Publications by authors named "E-Shyong Tai"

380 Publications

APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups.

Lipids Health Dis 2021 Sep 21;20(1):113. Epub 2021 Sep 21.

Duke-NUS Medical School, Singapore, 169857, Singapore.

Background: Hypertriglyceridemia has emerged as a critical coronary artery disease (CAD) risk factor. Rare loss-of-function (LoF) variants in apolipoprotein C-III have been reported to reduce triglycerides (TG) and are cardioprotective in American Indians and Europeans. However, there is a lack of data in other Europeans and non-Europeans. Also, whether genetically increased plasma TG due to ApoC-III is causally associated with increased CAD risk is still unclear and inconsistent. The objectives of this study were to verify the cardioprotective role of earlier reported six LoF variants of APOC3 in South Asians and other multi-ethnic cohorts and to evaluate the causal association of TG raising common variants for increasing CAD risk.

Methods: We performed gene-centric and Mendelian randomization analyses and evaluated the role of genetic variation encompassing APOC3 for affecting circulating TG and the risk for developing CAD.

Results: One rare LoF variant (rs138326449) with a 37% reduction in TG was associated with lowered risk for CAD in Europeans (p = 0.007), but we could not confirm this association in Asian Indians (p = 0.641). Our data could not validate the cardioprotective role of other five LoF variants analysed. A common variant rs5128 in the APOC3 was strongly associated with elevated TG levels showing a p-value 2.8 × 10. Measures of plasma ApoC-III in a small subset of Sikhs revealed a 37% increase in ApoC-III concentrations among homozygous mutant carriers than the wild-type carriers of rs5128. A genetically instrumented per 1SD increment of plasma TG level of 15 mg/dL would cause a mild increase (3%) in the risk for CAD (p = 0.042).

Conclusions: Our results highlight the challenges of inclusion of rare variant information in clinical risk assessment and the generalizability of implementation of ApoC-III inhibition for treating atherosclerotic disease. More studies would be needed to confirm whether genetically raised TG and ApoC-III concentrations would increase CAD risk.
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http://dx.doi.org/10.1186/s12944-021-01531-8DOI Listing
September 2021

A Multiplex Thyroid-Specific Assay for Quantification of Circulating Thyroid Cell-Free RNA in Plasma of Thyroid Cancer Patients.

Front Genet 2021 25;12:721832. Epub 2021 Aug 25.

Endocrinology Division, Department of Medicine, National University Hospital, Singapore, Singapore.

Background: The standard of care for thyroid cancer management is thyroidectomy and adjuvant radioactive iodine (RAI). There is a paucity of clinical tool that quantifies residual thyroid volume reliably for precise adjuvant RAI dosing. Serum thyroglobulin (TG), tumour marker for thyroid cancer, takes 4 weeks for complete clearance due to its long half-life, and might be undetectable in 12% of structural disease patients. It detects recurrence with a sensitivity of 19-40%, mainly attributed to issue of TG antibody interference with TG immunometric assay. We hypothesise that the quantity of thyroid-specific cell-free RNA (cfRNA) is indicative of amount of thyroid tissues, and that during thyroid surgery, cfRNA levels decrease accordingly.

Methods: We identified 11 biologically significant and highly expressed thyroid-specific targets from Human Protein Atlas and literature. To assess for a fall in thyroid-specific cfRNA level, we recruited 16 patients undergoing thyroid surgery or RAI for malignant or benign thyroid disease, and tracked longitudinal trend of cfRNA. To assess the utility of cfRNA in detecting metastatic thyroid cancer, cfRNA of 11 patients at intermediate to high risk of recurrence was measured during surveillance and at time of clinical recurrence.

Results: The multiplex assay was capable of amplifying and quantifying multiple thyroid-specific genes in a single reaction. The selected targets were amplified successfully from RNA extracted directly from the thyroid (positive control), indicating that they were highly expressed within thyroid tissue. These cfRNAs were present in plasma, in amounts quantifiable using qRT-PCR. Four cfRNA transcripts (TPO, GFRA2, IVD, TG) fell post-treatment in more than 50% of cohort. The thyroid peroxidase (TPO) cfRNA fell post-therapy in 63% of cohort by 80%, as early as 1 day post-treatment, supporting the potential role as early indicator of remnant thyroid tissue volume. We demonstrated the clinical relevance of circulating TPO cfRNA by tracking temporal changes in setting of peri-treatment, recurrence, and TG Ab positive state.

Conclusion: Using a multiplex pre-amplification approach, the TPO cfRNA was a potential biomarker that can track residual thyroid mass. It can be further optimised for quantification of thyroid volume to guide RAI doses and for detection of thyroid cancer recurrence.
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http://dx.doi.org/10.3389/fgene.2021.721832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425593PMC
August 2021

Transformation of Electronic Health Records and Questionnaire Data to OMOP CDM: A Feasibility Study Using SG_T2DM Dataset.

Appl Clin Inform 2021 08 11;12(4):757-767. Epub 2021 Aug 11.

Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, Singapore.

Background: Diabetes mellitus (DM) is an important public health concern in Singapore and places a massive burden on health care spending. Tackling chronic diseases such as DM requires innovative strategies to integrate patients' data from diverse sources and use scientific discovery to inform clinical practice that can help better manage the disease. The Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) was chosen as the framework for integrating data with disparate formats.

Objective: The study aimed to evaluate the feasibility of converting Singapore based data source, comprising of electronic health records (EHR), cognitive and depression assessment questionnaire data to OMOP CDM standard. Additionally, we also validate whether our OMOP CDM instance is fit for the purpose of research by executing a simple treatment pathways study using Atlas, a graphical user interface tool to conduct analysis on OMOP CDM data as a proof of concept.

Methods: We used de-identified EHR, cognitive, and depression assessment questionnaires data from a tertiary care hospital in Singapore to convert it to version 5.3.1 of OMOP CDM standard. We evaluate the OMOP CDM conversion by (1) assessing the mapping coverage (that is the percentage of source terms mapped to OMOP CDM standard); (2) local raw dataset versus CDM dataset analysis; and (3) Implementing Harmonized Intrinsic Data Quality Framework using an open-source R package called Data Quality Dashboard.

Results: The content coverage of OMOP CDM vocabularies is more than 90% for clinical data, but only around 11% for questionnaire data. The comparison of characteristics between source and target data returned consistent results and our transformed data did not pass 38 (1.4%) out of 2,622 quality checks.

