Integrated biomarker profiling of the metabolome associated with impaired fasting glucose and type 2 diabetes mellitus in large-scale Chinese patients.
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ABSTRACT:
SUBMITTER: Long J
PROVIDER: S-EPMC8167862 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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Integrated biomarker profiling of the metabolome associated with impaired fasting glucose and type 2 diabetes mellitus in large-scale Chinese patients.
Long Jianglan J Yang Hui H Yang Zhirui Z Jia Qingquan Q Liu Liwei L Kong Lingwei L Cui Huijing H Ding Suying S Qin Qian Q Zhang Nana N Feng Xingzhong X Yan Shuxun S Tang Jinfa J Chen Shuo S Han Yumei Y Jiang Tao T Wen Zhen Z Qi Ningning N Deng Kejun K Sun Zhi Z Lin Hao H Yan Dan D
Clinical and translational medicine 20210601 6
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Project description:BackgroundAround 308 million people worldwide are estimated to have impaired glucose tolerance (IGT); 25% to 75% of these will develop diabetes within a decade of initial diagnosis. At diagnosis, half will have tissue-related damage and all have an increased risk for coronary heart disease.ObjectivesThe objective of this review was to assess the effects and safety of Chinese herbal medicines for the treatment of people with impaired glucose tolerance or impaired fasting glucose (IFG).Search strategyWe searched the following databases: The Cochrane Library, PubMed, EMBASE, AMED, a range of Chinese language databases, SIGLE and databases of ongoing trials.Selection criteriaRandomised clinical trials comparing Chinese herbal medicines with placebo, no treatment, pharmacological or non-pharmacological interventions in people with IGT or IFG were considered.Data collection and analysisTwo authors independently extracted data. Trials were assessed for risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, outcome assessors and intervention providers, incomplete outcome data, selective outcome reporting and other sources of bias.Main resultsThis review examined 16 trials lasting four weeks to two years involving 1391 participants receiving 15 different Chinese herbal medicines in eight different comparisons. No trial reported on mortality, morbidity or costs. No serious adverse events like severe hypoglycaemia were observed. Meta-analysis of eight trials showed that those receiving Chinese herbal medicines combined with lifestyle modification were more than twice as likely to have their fasting plasma glucose levels return to normal levels (i.e. fasting plasma glucose <7.8 mmol/L and 2hr blood glucose <11.1 mmol/L) compared to lifestyle modification alone (RR 2.07; 95% confidence intervall (CI) 1.52 to 2.82). Those receiving Chinese herbs were less likely to progress to diabetes over the duration of the trial (RR 0.33; 95% CI 0.19 to 0.58). However, all trials had a considerable risk of bias and none of the specific herbal medicines comparison data was available from more than one study. Moreover, results could have been confounded by rates of natural reversion to normal glucose levels.Authors' conclusionsThe positive evidence in favour of Chinese herbal medicines for the treatment of IGT or IFG is constrained by the following factors: lack of trials that tested the same herbal medicine, lack of details on co-interventions, unclear methods of randomisation, poor reporting and other risks of bias.
| S-EPMC3191296 | biostudies-literature
Project description:IntroductionMetabolomic signatures of type 2 diabetes mellitus (T2DM) in Tibetan Chinese population, a group with high diabetes burden, remain largely unclear. Identifying the serum metabolite profile of Tibetan T2DM (T-T2DM) individuals may provide novel insights into early T2DM diagnosis and intervention.MethodsHence, we conducted untargeted metabolomics analysis of plasma samples from a retrospective cohort study with 100 healthy controls and 100 T-T2DM patients by using liquid chromatography-mass spectrometry.ResultsThe T-T2DM group had significant metabolic alterations that are distinct from known diabetes risk indicators, such as body mass index, fasting plasma glucose, and glycosylated hemoglobin levels. The optimal metabolite panels for predicting T-T2DM were selected using a tenfold cross-validation random forest classification model. Compared with the clinical features, the metabolite prediction model provided a better predictive value. We also analyzed the correlation of metabolites with clinical indices and found 10 metabolites that were independently predictive of T-T2DM.ConclusionBy using the metabolites identified in this study, we may provide stable and accurate biomarkers for early T-T2DM warning and diagnosis. Our study also provides a rich and open-access data resource for optimizing T-T2DM management.
