Publications by authors named "Ju-Sheng Zheng"

60 Publications

Precision nutrition for gut microbiome and diabetes research: Application of nutritional n-of-1 clinical trials.

J Diabetes 2021 Aug 28. Epub 2021 Aug 28.

Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1111/1753-0407.13220DOI Listing
August 2021

Circulating vitamin C concentration and risk of cancers: a Mendelian randomization study.

BMC Med 2021 Jul 30;19(1):171. Epub 2021 Jul 30.

Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Rd, Cloud Town, Hangzhou, 310024, China.

Background: Circulating vitamin C concentrations have been associated with several cancers in observational studies, but little is known about the causal direction of the associations. This study aims to explore the potential causal relationship between circulating vitamin C and risk of five most common cancers in Europe.

Methods: We used summary-level data for genetic variants associated with plasma vitamin C in a large vitamin C genome-wide association study (GWAS) meta-analysis on 52,018 Europeans, and the corresponding associations with lung, breast, prostate, colon, and rectal cancer from GWAS consortia including up to 870,984 participants of European ancestry. We performed two-sample, bi-directional Mendelian randomization (MR) analyses using inverse-variance-weighted method as the primary approach, while using 6 additional methods (e.g., MR-Egger, weighted median-based, and mode-based methods) as sensitivity analysis to detect and adjust for pleiotropy. We also conducted a meta-analysis of prospective cohort studies and randomized controlled trials to examine the association of vitamin C intakes with cancer outcomes.

Results: The MR analysis showed no evidence of a causal association of circulating vitamin C concentration with any examined cancer. Although the odds ratio (OR) per one standard deviation increase in genetically predicted circulating vitamin C concentration was 1.34 (95% confidence interval 1.14 to 1.57) for breast cancer in the UK Biobank, this association could not be replicated in the Breast Cancer Association Consortium with an OR of 1.05 (0.94 to 1.17). Smoking initiation, as a positive control for our reverse MR analysis, showed a negative association with circulating vitamin C concentration. However, there was no strong evidence of a causal association of any examined cancer with circulating vitamin C. Sensitivity analysis using 6 different analytical approaches yielded similar results. Moreover, our MR results were consistent with the null findings from the meta-analysis exploring prospective associations of dietary or supplemental vitamin C intakes with cancer risk, except that higher dietary vitamin C intake, but not vitamin C supplement, was associated with a lower risk of lung cancer (risk ratio: 0.84, 95% confidence interval 0.71 to 0.99).

Conclusions: These findings provide no evidence to support that physiological-level circulating vitamin C has a large effect on risk of the five most common cancers in European populations, but we cannot rule out very small effect sizes.
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http://dx.doi.org/10.1186/s12916-021-02041-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323227PMC
July 2021

Gut microbiota, inflammation, and molecular signatures of host response to infection.

J Genet Genomics 2021 May 3. Epub 2021 May 3.

College of Life Sciences, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, China; Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, China. Electronic address:

Gut microbial dysbiosis has been linked to many noncommunicable diseases. However, little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection. Here, we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers, which have recently been identified as molecular signatures predicting the progression of the COVID-19. We demonstrate that in our cohort of 990 healthy individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals. Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation. Overall, our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals. These results may provide novel insights into the cross-talk between gut microbiota and host immune system.
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http://dx.doi.org/10.1016/j.jgg.2021.04.002DOI Listing
May 2021

Individual Postprandial Glycemic Responses to Diet in n-of-1 Trials: Westlake N-of-1 Trials for Macronutrient Intake (WE-MACNUTR).

J Nutr 2021 Jul 13. Epub 2021 Jul 13.

Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.

Background: The role of different types and quantities of macronutrients on human health has been controversial, and the individual response to dietary macronutrient intake needs more investigation.

Objectives: We aimed to use an 'n-of-1' study design to investigate the individual variability in postprandial glycemic response when eating diets with different macronutrient distributions among apparently healthy adults.

Methods: Thirty apparently healthy young Chinese adults (women, 68%) aged between 22 and 34 y, with BMI between 17.2 and 31.9 kg/m2, were provided with high-fat, low-carbohydrate (HF-LC, 60-70% fat, 15-25% carbohydrate, 15% protein, of total energy) and low-fat, high-carbohydrate (LF-HC, 10-20% fat, 65-75% carbohydrate, 15% protein) diets, for 6 d wearing continuous glucose monitoring systems, respectively, in a randomized sequence, interspersed by a 6-d wash-out period. Three cycles were conducted. The primary outcomes were the differences of maximum postprandial glucose (MPG), mean amplitude of glycemic excursions (MAGE), and AUC24 between intervention periods of LF-HC and HF-LC diets. A Bayesian model was used to predict responders with the posterior probability of any 1 of the 3 outcomes reaching a clinically meaningful difference.

Results: Twenty-eight participants were included in the analysis. Posterior probability of reaching a clinically meaningful difference of MPG (0.167 mmol/L), MAGE (0.072 mmol/L), and AUC24 (13.889 mmol/L·h) between LF-HC and HF-LC diets varied among participants, and those with posterior probability >80% were identified as high-carbohydrate responders (n = 9) or high-fat responders (n = 6). Analyses of the Bayesian-aggregated n-of-1 trials among all participants showed a relatively low posterior probability of reaching a clinically meaningful difference of the 3 outcomes between LF-HC and HF-LC diets.

Conclusions: N-of-1 trials are feasible to characterize personal response to dietary intervention in young Chinese adults.
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http://dx.doi.org/10.1093/jn/nxab227DOI Listing
July 2021

The Association of Gut Microbiota with Osteoporosis is Mediated by Amino Acid Metabolism: Multiomics in a Large Cohort.