Conclusion: Adoption of OMOP CDM at our site demonstrated that EHR data are feasible for standardization with minimal information loss, whereas challenges remain for standardizing cognitive and depression assessment questionnaire data that requires further work.
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http://dx.doi.org/10.1055/s-0041-1732301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357458PMC
August 2021

Women's Usage Behavior and Perceived Usefulness with Using a Mobile Health Application for Gestational Diabetes Mellitus: Mixed-Methods Study.

Int J Environ Res Public Health 2021 06 21;18(12). Epub 2021 Jun 21.

Health Systems and Behavioral Sciences Domain, Saw Swee Hock School of Public Health, National University Singapore, 12 Science Drive 2, Singapore 117549, Singapore.

The prevalence of gestational diabetes mellitus (GDM) is increasing, and only a few mobile health (mHealth) applications are specifically designed to manage GDM. In this mixed-methods study, a follow-up study of a randomized controlled trial (RCT) analyzed a largely automated mHealth application-based lifestyle coaching program to (a) measure the application's usage behavior and (b) explore users' perceptions of its usefulness in GDM management. Quantitative data were collected from the 170 application users who had participated in the intervention arm of the RCT. Semi-structured interviews (n = 14) captured users' experiences when using the application. Data were collected from June 2019 to January 2020. Quantitative data were analyzed descriptively, and interviews were analyzed thematically. Only 57/170 users (34%) logged at least one meal, and only 35 meals on average were logged for eight weeks because of the incorrectly worded food items and limited food database. On the contrary, an average of 1.85 (SD = 1.60) weight values were logged per week since the weight tracking component was easy to use. Many users (6/14 (43%)) mentioned that the automatic coach messages created an immediate sense of self-awareness in food choices and motivated behavior. The findings suggest that for GDM management, a largely automated mHealth application has the potential to promote self-awareness of healthy lifestyle choices, reducing the need for intensive human resources. Additionally, several gaps in the application's design were identified which need to be addressed in future works.
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http://dx.doi.org/10.3390/ijerph18126670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296439PMC
June 2021

An open source tool to compute measures of inpatient glycemic control: translating from healthcare analytics research to clinical quality improvement.

JAMIA Open 2021 Apr 16;4(2):ooab033. Epub 2021 Jun 16.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.

Objectives: The objective of this study is to facilitate monitoring of the quality of inpatient glycemic control by providing an open-source tool to compute glucometrics. To allay regulatory and privacy concerns, the tool is usable locally; no data are uploaded to the internet.

Materials And Methods: We extended code, initially developed for healthcare analytics research, to serve the clinical need for quality monitoring of diabetes. We built an application, with a graphical interface, which can be run locally without any internet connection.

Results: We verified that our code produced results identical to prior work in glucometrics. We extended the prior work by including additional metrics and by providing user customizability. The software has been used at an academic healthcare institution.

Conclusion: We successfully translated code used for research methods into an open source, user-friendly tool which hospitals may use to expedite quality measure computation for the management of inpatients with diabetes.
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http://dx.doi.org/10.1093/jamiaopen/ooab033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206397PMC
April 2021

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes.

Nat Commun 2021 06 9;12(1):3505. Epub 2021 Jun 9.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.
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http://dx.doi.org/10.1038/s41467-021-23556-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190084PMC
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Decreased GLUT2 and glucose uptake contribute to insulin secretion defects in MODY3/HNF1A hiPSC-derived mutant β cells.

Nat Commun 2021 05 25;12(1):3133. Epub 2021 May 25.

Stem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.

Heterozygous HNF1A gene mutations can cause maturity onset diabetes of the young 3 (MODY3), characterized by insulin secretion defects. However, specific mechanisms of MODY3 in humans remain unclear due to lack of access to diseased human pancreatic cells. Here, we utilize MODY3 patient-derived human induced pluripotent stem cells (hiPSCs) to study the effect(s) of a causal HNF1A mutation on pancreatic function. Molecular dynamics simulations predict that the H126D mutation could compromise DNA binding and gene target transcription. Genome-wide RNA-Seq and ChIP-Seq analyses on MODY3 hiPSC-derived endocrine progenitors reveal numerous HNF1A gene targets affected by the mutation. We find decreased glucose transporter GLUT2 expression, which is associated with reduced glucose uptake and ATP production in the MODY3 hiPSC-derived β-like cells. Overall, our findings reveal the importance of HNF1A in regulating GLUT2 and several genes involved in insulin secretion that can account for the insulin secretory defect clinically observed in MODY3 patients.
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http://dx.doi.org/10.1038/s41467-021-22843-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149827PMC
May 2021

Plasma Metabolome and Lipidome Associations with Type 2 Diabetes and Diabetic Nephropathy.

Metabolites 2021 Apr 8;11(4). Epub 2021 Apr 8.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.

We conducted untargeted metabolomics analysis of plasma samples from a cross-sectional case-control study with 30 healthy controls, 30 patients with diabetes mellitus and normal renal function (DM-N), and 30 early diabetic nephropathy (DKD) patients using liquid chromatography-mass spectrometry (LC-MS). We employed two different modes of MS acquisition on a high-resolution MS instrument for identification and semi-quantification, and analyzed data using an advanced multivariate method for prioritizing differentially abundant metabolites. We obtained semi-quantification data for 1088 unique compounds (~55% lipids), excluding compounds that may be either exogenous compounds or treated as medication. Supervised classification analysis over a confounding-free partial correlation network shows that prostaglandins, phospholipids, nucleotides, sugars, and glycans are elevated in the DM-N and DKD patients, whereas glutamine, phenylacetylglutamine, 3-indoxyl sulfate, acetylphenylalanine, xanthine, dimethyluric acid, and asymmetric dimethylarginine are increased in DKD compared to DM-N. The data recapitulate the well-established plasma metabolome changes associated with DM-N and suggest uremic solutes and oxidative stress markers as the compounds indicating early renal function decline in DM patients.
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http://dx.doi.org/10.3390/metabo11040228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069978PMC
April 2021

Diabetes-related lower extremity complications in a multi-ethnic Asian population: a 10 year observational study in Singapore.

Diabetologia 2021 Jul 22;64(7):1538-1549. Epub 2021 Apr 22.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Republic of Singapore.

Aims/hypothesis: Diabetes progression and complication risk are different in Asian people compared with those of European ancestry. In this study, we sought to understand the epidemiology of diabetes-related lower extremity complications (DRLECs: symptomatic peripheral arterial disease, ulceration, infection, gangrene) and amputations in a multi-ethnic Asian population.

