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1.
Mech Ageing Dev ; 220: 111953, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38834155

ABSTRACT

Muscle aging contributed to morbidity and mortality in the elderly adults by leading to severe outcomes such as frailty, falls and fractures. Post-transcriptional regulation especially competing endogenous RNA (ceRNA) mechanism may modulate the process of skeletal muscle aging. RNA-seq was performed in quadriceps of 6-month-old (adult) and 22-month-old (aged) male mice to identify differentially expressed ncRNAs and mRNAs and further construct ceRNA networks. Decreased quadriceps-body weight ratio and muscle fiber cross-sectional area as well as histological characteristics of aging were observed in the aged mice. Besides, there were higher expressions of atrogin-1 and MuRF-1 and lower expression of Myog, Myf4 and Myod1 in the quadriceps of aged mice relative to that of adult mice. The expression of 85 lncRNAs, 52 circRNAs, 10 miRNAs and 277 mRNAs were significantly dysregulated in quadriceps between the two groups, among which two ceRNA networks lncRNA 2700081O15Rik/circRNA_0000820-miR-673-3p-Tmem120b were constructed. Level of triglycerides and expression of PPARγ, C/EBPα, FASN and leptin were elevated and the expression of adiponectin was reduced in quadriceps of aged mice compared with that of adult mice. LncRNA 2700081O15Rik/circRNA_0000820-miR-673-3p-Tmem120b were possibly associated with the adipogenesis and fat accumulation in skeletal muscle of age male mice.

2.
J Trace Elem Med Biol ; 80: 127295, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37660572

ABSTRACT

BACKGROUND: Selenium profile has been related with humoral immune response after vaccination, but evidence with regard to inactivated SARS-CoV-2 vaccine is lacking. OBJECTIVE: The current study aimed to examine the relationship between selenium profile and neutralizing antibody response to inactivated SARS-CoV-2 vaccine. METHODS: Plasma selenium and selenoprotein P concentrations, neutralizing antibody against the wild-type and Omicron variant were measured at baseline and at 14 days, 98 days after the third dose of inactivated SARS-CoV-2 vaccine. RESULTS: Neutralizing antibody against the wild-type and Omicron variant increased significantly after the third vaccination dose. Both higher plasma selenium and selenoprotein P were associated with increased neutralizing antibody against the wild-type strain at baseline. Moreover, higher plasma selenoprotein P was associated with increased neutralizing antibody against Omicron variant at baseline. However, nonsignificant association were observed after the third vaccine dose. CONCLUSION: Higher selenium profile was associated with neutralizing antibody response before the third dose of inactivated SARS-CoV-2 vaccine, but not after the third dose. Further prospective cohort studies are warranted to confirm our findings.


Subject(s)
COVID-19 , Selenium , Humans , COVID-19 Vaccines , SARS-CoV-2 , Selenoprotein P , COVID-19/prevention & control , Vaccination , Antibodies, Neutralizing
3.
Biofabrication ; 15(4)2023 07 25.
Article in English | MEDLINE | ID: mdl-37402381

ABSTRACT

Hepatocellular carcinoma (HCC) poses a significant threat to human health and medical care. Its dynamic microenvironment and stages of development will influence the treatment strategies in clinics. Reconstructing tumor-microvascular interactions in different stages of the microenvironment is an urgent need forin vitrotumor pathology research and drug screening. However, the absence of tumor aggregates with paracancerous microvascular and staged tumor-endothelium interactions leads to bias in the antitumor drug responses. Herein, a spheroid-on-demand manipulation strategy was developed to construct staged endothelialized HCC models for drug screening. Pre-assembled HepG2 spheroids were directly printed by alternating viscous and inertial force jetting with high cell viability and integrity. A semi-open microfluidic chip was also designed to form a microvascular connections with high density, narrow diameter, and curved morphologies. According to the single or multiple lesions in stages Ⅰ or Ⅰ HCC, endothelialized HCC models from micrometer to millimeter scale with dense tumor cell aggregation and paracancerous endothelial distribution were successively constructed. A migrating stage Ⅰ HCC model was further constructed under TGF-ßtreatment, where the spheroids exhibited a more mesenchymal phenotype with a loose cell connection and spheroid dispersion. Finally, the stage ⅠHCC model showed stronger drug resistance compared to the stage Ⅰ model, while the stage III showed a more rapid response. The corresponding work provides a widely applicable method for the reproduction of tumor-microvascular interactions at different stages and holds great promise for the study of tumor migration, tumor-stromal cell interactions, and the development of anti-tumor therapeutic strategies.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Drug Evaluation, Preclinical , Spheroids, Cellular/pathology , Printing, Three-Dimensional , Tumor Microenvironment
4.
Front Public Health ; 11: 1178057, 2023.
Article in English | MEDLINE | ID: mdl-37325320