J Clin Endocrinol Metab 2021 Jul 2. Epub 2021 Jul 2.

Guangdong Provincial Key Laboratory of Food, Nutrition and Health; Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Context: Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association.

Objective: This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using faecal and serum metabolomics.

Methods: We analysed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density (BMD) using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in faeces (15 categories) and serum (12 categories) were further analysed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).

Results: This study showed that osteoporosis was related to the beta diversity, taxonomy and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Faecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively.

Conclusion: This large population-based study provided robust evidence connecting gut dysbiosis, faecal metabolomics and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.
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http://dx.doi.org/10.1210/clinem/dgab492DOI Listing
July 2021

Genetically predicted circulating vitamin C in relation to cardiovascular disease.

Eur J Prev Cardiol 2021 May 31. Epub 2021 May 31.

Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobelsväg 13, Stockholm 17177, Sweden.

Aim: We conducted a two-sample Mendelian randomization (MR) study to assess the associations of genetically predicted circulating vitamin C levels with cardiovascular diseases (CVDs).

Methods And Results: Ten lead single-nucleotide polymorphisms associated with plasma vitamin C levels at the genome-wide significance level were used as instrumental variables. Summary-level data for 15 CVDs were obtained from corresponding genetic consortia, the UK Biobank study, and the FinnGen consortium. The inverse-variance-weighted method was the primary analysis method, supplemented by the weighted median and MR-Egger methods. Estimates for each CVD from different sources were combined. Genetically predicted vitamin C levels were not associated with any CVD after accounting for multiple testing. However, there were suggestive associations of higher genetically predicted vitamin C levels (per 1 standard deviation increase) with lower risk of cardioembolic stroke [odds ratio, 0.79; 95% confidence interval (CI), 0.64, 0.99; P = 0.038] and higher risk of atrial fibrillation (odds ratio, 1.09; 95% CI, 1.00, 1.18; P = 0.049) in the inverse-variance-weighted method and with lower risk of peripheral artery disease (odds ratio, 0.76, 95% CI, 0.62, 0.93; P = 0.009) in the weighted median method.

Conclusion: We found limited evidence with MR techniques for an overall protective role of vitamin C in the primary prevention of CVD. The associations of vitamin C levels with cardioembolic stroke, atrial fibrillation, and peripheral artery disease need further study.
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http://dx.doi.org/10.1093/eurjpc/zwab081DOI Listing
May 2021

Multi-omics analyses reveal relationships among dairy consumption, gut microbiota and cardiometabolic health.

EBioMedicine 2021 Apr 19;66:103284. Epub 2021 Mar 19.

School of Life Sciences, Fudan University, Shanghai, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. Electronic address:

Background: Little is known about the interplay among dairy intake, gut microbiota and cardiometabolic health in human prospective cohort studies.

Methods: The present study included 1780 participants from the Guangzhou Nutrition and Health Study. We examined the prospective association between habitual dairy consumption (total dairy, milk, yogurt) and gut microbial composition using linear regression after adjusting for socio-demographic, lifestyle and dietary factors. The cross-sectional association of dairy-associated microbial features with cardiometabolic risk factors was examined with a linear regression model, adjusting for potential confounders. Serum metabolomic profiles were analyzed by partial correlation analysis.

Findings: There was a significant overall difference in gut microbial community structure (β-diversity) comparing the highest with the lowest category for each of total dairy, milk and yogurt (P < 0.05). We observed that dairy-associated microbes and α-diversity indices were inversely associated with blood triglycerides, while positively associated with high-density lipoprotein cholesterol. A follow-up metabolomics analysis revealed the association of targeted serum metabolites with dairy-microbial features and cardiometabolic traits. Specifically, 2-hydroxy-3-methylbutyric acid, 2-hydroxybutyric acid and L-alanine were inversely associated with dairy-microbial score, while positively associated with triglycerides (FDR-corrected P < 0.1).

Interpretation: Dairy consumption is associated with the gut microbial composition and a higher α-diversity, which provides new insights into the understanding of dairy-gut microbiota interactions and their relationship with cardiometabolic health.

Funding: This work was supported by the National Natural Science Foundation of China, Zhejiang Ten-thousand Talents Program, Westlake University and the 5010 Program for Clinical Researches of the Sun Yat-sen University.
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http://dx.doi.org/10.1016/j.ebiom.2021.103284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985282PMC
April 2021

Dietary camellia (Camellia oleifera Abel) seed oil in traditional Chinese cooking for high-risk cardiovascular disease: A three-arm double-blind randomized controlled feeding trial protocol.

Asia Pac J Clin Nutr 2020 ;29(4):751-762

Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou, China. Email:

Background And Objectives: As the Chinese economy has developed, dietary patterns have modernized, thereby increasing the incidence of chronic diseases such as cardiovascular disease (CVD). Many observational studies have shown that the Mediterranean diet based on olive oil is associated with a decreased incidence of CVD. This article aims to study the possible effects of dietary models by using three edible oils: olive oil, camellia seed oil (CSO), and soybean oil. CSO has a fatty acid composition similar to that olive oil and is unique in China, and soybean oil is a dietary oil used in traditional Chinese cooking.

Methods And Study Design: This intervention is designed based on a three-arm double-blind randomized controlled feeding trial. Three dietary models are established according to traditional Chinese cooking methods, each using one of the three plant edible oils mentioned above as a leading factor. Participants will be randomly assigned to each group and provided with a designated diet for 3 months.

Results: The study population is planned to be women with a high risk of CVD and aged between 35 and 69 years. Weight and other CVD-related factors are treated as primary and secondary outcomes, respectively.