Methods: This was a retrospective observational study using data obtained from one of three integrated public healthcare clusters in Singapore. The population consisted of individuals with incident type 2 diabetes who were of Chinese, Malay, Indian or Other ethnicity. We examined incidence, time to event and risk factors of DRLECs and amputation.

Results: Between 2007 and 2017, of the 156,593 individuals with incident type 2 diabetes, 20,744 developed a DRLEC, of whom 1208 underwent amputation. Age- and sex-standardised incidence of first DRLEC and first amputation was 28.29/1000 person-years of diabetes and 8.18/1000 person-years of DRLEC, respectively. Incidence of both was highest in individuals of Malay ethnicity (DRLEC, 36.09/1000 person-years of diabetes; amputation, 12.96/1000 person-years of DRLEC). Median time from diabetes diagnosis in the public healthcare system to first DRLEC was 30.5 months for those without subsequent amputation and 10.9 months for those with subsequent amputation. Median time from DRLEC to first amputation was 2.3 months. Older age (p < 0.001), male sex (p < 0.001), Malay ethnicity (p < 0.001), Indian ethnicity (p = 0.014), chronic comorbidities (nephropathy [p < 0.001], heart disease [p < 0.001], stroke [p < 0.001], retinopathy [p < 0.001], neuropathy [p < 0.001]), poorer or missing HbA (p < 0.001), lower (p < 0.001) or missing (p = 0.002) eGFR, greater or missing BMI (p < 0.001), missing LDL-cholesterol (p < 0.001) at diagnosis, and ever-smoking (p < 0.001) were associated with higher hazard of DRLEC. Retinopathy (p < 0.001), peripheral vascular disease (p < 0.001), poorer HbA (p < 0.001), higher (p = 0.009) or missing (p < 0.001) LDL-cholesterol and missing BMI (p = 0.008) were associated with higher hazard of amputation in those with DRLEC. Indian ethnicity (p = 0.007) was associated with significantly lower hazard of amputation.

Conclusions/interpretation: This study has revealed important ethnic differences in risk of diabetes-related lower limb complications, with Malays most likely to progress to DRLEC. Greater research efforts are needed to understand the aetiopathological and sociocultural processes that contribute to the higher risk of lower extremity complications among these ethnic groups.
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http://dx.doi.org/10.1007/s00125-021-05441-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187215PMC
July 2021

Comparing conventional and high sensitivity troponin T measurements in identifying adverse cardiac events in patients admitted to an Asian emergency department chest pain observation unit.

Int J Cardiol Heart Vasc 2021 Jun 25;34:100758. Epub 2021 Mar 25.

Department of Cardiology, National Heart Centre, Singapore.

Background: High sensitive cardiac troponin assays can be used for prediction of major adverse cardiac events (MACE) in patients with chest pain.

Methods: We included patients with symptoms suggestive of acute coronary syndrome in the emergency department observation unit. We compared the accuracy of conventional troponin T (cTnT) with high sensitive troponin T (hsTnT) at various ranges, as well as the utility of hsTnT and cTnT in prediction of 30-day and 1-year MACE.

Results: 1023 patients were included (68.1% male, median age 56 years). There were 2712 hsTnT and cTnT values compared. hsTnT had a higher AUC than cTnT for 30-day and 1-year MACE. The optimal cut-off of 0-hour hsTnT for 30-day (PPV 34%, NPV 96.6%) and 1-year MACE (PPV 40.2%, NPV 94.2%) was 16 ng/L.For 844 patients who had values for both 0 and 2 h hsTnT, we proposed a rule-out cut-off of 0 and 2 h hsTnT < 16 ng/L (NPV 97.0%, 95%CI 95.5-98.1%) and a rule-in cut-off of 0 and 2 h hsTnT ≥ 26 ng/L (PPV 58.8%, 95%CI 40.7%-75.4%) for 30-day MACE. Negative 0-2 h delta-hsTnT had poor predictive discriminant capabilities on 30-day (PPV 8.2%) and 1-year MACE (PPV 12.3%).

Conclusion: The cut off values of hsTnT used in the 0 and 2-hour algorithm to rule-out (16 ng/L) and rule-in MACE (26 ng/L) are in the range that previous cTnT assays are unable to measure accurately. Risk scores can be used to further improve NPV of the rule-out group. A fall in hsTnT level acutely is not predictive of MACE.
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http://dx.doi.org/10.1016/j.ijcha.2021.100758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027767PMC
June 2021

Neutrophil-to-Lymphocyte Ratio Predicts Development of Immune-Related Adverse Events and Outcomes from Immune Checkpoint Blockade: A Case-Control Study.

Cancers (Basel) 2021 Mar 15;13(6). Epub 2021 Mar 15.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR < 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.
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http://dx.doi.org/10.3390/cancers13061308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001500PMC
March 2021

A Smartphone App to Restore Optimal Weight (SPAROW) in Women With Recent Gestational Diabetes Mellitus: Randomized Controlled Trial.

JMIR Mhealth Uhealth 2021 03 16;9(3):e22147. Epub 2021 Mar 16.

Department of Obstetrics and Gynecology, National University Hospital, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Background: Women with a history of gestational diabetes mellitus (GDM) are at an increased risk of developing type 2 diabetes mellitus (T2DM). Lifestyle interventions aimed at postpartum weight loss to reduce T2DM risk have been reported, but poor compliance remains a barrier. Smartphone-based interventions may improve compliance, but data on its use in women with recent GDM are limited.

Objective: This trial aimed to investigate the efficacy of a smartphone app in restoring optimal weight following delivery in women with GDM, in the setting of a population with high rates of GDM and type 2 diabetes.

Methods: In this unblinded randomized controlled trial, 200 women with GDM were randomized to receive the intervention or standard care following delivery. The intervention enabled logging of weight, meals, and activity, with web-based interaction with a team comprising dieticians, a physiotherapist, and an occupational therapist. The primary outcome was an achievement of optimal weight (defined as the restoration of first trimester weight if first trimester BMI≤23 kg/m or weight loss of at least 5% from first trimester weight if first trimester BMI>23 kg/m) at 4 months post partum. Secondary outcome measures included absolute weight loss, serum metabolic markers, self-reported nutritional intake, health education, and quality of life via questionnaires and user engagement in the intervention group.