ABSTRACT

Background: The study regarding phthalate metabolites and mortality among diabetes mellitus (DM) is limited. We aimed to examine the association of urinary phthalate metabolites with all-cause and cardiovascular disease (CVD) mortality among adults with DM. Methods: This study included 8,931 adults from the National Health and Nutrition Examination Survey (NHANES) from 2005-2006 to 2013-2014. Mortality data were linked to National Death Index public access files through December 31, 2015. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidences (CIs) for mortality. Results: We identified 1,603 adults with DM [mean ± SE age, 47.08 ± 0.30 years; 50.5% (833) were men]. Mono-(carboxynonyl) phthalate (MCNP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), and the sum of Di (2-ethylhexyl) phthalate (DEHP) metabolites (∑DEHP) were positively associated with DM (MCNP: OR = 1.53, 95%CI = 1.16-2.01; MECPP: OR = 1.17, 95% CI = 1.03-1.32; ∑DEHP: OR = 1.14, 95% CI = 1.00-1.29). Among DM patients, mono-(3-carboxypropyl) phthalate (MCPP) was associated with a 34% (HR 1.34, 95% CI 1.12-1.61) increased risk of all-cause mortality while the HRs (95%CI) of CVD mortality were 2.02 (1.13-3.64) for MCPP, 2.17 (1.26-3.75) for mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), 2.47 (1.43-4.28) for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), 2.65 (1.51-4.63) for MECPP, and 2.56 (1.46-4.46) for ∑DEHP, respectively. Conclusion: This study is an academic exploration of the association between urinary phthalate metabolites and mortality among adults with DM, suggesting that exposure to phthalates might be associated with an increased risk of all-cause and CVD mortality in DM. These findings suggest that patients with DM should carefully use plastics products.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Phthalic Acids , Male , Humans , Adult , Middle Aged , Female , Environmental Exposure/adverse effects , Nutrition Surveys , Phthalic Acids/adverse effects , Phthalic Acids/urine , Diabetes Mellitus/epidemiology
5.
Front Nutr ; 10: 1167920, 2023.
Article in English | MEDLINE | ID: mdl-37260517

ABSTRACT

Background: Fat-soluble vitamins (A, D, and E) are essential for the proper functioning of the immune system and are of central importance for infection risk in humans. Vitamins A, D, and E have been reported to be associated with the immune response following vaccination; however, their effects on the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination remain unknown. Methods: We measured the neutralizing antibody titers against wild type and omicron within 98 days after the third homologous boosting shot of inactivated SARS-CoV-2 vaccine (BBIBP-CorV or CoronaVac) in 141 healthy adults in a prospective, open-label study. High-performance liquid chromatography-tandem mass spectroscopy was used to determine the concentrations of plasma vitamins A, D, and E. Results: We found that the anti-wide-type virus and anti-omicron variant antibody levels significantly increased compared with baseline antibody levels (P < 0.001) after the third vaccination. 25(OH)D3 was significantly negatively associated with the baseline anti-wide-type virus antibody concentrations [beta (95% CI) = -0.331 (-0.659 ~ -0.003)] after adjusting for covariates. A potentially similar association was also observed on day 98 after the third vaccination [beta (95% CI) = -0.317 (-0.641 ~ 0.007)]. After adjusting for covariates, we also found that 25(OH)D3 was significantly negatively associated with the seropositivity of the anti-omicron variant antibody at day 98 after the third vaccination [OR (95% CI) = 0.940 (0.883 ~ 0.996)]. The association between plasma 25(OH)D3 with anti-wild-type virus antibody levels and seropositivity of anti-omicron variant antibodies were persistent in subgroup analyses. We observed no association between retinol/α-tocopherol and anti-wide-type virus antibody levels or anti-omicron variant antibody seropositive in our study. Conclusion: The third inactivated SARS-CoV-2 vaccination significantly improved the ability of anti-SARS-CoV-2 infection in the human body. Higher vitamin D concentrations could significantly decrease the anti-wide-type virus-neutralizing antibody titers and anti-omicron variant antibody seropositive rate after the inactivated SARS-CoV-2 vaccination in people with adequate levels of vitamin D, better immune status, and stronger immune response; further studies comprising large cohorts of patients with different nutritional status are warranted to verify our results.