Conclusions: This trial may inform dietary nutrition policies to a certain extent, especially concerning traditional Chinese cooking methods, for weight control and the improvement of cardiovascular-related risk factors in women with a high risk of CVD.
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http://dx.doi.org/10.6133/apjcn.202012_29(4).0010DOI Listing
January 2020

Interpretable Machine Learning Framework Reveals Robust Gut Microbiome Features Associated With Type 2 Diabetes.

Diabetes Care 2021 02 7;44(2):358-366. Epub 2020 Dec 7.

Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China

Objective: To identify the core gut microbial features associated with type 2 diabetes risk and potential demographic, adiposity, and dietary factors associated with these features.

Research Design And Methods: We used an interpretable machine learning framework to identify the type 2 diabetes-related gut microbiome features in the cross-sectional analyses of three Chinese cohorts: one discovery cohort ( = 1,832, 270 cases of type 2 diabetes) and two validation cohorts (cohort 1: = 203, 48 cases; cohort 2: = 7,009, 608 cases). We constructed a microbiome risk score (MRS) with the identified features. We examined the prospective association of the MRS with glucose increment in 249 participants without type 2 diabetes and assessed the correlation between the MRS and host blood metabolites ( = 1,016). We transferred human fecal samples with different MRS levels to germ-free mice to confirm the MRS-type 2 diabetes relationship. We then examined the prospective association of demographic, adiposity, and dietary factors with the MRS ( = 1,832).

Results: The MRS (including 14 microbial features) consistently associated with type 2 diabetes, with risk ratio for per 1-unit change in MRS 1.28 (95% CI 1.23-1.33), 1.23 (1.13-1.34), and 1.12 (1.06-1.18) across three cohorts. The MRS was positively associated with future glucose increment ( < 0.05) and was correlated with a variety of gut microbiota-derived blood metabolites. Animal study further confirmed the MRS-type 2 diabetes relationship. Body fat distribution was found to be a key factor modulating the gut microbiome-type 2 diabetes relationship.

Conclusions: Our results reveal a core set of gut microbiome features associated with type 2 diabetes risk and future glucose increment.
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http://dx.doi.org/10.2337/dc20-1536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818326PMC
February 2021

Dietary fruit and vegetable intake, gut microbiota, and type 2 diabetes: results from two large human cohort studies.

BMC Med 2020 12 3;18(1):371. Epub 2020 Dec 3.

Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.

Background: Little is known about the inter-relationship among fruit and vegetable intake, gut microbiota and metabolites, and type 2 diabetes (T2D) in human prospective cohort study. The aim of the present study was to investigate the prospective association of fruit and vegetable intake with human gut microbiota and to examine the relationship between fruit and vegetable-related gut microbiota and their related metabolites with type 2 diabetes (T2D) risk.

Methods: This study included 1879 middle-age elderly Chinese adults from Guangzhou Nutrition and Health Study (GNHS). Baseline dietary information was collected using a validated food frequency questionnaire (2008-2013). Fecal samples were collected at follow-up (2015-2019) and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Blood samples were collected and analyzed for glucose, insulin, and glycated hemoglobin. We used multivariable linear regression and logistic regression models to investigate the prospective associations of fruit and vegetable intake with gut microbiota and the association of the identified gut microbiota (fruit/vegetable-microbiota index) and their related fecal metabolites with T2D risk, respectively. Replications were performed in an independent cohort involving 6626 participants.

Results: In the GNHS, dietary fruit intake, but not vegetable, was prospectively associated with gut microbiota diversity and composition. The fruit-microbiota index (FMI, created from 31 identified microbial features) was positively associated with fruit intake (p < 0.001) and inversely associated with T2D risk (odds ratio (OR) 0.83, 95%CI 0.71-0.97). The FMI-fruit association (p = 0.003) and the FMI-T2D association (OR 0.90, 95%CI 0.84-0.97) were both successfully replicated in the independent cohort. The FMI-positive associated metabolite sebacic acid was inversely associated with T2D risk (OR 0.67, 95%CI 0.51-0.86). The FMI-negative associated metabolites cholic acid (OR 1.35, 95%CI 1.13-1.62), 3-dehydrocholic acid (OR 1.30, 95%CI 1.09-1.54), oleylcarnitine (OR 1.77, 95%CI 1.45-2.20), linoleylcarnitine (OR 1.66, 95%CI 1.37-2.05), palmitoylcarnitine (OR 1.62, 95%CI 1.33-2.02), and 2-hydroglutaric acid (OR 1.47, 95%CI 1.25-1.72) were positively associated with T2D risk.

Conclusions: Higher fruit intake-associated gut microbiota and metabolic alteration were associated with a lower risk of T2D, supporting the public dietary recommendation of adopting high fruit intake for the T2D prevention.
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http://dx.doi.org/10.1186/s12916-020-01842-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712977PMC
December 2020

Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.

Diabetes Care 2021 01 17;44(1):98-106. Epub 2020 Nov 17.

Unit of Nutrition and Cancer, Cancer Epidemiology Research Program and Translational Research Laboratory; Catalan Institute of Oncology - ICO, Group of Research on Nutrition and Cancer, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet of Llobregat, Barcelona, Spain.

Objective: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

Research Design And Methods: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.

Results: We identified 11 genomic regions associated with plasma vitamin C ( < 5 × 10), with the strongest signal at , and 10 novel genetic loci including , , , , , , , , , and . Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).

Conclusions: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
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http://dx.doi.org/10.2337/dc20-1328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783939PMC
January 2021

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis.

PLoS Med 2020 10 16;17(10):e1003394. Epub 2020 Oct 16.

Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

Background: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis.

Methods And Findings: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities.

