Metabolomic profiling in the prediction of gestational diabetes mellitus

Bentley‐Lewis, Rhonda; Huynh, Jennifer; Xiong, Grace; Lee, Hang; Wenger, Julia; Clish, Clary B.; Nathan, David M.; Thadhani, Ravi; Gerszten, Robert E.

doi:10.1007/s00125-015-3553-4

Cited by 89 publications

(79 citation statements)

References 9 publications

(14 reference statements)

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“…In contrast, we found no differences in BCAA, leucine, and valine levels between GDM patients and controls, which is not consistent with some previous reports on T2DM [13,14,16]. However, this finding is in agreement with Bentley-Lewis et al (2015) who found that there are differences in metabolic levels, despite several similarities between T2DM and GDM [38]. Ferrannini et al (2012) observed that patients who developed T2DM later had increased BCAA levels, including those of leucine and valine, and of three major glucogenic amino acids (including arginine), whereas glycine was significantly decreased [44].…”

Section: Resultscontrasting

confidence: 69%

“…No difference was found in BCAA levels. This showed that the metabolites studied were not altered in GDM to a similar degree as in T2DM [38].…”

Section: Resultsmentioning

confidence: 63%

“…Some metabolites correlate with age and BMI [46,47]. For example, glutamate and serine have been found to correlate with BMI and parity, while glutamate also correlates with gravidity [38].…”

Section: Resultsmentioning

confidence: 99%

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First-Trimester Maternal Serum Amino Acids and Acylcarnitines Are Significant Predictors of Gestational Diabetes

et al. 2016

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■ AbstractBACKGROUND: Current screening methods for gestational diabetes mellitus (GDM) are insufficient in detecting the risk of GDM in the first trimester of the pregnancy. Recent metabolomic studies have detected altered amino acid and acylcarnitine concentrations in type 2 diabetes (T2D). Because of the similarities between T2D and GDM, the determination of these metabolites may be useful in early screening for GDM. AIM: To evaluate the association between GDM and first-trimester maternal serum concentrations of ten amino acids and 31 acylcarnitines. METHODS: This retrospective case-control study included data from pregnant women screened at Oulu University Hospital between 1. 1.2008 and 31.12.2011. A total of 31,146 women participated voluntarily in a first-trimester combined screening (for chromosomal abnormalities). The study population included 69 women who developed GDM during pregnancy and 295 women without diabetes before or after pregnancy. The serum concentrations of ten amino acids and 31 acylcarnitines were analyzed from frozen serum samples taken in the first-trimester screening. Multiple of median (MoM) values were compared between the two groups. RESULTS: In the GDM group, serum levels of arginine were significantly higher (1.13 MoM vs. 0.97 MoM), and those of glycine (0.93 MoM vs. 1.03 MoM) and 3-hydroxyisovalerylcarnitine (0.86 MoM vs. 1.03 MoM) significantly lower compared to the control group (all p < 0.01). In each case, arginine, glycine, and 3-hydroxy-isovaleryl-carnitine would have detected 46%, 32%, and 39% of GDM cases, with a false-positive rate of 20%. Combining these three metabolites with the first-trimester serum marker pregnancy-associated plasma protein A (PAPP-A) and prior risk (age, BMI, and smoking) achieved a detection rate of 72%. CONCLUSION: There are significant differences in the serum levels of arginine, glycine, and 3-hydroxy-isovalerylcarnitine between controls and women who subsequently develop GDM. These differences were already existent in the first trimester of the pregnancy. The use of metabolites in combination with prior risk and first-trimester PAPP-A represents a reliable method to identify women at risk of GDM.

