Metabolomics profiles associated with HbA1c levels in patients with type 2 diabetes

Yun, Jun Ho; Lee, Heun Sik; Yu, Ho Yeong; Kim, Yeon Jung; Jeon, Hyun Jeong; Oh, Tae Jung; Kim, Bong-Jo; Choi, Hyo Geun; Kim, Jeong‐Min

doi:10.1371/journal.pone.0224274

Cited by 15 publications

(14 citation statements)

References 22 publications

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“…9 However, a Korean cohort study did not mention 3-HB. 7 Factors that affect 3-HB are unclear. For the untreated patients with MetS in this study, we suggest that the elevated 3-HB is a result of a compensatory response because they have a ketogenic tendency.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have found higher 3‐HB in the plasma and urine of patients with T2D, including data from a Chinese cohort study 9 . However, a Korean cohort study did not mention 3‐HB 7 . Factors that affect 3‐HB are unclear.…”

Section: Discussionmentioning

confidence: 99%

“…A study based on a cohort in Singapore found higher levels of BCAAs in the blood in subjects with impaired fasting blood glucose (FBG) 5 . However, one study in Japan 6 and another study in Korea 7 got the contradictory results. They found the blood BCAAs were higher in the normal subjects.…”

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confidence: 99%

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Serum Metabolomic Profiles Associated With Untreated Metabolic Syndrome Patients in the Chinese Population

Wang

Zhuang

et al. 2020

Clinical Translational Sci

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Metabolomics is a promising technology for elucidating the mechanisms of metabolic syndrome (MetS). However, measurements in patients with MetS under different conditions vary. Metabolomics experiments in different populations and pathophysiological conditions are, therefore, indispensable. We performed a serum metabolomics investigation in untreated patients with MetS in the Chinese population. Untreated patients with MetS were recruited to this study. Metabolites were measured using a traditional 1H nuclear magnetic resonance (NMR) experiment followed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS‐DA). Key metabolic pathways were identified by searching the Kyoto Encyclopedia of Genes and Genomes Pathway Database. A total of 28 patients with MetS and 30 healthy subjects were enrolled. All patients were untreated because they were unaware of or neglected to treat their MetS. By 1H NMR, we identified 49 known substances. Following PCA and OPLS‐DA, 36 metabolites were confirmed to be closely associated with MetS compared with the control group; 33 metabolites were increased, whereas 3 metabolites were reduced. Importantly, 14 metabolites that changed in the serum of these untreated patients with MetS were previously unreported. Pathway analysis revealed the top 15 metabolic pathways associated with untreated MetS, which included 3 amino acid metabolic pathways. Our data suggest that untreated patients exhibit a worse pathophysiologic manifestation, which may result in more rapid progression of MetS. Thus, we propose that health education be reinforced to improve the public’s knowledge, attitude, and practice regarding MetS. The rates of “untreated” patients due to unawareness and neglect must be reduced immediately.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Serum Metabolomic Profiles Associated With Untreated Metabolic Syndrome Patients in the Chinese Population

Wang

Zhuang

et al. 2020

Clinical Translational Sci

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“…Metabolites with significant differences in their concentrations in the different analysis groups were identified. All procedures were performed as described previously [ 16 , 17 ]. Briefly, the serum samples were analyzed using the API 4000 QTRAP LC/MS/MS system (Applied Biosystems, Foster City, CA, USA) and the Agilent 1200 HPLC system (Agilent Technologies, Santa Clara, CA, USA), following the manufacturers’ instructions.…”

Section: Methodsmentioning

confidence: 99%

Metabolomics profiles associated with diabetic retinopathy in type 2 diabetes patients

et al. 2020

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Diabetic retinopathy (DR) is a common complication of diabetes, and it is the consequence of microvascular retinal changes due to high glucose levels over a long time. Metabolomics profiling is a rapidly evolving method used to identify the metabolites in biological fluids and investigate disease progression. In this study, we used a targeted metabolomics approach to quantify the serum metabolites in type 2 diabetes (T2D) patients. Diabetes patients were divided into three groups based on the status of their complications: non-DR (NDR, n = 143), non-proliferative DR (NPDR, n = 123), and proliferative DR (PDR, n = 51) groups. Multiple logistic regression analysis and multiple testing corrections were performed to identify the significant differences in the metabolomics profiles of the different analysis groups. The concentrations of 62 metabolites of the NDR versus DR group, 53 metabolites of the NDR versus NPDR group, and 30 metabolites of the NDR versus PDR group were found to be significantly different. Finally, sixteen metabolites were selected as specific metabolites common to NPDR and PDR. Among them, three metabolites including total DMA, tryptophan, and kynurenine were potential makers of DR progression in T2D patients. Additionally, several metabolites such as carnitines, several amino acids, and phosphatidylcholines also showed a marker potential. The metabolite signatures identified in this study will provide insight into the mechanisms underlying DR development and progression in T2D patients in future studies.

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“…In targeted metabolomics, absolute concentrations of a limited number of known metabolites are quantified, giving this method high sensitivity and selectivity [ 10 ]. In T2DM, metabolomics has led to the discovery of several metabolic biomarkers closely related to the occurrence, development and progress of the disease [ 11 ]. Various regulatory pathways, including the regulation of sugar, fat and protein are found to be disturbed in T2DM [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research

et al. 2021

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Oxidative stress plays a key role in the development of chronic diabetes-related complications. Previous metabolomic studies showed a positive association of diabetes and insulin resistance with branched-chain amino acids (AAs) and aromatic AAs. The purpose of this research is to identify distinct metabolic changes associated with increased oxidative stress, as assessed by nitrotyrosine levels, in type 2 diabetes (T2DM). Serum samples of 80 patients with insulin-treated T2DM are analyzed by AA-targeted metabolomics using ultrahigh-performance liquid chromatography/mass spectrometry. Patients are divided into two groups based on their nitrotyrosine levels: the highest level of oxidative stress (Q4 nitrotyrosine) and lower levels (Q1–Q3 nitrotyrosine). The identification of biomarkers is performed in MetaboAnalyst version 5.0 using a t-test corrected for false discovery rate, unsupervised principal component analysis and supervised partial least-squares discriminant analysis (PLS-DA). Four AAs have significantly different levels between the groups for highest and lower oxidative stress. Cysteine, phenylalanine and tyrosine are substantially increased while citrulline is decreased (p-value <0.05 and variable importance in the projection [VIP] >1). Corresponding pathways that might be disrupted in patients with high oxidative stress are phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, phenylalanine metabolism, cysteine and methionine metabolism and tyrosine metabolism.

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Metabolomics profiles associated with HbA1c levels in patients with type 2 diabetes

Cited by 15 publications

References 22 publications

Serum Metabolomic Profiles Associated With Untreated Metabolic Syndrome Patients in the Chinese Population

Serum Metabolomic Profiles Associated With Untreated Metabolic Syndrome Patients in the Chinese Population

Metabolomics profiles associated with diabetic retinopathy in type 2 diabetes patients

Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research

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