Conclusions: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.
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http://dx.doi.org/10.1371/journal.pmed.1003394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567390PMC
October 2020

The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for complex human diseases.

Microbiome 2020 10 8;8(1):145. Epub 2020 Oct 8.

Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.

Background: Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear.

Results: This analysis was based on a Chinese population with 1475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, an undefined genus in the family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features.

Conclusions: These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans. Video Abstract.
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http://dx.doi.org/10.1186/s40168-020-00923-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545574PMC
October 2020

Application of -of-1 Clinical Trials in Personalized Nutrition Research: A Trial Protocol for Westlake N-of-1 Trials for Macronutrient Intake (WE-MACNUTR).

Curr Dev Nutr 2020 Sep 26;4(9):nzaa143. Epub 2020 Aug 26.

Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.

Personalized dietary recommendations can help with more effective disease prevention. This study aims to investigate the individual postprandial glucose response to diets with diverse macronutrient proportions at both the individual level and population level, and explore the potential of the novel single-patient (-of-1) trial for personalization of diet. Secondary outcomes include individual phenotypic responses and the effects of dietary ingredients on the composition of gut microbiota. Westlake N-of-1 Trials for Macronutrient Intake is a multiple crossover feeding trial consisting of 3 successive 12-d dietary intervention pairs including a 6-d washout period before each 6-d isocaloric dietary intervention: a 6-d high-fat, low-carbohydrate diet, and a 6-d low-fat, high-carbohydrate diet. The results will help provide personalized dietary recommendations for macronutrients in terms of postprandial blood glucose responses. The proposed -of-1 trial methods could help in optimizing individual health and advancing health care. This trial was registered with clinicaltrials.gov (NCT04125602).
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http://dx.doi.org/10.1093/cdn/nzaa143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494402PMC
September 2020

Erythrocyte n-6 Polyunsaturated Fatty Acids, Gut Microbiota, and Incident Type 2 Diabetes: A Prospective Cohort Study.

Diabetes Care 2020 10 28;43(10):2435-2443. Epub 2020 Jul 28.

Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translation Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China

Objective: To examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association.

Research Design And Methods: We evaluated 2,731 participants without type 2 diabetes recruited between 2008 and 2013 in the Guangzhou Nutrition and Health Study (Guangzhou, China). Case subjects with type 2 diabetes were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset ( = 1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident type 2 diabetes and diversity and composition of gut microbiota.

Results: Over 6.2 years of follow-up, 276 case subjects with type 2 diabetes were identified (risk 0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% CI 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both < 0.05) during follow-up and significantly associated with microbiota β-diversity ( = 0.002). α-Diversity acted as a potential mediator in the association between GLA and type 2 diabetes ( < 0.05). Seven genera (, , , , , , and ) were enriched in quartile 1 of GLA and in participants without type 2 diabetes.

Conclusions: Relative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and type 2 diabetes etiology.
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http://dx.doi.org/10.2337/dc20-0631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510039PMC
October 2020

Integration of an interpretable machine learning algorithm to identify early life risk factors of childhood obesity among preterm infants: a prospective birth cohort.

BMC Med 2020 07 10;18(1):184. Epub 2020 Jul 10.

Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, 18 Shilongshan Rd, Cloud Town, Hangzhou, 310024, China.

Background: The early life risk factors of childhood obesity among preterm infants are unclear and little is known about the influence of the feeding practices. We aimed to identify early life risk factors for childhood overweight/obesity among preterm infants and to determine feeding practices that could modify the identified risk factors.

Methods: A total of 338,413 mother-child pairs were enrolled in the Jiaxing Birth Cohort (1999 to 2013), and 2125 eligible singleton preterm born children were included for analyses. We obtained data on health examination, anthropometric measurement, lifestyle, and dietary habits of each participant at their visits to clinics. An interpretable machine learning-based analytic framework was used to identify early life predictors for childhood overweight/obesity, and Poisson regression was used to examine the associations between feeding practices and the identified leading predictor.

Results: Of the eligible 2125 preterm infants (863 [40.6%] girls), 274 (12.9%) developed overweight/obesity at age 4-7 years. We summarized early life variables into 25 features and identified two most important features as predictors for childhood overweight/obesity: trajectory of infant BMI (body mass index) Z-score change during the first year of corrected age and maternal BMI at enrollment. According to the impacts of different BMI Z-score trajectories on the outcome, we classified this feature into the favored and unfavored trajectories. Compared with early introduction of solid foods (≤ 3 months of corrected age), introducing solid foods after 6 months of corrected age was significantly associated with 11% lower risk (risk ratio, 0.89; 95% CI, 0.82 to 0.97) of being in the unfavored trajectory.

Conclusions: The trajectory of BMI Z-score change within the first year of life is the most important predictor for childhood overweight/obesity among preterm infants. Introducing solid foods after 6 months of corrected age is a recommended feeding practice for mitigating the risk of being in the unfavored trajectory.
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http://dx.doi.org/10.1186/s12916-020-01642-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350615PMC
July 2020

Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries.

BMJ 2020 07 8;370:m2194. Epub 2020 Jul 8.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Objective: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.

Design: Prospective case-cohort study.

Setting: Populations from eight European countries.

Participants: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.

Main Outcome Measure: Incident type 2 diabetes.

Results: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.

Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
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http://dx.doi.org/10.1136/bmj.m2194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341350PMC
July 2020

Regulobiosis: A regulatory and food system-sensitive role for fungal symbionts in human evolution and ecobiology.

Asia Pac J Clin Nutr 2020 ;29(1):9-15

Institute of Nutrition and Health, Qingdao University, Qingdao, China.