Results: In total, 40% (38/96) of women in the intervention group achieved optimal weight at 4 months post delivery compared with 32% (28/93) in the control group (P=.27). Compared with the control group, women in the intervention group reported significantly reduced caloric intake at 4 months after delivery (P<.001) and higher health-directed behavior scores (P=.045). The intervention group also reported increased emotional distress scores (P=.01). At 4 months, participant engagement with the intervention was maintained at 60.8% (SD 33.9%).

Conclusions: Although a statistically significant increase in women achieving healthy weight was not observed, this app remains promising, as women in the intervention group reported improved health behaviors and lower caloric intake. Importantly, the high retention rates suggest that a larger study with a longer follow-up period might confirm the effectiveness of this app for weight management.

Trial Registration: ClinicalTrials.gov NCT03324737; https://clinicaltrials.gov/ct2/show/NCT03324737.

International Registered Report Identifier (irrid): RR2-10.1186/s12889-019-7691-3.
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http://dx.doi.org/10.2196/22147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088857PMC
March 2021

Making novel staple foods the norm: perspectives from adult consumers with and without diabetes.

Appetite 2021 07 2;162:105189. Epub 2021 Mar 2.

Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, 12 Science Drive 2, 117549, Singapore. Electronic address:

Novel staple foods are staple foods that are modified with the purpose of improving their nutritional properties. However, consumers' acceptance towards novel staple foods remains to be evaluated, especially in Asian populations where staple foods like white rice are a major source of energy. The objective of this study was to explore consumers' attitudes and perceptions towards novel staple foods in a multi-ethnic Asian population. We conducted 11 focus group discussions, with 37 healthy participants and 22 participants with diabetes recruited through newspaper, email and poster advertisement and in-person recruitment at a clinic. Thematic analysis using the general inductive approach was performed. We found that participants' conceptual understanding of the modification process affected their acceptance towards novel staple foods. Plant-based modifications were considered natural and acceptable while genetic modification and use of chemicals were unnatural and undesirable. Participants expected novel staple foods to be more expensive and less tasty and this was largely due to their perceptions and experiences with healthy eating. Participants with diabetes or family history of diabetes were generally more willing to compromise taste and cost for healthier staple foods, and this appeared to be driven by concerns about diabetes and its related co-morbidities. The appearance of food was an important influence on participants' initial impression of the food, which appeared to be mediated by taste expectations. Participants' trust of novel staple foods was largely influenced by their trust in food industry, governmental authorities and nutrition science that was mediated through pathways of information and food safety.
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http://dx.doi.org/10.1016/j.appet.2021.105189DOI Listing
July 2021

Retinal microvascular signs and risk of diabetic kidney disease in asian and white populations.

Sci Rep 2021 Mar 1;11(1):4898. Epub 2021 Mar 1.

Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore, 168751, Singapore.

The objective was to examine prospectively the association between retinal microvascular signs and development of diabetic kidney disease (DKD) in Asian and White populations. We analysed two population-based cohorts, composing of 1,221 Asians (SEED) and 703 White (WESDR) adults with diabetes. Retinal microvascular signs at baseline included vascular caliber (arteriolar-CRAE, and venular-CRVE) and diabetic retinopathy (DR). Incident cases of DKD were identified after ~ 6-year. Incident cases were defined based on eGFR in SEED and proteinuria or history of renal dialysis in WESDR. The incidence of DKD were 11.8% in SEED and 14.0% in WESDR. Wider CRAE in SEED (OR = 1.58 [1.02, 2.45]) and wider CRVE (OR = 1.69 [1.02, 2.80)) in WESDR were associated with increased risk of DKD. Presence of DR was associated with an increased risk of DKD in both cohorts (SEED: OR = 1.91 [1.21, 3.01] in SEED, WESDR: OR = 1.99 [1.18, 3.35]). Adding DR and retinal vascular calibers in the model beyond traditional risk factors led to an improvement of predictive performance of DKD risk between 1.1 and 2.4%; and improved classification (NRI 3 between 9%). Microvascular changes in the retina are longitudinally associated with risk of DKD.
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http://dx.doi.org/10.1038/s41598-021-84464-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921402PMC
March 2021

Association between body mass index and diabetic retinopathy in Asians: the Asian Eye Epidemiology Consortium (AEEC) study.

Br J Ophthalmol 2021 Feb 23. Epub 2021 Feb 23.

Beijing Institute of Ophthalmology, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Background/aims: Obesity is a well-known risk factor for diabetes, but its association with diabetic retinopathy (DR) is inconclusive, in particular in Asians. We aimed to assess whether body mass index (BMI) is associated with the presence and severity of DR in Asian populations with diabetes.

Methods: Pooled analysis of individual-level cross-sectional data from 10 010 adults with diabetes who participated in 12 population-based studies conducted in China, India, Japan, Russia (Asian), Singapore and South Korea that were part of the Asian Eye Epidemiology Consortium (AEEC). BMI was calculated as weight in kilograms divided by height in square metres and categorised into normal (<25 kg/m, reference), overweight (25-29.9 kg/m) and obese (≥30 kg/m). Any-DR (n=1669) and vision-threatening DR (VTDR, n=489) were assessed from digital retinal photographs and graded according to standard protocols. Each study was analysed separately using multivariable logistic regression models adjusted for age, sex, haemoglobin A1c%, systolic blood pressure and diabetes duration, and the estimated odds ratios (ORs) and 95% confidence interval (CIs) from all studies were then combined using random-effects models.

Results: In multivariable models, obesity showed a significant inverse association with any-DR (pooled OR (95% CI) =0.74 (0.59 to 0.91)) and VTDR (0.75 (0.60 to 0.93)). Similarly, in continuous analysis, BMI showed a significant inverse association with both any-DR (0.93 (0.87 to 0.99)) and VTDR (0.79 (0.68 to 0.92) per SD increase). Overweight did not show a significant association with any-DR.

Conclusions: Among Asian adults with diabetes, both BMI and obesity showed an inverse association with DR. These findings warrant confirmation in further longitudinal studies.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318208DOI Listing
February 2021

Dietary Fat and Protein Intake in Relation to Plasma Sphingolipids as Determined by a Large-Scale Lipidomic Analysis.

Metabolites 2021 Feb 8;11(2). Epub 2021 Feb 8.

Saw Swee Hock School of Public Health, National University of Singapore (NUS), Singapore 117549, Singapore.

