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Altered asparagine and glutamate homeostasis precede coronary artery disease and type 2 diabetes

Ottosson, Filip LU ; Smith, Einar LU ; Melander, Olle LU and Fernandez, Céline LU (2018) In Journal of Clinical Endocrinology and Metabolism 103(8). p.3060-3069
Abstract

Context: Type 2 diabetes mellitus (T2DM) is accompanied by an increased risk for coronary artery disease (CAD), but the overlapping metabolic disturbances preceding both diseases are insufficiently described. Objective:Wehypothesized that alterations in metabolism occur years before clinical manifestation of T2DM and CAD and that these alterations are reflected in the plasma metabolome. We thus aimed to identify plasma metabolites that predict future T2DM and CAD. Design: Through use of targeted liquid chromatography-mass spectrometry, 35 plasma metabolites (amino acid metabolites and acylcarnitines) were quantified in 1049 individuals without CAD and diabetes, drawn from a population sample of 5386 in the Malmo Preventive Project (mean... (More)

Context: Type 2 diabetes mellitus (T2DM) is accompanied by an increased risk for coronary artery disease (CAD), but the overlapping metabolic disturbances preceding both diseases are insufficiently described. Objective:Wehypothesized that alterations in metabolism occur years before clinical manifestation of T2DM and CAD and that these alterations are reflected in the plasma metabolome. We thus aimed to identify plasma metabolites that predict future T2DM and CAD. Design: Through use of targeted liquid chromatography-mass spectrometry, 35 plasma metabolites (amino acid metabolites and acylcarnitines) were quantified in 1049 individuals without CAD and diabetes, drawn from a population sample of 5386 in the Malmo Preventive Project (mean age, 69.5 years; 31% women). The sample included 204 individuals who developed T2DM, 384 who developed CAD, and 496 who remained T2DM and CAD free during a mean follow-up of 6.1 years. Results: In total, 16 metabolites were significantly associated with risk for developing T2DM according to logistic regression models. Glutamate (OR, 1.96; P = 5.4e-12) was the most strongly associated metabolite, followed by increased levels of branched-chain amino acids. Incident CAD was predicted by three metabolites: glutamate (OR, 1.28; P = 6.6e-4), histidine (OR, 0.76; P = 5.1e-4), and asparagine (OR, 0.80; P = 2.2e-3). Glutamate (OR, 1.48; P = 1.6e-8) and asparagine (OR, 0.75; P = 1.8e-5) were both associated with a composite endpoint of developing T2DM or CAD. Conclusion: Several plasma metabolites were associated with incidence of T2DM and CAD; elevated glutamate and reduced asparagine levels were associated with both diseases. We thus discovered associations that might help shed additional light on why T2DM and CAD commonly co-occur.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
103
issue
8
pages
10 pages
publisher
The Endocrine Society
external identifiers
  • scopus:85054970279
  • pmid:29788285
ISSN
0021-972X
DOI
10.1210/jc.2018-00546
language
English
LU publication?
yes
id
aedd1933-98ce-420f-aabe-a40ab0aad685
date added to LUP
2018-11-06 12:23:29
date last changed
2020-01-16 03:36:13
@article{aedd1933-98ce-420f-aabe-a40ab0aad685,
  abstract     = {<p>Context: Type 2 diabetes mellitus (T2DM) is accompanied by an increased risk for coronary artery disease (CAD), but the overlapping metabolic disturbances preceding both diseases are insufficiently described. Objective:Wehypothesized that alterations in metabolism occur years before clinical manifestation of T2DM and CAD and that these alterations are reflected in the plasma metabolome. We thus aimed to identify plasma metabolites that predict future T2DM and CAD. Design: Through use of targeted liquid chromatography-mass spectrometry, 35 plasma metabolites (amino acid metabolites and acylcarnitines) were quantified in 1049 individuals without CAD and diabetes, drawn from a population sample of 5386 in the Malmo Preventive Project (mean age, 69.5 years; 31% women). The sample included 204 individuals who developed T2DM, 384 who developed CAD, and 496 who remained T2DM and CAD free during a mean follow-up of 6.1 years. Results: In total, 16 metabolites were significantly associated with risk for developing T2DM according to logistic regression models. Glutamate (OR, 1.96; P = 5.4e-12) was the most strongly associated metabolite, followed by increased levels of branched-chain amino acids. Incident CAD was predicted by three metabolites: glutamate (OR, 1.28; P = 6.6e-4), histidine (OR, 0.76; P = 5.1e-4), and asparagine (OR, 0.80; P = 2.2e-3). Glutamate (OR, 1.48; P = 1.6e-8) and asparagine (OR, 0.75; P = 1.8e-5) were both associated with a composite endpoint of developing T2DM or CAD. Conclusion: Several plasma metabolites were associated with incidence of T2DM and CAD; elevated glutamate and reduced asparagine levels were associated with both diseases. We thus discovered associations that might help shed additional light on why T2DM and CAD commonly co-occur.</p>},
  author       = {Ottosson, Filip and Smith, Einar and Melander, Olle and Fernandez, Céline},
  issn         = {0021-972X},
  language     = {eng},
  number       = {8},
  pages        = {3060--3069},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Altered asparagine and glutamate homeostasis precede coronary artery disease and type 2 diabetes},
  url          = {http://dx.doi.org/10.1210/jc.2018-00546},
  doi          = {10.1210/jc.2018-00546},
  volume       = {103},
  year         = {2018},
}