The role of microbiomes in human biology and health are being extensively investigated, yet how the fungal community or mycobiome contributes to an integral microbiome is unclear and probably underestimated. We review the roles of fungi from the perspectives of their functionality in human biology, their cross-kingdom talk with other human microbial organisms, their dependence on diet and their involvement in human health and diseases. We hypothesize that members of the fungal community may interact as necessary symbionts with members of other human microbiome communities, and play a key role in human biology, yet to be fully understood. We propose further that "regulobiosis", whereby fungi play a regulatory role in human ecobiology, is operative in humans as probably obtains in other forms of life. Fungally-dependent regulobiosis would characterise, at first, microbiomes which include, but are not limited to, bacteria, archaea, and viruses; then, their human host; and, next, provide ecological connectedness.
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http://dx.doi.org/10.6133/apjcn.202003_29(1).0002DOI Listing
January 2021

Legume and soy intake and risk of type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.

Am J Clin Nutr 2020 03;111(3):677-688

Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China.

Background: Previous findings on the associations of legume and soy intake with the risk of type 2 diabetes are conflicting.

Objective: We aimed to summarize the longitudinal associations between legume and soy intake and risk of type 2 diabetes.

Methods: We searched for relevant prospective cohort studies in PubMed, EMBASE, and Ovid up to August 2019. Study-specific, multivariable-adjusted RRs and 95% CIs were pooled by random-effects models.

Results: We identified 15 unique cohorts including 565,810 individuals and 32,093 incident cases. The summary RRs (95% CIs) of incident type 2 diabetes were 0.95 (0.79, 1.14; NS) for total legumes, 0.83 (0.68, 1.01; NS) for total soy, 0.89 (0.71, 1.11; NS) for soy milk, 0.92 (0.84, 0.99) for tofu, 0.84 (0.75, 0.95) for soy protein, and 0.88 (0.81, 0.96) for soy isoflavones, respectively. High heterogeneity was found for total legumes (I2 = 84.8%), total soy (I2 = 90.8%), and soy milk (I2 = 91.7%). Potential sources of heterogeneity were not evident for total legumes or soy milk, whereas for total soy, geographic location (Asia, United States; P = 0.04) and study quality (high, moderate, or low; P = 0.02) significantly predicted heterogeneity. In dose-response analysis, significant linear inverse associations were observed for tofu, soy protein, and soy isoflavones (all P < 0.05). Overall quality of evidence was rated as moderate for total legumes and low for total soy and soy subtypes.

Conclusions: Dietary intakes of tofu, soy protein, and soy isoflavones, but not total legumes or total soy, are inversely associated with incident type 2 diabetes. Our findings support recommendations to increase intakes of certain soy products for the prevention of type 2 diabetes. However, the overall quality of evidence was low and more high-quality evidence from prospective studies is needed. This trial was registered as PROSPERO CRD42019126403 (https://www.crd.york.ac.uk/PROSPERO).
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http://dx.doi.org/10.1093/ajcn/nqz338DOI Listing
March 2020

Fast-food restaurant, unhealthy eating, and childhood obesity: A systematic review and meta-analysis.

Obes Rev 2021 02 10;22 Suppl 1:e12944. Epub 2019 Sep 10.

International Institute of Spatial Lifecourse Epidemiology (ISLE), the Netherlands.

Excessive access to fast-food restaurants (FFRs) in the neighbourhood is thought to be a risk factor for childhood obesity by discouraging healthful dietary behaviours while encouraging the exposure to unhealthful food venues and hence the compensatory intake of unhealthy food option. A literature search was conducted in the PubMed, Web of Science, and Embase for articles published until 1 January 2019 that analysed the association between access to FFRs and weight-related behaviours and outcomes among children aged younger than 18. Sixteen cohort studies and 71 cross-sectional studies conducted in 14 countries were identified. While higher FFR access was not associated with weight-related behaviours (eg, dietary quality score and frequency of food consumption) in most studies, it was commonly associated with more fast-food consumption. Despite that, insignificant results were observed for all meta-analyses conducted by different measures of FFR access in the neighbourhood and weight-related outcomes, although 17 of 39 studies reported positive associations when using overweight/obesity as the outcome. This systematic review and meta-analysis revealed a rather mixed relationship between FFR access and weight-related behaviours/outcomes among children and adolescents.
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http://dx.doi.org/10.1111/obr.12944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988557PMC
February 2021

Gene-lifestyle interaction on risk of type 2 diabetes: A systematic review.

Obes Rev 2019 11 2;20(11):1557-1571. Epub 2019 Sep 2.

Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam Rehbruecke, Nuthetal, Germany.

The pathophysiological influence of gene-lifestyle interactions on the risk to develop type 2 diabetes (T2D) is currently under intensive research. This systematic review summarizes the evidence for gene-lifestyle interactions regarding T2D incidence. MEDLINE, EMBASE, and Web of Science were systematically searched until 31 January 2019 to identify publication with (a) prospective study design; (b) T2D incidence; (c) gene-diet, gene-physical activity, and gene-weight loss intervention interaction; and (d) population who are healthy or prediabetic. Of 66 eligible publications, 28 reported significant interactions. A variety of different genetic variants and dietary factors were studied. Variants at TCF7L2 were most frequently investigated and showed interactions with fiber and whole grain on T2D incidence. Further gene-diet interactions were reported for, eg, a western dietary pattern with a T2D-GRS, fat and carbohydrate with IRS1 rs2943641, and heme iron with variants of HFE. Physical activity showed interaction with HNF1B, IRS1, PPARγ, ADRA2B, SLC2A2, and ABCC8 variants and weight loss interventions with ENPP1, PPARγ, ADIPOR2, ADRA2B, TNFα, and LIPC variants. However, most findings represent single study findings obtained in European ethnicities. Although some interactions have been reported, their conclusiveness is still low, as most findings were not yet replicated across multiple study populations.
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http://dx.doi.org/10.1111/obr.12921DOI Listing
November 2019

Changes in plasma phospholipid fatty acid profiles over 13 years and correlates of change: European Prospective Investigation into Cancer and Nutrition-Norfolk Study.