Sphingolipid concentrations have been associated with risk of type 2 diabetes and cardiovascular diseases. Because sphingolipids can be synthesized de novo from saturated fatty acids (SFA), dietary fatty acids may affect plasma sphingolipid concentrations. We aimed to evaluate dietary fat and protein intakes in relation to circulating sphingolipid levels. We used cross-sectional data from 2860 ethnic Chinese Singaporeans collected from 2004-2007. Nutrient intakes were estimated on the basis of a validated 159-item food frequency questionnaire. We quantified 79 molecularly distinct sphingolipids in a large-scale lipidomic evaluation from plasma samples. Higher saturated fat intake was associated with higher concentrations of 16:1;O2 sphingolipids including ceramides, monohexosylcermides, dihexosylceramides, sphingomyelins, and sphingosine 1-phosphates. Higher polyunsaturated fat intake was associated with lower plasma long-chain ceramides and long-chain monohexosylcermide concentrations. Protein intake was inversely associated with concentrations of most subclasses of sphingolipids, with the exception of sphingolipids containing a 16:1;O2 sphingoid base. Lower intake of saturated fat and higher intake of polyunsaturated fat and protein may decrease plasma concentrations of several sphingolipid classes. These findings may represent a novel biological mechanism for the impact of nutrient intakes on cardio-metabolic health.
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http://dx.doi.org/10.3390/metabo11020093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915172PMC
February 2021

Branched-Chain Amino Acid Supplementation Does Not Preserve Lean Mass or Affect Metabolic Profile in Adults with Overweight or Obesity in a Randomized Controlled Weight Loss Intervention.

J Nutr 2021 04;151(4):911-920

Clinical Nutrition Research Center, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore.

Background: Branched-chain amino acid (BCAA) supplementation has been shown to increase muscle mass or prevent muscle loss during weight loss.

Objective: We aimed to investigate the effects of a BCAA-supplemented hypocaloric diet on lean mass preservation and insulin sensitivity.

Methods: A total of 132 Chinese adults (63 men and 69 women aged 21-45 y, BMI 25-36 kg/m2) were block randomly assigned by gender and BMI into 3 hypocaloric diet (deficit of 500 kcal/d) groups: standard-protein (14%) with placebo (control, CT) or BCAA supplements at 0.1 g · kg-1 body weight · d-1 (BCAA) or high-protein (27%) with placebo (HP). The subjects underwent 16 wk of dietary intervention with provision of meals and supplements, followed by 8 wk of weight maintenance with provision of supplements only. One-way ANOVA analysis was conducted to analyze the primary (lean mass and insulin sensitivity) and secondary outcomes (anthropometric and metabolic parameters) among the 3 groups. Paired t-test was used to analyze the change in each group.

Results: The 3 groups demonstrated similar significant reductions in body weight (7.97%), fat mass (13.8%), and waist circumference (7.27%) after 16 wk of energy deficit. Lean mass loss in BCAA (4.39%) tended to be lower than in CT (5.39%) and higher compared with HP (3.67%) (P = 0.06). Calf muscle volume increased 3.4% in BCAA and intramyocellular lipids (IMCLs) decreased in BCAA (17%) and HP (18%) (P < 0.05) over 16 wk. During the 8 wk weight maintenance period, lean mass gain in BCAA (1.03%) tended to be lower compared with CT (1.58%) and higher than in HP (-0.002%) (P = 0.04). Lean mass gain differed significantly between CT and HP (P = 0.03). Insulin sensitivity and metabolic profiles did not differ among the groups throughout the study period.

Conclusions: BCAA supplementation does not preserve lean mass or affect insulin sensitivity in overweight and obese adults during weight loss. A higher protein diet may be more advantageous for lean mass preservation.
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http://dx.doi.org/10.1093/jn/nxaa414DOI Listing
April 2021

A deep learning algorithm to detect chronic kidney disease from retinal photographs in community-based populations.

Lancet Digit Health 2020 06 12;2(6):e295-e302. Epub 2020 May 12.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore. Electronic address:

Background: Screening for chronic kidney disease is a challenge in community and primary care settings, even in high-income countries. We developed an artificial intelligence deep learning algorithm (DLA) to detect chronic kidney disease from retinal images, which could add to existing chronic kidney disease screening strategies.

Methods: We used data from three population-based, multiethnic, cross-sectional studies in Singapore and China. The Singapore Epidemiology of Eye Diseases study (SEED, patients aged ≥40 years) was used to develop (5188 patients) and validate (1297 patients) the DLA. External testing was done on two independent datasets: the Singapore Prospective Study Program (SP2, 3735 patients aged ≥25 years) and the Beijing Eye Study (BES, 1538 patients aged ≥40 years). Chronic kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min per 1·73m. Three models were trained: 1) image DLA; 2) risk factors (RF) including age, sex, ethnicity, diabetes, and hypertension; and 3) hybrid DLA combining image and RF. Model performances were evaluated using the area under the receiver operating characteristic curve (AUC).

Findings: In the SEED validation dataset, the AUC was 0·911 for image DLA (95% CI 0·886 -0·936), 0·916 for RF (0·891-0·941), and 0·938 for hybrid DLA (0·917-0·959). Corresponding estimates in the SP2 testing dataset were 0·733 for image DLA (95% CI 0·696-0·770), 0·829 for RF (0·797-0·861), and 0·810 for hybrid DLA (0·776-0·844); and in the BES testing dataset estimates were 0·835 for image DLA (0·767-0·903), 0·887 for RF (0·828-0·946), and 0·858 for hybrid DLA (0·794-0·922). AUC estimates were similar in subgroups of people with diabetes (image DLA 0·889 [95% CI 0·850-0·928], RF 0·899 [0·862-0·936], hybrid 0·925 [0·893-0·957]) and hypertension (image DLA 0·889 [95% CI 0·860-0·918], RF 0·889 [0·860-0·918], hybrid 0·918 [0·893-0·943]).

Interpretation: A retinal image DLA shows good performance for estimating chronic kidney disease, underlying the feasibility of using retinal photography as an adjunctive or opportunistic screening tool for chronic kidney disease in community populations.

Funding: National Medical Research Council, Singapore.
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http://dx.doi.org/10.1016/S2589-7500(20)30063-7DOI Listing
June 2020

Evaluating the effectiveness of a multi-faceted inpatient diabetes management program among hospitalised patients with diabetes mellitus.

Clin Diabetes Endocrinol 2020 Nov 5;6(1):21. Epub 2020 Nov 5.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.

