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

Moh, Mei Chung / Low, Serena / Shao, Yi-Ming / Subramaniam, Tavintharan / Sum, Chee Fang / Lim, Su Chi

2023 Volume 199, Page(s) 110634

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Adult ; Humans ; Body Water/metabolism ; Water/metabolism ; Diabetes Mellitus, Type 2 ; Neutrophils ; Longitudinal Studies ; Kidney ; Lymphocytes ; Renal Insufficiency
Chemical Substances	Water (059QF0KO0R)
Language	English
Publishing date	2023-03-21
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	632523-3
ISSN	1872-8227 ; 0168-8227
ISSN (online)	1872-8227
ISSN	0168-8227
DOI	10.1016/j.diabres.2023.110634
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Article ; Online: The Role of Triglyceride-Glucose Index in the Prediction of the Development of Hypertension - Findings from a Community Cohort in Singapore.

Khoo, Jonathon Kc / Low, Serena / Irwan, Bastari / Tang, Justin Is / Sum, Chee Fang / Subramaniam, Tavintharan / Lim, Su Chi

Journal of the ASEAN Federation of Endocrine Societies

2023 Volume 38, Issue 1, Page(s) 62–67

Abstract: 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 ... ...

Abstract	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)] ( 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.
MeSH term(s)	Humans ; Triglycerides ; Risk Factors ; Glucose ; Retrospective Studies ; Singapore/epidemiology ; Hypertension/diagnosis
Chemical Substances	Triglycerides ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-01-16
Publishing country	Philippines
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2893162-2
ISSN	2308-118X ; 0857-1074
ISSN (online)	2308-118X
ISSN	0857-1074
DOI	10.15605/jafes.038.01.09
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Article: Association between self-care and chronic kidney disease in patients with type 2 diabetes mellitus.

Lim, Gwyneth Joy / Low, Serena / Liu, Allen Yan Lun / Shao, Yi Ming / Subramaniam, Tavintharan / Sum, Chee Fang / Lim, Su Chi

Annals of the Academy of Medicine, Singapore

2023 Volume 52, Issue 1, Page(s) 52–54

MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/therapy ; Self Care ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/therapy ; Renal Insufficiency, Chronic/complications
Language	English
Publishing date	2023-02-01
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	604527-3
ISSN	0304-4602
ISSN	0304-4602
DOI	10.47102/annals-acadmedsg.2022299
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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: Chylomicronemia through a burr hole: A case report.

Loh, Wann Jia / Bakthavachalam, Ramesh / Subramaniam, Tavintharan / Pek, Sharon / Chua, Fionn / Lee, Lester / Watts, Gerald F

Frontiers in cardiovascular medicine

2022 Volume 9, Page(s) 1020397

Abstract: Chylomicronemia has either a monogenic or multifactorial origin. Multifactorial chylomicronemia is the more common form and is due to the interaction of genetic predisposition and secondary factors such as obesity, diabetes, unhealthy diet, and ... ...

Abstract	Chylomicronemia has either a monogenic or multifactorial origin. Multifactorial chylomicronemia is the more common form and is due to the interaction of genetic predisposition and secondary factors such as obesity, diabetes, unhealthy diet, and medications. We report a case of a 38-year-old man who was diagnosed with multifactorial chylomicronemia following presentation with a subarachnoid hemorrhage requiring emergency surgery through a burr hole; lactescent cerebrospinal fluid mixed with blood was observed through the burr hole. The serum triglyceride concentration was 52⋅4 mmol/L with a detectable triglyceride concentration in the cerebrospinal fluid. Rapid weight gain leading to obesity and related unfavorable lifestyle factors were identified as key secondary causes of chylomicronemia. Gene testing revealed a homozygous variant in
Language	English
Publishing date	2022-10-12
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2022.1020397
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Article ; Online: Roux-en-Y gastric bypass versus best medical treatment for type 2 diabetes mellitus in adults with body mass index between 27 and 32 kg/m

Cheng, Anton / Yeoh, Ester / Moh, Angela / Low, Serena / Tan, Chun Hai / Lam, Benjamin / Sum, Chee Fang / Subramaniam, Tavintharan / Lim, Su Chi

Diabetes research and clinical practice

2022 Volume 188, Page(s) 109900

Abstract: Aims: 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.: Methods: In this 5-year single-centre, open-label randomized controlled trial, ... ...

Abstract	Aims: 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. Methods: 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. Results: 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/m Conclusions: Over 5 years, RYGB outperforms best medical treatment in glycemia and weight improvements for Asians with T2DM and class I obesity.
MeSH term(s)	Adult ; Blood Glucose ; Blood Glucose Self-Monitoring ; Body Mass Index ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/surgery ; Female ; Gastric Bypass ; Glycated Hemoglobin A ; Humans ; Male ; Middle Aged ; Obesity/complications ; Obesity, Morbid/complications ; Treatment Outcome
Chemical Substances	Blood Glucose ; Glycated Hemoglobin A
Language	English
Publishing date	2022-05-02
Publishing country	Ireland
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	632523-3
ISSN	1872-8227 ; 0168-8227
ISSN (online)	1872-8227
ISSN	0168-8227
DOI	10.1016/j.diabres.2022.109900
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