6.
JAMA Neurol ; 80(5): 455-461, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36912851

ABSTRACT

Importance: Cross-sectional evidence implicates high prevalent frailty in patients with Parkinson disease (PD), whereas the longitudinal association remains unknown. Objectives: To examine the longitudinal association of the frailty phenotype with the development of PD and to explore the modification role of genetic risk of PD in such an association. Design, Setting, and Participants: This prospective cohort study launched in 2006 to 2010 with a follow-up of 12 years. Data were analyzed from March 2022 to December 2022. The UK Biobank recruited over 500 000 middle-aged and older adults from 22 assessment centers across the United Kingdom. Participants who were younger than 40 years (n = 101), diagnosed with dementia or PD at baseline, and developed dementia, PD, or died within 2 years from baseline were excluded (n = 4050). Participants who had no genetic data or mismatch between genetic sex and reported gender (n = 15 350), were not of self-reported British White descent (n = 27 850), and had no data for frailty assessment (n = 100 450) or any covariates were also excluded (n = 39 706). The final analysis included 314 998 participants. Exposures: The physical frailty was assessed by the Fried criteria's frailty phenotype through 5 domains, ie, weight loss, exhaustion, low physical activity, slow walking speed, and low grip strength. The polygenic risk score (PRS) for PD comprised 44 single-nucleotide variants. Main Outcomes and Measures: New-onset PD was identified through the hospital admission electronic health records and death register. Results: Among 314 998 participants (mean age, 56.1 years; 49.1% male), 1916 new-onset PD cases were documented. Compared with nonfrailty, the hazard ratio (HR) of incident PD in prefrailty and frailty was 1.26 (95% CI, 1.15-1.39) and 1.87 (95% CI, 1.53-2.28), respectively, and the absolute rate difference per 100 000 person-years was 1.6 (95% CI, 1.0-2.3) for prefrailty and 5.1 (95% CI, 2.9-7.3) for frailty. Exhaustion (HR, 1.41; 95% CI, 1.22-1.62), slow gait speed (HR, 1.32; 95% CI, 1.13-1.54), low grip strength (HR, 1.27; 95% CI, 1.13-1.43), and low physical activity (HR, 1.12; 95% CI, 1.00-1.25) were associated with incident PD. A significant interaction between frailty and PRS on PD was found and the highest hazard was observed in participants with frailty and high genetic risk. Conclusions and Relevance: Physical prefrailty and frailty were associated with incident PD independent of sociodemographic factors, lifestyles, multiple morbidities, and genetic background. These findings may have implications for the assessment and management of frailty for PD prevention.


Subject(s)
Dementia , Frailty , Parkinson Disease , Male , Humans , Aged , Female , Frailty/epidemiology , Frailty/genetics , Frail Elderly , Genetic Predisposition to Disease/genetics , Prospective Studies , Parkinson Disease/epidemiology , Parkinson Disease/genetics , Cross-Sectional Studies
7.
Nutrients ; 14(14)2022 Jul 19.
Article in English | MEDLINE | ID: mdl-35889910

ABSTRACT

Plasma transthyretin may be engaged in glucose regulation. We aimed to investigate the association between plasma transthyretin levels and the risk of newly diagnosed T2DM and impaired glucose regulation (IGR) in a Chinese population. We conducted a case-control study including 1244 newly diagnosed T2DM patients, 837 newly diagnosed IGR patients, and 1244 individuals with normal glucose tolerance (NGT) matched by sex and age. Multivariate logistic regression analysis was utilized to estimate the independent association of plasma transthyretin concentrations with the risk of T2DM and IGR. Plasma transthyretin concentrations were significantly higher in T2DM and IGR patients compared with control subjects (p < 0.005). After multiple adjustment and comparison with the lowest quartile of plasma transthyretin concentrations, the odds ratios (95% confidence intervals) of T2DM and IGR in the highest quartile were 2.22 (1.66, 2.98) and 2.29 (1.72, 3.05), respectively. Plasma transthyretin concentrations also showed a great performance in predicting the risk of T2DM (AUC: 0.76). Moreover, a potential nonlinear trend was observed. Our results demonstrated that higher plasma transthyretin concentrations, especially more than 290 mg/L, were associated with an increased risk of T2DM and IGR. Further studies are warranted to confirm our findings and elucidate the potential mechanisms.


Subject(s)
Diabetes Mellitus, Type 2 , Glucose Intolerance , Blood Glucose/analysis , Case-Control Studies , China/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Glucose , Glucose Intolerance/epidemiology , Humans , Prealbumin/analysis
8.
Front Nutr ; 9: 836115, 2022.
Article in English | MEDLINE | ID: mdl-35600822