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Section: Resultscontrasting

confidence: 69%

“…No difference was found in BCAA levels. This showed that the metabolites studied were not altered in GDM to a similar degree as in T2DM [38].…”

Section: Resultsmentioning

confidence: 63%

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First-Trimester Maternal Serum Amino Acids and Acylcarnitines Are Significant Predictors of Gestational Diabetes

et al. 2016

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“…Interestingly, multiple fatty acids were decreased in the subjects destined for incident diabetes as well. In contrast, metabolomic profiling of 96 women with GDM versus 96 women matched by age, BMI and gravidity with normal glucose tolerance found 6 metabolites to be different between the groups, anthranilic acid, alanine, glutamate, creatinine, allantoin and serine, but no differences in BCAA, aromatic amino acids, or glycine (Bentley-Lewis et al, 2015). Similarly, few metabolites associated with fasting plasma glucose levels in 400 pregnant women of European descent from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort (Scholtens et al, 2013).…”

Section: Metabolomics Reveals Associations Of Metabolites With Cardiomentioning

confidence: 98%

Metabolomics and Metabolic Diseases: Where Do We Stand?

2017

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Metabolomics, or the comprehensive profiling of small molecule metabolites in cells, tissues, or whole organisms, has undergone a rapid technological evolution in the past two decades. These advances have led to application of metabolomics for defining predictive biomarkers for incident cardiometabolic diseases, and increasingly, as a blueprint for understanding their pathophysiologic mechanisms. Progress in this area and challenges for the future are reviewed here.

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“…Inflammation-induced indoleamine 2,3-dioxygenase-1 (IDO) or stress-induced tryptophan 2,3-dioxygenase-2 (TDO) activate Trp conversion into Kyn, a precursor of anthranilic (AA), kynurenic (KYNA), and (via 3-hydroxykynurenine, 3-HK) xanthurenic (XA) acids [7] (Figure 1). Elevated AA was found to predict the development of gestational diabetes [8] but not T2D [9]. However, we are not aware of clinical assessments of AA in T1D – the major aim of the present study.…”

Section: Introductionmentioning

confidence: 93%

Elevated anthranilic acid plasma concentrations in type 1 but not type 2 diabetes mellitus

Oxenkrug¹,

Hart²,

Summergrad³

2015

Integr Mol Med

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Experimental data suggested involvement of tryptophan (Trp) – kynurenine (Kyn) pathway (TKP) in mechanisms of autoimmune, type 1 (T1D), and metabolic, type 2 (T2D), diabetes. However, clinical evaluations of TKP metabolites were limited to T2D. We assessed Trp, Kyn and TKP metabolites: anthranilic (AA), kynurenic (KYNA) and xanthurenic (XA) acids, in plasma samples of fifteen T1D, thirty T2D patients and twenty eight non-diabetic subjects by HPLC-mass spectrometry. Trp concentrations were higher in T1D than in T2D and controls while Kyn concentrations were not changed suggesting down-regulation of indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme of TKP, in T1D. AA concentrations were 2.3-fold higher in T1D than in T2D and in controls. KYNA and XA concentrations were higher in T1D than in controls, and in previously reported T2D. AA elevation might be a specific feature of T1D. TKP shift towards AA formation in T1D may result from riboflavin deficiency, that increases AA in rats and baboons, and is highly associated with T1D but not T2D. AA augments autoimmune-induced apoptosis of pancreatic cells (PC) by increasing formation of antibodies to PC auto-antigen. Marked increase of AA was reported in rheumatoid arthritis, another autoimmune disorder. Trp, an essential amino acid for humans, is synthesized from AA by diabetogenic intestinal microbiome. AA down-regulates IDO by inhibition of Trp entry into cells. Resulting elevation of Trp attenuates Trp depletion-induced protection of PC against autoimmunity. Further studies of TKP might offer new tools for prevention and treatment of T1D and other autoimmune disorders.

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Metabolomic profiling in the prediction of gestational diabetes mellitus

Cited by 89 publications

References 9 publications

First-Trimester Maternal Serum Amino Acids and Acylcarnitines Are Significant Predictors of Gestational Diabetes

First-Trimester Maternal Serum Amino Acids and Acylcarnitines Are Significant Predictors of Gestational Diabetes

Metabolomics and Metabolic Diseases: Where Do We Stand?

Elevated anthranilic acid plasma concentrations in type 1 but not type 2 diabetes mellitus

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