Am J Clin Nutr 2019 06;109(6):1527-1534

MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.

Background: Little is known about changes in blood fatty acid compositions over time and the correlates of any changes in a general population.

Objective: The aim of this study was to estimate changes in 27 individual plasma phospholipid fatty acids and fatty acid groups over time, and to identify potential correlates of these changes.

Methods: Plasma phospholipid fatty acids were profiled at 3 time-points (1993-1997, 1998-2000, 2004-2011) among 722 participants in the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, UK. Linear regression models were used to estimate both 1) mean changes over time in 27 individual fatty acids and 8 prespecified fatty acid groups and 2) associations of changes in dietary and lifestyle factors with changes in the 8 fatty acid groups, mutually adjusted for dietary/lifestyle factors and other confounders. The prespecified fatty acid groups were odd-chain saturated fatty acids (SFAs), even-chain SFAs, very-long-chain SFAs, marine n-3 polyunsaturated fatty acids (PUFAs), plant n-3 PUFA, n-6 PUFAs, monounsaturated fatty acids (MUFAs), and trans-fatty acids (TFAs).

Results: Adjusted for confounders, fatty acid concentrations decreased for odd-chain SFAs (annual percentage difference in mol percentage: -0.63%), even-chain SFAs (-0.05%), n-6 PUFAs (-0.25%), and TFAs (-7.84%). In contrast, concentrations increased for marine n-3 PUFAs (1.28%) and MUFAs (0.45%), but there were no changes in very-long-chain SFAs or plant n-3 PUFA. Changes in fatty acid levels were associated with consumption of different food groups. For example, a mean 100 g/d increase in fatty fish intake was associated with a 19.3% greater annual increase in marine n-3 PUFAs.

Conclusions: Even-chain SFAs and TFAs declined and marine n-3 PUFAs increased over time. These changes were partially explained by changes in dietary habits, and could potentially help interpret associations of baseline fatty acid composition with future disease risk.
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http://dx.doi.org/10.1093/ajcn/nqz030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537938PMC
June 2019

Corrigendum to "Replication of a gene-diet interaction at CD36, NOS3 and PPARG in response to omega-3 fatty acid supplements on blood lipids: A double-blind randomized controlled trial" (EBioMedicine May 2018;31:150-156).

Authors:
Ju-Sheng Zheng

EBioMedicine 2019 02 14;40:751-752. Epub 2019 Jan 14.

School of Life Sciences, Westlake University, Hangzhou 310024, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, China. Electronic address:

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http://dx.doi.org/10.1016/j.ebiom.2019.01.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413348PMC
February 2019

Association between erythrocyte fatty acids in de novo lipogenesis pathway and DXA-derived body fat and trunk fat distribution in Chinese adults: a prospective study.

Eur J Nutr 2019 Dec 23;58(8):3229-3239. Epub 2018 Nov 23.

Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.

Purpose: Higher levels of fatty acids (FAs) in the de novo lipogenesis (DNL) pathway might be associated with higher levels of fat mass (FM), while limited evidence is available from the general population. We aimed to examine the associations between DNL-FAs and body fat and fat distribution in a general population of Chinese adults.

Methods: This community-based prospective cohort study included 3,075 participants (68% women) aged 40-75 years in urban Guangzhou, China. We measured erythrocyte DNL-FAs composition (including C16:0, C16:1n-7, C18:0, and C18:1n-9) at baseline and %FM over the total body (TB), trunk, limbs, android (A) and gynoid (G) regions after 3.2 years and 6.3 years of follow-up, respectively.

Results: Generally, higher proportions of individual erythrocyte DNL-FAs and their combined index were positively associated with adipose indices in the multivariable cross-sectional and longitudinal analyses. The cross-sectional percentage mean differences in quartile 4 (vs. 1) of the DNL index were 3.43% (TB), 4.56% (trunk), and 2.67% (A/G ratio) (all P trends < 0.01). The corresponding values in longitudinal changes of adipose indices were 1.40% (TB), 1.78% (trunk), and 1.32% (A) (all P trends < 0.05). The above associations tended to be more pronounced in the trunk and android area than the limbs and gynoid area.

Conclusions: Erythrocyte DNL-FAs may contribute to an increase in total body fat in Chinese adults, particularly FM distributed in trunk and abdominal regions.
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http://dx.doi.org/10.1007/s00394-018-1866-zDOI Listing
December 2019

Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study.

J Clin Endocrinol Metab 2019 04;104(4):1293-1303

National Institute for Public Health and the Environment, Bilthoven, Netherlands.

Background: Existing evidence for the prospective association of vitamin D status with type 2 diabetes (T2D) is focused almost exclusively on circulating total 25-hydroxyvitamin D [25(OH)D] without distinction between its subtypes: nonepimeric and epimeric 25(OH)D3 stereoisomers, and 25(OH)D2, the minor component of 25(OH)D. We aimed to investigate the prospective associations of circulating levels of the sum and each of these three metabolites with incident T2D.

Methods: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study for T2D included 9671 incident T2D cases and 13,562 subcohort members. Plasma vitamin D metabolites were quantified by liquid chromatography-mass spectrometry. We used a multivariable Prentice-weighted Cox regression to estimate hazard ratios (HRs) of T2D for each metabolite. Analyses were performed separately within country, and estimates were combined across countries using random-effects meta-analysis.

