segregation, DNA repair ...

Abstract	Cohesin is a ring-shaped protein complex which comprises the Smc1, Smc3 and Scc1 subunits. It topologically embraces chromosomal DNA to connect sister chromatids and stabilize chromatin loops. It is required for proper chromosomal segregation, DNA repair and transcriptional regulation. We have recently reported that cohesin rings can adopt a “collapsed” rod-like conformation which is driven by the interaction between the Smc1 and Smc3 coiled coil arms and is regulated by post-translational modifications. The “collapsed” conformation plays a role in cohesin ring assembly and its loading on the DNA. Here we speculate about the mechanism of cohesin's conformational transitions in relation to its loading on the DNA and draw parallels with other Smc-like complexes.
Keywords	DNA ; DNA repair ; chromatids ; chromatin ; chromosome segregation ; transcription (genetics)
Language	English
Dates of publication	2017-0504
Size	p. 261-267.
Publishing place	Taylor & Francis
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2619626-8
ISSN	1949-1042 ; 1949-1034
ISSN (online)	1949-1042
ISSN	1949-1034
DOI	10.1080/19491034.2017.1295200
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Article ; Online: The torments of the cohesin ring.

Chavda, Alap P / Ang, Keven / Ivanov, Dmitri

Nucleus (Austin, Tex.)

2017 Volume 8, Issue 3, Page(s) 261–267

Abstract	Cohesin is a ring-shaped protein complex which comprises the Smc1, Smc3 and Scc1 subunits. It topologically embraces chromosomal DNA to connect sister chromatids and stabilize chromatin loops. It is required for proper chromosomal segregation, DNA repair and transcriptional regulation. We have recently reported that cohesin rings can adopt a "collapsed" rod-like conformation which is driven by the interaction between the Smc1 and Smc3 coiled coil arms and is regulated by post-translational modifications. The "collapsed" conformation plays a role in cohesin ring assembly and its loading on the DNA. Here we speculate about the mechanism of cohesin's conformational transitions in relation to its loading on the DNA and draw parallels with other Smc-like complexes.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Animals ; Cell Cycle Proteins/chemistry ; Cell Cycle Proteins/metabolism ; Chromosomal Proteins, Non-Histone/chemistry ; Chromosomal Proteins, Non-Histone/metabolism ; DNA/genetics ; DNA/metabolism ; Humans ; Hydrolysis ; Protein Conformation ; Protein Processing, Post-Translational ; Cohesins
Chemical Substances	Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; Adenosine Triphosphate (8L70Q75FXE) ; DNA (9007-49-2)
Language	English
Publishing date	2017-02-27
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2619626-8
ISSN	1949-1042 ; 1949-1042
ISSN (online)	1949-1042
ISSN	1949-1042
DOI	10.1080/19491034.2017.1295200
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Article ; Online: Longitudinal profiling and tracking stability in the Singapore study of macro-angiopathy and microvascular reactivity in type 2 diabetes cohort.

Low, Serena / Zheng, Huili / Liu, Jian-Jun / Moh, Angela / Ang, Keven / Tang, Wern Ee / Lim, Ziliang / Subramaniam, Tavintharan / Sum, Chee Fang / Lim, Su Chi

Diabetes & vascular disease research

2023 Volume 20, Issue 6, Page(s) 14791641231218453

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/diagnosis ; Prospective Studies ; Singapore/epidemiology ; Risk Factors ; Hypertension/complications ; Blood Pressure/physiology ; Longitudinal Studies
Language	English
Publishing date	2023-12-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2250793-0
ISSN	1752-8984 ; 1479-1641
ISSN (online)	1752-8984
ISSN	1479-1641
DOI	10.1177/14791641231218453
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