ABSTRACT

Background: Limited studies have explored the difference of fatty acid profile between women with and without gestational diabetes mellitus (GDM), and the results were inconsistent. Individual fatty acids tend to be interrelated because of the shared food sources and metabolic pathways. Thus, whether fatty acid patters during pregnancy were related to GDM odds needs further exploration. Objective: To identify plasma fatty acid patters during pregnancy and their associations with odds of GDM. Methods: A hospital-based case-control study including 217 GDM cases and 217 matched controls was carried out in urban Wuhan, China from August 2012 to April 2015. All the participants were enrolled at the time of GDM screening and provided fasting blood samples with informed consent. We measured plasma concentrations of fatty acids by gas chromatography-mass spectrometry, and derived potential fatty acid patterns (FAPs) through principal components analysis. Conditional logistic regression and restricted cubic spline model were used to evaluate the associations between individual fatty acids or FAPs and odds of GDM. Results: Twenty individual fatty acids with relative concentrations ≥0.05% were included in the analyses. Compared with control group, GDM group had significantly higher concentrations of total fatty acids, 24:1n-9, and relatively lower levels of 14:0, 15:0, 17:0, 18:0, 24:0, 16:1n-7, 20:1n-9,18:3n-6, 20:2n-6, 18:3n-3, 20:3n-3, 22:5n-3. Two novel patterns of fatty acids were identified to be associated with lower odds of GDM: (1) relatively higher odd-chain fatty acids, 14:0, 18:0, 18:3n-3, 20:2n-6, 20:3n-6 and lower 24:1n-9 and 18:2n-6 [adjusted odds ratio (OR) (95% confidence interval) (CI) for quartiles 4 vs. 1: 0.42 (0.23-0.76), P-trend = 0.002], (2) relatively higher n-3 polyunsaturated fatty acids, 24:0, 18:3n-6 and lower 16:0 and 20:4n-6 [adjusted OR (95% CI) for quartiles 4 vs. 1: 0.48 (0.26-0.90), P-trend = 0.018]. Conclusion: Our findings suggested that two novel FAPs were inversely associated with GDM odds. The combination of circulating fatty acids could be a more significant marker of GDM development than individual fatty acids or their subgroups.

9.
Eur J Nutr ; 61(6): 3247-3254, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35459972

ABSTRACT

PURPOSE: Whole-grain intake assessed through self-reported methods has been suggested to be inversely associated with the metabolic syndrome (MetS) risk in epidemiological studies. However, few studies have evaluated the association between whole-grain intake and MetS risk using objective biomarkers of whole-grain intake. The aim of this study was to examine the association between plasma 3-(3,5-Dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, and MetS risk in a Chinese population. METHODS: A case-control study of 667 MetS cases and 667 matched controls was conducted based on baseline data of the Tongji-Ezhou Cohort study. Plasma DHPPA concentrations were assessed by high-performance liquid chromatography-tandem mass spectrometry. The MetS was defined based on criteria set by the Joint Interim Statement. RESULTS: Plasma DHPPA was inversely associated with MetS risk. After adjustment for age, sex, body mass index, smoking status, alcohol drinking status, physical activity and education level, the odds ratios (ORs) for MetS across increasing quartiles of plasma DHPPA concentrations were 1 (referent), 0.86 (0.58-1.26), 0.77 (0.52-1.15), and 0.59 (0.39-0.89), respectively. In addition, the cubic spline analysis revealed a potential nonlinear association between plasma DHPPA and MetS, with a steep reduction in the risk at the lower range of plasma DHPPA concentration. CONCLUSION: Our study revealed that individuals with higher DHPPA concentrations in plasma had lower odds of MetS compared to those with lower DHPPA concentrations in plasma. Our findings provided further evidence to support health benefits of whole grain consumption.


Subject(s)
Metabolic Syndrome , Whole Grains , Biomarkers , Case-Control Studies , Cohort Studies , Humans , Metabolic Syndrome/epidemiology , Phenylpyruvic Acids , Resorcinols , Secale/chemistry , Triticum/chemistry
10.
J Nutr ; 152(4): 1052-1058, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35091747

ABSTRACT

BACKGROUND: Epidemiologic studies consistently find associations between whole-grain intake and reduced risk of obesity and related metabolic diseases, yet data on the potential of whole grains to prevent fatty liver diseases are scarce. OBJECTIVES: To examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with nonalcoholic fatty liver disease (NAFLD). METHODS: This case-control study of Chinese adults enrolled 940 NAFLD cases and 940 age- and sex-matched non-NAFLD controls (mean age: 55.2 y; 65% males). NAFLD diagnosis was defined as individuals whose hepatic ultrasound disclosed hepatic steatosis at any stage, after the exclusion of alcohol abuse and other liver diseases. Fasting plasma DHPPA concentration was measured by LC-MS/MS. Multivariate adjusted ORs and 95% CIs were estimated to assess the association between plasma DHPPA and NAFLD using conditional logistic regression. RESULTS: Plasma concentration of DHPPA was significantly lower in patients with NAFLD compared with controls (median: 9.86 nmol/L compared with 10.9 nmol/L, P = 0.002). In multivariable logistic regression models, the ORs (95% CIs) for NAFLD across increasing tertiles of plasma DHPPA were 1 (reference), 0.76 (0.54, 1.05), and 0.65 (0.45, 0.93), respectively (P-trend = 0.026). In addition, the inverse associations persisted in subgroups stratified by sex, age, BMI, abdominal adiposity, smoking status, physical activity, diabetes, hypertension, and hyperlipidemia. CONCLUSIONS: These results indicate that increased plasma DHPPA concentration is associated with lower risk of NAFLD in Chinese adults, independently of well-known risk factors. Our finding provides evidence to support health benefits of whole-grain consumption on NAFLD. This trial was registered at clinicaltrials.gov as NCT03845868.