Results: The mean concentrations (SD) of total 25(OH)D, nonepimeric 25(OH)D3, epimeric 25(OH)D3, and 25(OH)D2 were 41.1 (17.2), 40.7 (17.3), 2.13 (1.31), and 8.16 (6.52) nmol/L, respectively. Plasma total 25(OH)D and nonepimeric 25(OH)D3 were inversely associated with incident T2D [multivariable-adjusted HR per 1 SD = 0.81 (95% CI, 0.77, 0.86) for both variables], whereas epimeric 25(OH)D3 was positively associated [per 1 SD HR = 1.16 (1.09, 1.25)]. There was no statistically significant association with T2D for 25(OH)D2 [per 1 SD HR = 0.94 (0.76, 1.18)].

Conclusions: Plasma nonepimeric 25(OH)D3 was inversely associated with incident T2D, consistent with it being the major metabolite contributing to total 25(OH)D. The positive association of the epimeric form of 25(OH)D3 with incident T2D provides novel information to assess the biological relevance of vitamin D epimerization and vitamin D subtypes in diabetes etiology.
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http://dx.doi.org/10.1210/jc.2018-01522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397435PMC
April 2019

Relationship between erythrocyte phospholipid fatty acid composition and obesity in children and adolescents.

J Clin Lipidol 2019 Jan - Feb;13(1):70-79.e1. Epub 2018 Sep 25.

Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China; Institute of Nutrition & Health, Qingdao University, Qingdao, China. Electronic address:

Background: Observational studies have reported inconsistent results on the association between circulating fatty acids and obesity.

Objective: The objective of this study was to investigate the relationship between erythrocyte phospholipid fatty acid composition and obesity in children and adolescents.

Methods: We conducted a case-control study including 1442 obese and 1442 normal-weight children and adolescents. Circulating fatty acid composition between cases and controls were compared both in the present study and literature-based meta-analysis. Individual fatty acids contributing most to discriminating cases and controls were identified by orthogonal partial least squares-discriminant analysis and their associations with obesity were explored by a conditional logistic regression model.

Results: Five saturated fatty acids (14:0, 16:0, 17:0, 18:0, 20:0) were higher, 9 polyunsaturated fatty acids (18:3n-3, 20:3n-3, 20:5n-3, 22:5n-3, 22:6n-3, 18:2n-6, 20:2n-6, 20:3n-6, 20:4n-6) were lower in cases than in controls, while pooled results from the comparative meta-analysis were only consistent in 22:5n-3, 22:6n-3 and 18:2n-6. The orthogonal partial least squares-discriminant analysis model indicated that 16:0, 18:0, 20:4n-6, and 22:6n-3 were the fatty acids contributing most to discriminating cases and controls. In the conditional logistic regression model, significant positive associations were found for 16:0 (per 1 SD OR = 1.43, 95% CI, 1.35-1.52) and 18:0 (per 1 SD OR = 1.12, 95% CI, 1.09-1.16), while significant inverse associations were found for 20:4n-6 (per 1 SD OR = 0.63, 95% CI, 0.58-0.69) and 22:6n-3 (per 1 SD OR = 0.56, 95% CI, 0.52-0.61).

Conclusions: Erythrocyte phospholipid 16:0 and 18:0 were positively and 20:4n-6 and 22:6n-3 were inversely associated with obesity in children and adolescents.
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http://dx.doi.org/10.1016/j.jacl.2018.09.013DOI Listing
May 2020

Association of erythrocyte n-3 polyunsaturated fatty acids with incident type 2 diabetes in a Chinese population.

Clin Nutr 2019 10 26;38(5):2195-2201. Epub 2018 Sep 26.

Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Medical Statistics & Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China. Electronic address:

Background & Aims: The association between circulating n-3 polyunsaturated fatty acid (PUFA) biomarkers and incident type 2 diabetes in Asian populations remains unclear. We aimed to examine the association of erythrocyte n-3 PUFA with incident type 2 diabetes in a Chinese population.

Methods: A total of 2671 participants, aged 40-75 y, free of type 2 diabetes at baseline, were included in the present analysis. Incident type 2 diabetes cases (n = 213) were ascertained during median follow-up of 5.6 years. Baseline erythrocyte fatty acids were measured by gas chromatography. We used multivariable Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of type 2 diabetes across quartiles of erythrocyte n-3 PUFA.

Results: After adjustment for potential confounders, HRs (95% CIs) of type 2 diabetes were 0.68 (0.47, 1.00), 0.77 (0.52, 1.15), and 0.63 (0.41, 0.95) in quartiles 2-4 of docosapentaenoic acid (C22:5n-3) (P-trend = 0.07), compared with quartile 1; and 1.08 (0.74, 1.60), 1.03 (0.70, 1.51), and 0.57 (0.38, 0.86) for eicosapentaenoic acid (C20:5n-3) (P-trend = 0.007). No association was found for docosahexaenoic acid (C22:6n-3) or alpha-linolenic acid (C18:3n-3).

Conclusions: Erythrocyte n-3 PUFA from marine sources (C22:5n-3 and C20:5n-3), as biomarkers of dietary marine n-3 PUFA, were inversely associated with incident type 2 diabetes in this Chinese population. Future prospective investigations in other Asian populations are necessary to confirm our findings.
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http://dx.doi.org/10.1016/j.clnu.2018.09.018DOI Listing
October 2019

Erythrocyte Saturated Fatty Acids and Incident Type 2 Diabetes in Chinese Men and Women: A Prospective Cohort Study.

Nutrients 2018 Oct 1;10(10). Epub 2018 Oct 1.

Guangdong Provincial Key Laboratory of Food, Nutrition and Health; Department of Medical Statistics & Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.

