Identification of metabolic markers predictive of prediabetes in a Korean population
Ontology highlight
ABSTRACT:
SUBMITTER: Lee H
PROVIDER: S-EPMC7738529 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundIdentifying the metabolite profile of individuals with prediabetes who turned to type 2 diabetes (T2D) may give novel insights into early T2D interception. The purpose of this study was to identify metabolic markers that predict the development of T2D from prediabetes in a Chinese population.MethodsWe used an untargeted metabolomics approach to investigate the associations between serum metabolites and risk of prediabetes who turned to overt T2D (n=153, mean follow up 5 years) in a Chinese population (REACTION study). Results were compared with matched controls who had prediabetes at baseline [age: 56 ± 7 years old, body mass index (BMI): 24.2 ± 2.8 kg/m2] and at a 5-year follow-up [age: 61 ± 7 years old, BMI: 24.5 ± 3.1 kg/m2]. Confounding factors were adjusted and the associations between metabolites and diabetes risk were evaluated with multivariate logistic regression analysis. A 10-fold cross-validation random forest classification (RFC) model was used to select the optimal metabolites panels for predicting the development of diabetes, and to internally validate the discriminatory capability of the selected metabolites beyond conventional clinical risk factors.FindingsMetabolic alterations, including those associated with amino acid and lipid metabolism, were associated with an increased risk of prediabetes progressing to diabetes. The most important metabolites were inosine [odds ratio (OR) = 19.00; 95% confidence interval (CI): 4.23-85.37] and carvacrol (OR = 17.63; 95% CI: 4.98-62.34). Thirteen metabolites were found to improve T2D risk prediction beyond eight conventional T2D risk factors [area under the curve (AUC) was 0.98 for risk factors + metabolites vs 0.72 for risk factors, P < 0.05].InterpretationsUse of the metabolites identified in this study may help determine patients with prediabetes who are at highest risk of progressing to diabetes.
| S-EPMC8766640 | biostudies-literature
Project description:Serum vitamin D status has been associated with prediabetes and metabolic syndrome. Evidence for the increased risk of metabolic disorders in individuals with prediabetes and a low vitamin D status is limited and uncertain. Furthermore, it has not been confirmed whether this possible relationship occurs in the Korean population. The aim of this study was to assess serum vitamin D status and to examine the relationship between serum vitamin D levels and metabolic risk factors in Korean adults with prediabetes. This cross-sectional study was conducted among 60 subjects aged 20-65 years. Participants had fasting glucose levels of 100 to 125 mg/dl. A questionnaire was used to assess vitamin D synthesis from sun exposure and a dietary intake examined using 3-days dietary records. Clinical and biochemical data were also collected. The 2009 harmonized definition of metabolic syndrome was used. Serum vitamin D levels were classified according to criteria from the 2011 Institute of Medicine report. The majority of subjects (75%) had a serum 25(OH)D level < 20 ng/ml, and among them, 31.1% were vitamin D deficiency (< 12 ng/ml). The proportion (42.9%) of subjects having low HDL-cholesterol was the highest among vitamin D deficiency (< 12 ng/ml) group (12 to < 20 ng/ml: 16.1%, ? 20 ng/ml: 6.7%). We observed an inverse relationship between 25(OH)D levels and TG, AI (? = -6.355, SE = 2.463; ? = -0.020, SE = 0.008) after adjusted confounders. Korean adults with prediabetes were more likely to have low serum 25(OH)D levels. A sufficient 25(OH)D level may have possible beneficial effects on lipid profiles.
| S-EPMC5082612 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-10-23 | GSE74303 | GEO
Project description:Introduction: Observational studies have demonstrated strong correlations between metabolic syndrome (MetS) and its related traits. To gain insight into the genetic architecture and molecular mechanism of MetS, we investigated the shared genetic basis of MetS and its related traits and further tested their causal relationships. Methods: Using summary statistics from genome-wide association analyses of about 72,000 subjects from the Korean Genome and Epidemiological Study (KoGES), we conducted genome-wide multi-trait analyses to quantify the overall genetic correlation and Mendelian randomization analyses to infer the causal relationships between traits of interest. Results: Genetic correlation analyses revealed a significant correlation of MetS with its related traits, such as obesity traits (body mass index and waist circumference), lipid traits (triglyceride and high-density lipoprotein cholesterol), glycemic traits (fasting plasma glucose and hemoglobin A1C), and blood pressure (systolic and diastolic). Mendelian randomization analyses further demonstrated that the MetS-related traits showing significant overall genetic correlation with MetS could be genetically determined risk factors for MetS. Discussion: Our study suggests a shared genetic basis of MetS and its related traits and provides novel insights into the biological mechanisms underlying these complex traits. Our findings further inform public health interventions by supporting the important role of the management of metabolic risk factors such as obesity, unhealthy lipid profiles, diabetes, and high blood pressure in the prevention of MetS.
| S-EPMC11266026 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Identification of genes that can predict the proliferation potential of multipotent stromal cells. Gene expression study by microarray and confirmation with RT-qPCR. Gene expression by microarray includes the 54 arrays originally present in GSE56362 and 9 additional arrays added to GSE56362 on October 23, 2015. These additional microarray datasets were completed in a randomized block design in combination with the microarray data originally present in GSE56362.