Subject(s)
Non-alcoholic Fatty Liver Disease , Adult , Biomarkers , Case-Control Studies , China/epidemiology , Chromatography, Liquid , Female , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/epidemiology , Resorcinols , Risk Factors , Secale , Tandem Mass Spectrometry , Whole Grains
11.
J Nutr ; 152(4): 1052-1058, 2022 04.
Article in English | MEDLINE | ID: mdl-36967162

ABSTRACT

BACKGROUND: Epidemiologic studies consistently find associations between whole-grain intake and reduced risk of obesity and related metabolic diseases, yet data on the potential of whole grains to prevent fatty liver diseases are scarce. OBJECTIVES: To examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with nonalcoholic fatty liver disease (NAFLD). METHODS: This case-control study of Chinese adults enrolled 940 NAFLD cases and 940 age- and sex-matched non-NAFLD controls (mean age: 55.2 y; 65% males). NAFLD diagnosis was defined as individuals whose hepatic ultrasound disclosed hepatic steatosis at any stage, after the exclusion of alcohol abuse and other liver diseases. Fasting plasma DHPPA concentration was measured by LC-MS/MS. Multivariate adjusted ORs and 95% CIs were estimated to assess the association between plasma DHPPA and NAFLD using conditional logistic regression. RESULTS: Plasma concentration of DHPPA was significantly lower in patients with NAFLD compared with controls (median: 9.86 nmol/L compared with 10.9 nmol/L, P = 0.002). In multivariable logistic regression models, the ORs (95% CIs) for NAFLD across increasing tertiles of plasma DHPPA were 1 (reference), 0.76 (0.54, 1.05), and 0.65 (0.45, 0.93), respectively (P-trend = 0.026). In addition, the inverse associations persisted in subgroups stratified by sex, age, BMI, abdominal adiposity, smoking status, physical activity, diabetes, hypertension, and hyperlipidemia. CONCLUSIONS: These results indicate that increased plasma DHPPA concentration is associated with lower risk of NAFLD in Chinese adults, independently of well-known risk factors. Our finding provides evidence to support health benefits of whole-grain consumption on NAFLD. This trial was registered at clinicaltrials.gov as NCT03845868.


Subject(s)
Non-alcoholic Fatty Liver Disease , Whole Grains , Adult , Female , Humans , Male , Middle Aged , Biomarkers , Case-Control Studies , Chromatography, Liquid , East Asian People , Non-alcoholic Fatty Liver Disease/epidemiology , Resorcinols , Risk Factors , Tandem Mass Spectrometry
12.
Chemosphere ; 267: 129224, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33341733

ABSTRACT

AIMS: We aimed to investigate the association of plasma cobalt with newly diagnosed type 2 diabetes (T2D) and further explore the potential interaction effects between cobalt and several redox metals, such as manganese, copper and selenium. DESIGN: A large case-control study including 4564 subjects was conducted. 2282 cases with newly diagnosed T2D and 2282 controls were matched by sex and age. The concentrations of cobalt and other metals in plasma were detected with inductively coupled plasma mass spectrometry (ICPMS). RESULTS: The medians of the cobalt concentrations in plasma were 1.68 µg/dL for controls and T2D. There was a U-shaped relation between T2D and plasma cobalt, which was categorized into quartiles. After multivariable adjusted for the confounding factors, the odds ratios (ORs) of T2D across quartiles were 1.22 (95% CI: 1.01, 1.46), 1.12 (95% CI: 0.94, 1.35), 1.00 (reference) and 1.46 (95% CI: 1.22, 1.75), respectively. The association was almost consistent in subgroup analyses. According to the restricted cubic spline analysis, the lowest ORs of T2D was observed at the plasma cobalt of 2.00 µg/dL. There was a significant interaction between plasma cobalt and copper (P < 0.01). The ORs of T2D in those with medium concentration of plasma cobalt and copper was the lowest. CONCLUSIONS: Higher or lower concentrations of plasma cobalt were related to higher ORs of T2D. The inter-relationship among redox metals in T2D should be further investigated.


Subject(s)
Cobalt , Diabetes Mellitus, Type 2 , Humans , Case-Control Studies , Cobalt/blood , Metals/blood , Plasma
13.
Diabetes Res Clin Pract ; 171: 108542, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33227361

ABSTRACT

OBJECTIVE: Circulating uric acid levels were associated with insulin resistance, but the causality is unclear. We aimed to investigate the association between plasma uric acid and insulin resistance in newly diagnosed type 2 diabetes (T2D). METHODS: We enrolled 1,938 patients who underwent a 75-g oral glucose tolerance test. Insulin resistance was estimated based on the homeostatic model assessment index (HOMA2-IR) and the Matsuda index. Uric acid was measured in fasting plasma by uricase-peroxidase method. We genotyped single nucleotide polymorphisms (SNPs) that were recently identified as top hits in genome-wide association studies of uric acid levels. A weighted genetic risk score (wGRS) was calculated based on the associations between selected SNPs and uric acid levels. RESULTS: The adjusted ß coefficients for Ln-transformed Matsuda index and HOMA2-IR per 1 mg/dL uric acid increment were -0.070 (95%CI: -0.089, -0.052) and 0.057 (95%CI: 0.039, 0.075). These associations were more pronounced among women than men. In Mendelian randomization analysis, the wGRS raised uric acid by 0.225 mg/dL (95%CI: 0.138, 0.312) per SD increase of the score. However, no association was observed between the wGRS and insulin resistance indices whether in men or women. CONCLUSIONS: Elevated plasma uric acid was associated with higher risk of insulin resistance, along with observation of gender difference in such association. However, our study does not support a causal role of plasma uric acid on insulin resistance among newly diagnosed T2D patients.