| S-EPMC10314538 | biostudies-literature
Project description:BACKGROUND The aim of this study was to compare the transcriptome between impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and further research their molecular mechanisms. MATERIAL AND METHODS The original microarray GSE21321, including miRNA and mRNA expression profiles, was downloaded from the GEO database. Data preprocessing was processed by limma package, and differentially expressed genes (DGs) and miRNA (DMs) were screened. Then, the regulatory relationships among miRNA, TF, and genes were screened and the regulatory network was constructed. Finally, DAVID was used for KEGG enrichment analysis. RESULTS There were 11 upregulated IFG-related DMs and five upregulated T2DM-related DMs. Three of the DMs overlapped. In addition, there were eight downregulated IFG-related DMs and two downregulated T2DM-related DMs. Only one downregulated DM overlapped. Similarly, there were 264 upregulated IFG-related DGs and 331 upregulated T2DM-related DGs; and 196 overlapping genes were obtained. In addition, there were 400 downregulated IFG-related DMs and 568 downregulated T2DM-related DMs. A total of 326 downregulated DMs were overlapped. The overlapped DGs were enriched in various pathways, including hematopoietic cell lineage, Fc gamma R-mediated phagocytosis, and MAPK signaling pathway. TAF1 (upregulated gene) and MAFK (downregulated gene) were hub nodes both in IFG- and T2DM-related miRNA-TF-gene regulatory network. In addition, miRNAs, including hsa-miR-29a, hsa-miR-192, and hsa-miR-144, were upregulated hub nodes in the two regulatory networks. CONCLUSIONS Genes including TAF1 and MAFK, and miRNAs including hsa-miR-29a, hsa-miR-192, and hsa-miR-144 might be potential target genes and important miRNAs for IFG and T2DM.
| S-EPMC5147684 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM) is a progressive disease. We utilized bioinformatics analysis and experimental research to identify biomarkers indicative of the progression of T2DM, aiming for early detection of the disease and timely clinical intervention. Integrating Mfuzz analysis with differential expression analysis, we identified 76 genes associated with the progression of T2DM, which were primarily enriched in signaling pathways such as apoptosis, p53 signaling, and necroptosis. Subsequently, using various analytical methods, including machine learning, we further narrowed down the hub genes to STK17A and CCT5. Based on the hub genes, we calculated the risk score for samples and interestingly found that the score correlated with multiple programmed cell death (PCD) pathways. Animal experiments revealed that the diabetes model exhibited higher levels of MDA and LDH, with lower expression of SOD, accompanied by islet cell apoptosis. In conclusion, our study suggests that during the progression of diabetes, STK17A and CCT5 may contribute to the advancement of the disease by regulating oxidative stress, programmed cell death pathways, and critical signaling pathways such as p53 and MAPK, thereby promoting the death of islet cells. This provides substantial evidence in support of further disease prevention and treatment strategies.
| S-EPMC10894242 | biostudies-literature
Project description:This study was designed to evaluate the effect of Korean red ginseng (KRG) supplementation on glucose control in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or newly diagnosed type 2 diabetes mellitus (T2DM). The study was a 12-week randomized, double-blinded, placebo-controlled (5?g of KRG [n=21] or placebo [n=20] in tablet form) trial. Glucose-related biomarkers, including serum and whole blood levels of glucose, insulin, and C-peptide, were measured by 2-h oral glucose tolerance tests (OGTTs) at baseline and after the 12-week intervention. After the intervention, the test group showed a significant decrease in serum levels of glucose at 30?min (-22.24±10.77?mg/dL) and whole blood levels of glucose at 30?min (-17.52±5.22?mg/dL). In addition, the test group tended to have lower whole blood levels of glucose at 0?min and glucose area under curve (AUC). However, the placebo group did not show any changes in blood glucose-related indices. The changes (difference from baseline) in serum glucose levels at 30?min, whole blood glucose levels at 60?min, and glucose AUC during OGTTs in the test group exhibited a tendency toward a decrease from those in the placebo group. There were significant decreases or trends toward a decrease in both serum insulin and C-peptide concentrations at most time intervals in the test group. In conclusion, KRG supplementation (5?g/day) may be beneficial for controlling serum and whole blood glucose levels compared with placebo among patients with IFG, IGT, or T2DM.