2015-10-23 | E-GEOD-74303 | biostudies-arrayexpress
Project description:Multipotent stromal cells (MSCs) are known for their distinctive ability to differentiate into different cell lineages such as adipocytes, chondrocytes and osteocytes. They can be isolated from numerous tissue sources including bone marrow, adipose tissue, skeletal muscle and others. Because of their differentiation potential and their secretion of growth factors, MSCs are believed to have an inherent quality of regeneration and immune suppression, which are considered advantageous in treating multiple disorders such as graft-versus-host disease. Since the number of MSCs derived from a tissue source is low, cellular expansion is necessary to obtain sufficient numbers for a desired cell therapy. However, after several rounds of passaging, our previous results have shown that MSCs exhibit reduced capacity for proliferation and differentiation. In this study, gene markers of MSC proliferation were identified and evaluated for their ability to predict the cell population proliferative quality. Microarray data of human bone marrow-derived MSCs were correlated with two proliferation assays. A collection of 24 genes were observed to significantly correlate with both proliferation assays (|r| > 0.70) for 8 MSC donors at multiple passages. These 24 identified genes were then confirmed using an additional set of MSCs from 8 new donors using RT-qPCR. The proliferative potential of the second set of MSCs was measured for each donor/passage by three proliferation assays for confluency fraction, fraction of EdU+ cells and population doubling time. The second set of MSCs exhibited a greater proliferative potential at passage 4 in comparison to passage 8, which was distinguishable by 15 genes; however, only 7 of the genes (BIRC5, CCNA2, CDC20, CDK1, PBK, PLK1, SPC25) demonstrated significant correlation (FDR: q < 0.05 and |r| > 0.62) with MSC proliferation regardless of passage. These 7 genes and the proliferative capacity of different non-MSC cell lines were assessed for comparison. Our analyses revealed that correlation between gene expression and proliferation was consistently reduced with the introduction of non-MSC cell lines; therefore this set of 7 genes may be more strongly associated with MSC proliferative quality. These correlative methods may be further used to identify additional markers that exhibit strong correlation with a particular MSC quality such as differentiation or immune suppression potential. Our results pave the way toward the identification of specific gene markers that could rapidly determine the quality of an MSC population for a particular cellular therapy in lieu of an extended in vitro or in vivo assay.
2016-07-01 | GSE74203 | GEO
Project description:Scoring systems for metabolic dysfunction-associated steatotic liver disease (MASLD) in individuals with prediabetes have not been extensively explored. This study aimed to investigate the prevalence of MASLD and to develop predictive tools for its detection in high cardiometabolic people with prediabetes. A cross-sectional study was conducted using baseline data from the prediabetes cohort. All participants underwent transient elastography to assess liver stiffness. MASLD was defined using a controlled attenuation parameter value > 275 dB/m and/or a liver stiffness measurement ≥ 7.0 kPa. Cases with secondary causes of hepatic steatosis were excluded. Out of 400 participants, 375 were included. The observed prevalence of MASLD in individuals with prediabetes was 35.7%. The most effective predictive model included FPG ≥ 110 mg/dL; HbA1c ≥ 6.0%; sex-specific cutoffs for HDL; ALT ≥ 30 IU/L; and BMI levels. This model demonstrated good predictive performance with an AUC of 0.80 (95% CI 0.73-0.86). At a cutoff value of 4.5, the sensitivity was 70.7%, the specificity was 72.3%, the PPV was 58.8%, and the NPV was 81.5%. Our predictive model is practical, easy to use, and relies on common parameters. The scoring system should aid clinicians in determining when further investigations of MASLD are warranted among individuals with prediabetes, especially in settings with limited resources.