Subject(s)
Diabetes Mellitus, Type 2/blood , Insulin Resistance/genetics , Mendelian Randomization Analysis/methods , Uric Acid/adverse effects , Female , Genotype , Humans , Male , Middle Aged , Uric Acid/blood
14.
J Atheroscler Thromb ; 28(4): 320-328, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-32641646

ABSTRACT

AIM: We aimed to investigate the relationship of trimethylamine N-oxide (TMAO) concentrations with ischemic stroke in a large-scale case-control study conducted among the hospital-based general population. METHODS: We recruited 953 case-control sex- and age-matched pairs, and cases were confined to first acute ischemic stroke in this study. Fasting plasma TMAO was measured using high-performance liquid chromatography-tandem mass spectroscopy. Conditional logistic regression analysis was conducted to calculate odds ratios (OR) for the association of plasma TMAO with ischemic stroke. RESULTS: We found that plasma TMAO concentrations in patients with ischemic stroke were significantly higher than that in the control group (median: 2.85 µmol/L vs. 2.33 µmol/L, P<0.001). In multivariable conditional logistic regression models, higher plasma TMAO concentrations were associated with increased odds of ischemic stroke [fully adjusted OR for highest vs. lowest TMAO quartile: 1.81; 95% confidence interval (CI): 1.27, 2.59; P for trend <0.001]. The multivariable-adjusted OR for ischemic stroke per 1 µmol/L increment of plasma TMAO was 1.05 (95% CI: 1.02, 1.08). Additionally, the positive association also persisted in subgroups stratified by age, sex, body mass index, smoking status, alcohol habits, history of diabetes, and history of hypertension. CONCLUSIONS: This study suggested a positive association between plasma TMAO and ischemic stroke. Further studies are required to explore the role of plasma TMAO concentrations in predicting stroke risk.


Subject(s)
Ischemic Stroke , Methylamines/blood , Age Factors , Alcohol Drinking/epidemiology , Body Mass Index , Case-Control Studies , China/epidemiology , Chromatography, Liquid/methods , Correlation of Data , Diabetes Mellitus/epidemiology , Female , Humans , Hypertension/epidemiology , Ischemic Stroke/blood , Ischemic Stroke/diagnosis , Ischemic Stroke/epidemiology , Male , Middle Aged , Risk Factors , Sex Factors , Smoking/epidemiology , Tandem Mass Spectrometry/methods
15.
Oxid Med Cell Longev ; 2020: 5343014, 2020.
Article in English | MEDLINE | ID: mdl-32377302

ABSTRACT

The relationship between selenium and metabolic syndrome (MetS) has been discussed controversially, and limited studies have examined the associations of single nucleotide polymorphisms in selenoproteins genes with MetS. Hence, to examine the associations of plasma selenium concentrations and selenoprotein P rs7579 polymorphism with MetS, a case-control study of 1279 MetS cases and 1279 sex- and age- (±2 years) matched controls was conducted based on the baseline data of the Tongji-Ezhou Cohort study. Plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry. MetS was defined using the definition of the Joint Interim Statement, adjusted for the Chinese population. In addition, the rs7579 polymorphism was genotyped by the Agena MassARRAY System. Plasma selenium concentrations in the MetS group were higher than in the control group (93.88 µg/L (83.17-107.41) vs. 92.66 µg/L (82.36-103.53), P < 0.05). Compared with quartile 4 (≥103.53 µg/L), the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) associated with MetS were 0.79 (0.59-1.06) for quartile 1 (<82.36 µg/L), 0.75 (0.56-1.01) for quartile 2 (82.37-92.66 µg/L), and 0.61 (0.45-0.83) for quartile 3 (92.67-103.52 µg/L). The cubic spline analyses revealed a U-shaped association between plasma selenium and MetS, with the lowest risk at around 93.69 µg/L. Moreover, in cubic spline analyses, plasma selenium showed U-shaped associations with central obesity and high blood pressure, positive associations with hypertriglyceridemia and hyperglycemia, and a negative association with low high-density lipoprotein cholesterol. Additionally, both the GA and GA+AA genotype carriers were associated with increased ORs of MetS comparing with the GG genotype carriers. Our findings suggested a U-shaped association between plasma selenium and MetS and diverse associations between plasma selenium and components of MetS. Furthermore, our study found that the A allele of rs7579 was associated with higher odds of MetS. Further studies are needed to confirm our findings and elucidate the underlying mechanisms.