| S-EPMC3901349 | biostudies-literature
Project description:BackgroundCurrent studies in most Western countries have largely focused on body mass index (BMI) as an important risk factor for impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which have different pathophysiological bases. In people with obesity, the prevalence of IGT is higher and the prevalence of IFG is lower. The prevalence of IGT in the Asian population is higher than that in the white population, and the obesity rate in China is still increasing. However, few cohort studies explore the relationship between BMI and the incidence of IGT and IFG in China. We aimed to explore the relationship between BMI and the risk of IGT and IFG in Chinese adults and analyze the differences between them.MethodsThe baseline data were obtained from the 2010 China Chronic Disease and Risk Factor Surveillance, of which 20 surveillance sites were followed up from 2016 to 2017. Finally, in this study, a total of 5,578 studies were grouped into BMI categories of underweight (BMI < 18.5 kg/m2), normal weight (18.5-23.9 kg/m2), overweight (24.0-27.9 kg/m2), and obesity (≥ 28.0 kg/m2). We used the unconditional logistic regression model to analyze the relationship between BMI and the risk of IGT and IFG.ResultsDuring an average follow-up of 6.4 years, 562 developed IGT and 257 developed IFG. After age, gender, urban and rural areas, physical activity, family history of diabetes, hypertension, abdominal obesity, dyslipidemia, and other factors were adjusted, overweight increased the risk of IGT by 35% [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.08-1.70], and obesity increased the risk of IGT by 77% (OR 1.77, 95% CI 1.27-1.47). After the factors consistent with the above were adjusted, only obesity increased the risk of IFG by 122% (OR 2.22, 95% CI 1.39-3.54).ConclusionsIn China, obesity is an important risk factor for IGT and IFG, and the risk of IGT increases during the overweight stage.
| S-EPMC9811686 | biostudies-literature
Project description:BackgroundGlycosylated hemoglobin (HbA1c) has been recommended as a diagnostic test for prediabetes and diabetes. Here, we evaluated the level of agreement between diagnoses based on fasting plasma glucose (FPG) versus HbA1c levels and determined optimal HbA1c cutoff values for these diseases in youth and young adults.MethodsThe study included 7,332 subjects (n=4,129, aged 10 to 19 years in youth group; and n=3,203 aged 20 to 29 years in young adult group) from the 2011 to 2016 Korea National Health and Nutrition Examination Survey. Prediabetes and diabetes were defined as 100 to 125 mg/dL (impaired fasting glucose [IFG]) and ≥126 mg/dL for FPG (diabetes mellitus [DM] by FPG [DMFPG]), and 5.7% to 6.4% and ≥6.5% for HbA1c, respectively.ResultsIn the youth group, 32.5% with IFG had an HbA1c level of 5.7% to 6.4%, and 72.2% with DMFPG had an HbA1c ≥6.5%. In the young adult group, 27.5% with IFG had an HbA1c level of 5.7% to 6.4%, and 66.6% with DMFPG had an HbA1c ≥6.5%. Kappa coefficients for agreement between the FPG and HbA1c results were 0.12 for the youth group and 0.19 for the young adult group. In receiver operating characteristic curve analysis, the optimal HbA1c cutoff for IFG and DMFPG were 5.6% and 5.9% in youths and 5.5% and 5.8% in young adults, respectively.ConclusionUsefulness of HbA1c for diagnosis of IFG and DMFPG in Koreans aged <30 years remains to be determined due to discrepancies between the results of glucose- and HbA1c-based tests. Additional testing might be warranted at lower HbA1c levels to detect IFG and DMFPG in this age group.