Background: Diabetes mellitus (DM) is one of the most common chronic diseases. Individuals with DM are more likely to be hospitalised and stay longer than those without DM. Inpatient hypoglycemia and hyperglycemia, which are associated with adverse outcomes, are common, but can be prevented through hospital quality improvement programs.

Methods: We designed a multi-faceted intervention program with the aim of reducing inpatient hypoglycemia and hyperglycemia. This was implemented over seven phases between September 2013 to January 2016, and covered all the non-critical care wards in a tertiary hospital. The program represented a pragmatic approach that leveraged on existing resources and infrastructure within the hospital. We calculated glucometric outcomes in June to August 2016 and compared them with those in June to August 2013 to assess the overall effectiveness of the program. We used regression models with generalised estimating equations to adjust for potential confounders and account for correlations of repeated outcomes within patients and admissions.

Results: We observed significant reductions in patient-days affected by hypoglycemia (any glucose reading < 4 mmol/L: OR = 0.71, 95% CI: 0.61 to 0.83, p <  0.001), and hyperglycemia (any glucose reading > 14 mmol/L: OR = 0.84, 95% CI: 0.71 to 0.99, p = 0.041). Similar findings were observed for admission-level hypoglycemia and hyperglycemia. Further analyses suggested that these reductions started to occur four to 6 months post-implementation.

Conclusions: Our program was associated with sustained improvements in clinically relevant outcomes. Our described intervention could be feasibly implemented by other secondary and tertiary care hospitals by leveraging on existing infrastructure and work force.
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http://dx.doi.org/10.1186/s40842-020-00107-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643419PMC
November 2020

"Who is watching the watchdog?": ethical perspectives of sharing health-related data for precision medicine in Singapore.

BMC Med Ethics 2020 11 19;21(1):118. Epub 2020 Nov 19.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

Background: We aimed to examine the ethical concerns Singaporeans have about sharing health-data for precision medicine (PM) and identify suggestions for governance strategies. Just as Asian genomes are under-represented in PM, the views of Asian populations about the risks and benefits of data sharing are under-represented in prior attitudinal research.

Methods: We conducted seven focus groups with 62 participants in Singapore from May to July 2019. They were conducted in three languages (English, Mandarin and Malay) and analysed with qualitative content and thematic analysis.

Results: Four key themes emerged: nuanced understandings of data security and data sensitivity; trade-offs between data protection and research benefits; trust (and distrust) in the public and private sectors; and governance and control options. Participants were aware of the inherent risks associated with data sharing for research. Participants expressed conditional support for data sharing, including genomic sequence data and information contained within electronic medical records. This support included sharing data with researchers from universities and healthcare institutions, both in Singapore and overseas. Support was conditional on the perceived social value of the research and appropriate de-identification and data security processes. Participants suggested that a data sharing oversight body would help strengthen public trust and comfort in data research for PM in Singapore.

Conclusion: Maintenance of public trust in data security systems and governance regimes can enhance participation in PM and data sharing for research. Contrary to themes in much prior research, participants demonstrated a sophisticated understanding of the inherent risks of data sharing, analysed trade-offs between risks and potential benefits of PM, and often adopted an international perspective.
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http://dx.doi.org/10.1186/s12910-020-00561-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678103PMC
November 2020

A Randomized Controlled Trial to Evaluate the Effects of a Smartphone Application-Based Lifestyle Coaching Program on Gestational Weight Gain, Glycemic Control, and Maternal and Neonatal Outcomes in Women With Gestational Diabetes Mellitus: The SMART-GDM Study.

Diabetes Care 2021 02 12;44(2):456-463. Epub 2020 Nov 12.

Department of Medicine, National University Hospital, Singapore.

Objective: SMART-GDM examined whether Habits-GDM, a smartphone application (app) coaching program, can prevent excessive gestational weight gain (EGWG) and improve glycemic control and maternal and neonatal outcomes in gestational diabetes mellitus (GDM).

Research Design And Methods: In this randomized controlled trial, women diagnosed with GDM between 12 and 30 weeks were randomly assigned to usual care (control) or to additional support from Habits-GDM that integrated dietary, physical activity, weight, and glucose monitoring (intervention). The primary outcome was the proportion of participants with EGWG. Secondary outcomes included absolute gestational weight gain (GWG), glycemic control, and maternal, delivery, and neonatal outcomes.

Results: In total, 340 women were randomized (170 intervention, 170 control; mean ± SD age 32.0 ± 4.2 years; mean BMI 25.6 ± 5.6 kg/m). There were no statistically significant differences in the proportions of women with EGWG, absolute GWG, or maternal and delivery outcomes between experimental groups. Average glucose readings were lower in the intervention group (mean difference -0.15 mmol/L [95% CI -0.26; -0.03], = 0.011) as were the proportions of glucose above targets (premeal: 17.9% vs. 23.3%, odds ratio 0.68 [95% CI 0.53; 0.87], = 0.003; 2-h postmeal: 19.9% vs. 50%, 0.54 [0.42; 0.70], < 0.001). When regarded as a composite (although not prespecified), the overall neonatal complications (including birth trauma, neonatal hypoglycemia, hyperbilirubinemia, respiratory distress, neonatal intensive care unit admission, and perinatal death) were significantly lower in the intervention group (38.1% vs. 53.7%, 0.53 [0.34; 0.84], = 0.006).

Conclusions: When added to usual care, Habits-GDM resulted in better maternal glycemic control and composite neonatal outcomes (nonprespecified) but did not reduce EGWG among women with GDM.
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http://dx.doi.org/10.2337/dc20-1216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818327PMC
February 2021

Coffee, Black Tea, and Green Tea Consumption in Relation to Plasma Metabolites in an Asian Population.

Mol Nutr Food Res 2020 Oct 29:e2000527. Epub 2020 Oct 29.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore.

Scope: Coffee and tea are among the most popular beverages in the world. However, the association between habitual coffee, green tea, and black tea consumption with metabolomics profiles in Asian populations remain largely unknown.

Methods And Results: 158 metabolites (14 amino acids, 45 acylcarnitines, and 99 sphingolipids) in the blood plasma of participants are measured from the population-based Singapore Prospective Study Program cohort using mass spectrometry (MS). Linear regression models are used to obtain the estimates for the association between coffee and tea consumption with metabolite levels, adjusted for potential confounders and false discovery rate (FDR). Coffee consumption is significantly associated with higher levels of 63 sphingolipids (29 sphingomyelins, 32 ceramides, a sphingosine-1-phosphate, and a sphingosine) and lower levels of 13 acylcarnitines and alanine. Black tea consumption is significantly associated with higher levels of eight sphingolipids, and lower levels of an amino acid, whereas green tea is significantly inversely associated with four metabolites (C8:1-OH acylcarnitine, ganglioside GM3 d18:1/16:0, sphingomyelins d18:2/18:0 and d18:1/14:0).

