Discovery and comparison of serum biomarkers for diabetes mellitus and metabolic syndrome based on UPLC-Q-TOF/MS

Li, Xuan; Gao, Xuelu; Zhang, Rui; Zi-yan, Liu; Shen, Na; Di, Yanbo; Fang, Tao; Li, Huanming; Tian, Fengshi

doi:10.1016/j.clinbiochem.2020.03.007

Cited by 24 publications

(20 citation statements)

References 34 publications

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“…In NHANES 1999–2004, MMA independently predicted all-cause and cause-specific mortality [ 29 ]. MMA levels were also associated with insulin resistance and metabolic syndrome [ 24 , 30 ], and this was confirmed with our study that MMA was associated with the risk of hypertension ( Table S3 ). Nevertheless, the relationship between MMA and NAFLD or NASH has not been investigated previously.…”

Section: Discussionsupporting

confidence: 88%

The Association between Non-Alcoholic Fatty Liver Disease (NAFLD) and Advanced Fibrosis with Serological Vitamin B12 Markers: Results from the NHANES 1999–2004

Huang

Yang

et al. 2022

Nutrients

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Background: There is evidence that vitamin B12 and associated metabolite levels are changed in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH); however, their association has been in dispute. Methods: We included 8397 individuals without previous liver condition or excess alcohol intake from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. NAFLD was diagnosed with Fatty Liver Index (FLI) ≥ 60 or USFLI ≥ 30, and participants with advanced fibrosis risks were identified with elevated non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis 4 index (FIB-4), or aspartate aminotransferase (AST)/platelet ratio index (APRI). Step-wide logistic regression adjusting for confounders was used to detect the association between NAFLD or advanced fibrosis with serum vitamin B12, folate, red blood cell folate (RBC folate), homocysteine (HCY), and methylmalonic acid (MMA). Results: The weighted prevalence of NAFLD was 44.2%. Compared with non-NAFLD participants, patients with NAFLD showed significantly increased RBC folate level and RBC counts, decreased serum vitamin B12 and folate, and similar HCY and MMA levels. NAFLD with advanced fibrosis risk had higher MMA and HCY, reduced serum vitamin B12, and similar serum folate and RBC folate levels than NAFLD with low fibrosis risk. Only RBC folate was independently associated with an increased risk of NAFLD (OR (95% CI): 2.24 (1.58, 3.18)). In all participants, MMA (OR: 1.41 (1.10, 1.80)) and HCY (OR: 2.76 (1.49, 5.11)) were independently associated with increased risk for advanced fibrosis. In participants with NAFLD, this independent association still existed (OR: 1.39 (1.04, 1.85) for MMA and 1.95 (1.09, 3.46) for HCY). In all patients, the area under the receiver operating characteristic curve (ROC AUC) on fibrosis was 0.6829 (0.6828, 0.6831) for MMA and 0.7319 (0.7318, 0.7320) for HCY; in participants with NAFLD, the corresponding ROC AUC was 0.6819 (0.6817, 0.6821) for MMA and 0.6926 (0.6925, 0.6928) for HCY. Conclusion: Among vitamin B12-associated biomarkers, RBC folate was independently associated with elevated NAFLD risk, whereas MMA and HCY were associated with increased risk for advanced fibrosis in the total population and NAFLD participants. Our study highlighted the clinical diagnostic value of vitamin B12 metabolites and the possibility that vitamin B12 metabolism could be a therapeutic target for NASH. Further studies using recent perspective data with biopsy proven NASH could be conducted to validate our results.

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Section: Discussionsupporting

confidence: 88%

The Association between Non-Alcoholic Fatty Liver Disease (NAFLD) and Advanced Fibrosis with Serological Vitamin B12 Markers: Results from the NHANES 1999–2004

Huang

Yang

et al. 2022

Nutrients

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“…α-Aminobutyric acid is one of three isomers of aminobutyric acid that is also known as homoalanine, which is a metabolite of isoleucine biosynthesis. Isoleucine has been reported as a biomarker for the risk of T2DM and metabolic syndrome [20,30]. The exact relationship between isoleucine and α-aminobutyrate as biomarkers is unclear, but to our knowledge, α-aminobutyrate has not been previously reported to be correlated with insulin or incretin levels.…”

Section: Discussionmentioning

confidence: 86%

Glycemic Control and Metabolic Adaptation in Response to High-Fat versus High-Carbohydrate Diets—Data from a Randomized Cross-Over Study in Healthy Subjects

et al. 2021

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Granular study of metabolic responses to alterations in the ratio of dietary macro-nutrients can enhance our understanding of how dietary modifications influence patients with impaired glycemic control. In order to study the effect of diets enriched in fat or carbohydrates, fifteen healthy, normal-weight volunteers received, in a cross-over design, and in a randomized unblinded order, two weeks of an iso-caloric high-fat diet (HFD: 60E% from fat) and a high-carbohydrate diet (HCD: 60E% from carbohydrates). A mixed meal test (MMT) was performed at the end of each dietary period to examine glucose clearance kinetics and insulin and incretin hormone levels, as well as plasma metabolomic profiles. The MMT induced almost identical glycemia and insulinemia following the HFD or HCD. GLP-1 levels were higher after the HFD vs. HCD, whereas GIP did not differ. The HFD, compared to the HCD, increased the levels of several metabolomic markers of risk for the development of insulin resistance, e.g., branched-chain amino acid (valine and leucine), creatine and α-hydroxybutyric acid levels. In normal-weight, healthy volunteers, two weeks of the HFD vs. HCD showed similar profiles of meal-induced glycemia and insulinemia. Despite this, the HFD showed a metabolomic pattern implying a risk for a metabolic shift towards impaired insulin sensitivity in the long run.

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“…VIP value > 1 and P < 0.05 were considered statistically significant. KEGG pathway annotation was performed as previously reported ( 23 ). Fisher’s Exact Test was used to analyze and calculate the significance level of the enrichment pathway.…”

Section: Methodsmentioning

confidence: 99%

Hormone Replacement Therapy Reverses Gut Microbiome and Serum Metabolome Alterations in Premature Ovarian Insufficiency

et al. 2021

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ObjectiveWe explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI.MethodsFecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman’s rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between Eggerthella and ovarian fibrosis, the mice were inoculated with Eggerthella lenta (E. lenta) through oral gavage.ResultsThe abundance of genus Eggerthella significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-β1 levels; this increase was reversed by HRT. The abundance of Eggerthella was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-β1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by E. lenta in mice.ConclusionsThe interactions between the gut microbiota, serum metabolites, and serum TGF-β1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-β1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.

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Discovery and comparison of serum biomarkers for diabetes mellitus and metabolic syndrome based on UPLC-Q-TOF/MS

Cited by 24 publications

References 34 publications

The Association between Non-Alcoholic Fatty Liver Disease (NAFLD) and Advanced Fibrosis with Serological Vitamin B12 Markers: Results from the NHANES 1999–2004

The Association between Non-Alcoholic Fatty Liver Disease (NAFLD) and Advanced Fibrosis with Serological Vitamin B12 Markers: Results from the NHANES 1999–2004

Glycemic Control and Metabolic Adaptation in Response to High-Fat versus High-Carbohydrate Diets—Data from a Randomized Cross-Over Study in Healthy Subjects

Hormone Replacement Therapy Reverses Gut Microbiome and Serum Metabolome Alterations in Premature Ovarian Insufficiency

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