| S-EPMC10743615 | biostudies-literature
Project description:Cholangiocarcinoma (CCA) is the most common malignant heterogeneous polygenetic carcinoma with a high incidence in Asia. Most patients would die within 1 year after diagnosis and the 5 year survival rate is less than 10-20% worldwide. Single nucleotide polymorphisms (SNPs) in genes regulate telomere maintenance, mitosis, and inflammation, and may help predict individual susceptibility to certain drugs, environmental factor, and risks to particular diseases. The gene-gene interaction and the regulation of SNPs have not been assessed extensively in CCA. According to our previous study, the GRB2-associated-binding protein (Gab1) gene rs3805246 (X(2) =5.015, P=0.025, OR=0.531, 95% CI 0.304-0.928) and epidermal growth factor receptor (EGFR) gene rs2007000 (X(2) =7.934, P=0.005, OR=2.148, 95% CI 1.255-3.675) presented significant difference between CCA patients and controls. This study conducted a population-based analysis using 225 CCA cases (153 biliary tract cancer patients and 72 gall bladder cancer patients) to assess the association between SNPs and progression of CCA patients, including the overall survival and the prognosis analysis. Results showed that an increased susceptibility of BTC was significantly associated with SNP loci distribution frequency in EGFR rs2107000 (X(2) =7.934, P=0.005, OR=2.148, 95% CI 1.255-3.675). Furthermore, multivariate factor regression analysis represented cholelithiasis medical history of BTC patients can be an effective evaluation criteria of BTC susceptibility in early stage. This study also assessed the relationship between these genotypic polymorphisms and clinicopathologic data, including tumor differentiation stage and overall survival. This is the first study identifying that EGFR polymorphisms are associated with BTC and EGFR rs2017000 polymorphisms may be an important survival predictor in BTC patients.
| S-EPMC4612998 | biostudies-literature
Project description:Multipotent stromal cells (MSCs) are known for their distinctive ability to differentiate into different cell lineages such as adipocytes, chondrocytes and osteocytes. They can be isolated from numerous tissue sources including bone marrow, adipose tissue, skeletal muscle and others. Because of their differentiation potential and their secretion of growth factors, MSCs are believed to have an inherent quality of regeneration and immune suppression, which are considered advantageous in treating multiple disorders such as graft-versus-host disease. Since the number of MSCs derived from a tissue source is low, cellular expansion is necessary to obtain sufficient numbers for a desired cell therapy. However, after several rounds of passaging, our previous results have shown that MSCs exhibit reduced capacity for proliferation and differentiation. In this study, gene markers of MSC proliferation were identified and evaluated for their ability to predict the cell population proliferative quality. Microarray data of human bone marrow-derived MSCs were correlated with two proliferation assays. A collection of 24 genes were observed to significantly correlate with both proliferation assays (|r| > 0.70) for 8 MSC donors at multiple passages. These 24 identified genes were then confirmed using an additional set of MSCs from 8 new donors using RT-qPCR. The proliferative potential of the second set of MSCs was measured for each donor/passage by three proliferation assays for confluency fraction, fraction of EdU+ cells and population doubling time. The second set of MSCs exhibited a greater proliferative potential at passage 4 in comparison to passage 8, which was distinguishable by 15 genes; however, only 7 of the genes (BIRC5, CCNA2, CDC20, CDK1, PBK, PLK1, SPC25) demonstrated significant correlation (FDR: q < 0.05 and |r| > 0.62) with MSC proliferation regardless of passage. These 7 genes and the proliferative capacity of different non-MSC cell lines were assessed for comparison. Our analyses revealed that correlation between gene expression and proliferation was consistently reduced with the introduction of non-MSC cell lines; therefore this set of 7 genes may be more strongly associated with MSC proliferative quality. These correlative methods may be further used to identify additional markers that exhibit strong correlation with a particular MSC quality such as differentiation or immune suppression potential. Our results pave the way toward the identification of specific gene markers that could rapidly determine the quality of an MSC population for a particular cellular therapy in lieu of an extended in vitro or in vivo assay. Microarray gene expression analysis with confirmation of genes by RT-qPCR
2016-07-01 | E-GEOD-74203 | biostudies-arrayexpress
Project description:Cowpea is one of the most essential legume crops providing inexpensive dietary protein and nutrients. The aim of this study was to understand the genetic diversity and population structure of global and Korean cowpea germplasms. A total of 384 cowpea accessions from 21 countries were genotyped with the Cowpea iSelect Consortium Array containing 51,128 single-nucleotide polymorphisms (SNPs). After SNP filtering, a genetic diversity study was carried out using 35,116 SNPs within 376 cowpea accessions, including 229 Korean accessions. Based on structure and principal component analysis, a total of 376 global accessions were divided into four major populations. Accessions in group 1 were from Asia and Europe, those in groups 2 and 4 were from Korea, and those in group 3 were from West Africa. In addition, 229 Korean accessions were divided into three major populations (Q1, Jeonra province; Q2, Gangwon province; Q3, a mixture of provinces). Additionally, the neighbor-joining tree indicated similar results. Further genetic diversity analysis within the global and Korean population groups indicated low heterozygosity, a low polymorphism information content, and a high inbreeding coefficient in the Korean cowpea accessions. The population structure analysis will provide useful knowledge to support the genetic potential of the cowpea breeding program, especially in Korea.
| S-EPMC7569878 | biostudies-literature