Conclusions: Coffee, black tea, and green tea consumption are associated with plasma levels of certain classes of sphingolipids and acylcarnitines in an Asian population, particularly sphingomyelins, which may mediate the health benefits of these beverages.
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http://dx.doi.org/10.1002/mnfr.202000527DOI Listing
October 2020

Branched-Chain Amino Acid Oxidation Is Elevated in Adults with Morbid Obesity and Decreases Significantly after Sleeve Gastrectomy.

J Nutr 2020 12;150(12):3180-3189

USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.

Background: Plasma concentrations of branched-chain amino acids (BCAAs) are elevated in obese individuals with insulin resistance (IR) and decrease after bariatric surgery. However, the metabolic mechanisms are unclear.

Objectives: Our objectives are to compare leucine kinetics between morbidly obese and healthy-weight individuals cross-sectionally, and to prospectively evaluate changes in the morbidly obese after sleeve gastrectomy. We hypothesized that leucine oxidation is slower in obese individuals and increases after surgery.

Methods: Ten morbidly obese [BMI (in kg/m2) ≥32.5, age 21-50 y] and 10 healthy-weight participants (BMI <25), matched for age (median ∼30 y) but not gender, were infused with [U-13C6] leucine and [2H5] glycerol to quantify leucine and glycerol kinetics. Morbidly obese participants were studied again 6 mo postsurgery. Primary outcomes were kinetic parameters related to BCAA metabolism. Data were analyzed by nonparametric methods and presented as median (IQR).

Results: Participants with obesity had IR with an HOMA-IR (4.89; 4.36-8.76) greater than that of healthy-weight participants (1.32; 0.99-1.49; P < 0.001) and had significantly faster leucine flux [218; 196-259 compared with 145; 138-149 μmol · kg fat-free mass (FFM)-1 · h-1], oxidation (24.0; 17.9-29.8 compared with 16.1; 14.3-18.5 μmol · kg FFM-1 · h-1), and nonoxidative disposal (204; 190-247 compared with 138; 129-140 μmol · kg FFM-1 · h-1) (P < 0.017 for all). After surgery, the morbidly obese had a marked improvement in IR (3.54; 3.06-6.08; P = 0.008) and significant reductions in BCAA concentrations (113; 95-157 μmol/L) and leucine oxidation (9.37; 6.85-15.2 μmol · kg FFM-1 · h-1) (P = 0.017 for both). Further, leucine flux in this group correlated significantly with IR (r = 0.78, P < 0.001).

Conclusions: BCAA oxidation is not impaired but elevated in individuals with morbid obesity. Plasma BCAA concentrations are lowered after surgery owing to slower breakdown of body proteins as insulin's ability to suppress proteolysis is restored. These findings suggest that IR is the underlying cause and not the consequence of elevated BCAAs in obesity.
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http://dx.doi.org/10.1093/jn/nxaa298DOI Listing
December 2020

Serum acylcarnitines and amino acids and risk of type 2 diabetes in a multiethnic Asian population.

BMJ Open Diabetes Res Care 2020 10;8(1)

Saw Swee Hock School of Public Health, National University of Singapore, Singapore.

Introduction: We evaluated whether concentrations of serum acylcarnitines and amino acids are associated with risk of type 2 diabetes and can improve predictive diabetes models in an Asian population.

Research Design And Methods: We used data from 3313 male and female participants from the Singapore Prospective Study Program cohort who were diabetes-free at baseline. The average age at baseline was 48.0 years (SD: 11.9 years), and participants were of Chinese, Malay, and Indian ethnicity. Diabetes cases were identified through self-reported physician diagnosis, fasting glucose and glycated hemoglobin concentrations, and linkage to national disease registries. We measured fasting serum concentrations of 45 acylcarnitines and 14 amino acids. The association between metabolites and incident diabetes was modeled using Cox proportional hazards regression with adjustment for age, sex, ethnicity, height, and parental history of diabetes, and correction for multiple testing. Metabolites were added to the Atherosclerosis Risk in Communities (ARIC) predictive diabetes risk model to assess whether they could increase the area under the receiver operating characteristic curve (AUC).

Results: Participants were followed up for an average of 8.4 years (SD: 2.1 years), during which time 314 developed diabetes. Branched-chain amino acids (HR: 1.477 per SD; 95% CI 1.325 to 1.647) and the alanine to glycine ratio (HR: 1.572; 95% CI 1.426 to 1.733) were most strongly associated with diabetes risk. Additionally, the acylcarnitines C4 and C16-OH, and the amino acids alanine, combined glutamate/glutamine, ornithine, phenylalanine, proline, and tyrosine were significantly associated with higher diabetes risk, and the acylcarnitine C8-DC and amino acids glycine and serine with lower risk. Adding selected metabolites to the ARIC model resulted in a significant increase in AUC from 0.836 to 0.846.

Conclusions: We identified acylcarnitines and amino acids associated with risk of type 2 diabetes in an Asian population. A subset of these modestly improved the prediction of diabetes when added to an established diabetes risk model.
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http://dx.doi.org/10.1136/bmjdrc-2020-001315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534670PMC
October 2020

MRMkit: Automated Data Processing for Large-Scale Targeted Metabolomics Analysis.

Anal Chem 2020 10 28;92(20):13677-13682. Epub 2020 Sep 28.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E, Kent Ridge Road, NUHS Tower Block, Level 10, Singapore 119228.

MRMkit is an open-source software package designed for automated processing of large-scale targeted mass spectrometry-based metabolomics data. With improvements in the automation of sample preparation for LC-MS analysis, a challenging next step is to fully automate the workflow to process raw data and ensure the quality of measurements in large-scale analysis settings. MRMkit capitalizes on the richness of large-sample data in capturing peak shapes and interference patterns of transitions across many samples and delivers fully automated, reproducible peak integration results in a scalable and time-efficient manner. In addition to fast and accurate peak integration, the tool also provides reliable data normalization functions and quality metrics along with visualizations for fast data quality evaluation. In addition, MRMkit learns retention time offset patterns by user-specified compound classes and makes recommendations for peak picking in multimodal ion chromatograms. In summary, MRMkit offers highly consistent and scalable data processing capacity for targeted metabolomics, substantially curtailing the time required to produce the final quantification results after LC-MS analysis.
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http://dx.doi.org/10.1021/acs.analchem.0c03060DOI Listing
October 2020

Acute Bacterial Suppurative Thyroiditis following Fine Needle Aspiration: A Case Report and Review of the Literature.