Subject(s)
Metabolic Syndrome/genetics , Polymorphism, Genetic/genetics , Polymorphism, Single Nucleotide/genetics , Selenium/blood , Selenoprotein P/blood , Case-Control Studies , Female , Humans , Male , Middle Aged , Risk Factors
16.
Diabetologia ; 63(5): 954-963, 2020 05.
Article in English | MEDLINE | ID: mdl-32034441

ABSTRACT

AIMS/HYPOTHESIS: There is evidence for a bidirectional association between type 2 diabetes and Alzheimer's disease. Plasma ß-amyloid (Aß) is a potential biomarker for Alzheimer's disease. We aimed to investigate the association of plasma Aß40 and Aß42 with risk of type 2 diabetes. METHODS: We performed a case-control study and a nested case-control study within a prospective cohort study. In the case-control study, we included 1063 newly diagnosed individuals with type 2 diabetes and 1063 control participants matched by age (±3 years) and sex. In the nested case-control study, we included 121 individuals with incident type 2 diabetes and 242 matched control individuals. Plasma Aß40 and Aß42 concentrations were simultaneously measured with electrochemiluminescence immunoassay. Conditional logistic regression was used to evaluate the association of plasma Aß40 and Aß42 concentrations with the likelihood of type 2 diabetes. RESULTS: In the case-control study, the multivariable-adjusted ORs for type 2 diabetes, comparing the highest with the lowest quartile of plasma Aß concentrations, were 1.97 (95% CI 1.46, 2.66) for plasma Aß40 and 2.01 (95% CI 1.50, 2.69) for plasma Aß42. Each 30 ng/l increment of plasma Aß40 was associated with 28% (95% CI 15%, 43%) higher odds of type 2 diabetes, and each 5 ng/l increment of plasma Aß42 was associated with 37% (95% CI 21%, 55%) higher odds of type 2 diabetes. Individuals in the highest tertile for both plasma Aß40 and Aß42 concentrations had 2.96-fold greater odds of type 2 diabetes compared with those in the lowest tertile for both plasma Aß40 and Aß42 concentrations. In the nested case-control study, the multivariable-adjusted ORs for type 2 diabetes for the highest vs the lowest quartile were 3.79 (95% CI 1.81, 7.94) for plasma Aß40 and 2.88 (95% CI 1.44, 5.75) for plasma Aß42. The multivariable-adjusted ORs for type 2 diabetes associated with each 30 ng/l increment in plasma Aß40 and each 5 ng/l increment in plasma Aß42 were 1.44 (95% CI 1.18, 1.74) and 1.47 (95% CI 1.15, 1.88), respectively. CONCLUSIONS/INTERPRETATION: Our findings suggest positive associations of plasma Aß40 and Aß42 concentration with risk of type 2 diabetes. Further studies are warranted to elucidate the underlying mechanisms and explore the potential roles of plasma Aß in linking type 2 diabetes and Alzheimer's disease.


Subject(s)
Amyloid beta-Peptides/blood , Diabetes Mellitus, Type 2/blood , Adult , Biomarkers/blood , Case-Control Studies , China , Female , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies
17.
Am J Clin Nutr ; 110(2): 525-526, 2019 08 01.
Article in English | MEDLINE | ID: mdl-31367764
18.
Am J Clin Nutr ; 109(2): 1-7, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30753322

ABSTRACT

Background: Epidemiologic studies on whole grains and risk of stroke have reported inconsistent results, with some suggesting a protective effect but others showing a null association. Objectives: The aim of this study was to examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with risk of ischemic stroke. Methods: A hospital-based case-control study was conducted between March 2011 and May 2016. Cases (n = 990) with first ischemic stroke were matched to controls (n = 990) by sex and age. Concentrations of plasma DHPPA were determined by high-performance liquid chromatography-tandem mass spectrometry. We calculated ORs for the association of plasma DHPPA concentrations with ischemic stroke risk through the use of logistic regression. Results: Plasma DHPPA was inversely associated with ischemic stroke risk. After adjustment for potential confounding factors, the ORs for ischemic stroke across increasing quartiles of plasma DHPPA concentrations were 1 (referent), 0.76 (95% CI: 0.58, 0.99), 0.71 (95% CI: 0.54, 0.92), and 0.59 (95% CI: 0.45, 0.77), respectively (P-trend = 0.001). The inverse association was also observed in all subgroups of participants according to sex, age, body mass index, smoking status, alcohol consumption, history of hypertension, and history of diabetes. Conclusions: Our study showed that higher plasma DHPPA concentrations were associated with lower risk of ischemic stroke. This finding provides further evidence to support the health benefits of whole-grain consumption.


