Comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry for metabonomics: Biomarker discovery for diabetes mellitus

Li, Xiang; Xu, Zhiliang; Lü, Xin; Yang, Xuehui; Yin, Peiyuan; Kong, Hongwei; Yu, Ying; Xu, Guowang

doi:10.1016/j.aca.2008.11.058

Cited by 227 publications

(159 citation statements)

References 31 publications

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“…In accordance with genetic rat models (Williams et al 2006b, Salek et al 2007, increased fatty acid levels were detected in T2DM patients (Yi et al 2006, 2007, Li et al 2009, Suhre et al 2010 as well as in subjects with impaired glucose tolerance (Zhao et al 2010b). Changes in as many as 18 fatty acids, including SFA, MUFA and PUFA, were found in one study.…”

Section: Patient Investigationsmentioning

confidence: 72%

“…These findings from human patients can be summarised as follows: i) As expected, diabetic patients exhibited differences in glucose metabolism. Patients with T1DM under insulin deprivation (Lanza et al 2010) or in T2DM (Li et al 2009, Suhre et al 2010) demonstrated elevated glucose or mannose levels compared with healthy controls. Furthermore, in both T1DM and T2DM patients (Messana et al 1998, Zuppi et al 2002 increased lactate levels were observed, at which these levels increased with the grade of glucosuria in T2DM patients (Messana et al 1998).…”

Section: Patient Investigationsmentioning

confidence: 99%

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Metabolomics in diabetes research

Friedrich¹

2012

Journal of Endocrinology

124

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Diabetes represents one of the most important global health problems because it is associated with a large economic burden on the health systems of many countries. Whereas the diagnosis and treatment of manifest diabetes have been well investigated, the identification of novel pathways or early biomarkers indicative of metabolic alterations or insulin resistance related to the development of diabetes is still in progress. Over half of the type 2 diabetes patients show manifestations of diabetes-related diseases, which highlight the need for early screening markers of diabetes. During the last decade, the rapidly growing research field of metabolomics has introduced new insights into the pathology of diabetes as well as methods to predict disease onset and has revealed new biomarkers. Recent epidemiological studies first used metabolism to predict incident diabetes and revealed branched-chain and aromatic amino acids including isoleucine, leucine, valine, tyrosine and phenylalanine as highly significant predictors of future diabetes. This review summarises the current findings of metabolic research regarding diabetes in animal models and human investigations.

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Section: Patient Investigationsmentioning

confidence: 72%

Section: Patient Investigationsmentioning

confidence: 99%

Metabolomics in diabetes research

Friedrich¹

2012

Journal of Endocrinology

124

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“…Within the framework of systems biology, metabolomics focuses on the quantitative measurement of holistic endogenous metabolites and is increasingly used in clinical fields that focus on the pathophysiological and diagnostic study of diseases (6). Metabolic fingerprinting and metabolite biomarkers have been studied for use in the discrimination or diagnosis of carcinoma (7,8), diabetes mellitus (9) and inborn errors (10). Nontarget metabolomics approaches have also been used to search for new biomarkers and to explore the mechanism of carcinogenesis in hepatic diseases (11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

Section: Hepatocellular Carcinoma (Hcc)mentioning

confidence: 99%

Metabolomics Study of Stepwise Hepatocarcinogenesis From the Model Rats to Patients: Potential Biomarkers Effective for Small Hepatocellular Carcinoma Diagnosis

Tan

Yin

Tang

et al. 2012

Molecular & Cellular Proteomics

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137

126

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The aim of this study is to find the potential biomarkers from the rat hepatocellular carcinoma (HCC) disease model by using a non-target metabolomics method, and test their usefulness in early human HCC diagnosis. The serum metabolic profiling of the diethylnitrosamine-induced rat HCC model, which presents a stepwise histopathological progression that is similar to human HCC, was performed using liquid chromatography-mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. Three metabolites, taurocholic acid, lysophosphoethanolamine 16:0, and lysophosphatidylcholine 22:5, were defined as "marker metabolites," which can be used to distinguish the different stages of chemical hepatocarcinogenesis. These metabolites represented the abnormal metabolism during the progress of hepatocarcinogenesis, which could also be found in patients. To test their diagnosis potential 412 sera from 262 patients with HCC, 76 patients with cirrhosis and 74 patients with chronic hepatitis B were collected and studied, it was found that 3 marker metabolites were effective for the discrimination of small liver tumor (solitary nodules of less than 2 cm in diameter) patients, achieved a sensitivity of 80.5% and a specificity of 80.1%,which is better than those of ␣-fetoprotein (53 and 64%, respectively). Moreover, they were also effective for the discrimination of all HCCs and chronic liver disease patients, which could achieve a sensitivity of 87.5% and a specificity of 72.3%, better than those of ␣-fetoprotein (61.2 and 64%). These results indicate metabolomics method has

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“…The study of metabolic phenotypes (metabotypes) in association with disease states may reveal new knowledge in disease mechanism and pathophysiology (12). Recent metabonomic studies have uncovered plasma and sera metabolic signatures associated with, or predictive of, impaired glucose tolerance and diabetes (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Furthermore, DR is a complex disease where findings from genomewide association studies have not been conclusive (23).…”

mentioning

confidence: 99%

Plasma Metabonomic Profiling of Diabetic Retinopathy

et al. 2016

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Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of visual impairment in working-age adults. Patients with diabetes often develop DR despite appropriate control of systemic risk factors, suggesting the involvement of other pathogenic factors. We hypothesize that the plasma metabolic signature of DR is distinct and resolvable from that of diabetes alone. A nested populationbased case-control metabonomic study was first performed on 40 DR cases and 40 control subjects with diabetes using gas chromatography-mass spectrometry. Eleven metabolites were found to be correlated with DR, and the majority were robust when adjusted for metabolic risk factors and confounding kidney disease. The metabolite markers 2-deoxyribonic acid; 3,4-dihydroxybutyric acid; erythritol; gluconic acid; and ribose were validated in an independent sample set with 40 DR cases, 40 control subjects with diabetes, and 40 individuals without diabetes. DR cases and control subjects with diabetes were matched by HbA 1c in the validation set. Activation of the pentose phosphate pathway was identified from the list of DR metabolite markers. The identification of novel metabolite markers for DR provides insights into potential new pathogenic pathways for this microvascular complication and holds translational value in DR risk stratification and the development of new therapeutic measures.Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of visual impairment in working-age adults worldwide (1,2). The global prevalence of diabetes is rising and the number of people with diabetes is projected to increase by 54% in 2030, compared with 2010 (3). The public health burden of diabetes and DR would thus increase correspondingly. The major risk factors of DR are poor glycemic control and hypertension, as well as the duration of diabetes (4,5), but their relative importance varies between studies (2,6). Although the risks of DR progression and vision loss are reduced with intensive control of risk factors (7,8), many patients with diabetes continue to develop complications despite tight glycemic and blood pressure control. There is increasing evidence to suggest that "metabolic memory" is responsible for this observation. The term metabolic memory refers to the persistent epigenetic modifications caused by early exposure to hyperglycemia that, in turn, predispose individuals to the development of diabetes complications even after good glycemic control

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Comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry for metabonomics: Biomarker discovery for diabetes mellitus

Cited by 227 publications

References 31 publications

Metabolomics in diabetes research

Metabolomics in diabetes research

Metabolomics Study of Stepwise Hepatocarcinogenesis From the Model Rats to Patients: Potential Biomarkers Effective for Small Hepatocellular Carcinoma Diagnosis

Plasma Metabonomic Profiling of Diabetic Retinopathy

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