Case Rep Endocrinol 2020 25;2020:7104806. Epub 2020 Aug 25.

Division of Endocrinology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Level 10, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228.

Background: Fine needle aspiration (FNA) of thyroid nodules is a simple, reliable, and inexpensive procedure performed on suspicious thyroid nodules found in thyroid ultrasound (US). Acute bacterial suppurative thyroiditis is an uncommon complication of FNA which, however, can be life threatening. . A 49-year-old lady presented with fever and neck pain 1 month after FNA with biochemical evidence of thyrotoxicosis. Repeat US of the thyroid showed interval enlargement of the thyroid nodule, and the culture of the cystic fluid of repeat FNA grew . She responded well to bedside aspiration and 2 weeks of antibiotic therapy without requiring surgical intervention. . Acute bacterial suppurative thyroiditis following FNA has been increasingly reported in immunocompetent hosts. There are 2 peculiar features in our case: a smoldering course caused by an indolent organism and a significant time lag between initial FNA and clinical presentation. On literature review, it was found that the onset of acute bacterial suppurative thyroiditis after FNA can range from a few days to up to 3 months. Clinicians should be aware of this complication even if FNA has been performed a few months ago. Thyroid US and US-guided FNA are useful initial investigations. Conventional management of acute bacterial suppurative thyroiditis has been surgery combined with antimicrobial therapy. However, recently, a more conservative approach has been reported to be effective in the treatment of acute bacterial suppurative thyroiditis as well.

Conclusion: Proper infection control practices are necessary in performing the FNA. Initial management (conservative versus surgical) of acute bacterial thyroiditis should be based on the patient's clinical status and the extent of infective focus.
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http://dx.doi.org/10.1155/2020/7104806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471785PMC
August 2020

Diet, Physical Activity and Adiposity as Determinants of Circulating Amino Acid Levels in a Multiethnic Asian Population.

Nutrients 2020 Aug 27;12(9). Epub 2020 Aug 27.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore.

Profiles of circulating amino acids have been associated with cardiometabolic diseases. We investigated the associations between dietary protein intake, physical activity and adiposity and serum amino acid profiles in an Asian population. We used data from 3009 male and female participants from the Singapore Prospective Study Program cohort. Dietary and physical activity data were obtained from validated questionnaires; anthropometric measurements were collected during a health examination; and fasting concentrations of 16 amino acids were measured using targeted LC-MS. The association between lifestyle factors and amino acid levels was modeled using multiple linear regression with adjustment for other sociodemographic and lifestyle factors and correction for multiple testing. We observed significant associations between seafood intake (-coefficient 0.132, 95% CI 0.006, 0.257 for a 100% increment), physical activity (-coefficient -0.096, 95% CI -0.183, -0.008 in the highest versus lowest quartile) and adiposity (BMI -coefficient 0.062, 95% CI 0.054, 0.070 per kg/m; waist circumference -coefficient 0.034, 95% CI 0.031, 0.037 per cm) and branched-chain amino acid levels (expressed per-SD). We also observed significant interactions with sex for the association between meat and seafood and total intakes and BCAA levels ( for interaction 0.007), which were stronger in females than in males. Our findings suggest novel associations between modifiable lifestyle factors and amino acid levels in Asian populations.
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http://dx.doi.org/10.3390/nu12092603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551953PMC
August 2020

Shared signaling pathways in Alzheimer's and metabolic disease may point to new treatment approaches.

FEBS J 2021 06 10;288(12):3855-3873. Epub 2020 Sep 10.

Science Division, Yale- NUS College, Singapore, Singapore.

'A peculiar severe disease process of the cerebral cortex' are the exact words used by A. Alzheimer in 1906 to describe a patient's increasingly severe condition of memory loss, changes in personality, and sleep disturbance. A century later, this 'peculiar' disease has become widely known as Alzheimer's disease (AD), the world's most common neurodegenerative disease, affecting more than 35 million people globally. At the same time, its pathology remains unclear and no successful treatment exists. Several theories for AD etiology have emerged throughout the past century. In this review, we focus on the metabolic mechanisms that are similar between AD and metabolic diseases, based on the results from genome-wide association studies. We discuss signaling pathways involved in both types of disease and look into new optogenetic methods to study the in vivo mechanisms of AD.
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http://dx.doi.org/10.1111/febs.15540DOI Listing
June 2021

Plasma sphingolipids and risk of cardiovascular diseases: a large-scale lipidomic analysis.

Metabolomics 2020 08 20;16(9):89. Epub 2020 Aug 20.

Saw Swee Hock School of Public Health, National University of Singapore (NUS), 12 Science Drive 2, #10-01, Singapore, 117549, Singapore.

Introduction: Sphingolipids are a diverse class of lipids with various roles in cell functions and subclasses such as ceramides have been associated with cardiovascular diseases (CVD) in previous studies.

Objectives: We aimed to measure molecularly-distinct sphingolipids via a large-scale lipidomic analysis and expand the literature to an Asian population.

Methods: We performed a lipidomics evaluation of 79 molecularly distinct sphingolipids in the plasma of 2627 ethnically-Chinese Singaporeans.

Results: During a mean follow-up of 12.9 years, we documented 152 cases of major CVD (non-fatal myocardial infarction, stroke and cardiovascular death). Total ceramide concentrations were not associated with CVD risk [hazard ratio (HR), 0.99; 95% CI 0.81-1.21], but higher circulating total monohexosylceramides (HR, 1.22; 95% CI 1.03, 1.45), total long-chain sphingolipids (C16-C18) (HR, 1.22; 95% CI 1.02, 1.45) and total 18:1 sphingolipids (HR, 1.21; 95% CI 1.01, 1.46) were associated with higher CVD risk after adjusting for conventional CVD risk factors.

Conclusions: Our results do not support the hypothesis that higher ceramide concentrations are linked to higher CVD risk, but suggest that other classes of sphingolipids may affect CVD risk.
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http://dx.doi.org/10.1007/s11306-020-01709-8DOI Listing
August 2020
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