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Plasma metabolites associate with all-cause mortality in individuals with type 2 diabetes

Ottosson, Filip LU ; Smith, Einar LU ; Fernandez, Céline LU and Melander, Olle LU orcid (2020) In Metabolites 10(8).
Abstract

Alterations in the human metabolome occur years before clinical manifestation of type 2 diabetes (T2DM). By contrast, there is little knowledge of how metabolite alterations in individuals with diabetes relate to risk of diabetes complications and premature mortality. Metabolite profiling was performed using liquid chromatography-mass spectrometry in 743 participants with T2DM from the population-based prospective cohorts The Malmö Diet and Cancer-Cardiovascular Cohort (MDC-CC) and The Malmö Preventive Project (MPP). During follow-up, a total of 175 new-onset cases of cardiovascular disease (CVD) and 298 deaths occurred. Cox regressions were used to relate baseline levels of plasma metabolites to incident CVD and all-cause mortality. A... (More)

Alterations in the human metabolome occur years before clinical manifestation of type 2 diabetes (T2DM). By contrast, there is little knowledge of how metabolite alterations in individuals with diabetes relate to risk of diabetes complications and premature mortality. Metabolite profiling was performed using liquid chromatography-mass spectrometry in 743 participants with T2DM from the population-based prospective cohorts The Malmö Diet and Cancer-Cardiovascular Cohort (MDC-CC) and The Malmö Preventive Project (MPP). During follow-up, a total of 175 new-onset cases of cardiovascular disease (CVD) and 298 deaths occurred. Cox regressions were used to relate baseline levels of plasma metabolites to incident CVD and all-cause mortality. A total of 11 metabolites were significantly (false discovery rate (fdr) <0.05) associated with all-cause mortality. Acisoga, acylcarnitine C10:3, dimethylguanidino valerate, homocitrulline, N2,N2-dimethylguanosine, 1-methyladenosine and urobilin were associated with an increased risk, while hippurate, lysine, threonine and tryptophan were associated with a decreased risk. Ten out of 11 metabolites remained significantly associated after adjustments for cardiometabolic risk factors. The associations between metabolite levels and incident CVD were not as strong as for all-cause mortality, although 11 metabolites were nominally significant (p < 0.05). Further examination of the mortality-related metabolites may shed more light on the pathophysiology linking diabetes to premature mortality.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiovascular disease, Diabetes, Metabolomics, Mortality, N2,N2-dimethylguanosine and dimethylguanidino valerate
in
Metabolites
volume
10
issue
8
article number
315
pages
11 pages
publisher
MDPI AG
external identifiers
  • pmid:32751974
  • scopus:85088956061
ISSN
2218-1989
DOI
10.3390/metabo10080315
project
AIR Lund - Artificially Intelligent use of Registers
language
English
LU publication?
yes
id
cf271c56-014c-4422-b0a6-bfe4c8e7beff
date added to LUP
2020-08-11 13:42:42
date last changed
2024-05-15 15:56:49
@article{cf271c56-014c-4422-b0a6-bfe4c8e7beff,
  abstract     = {{<p>Alterations in the human metabolome occur years before clinical manifestation of type 2 diabetes (T2DM). By contrast, there is little knowledge of how metabolite alterations in individuals with diabetes relate to risk of diabetes complications and premature mortality. Metabolite profiling was performed using liquid chromatography-mass spectrometry in 743 participants with T2DM from the population-based prospective cohorts The Malmö Diet and Cancer-Cardiovascular Cohort (MDC-CC) and The Malmö Preventive Project (MPP). During follow-up, a total of 175 new-onset cases of cardiovascular disease (CVD) and 298 deaths occurred. Cox regressions were used to relate baseline levels of plasma metabolites to incident CVD and all-cause mortality. A total of 11 metabolites were significantly (false discovery rate (fdr) &lt;0.05) associated with all-cause mortality. Acisoga, acylcarnitine C10:3, dimethylguanidino valerate, homocitrulline, N2,N2-dimethylguanosine, 1-methyladenosine and urobilin were associated with an increased risk, while hippurate, lysine, threonine and tryptophan were associated with a decreased risk. Ten out of 11 metabolites remained significantly associated after adjustments for cardiometabolic risk factors. The associations between metabolite levels and incident CVD were not as strong as for all-cause mortality, although 11 metabolites were nominally significant (p &lt; 0.05). Further examination of the mortality-related metabolites may shed more light on the pathophysiology linking diabetes to premature mortality.</p>}},
  author       = {{Ottosson, Filip and Smith, Einar and Fernandez, Céline and Melander, Olle}},
  issn         = {{2218-1989}},
  keywords     = {{Cardiovascular disease; Diabetes; Metabolomics; Mortality; N2,N2-dimethylguanosine and dimethylguanidino valerate}},
  language     = {{eng}},
  number       = {{8}},
  publisher    = {{MDPI AG}},
  series       = {{Metabolites}},
  title        = {{Plasma metabolites associate with all-cause mortality in individuals with type 2 diabetes}},
  url          = {{http://dx.doi.org/10.3390/metabo10080315}},
  doi          = {{10.3390/metabo10080315}},
  volume       = {{10}},
  year         = {{2020}},
}