The association between circulating saturated fatty acids (SFAs) and incident type 2 diabetes (T2D) is reported in Western populations with inconsistent results, while evidence from Asian populations is scarce. We aimed to examine the associations between erythrocyte SFAs and incident T2D in a Chinese population. Between 2008 and 2013, a total of 2683 participants, aged 40⁻75 years, free of diabetes were included in the present analyses. Incident T2D cases were ascertained during follow-up visits. Gas chromatography was used to measure erythrocyte fatty acids at baseline. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During 13,508 person years of follow-up, 216 T2D cases were identified. Compared with the first quartile, multivariable-adjusted HRs (95% CIs) of the fourth quartile were 1.20 (0.82⁻1.76; = 0.242) for myristic acid (14-carbon tail, zero double bonds; 14:0), 0.69 (0.48⁻0.99; = 0.080) for palmitic acid (16:0), 1.49 (1.02⁻2.19; = 0.047) for stearic acid (18:0), 1.46 (1.00⁻2.12; = 0.035) for arachidic acid (20:0), 1.48 (0.99⁻2.22; = 0.061) for behenic acid (22:0), and 1.08 (0.74⁻1.56; = 0.913) for lignoceric acid (24:0). Our findings indicate that individual erythrocyte SFAs are associated with T2D in different directions, with 18:0 and 20:0 SFAs positively associated with the risk, whereas no convincing inverse association for 16:0 SFAs.
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http://dx.doi.org/10.3390/nu10101393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212875PMC
October 2018

Replication of a Gene-Diet Interaction at CD36, NOS3 and PPARG in Response to Omega-3 Fatty Acid Supplements on Blood Lipids: A Double-Blind Randomized Controlled Trial.

EBioMedicine 2018 May 17;31:150-156. Epub 2018 Apr 17.

Institute of Nutrition and Health, Qingdao University, Qingdao 266071, China; Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310058, China. Electronic address:

Background: Modulation of genetic variants on the effect of omega-3 fatty acid supplements on blood lipids is still unclear.

Methods: In a double-blind randomized controlled trial, 150 patients with type 2 diabetes (T2D) were randomized into omega-3 fatty acid group (n = 56 for fish oil and 44 for flaxseed oil) and control group (n = 50) for 180 days. All patients were genotyped for genetic variants at CD36 (rs1527483), NOS3 (rs1799983) and PPARG (rs1801282). Linear regression was used to examine the interaction between omega-3 fatty acid intervention and CD36, NOS3 or PPARG variants for blood lipids.

Findings: Significant interaction with omega-3 fatty acid supplements was observed for CD36 on triglycerides (p-interaction = 0.042) and PPAGR on low-density lipoprotein-cholesterol (p-interaction = 0.02). We also found a significant interaction between change in erythrocyte phospholipid omega-3 fatty acid composition and NOS3 genotype on triglycerides (p-interaction = 0.042), total cholesterol (p-interaction = 0.013) and ratio of total cholesterol to high-density lipoprotein cholesterol (p-interaction = 0.015). The T2D patients of CD36-G allele, PPARG-G allele and NOS3-A allele tended to respond better to omega-3 fatty acids in improving lipid profiles. The interaction results of the omega-3 fatty acid group were mainly attributed to the fish oil supplements.

Interpretation: This study suggests that T2D patients with different genotypes at CD36, NOS3 and PPARG respond differentially to intervention of omega-3 supplements in blood lipid profiles.
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http://dx.doi.org/10.1016/j.ebiom.2018.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013782PMC
May 2018

Association between Erythrocyte Membrane Phospholipid Fatty Acids and Sleep Disturbance in Chinese Children and Adolescents.

Nutrients 2018 Mar 12;10(3). Epub 2018 Mar 12.

Department of Food Science and Nutrition, Zhejiang University, 866 Yu-hang-tang Road, Hangzhou 310058, China.

The relationship between circulating fatty acid (FA) composition and childhood sleep disturbance remains largely unclear. We aimed to investigate the association of erythrocyte membrane FA composition with prevalence of sleep disturbance in Chinese children and adolescents. A cross-sectional survey was conducted among 2337 school-aged children and adolescents who completed a clinical assessment in Beijing, China. Presence of sleep disturbance was self-reported or parent-reported by questionnaires. Erythrocyte FAs were measured by gas chromatography, and desaturase activities were estimated by FA ratios. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for sleep disturbance across FA quartiles were calculated by a logistical regression model. We found higher proportions of erythrocyte phospholipid 24:0, 24:1n-9, and lower proportions of total n-3 polyunsaturated FA (PUFA), 22:5n-3 and 22:6n-3 in participants with sleep disturbance compared with those without. In the logistical regression models, significant inverse associations were found for total n-3 PUFA, 22:5n-3 and 22:6n-3, the highest versus lowest quartile ORs and 95% CIs were 0.57 (0.40, 0.82), 0.67 (0.47, 0.97) and 0.69 (0.49, 0.96), respectively. For per 1 SD difference of proportion, OR and 95% CI of prevalence of sleep disturbance was 0.91 (0.86, 0.97) for total n-3 PUFA, 0.90 (0.82, 0.98) for 22:5n-3, and 0.92 (0.86, 0.99) for 22:6n-3, respectively. No significant association was found for saturated fatty acids, monounsaturated fatty acids, n-6 polyunsaturated fatty acids or FA ratios. The present study suggested that erythrocyte n-3 PUFAs, especially 22:5n-3 and 22:6n-3, are inversely associated with prevalence of sleep disturbance in Chinese children and adolescents.
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http://dx.doi.org/10.3390/nu10030344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872762PMC
March 2018
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