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Metabonomic fingerprints of fasting plasma and spot urine reveal human pre-diabetic metabolic traits.

ABSTRACT: Impaired glucose tolerance (IGT) which precedes overt type 2 diabetes (T2DM) for decades is associated with multiple metabolic alterations in insulin sensitive tissues. In an UPLC-qTOF-mass spectrometry-driven non-targeted metabonomics approach we investigated plasma as well as spot urine of 51 non-diabetic, overnight fasted individuals aiming to separate subjects with IGT from controls thereby identify pathways affected by the pre-diabetic metabolic state. We could clearly demonstrate that normal glucose tolerant (NGT) and IGT subjects clustered in two distinct groups independent of the investigated metabonome. These findings reflect considerable differences in individual metabolite fingerprints, both in plasma and urine. Pre-diabetes associated alterations in fatty acid-, tryptophan-, uric acid-, bile acid-, and lysophosphatidylcholine-metabolism, as well as the TCA cycle were identified. Of note, individuals with IGT also showed decreased levels of gut flora-associated metabolites namely hippuric acid, methylxanthine, methyluric acid, and 3-hydroxyhippuric acid. The findings of our non-targeted UPLC-qTOF-MS metabonomics analysis in plasma and spot urine of individuals with IGT vs NGT offers novel insights into the metabolic alterations occurring in the long, asymptomatic period preceding the manifestation of T2DM thereby giving prospects for new intervention targets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-010-0203-1) contains supplementary material, which is available to authorized users.

SUBMITTER: Zhao X

PROVIDER: S-EPMC2899018 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Metabonomic fingerprints of fasting plasma and spot urine reveal human pre-diabetic metabolic traits.

Zhao Xinjie X Fritsche Jens J Wang Jiangshan J Chen Jing J Rittig Kilian K Schmitt-Kopplin Philippe P Fritsche Andreas A Häring Hans-Ulrich HU Schleicher Erwin D ED Xu Guowang G Lehmann Rainer R

Metabolomics : Official journal of the Metabolomic Society 20100307 3

Impaired glucose tolerance (IGT) which precedes overt type 2 diabetes (T2DM) for decades is associated with multiple metabolic alterations in insulin sensitive tissues. In an UPLC-qTOF-mass spectrometry-driven non-targeted metabonomics approach we investigated plasma as well as spot urine of 51 non-diabetic, overnight fasted individuals aiming to separate subjects with IGT from controls thereby identify pathways affected by the pre-diabetic metabolic state. We could clearly demonstrate that norm ...[more]

PMID: 20676218

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Project description:IntroductionPrevious studies based on a single measure of fasting plasma glucose (FPG) showed an inconsistent conclusion about the association between FPG and osteoporosis risk. Not accounting for time-varying and cumulative average of FPG over time could bias the true relation between FPG and osteoporosis. Our study aims to investigate the association between the trajectories of FPG and osteoporosis risk for non-diabetic and diabetic populations.MethodsA total of 18,313 participants who attended physical examinations during 2008-2018 were included. They were free of osteoporosis at their first physical examination and followed until their last physical examination before December 31, 2018. We recorded their incidence of osteoporosis and at least three FPG values during follow-up. Their longitudinal FPG trajectories were identified by the latent class growth analysis model based on the changes in FPG. Multivariable logistic regression models were used to analyze the association between the trajectories of FPG and osteoporosis diagnosed in the follow-up physical examination in both non-diabetics and diabetics.ResultsThere were 752 incident osteoporosis among 16,966 non-diabetic participants, and 57 incident osteoporosis among 1,347 diabetic participants. Among non-diabetics, the elevated-increasing FPG trajectory was negatively associated with osteoporosis risk in women (odds ratio (OR), 0.62; 95% confidence interval (CI), 0.43-0.88). Premenopausal women with elevated-increasing FPG trajectory had lower osteoporosis risk than those women with normal-stable FPG trajectory (OR, 0.41; 95% CI, 0.20-0.88), while this association was insignificant in postmenopausal women. Among diabetics, those whose longitudinal FPG is kept at a very high level had the highest risk of osteoporosis (OR, 3.09; 95% CI, 1.16-8.22), whereas those whose FPG starts with the high level and keeps on increasing did not exhibit a significantly increased risk (OR, 1.75; 95% CI, 0.81-3.76) compared with those who keep stable moderate-high level of FPG, except in men (OR, 2.49; 95% CI, 1.02-6.12).ConclusionDistinct trajectories of FPG are associated with differential risk of osteoporosis in non-diabetic and diabetic populations. Controlling a proper FPG level in different populations is necessary for osteoporosis prevention.

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Metabonomic fingerprints of fasting plasma and spot urine reveal human pre-diabetic metabolic traits.

Publications

Metabonomic fingerprints of fasting plasma and spot urine reveal human pre-diabetic metabolic traits.

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