| S-EPMC6470094 | biostudies-literature
Project description:The 5-amino acid (AA) signature, including isoleucine, leucine, valine, tyrosine, and phenylalanine, has been associated with incident diabetes mellitus and insulin resistance. We investigated whether this same AA signature, single-nucleotide polymorphisms in genes in their catabolic pathway, was associated with development of impaired fasting glucose (IFG) after atenolol treatment.Among 234 European American participants enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study and treated with atenolol for 9 weeks, we prospectively followed a nested cohort that had both metabolomics profiling and genotype data available for the development of IFG. We assessed the association between baseline circulating levels of isoleucine, leucine, valine, tyrosine, and phenylalanine, as well as single-nucleotide polymorphisms in branched-chain amino-acid transaminase 1 (BCAT1) and phenylalanine hydroxylase (PAH) with development of IFG. All baseline AA levels were strongly associated with IFG development. Each increment in standard deviation of the 5 AAs was associated with the following odds ratio and 95% confidence interval for IFG based on a fully adjusted model: isoleucine 2.29 (1.31-4.01), leucine 1.80 (1.10-2.96), valine 1.77 (1.07-2.92), tyrosine 2.13 (1.20-3.78), and phenylalanine 2.04 (1.16-3.59). The composite P value was 2×10(-5). Those with PAH (rs2245360) AA genotype had the highest incidence of IFG (P for trend=0.0003).Our data provide important insight into the metabolic and genetic mechanisms underlying atenolol-associated adverse metabolic effects. Clinical Trial Registration- http://www.clinicaltrials.gov; Unique Identifier: NCT00246519.
| S-EPMC4050976 | biostudies-literature
Project description:BackgroundAnimal studies suggest sphingolipids as an early marker of impaired glucose metabolism; however, research in humans is limited. We evaluated whether individual sphingolipid species were associated with fasting plasma glucose and incident impaired fasting glucose in a longitudinal cohort study.MethodsWe measured 15 sphingolipid species from blood samples collected in 2001-2003 from 2145 participants without prevalent diabetes in the Strong Heart Family Study. Fasting plasma glucose was measured in blood samples collected at baseline and follow-up (mean 5.5 years after baseline).FindingsThe average age of study participants was 38 years; 41% were men. Ceramide, sphingomyelin, and glucosylceramide species levels were higher in older participants; lactosyl-ceramide levels were higher in participants with lower BMIs. In adjusted analyses, greater concentrations of most ceramide species and lower lactosyl-ceramide with palmitic acid (LC-16) were associated with higher glucose levels at baseline. We did not observe associations of sphingomyelin species or glucosyl-ceramide species with glucose levels. Associations of sphingolipid levels with fasting glucose levels at follow-up were similar but had greater uncertainty than associations with baseline glucose. Although no statistically significant associations of sphingolipids with incident impaired fasting glucose were present, results were similar to glucose analyses.InterpretationWe identified several ceramide species associated with higher fasting glucose levels and one sphingolipid, LC-16, that was associated with lower fasting glucose levels. These findings compliment previous research, which linked these sphingolipids with fasting insulin levels, and suggest that higher levels of these ceramides and lower LC-16 may be an early marker of impaired glucose metabolism. FUND: US National Institutes Health.
| S-EPMC6444022 | biostudies-literature
Project description:Mitochondrial RNR-2 (mt-RNR2, humanin) has been shown to play a role in protecting several types of cells and tissues from the effects of oxidative stress. Humanin (HN) functions through extracellular and intracellular pathways adjusting mitochondrial oxidative phosphorylation and ATP production. Addition of HN improved insulin sensitivity in animal models of diabetes mellitus but no clinical studies have been carried out to measure HN levels in humans associated with hyperglycemia. The plasma levels of HN in participants attending a diabetes complications screening clinic were measured. Clinical history and anthropometric data were obtained from all participants. Plasma levels of HN were measured by a commercial ELISA kit. All data were analyzed applying nonparametric statistics and general linear modeling to correct for age and gender. A significant decrease (P = 0.0001) in HN was observed in the impaired fasting glucose (IFG) group (n = 23; 204.84 ± 92.87 pg mL(-1)) compared to control (n = 58; 124.3 ± 83.91 pg mL(-1)) consistent with an adaptive cellular response by HN to a slight increase in BGL.
| S-EPMC4873641 | biostudies-other