Subject(s)
Diet , Propionates/blood , Resorcinols/blood , Secale/chemistry , Stroke/blood , Triticum/chemistry , Whole Grains/chemistry , Aged , Biomarkers/blood , Brain Ischemia/blood , Brain Ischemia/prevention & control , Case-Control Studies , Dietary Fiber/administration & dosage , Dietary Fiber/therapeutic use , Feeding Behavior , Female , Humans , Logistic Models , Male , Middle Aged , Phenylpropionates/blood , Stroke/prevention & control
19.
Clin Nutr ; 38(6): 2922-2927, 2019 12.
Article in English | MEDLINE | ID: mdl-30661907

ABSTRACT

BACKGROUND & AIMS: Emerging findings have raised concerns about significant associations between excessive copper (Cu) and abnormal glucose metabolism. Nevertheless, related researches on the relationship of Cu concentration and gestational diabetes mellitus (GDM) are limited. The objective of this study was to determine whether plasma Cu concentration is associated with GDM. METHODS: A case-control study of 248 cases of GDM and 248 age-, parity- and gestational age-matched controls was conducted in Wuhan, China between August 2012 and April 2015. Fasting blood samples of participants were collected at the time of GDM screening (≥24 weeks of gestation). Plasma Cu concentrations were detected by inductively coupled plasma mass spectrometry. The strength of the association of plasma Cu with GDM odds was evaluated by odds ratios (ORs) with 95% confidence intervals (CIs) from conditional logistic regression. Partial Spearman or Pearson correlation coefficients were calculated to estimate the interrelationship between plasma Cu and the risk factors of GDM. RESULTS: Plasma Cu concentrations in the GDM group (mean ± SD: 1960.24 ± 391.98 µg/L) were higher than in the control group (mean ± SD: 1842.43 ± 387.09 µg/L) (P = 0.001). After adjustment for possible confounders, the ORs (95% CIs) of GDM across increasing quartiles of plasma Cu levels were 1.00 (referent), 1.79 (0.90-3.55), 2.72 (1.35-5.48) and 2.91 (1.48-5.75), respectively; the OR (95% CI) of GDM was 1.33 (1.06-1.67) for each standard deviation increment of plasma Cu. Moreover, Cu concentrations were positively associated with fasting plasma glucose, 1-h post-glucose load and 2-h post-glucose load (all P < 0.05). CONCLUSIONS: The present study indicated a significantly increased odds of GDM in association with higher concentrations of plasma Cu. Prospective cohort studies in other populations are needed to confirm our findings.


Subject(s)
Copper/blood , Diabetes, Gestational/blood , Diabetes, Gestational/epidemiology , Adult , Case-Control Studies , China/epidemiology , Female , Humans , Pregnancy
20.
Am J Clin Nutr ; 108(3): 603-610, 2018 09 01.
Article in English | MEDLINE | ID: mdl-30535087

ABSTRACT

Background: The microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) has been reported as a novel and independent risk factor for the development of cardiovascular and metabolic diseases, but the association with gestational diabetes mellitus (GDM) remains unclear. Objective: The aim of this study was to investigate the association between plasma TMAO concentration and GDM in a 2-phase study. Design: A 2-phase design was used in the current study. An initial phase included 866 participants (433 GDM cases and 433 matched controls) with fasting blood samples collected at the time of GDM screening (24-32 wk of gestation). An independent-phase study, with 276 GDM cases and 552 matched controls who provided fasting blood samples before 20 wk of gestation and who had GDM screened during 24-32 wk of gestation, was nested within a prospective cohort study. These 2 studies were both conducted in Wuhan, China, and the incidence of GDM in the cohort study was 10.8%. Plasma TMAO concentrations were determined by stable isotope dilution liquid chromatography-tandem mass spectrometry. GDM was diagnosed according to the American Diabetes Association criteria by using an oral-glucose-tolerance test. Results: In the initial case-control study, the adjusted OR of GDM comparing the highest TMAO quartile with the lowest quartile was 1.94 (95% CI: 1.28, 2.93). Each SD increment of ln-transformed plasma TMAO was associated with 22% (95% CI: 5%, 41%) higher odds of GDM. In the nested case-control study, women in the highest quartile also had increased odds of GDM (adjusted OR: 2.06; 95% CI: 1.28, 3.31) compared with women in the lowest quartile, and the adjusted OR for GDM per SD increment of ln-transformed plasma TMAO was 1.26 (95% CI: 1.08, 1.47). Conclusions: Consistent findings from this 2-phase study indicate a positive association between plasma TMAO concentrations and GDM. Future studies are warranted to elucidate the underlying mechanisms. This trial was registered at www.clinicaltrials.gov as NCT03415295.


Subject(s)
Diabetes, Gestational/blood , Methylamines/blood , Adult , Case-Control Studies , Cohort Studies , Fasting , Female , Gestational Age , Glucose Tolerance Test , Humans , Odds Ratio , Pregnancy , Prospective Studies , Risk Factors
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