Purine Metabolites and Carnitine Biosynthesis Intermediates Are Biomarkers for Incident Type 2 Diabetes
Ottosson, Filip LU ; Smith, Einar LU ; Gallo, Widet LU
; Fernandez, Céline
LU
and Melander, Olle
LU
(2019)
In The Journal of clinical endocrinology and metabolism
104(10).
p.4921-4930
- Abstract
CONTEXT: Metabolomics has the potential to generate biomarkers that can facilitate understanding relevant pathways in the pathophysiology of type 2 diabetes (T2DM). METHODS: Nontargeted metabolomics was performed, via liquid chromatography-mass spectrometry, in a discovery case-cohort study from the Malmö Preventive Project (MPP), which consisted of 698 metabolically healthy participants, of whom 202 developed T2DM within a follow-up time of 6.3 years. Metabolites that were significantly associated with T2DM were replicated in the population-based Malmö Diet and Cancer-Cardiovascular Cohort (MDC-CC) (N = 3423), of whom 402 participants developed T2DM within a follow-up time of 18.2 years. RESULTS: Using nontargeted metabolomics, we... (More)
CONTEXT: Metabolomics has the potential to generate biomarkers that can facilitate understanding relevant pathways in the pathophysiology of type 2 diabetes (T2DM). METHODS: Nontargeted metabolomics was performed, via liquid chromatography-mass spectrometry, in a discovery case-cohort study from the Malmö Preventive Project (MPP), which consisted of 698 metabolically healthy participants, of whom 202 developed T2DM within a follow-up time of 6.3 years. Metabolites that were significantly associated with T2DM were replicated in the population-based Malmö Diet and Cancer-Cardiovascular Cohort (MDC-CC) (N = 3423), of whom 402 participants developed T2DM within a follow-up time of 18.2 years. RESULTS: Using nontargeted metabolomics, we observed alterations in nine metabolite classes to be related to incident T2DM, including 11 identified metabolites. N2,N2-dimethylguanosine (DMGU) (OR = 1.94; P = 4.9e-10; 95% CI, 1.57 to 2.39) was the metabolite most strongly associated with an increased risk, and beta-carotene (OR = 0.60; P = 1.8e-4; 95% CI, 0.45 to 0.78) was the metabolite most strongly associated with a decreased risk. Identified T2DM-associated metabolites were replicated in MDC-CC. Four metabolites were significantly associated with incident T2DM in both the MPP and the replication cohort MDC-CC, after adjustments for traditional diabetes risk factors. These included associations between three metabolites, DMGU, 7-methylguanine (7MG), and 3-hydroxytrimethyllysine (HTML), and incident T2DM. CONCLUSIONS: We used nontargeted metabolomics in two Swedish prospective cohorts comprising >4000 study participants and identified independent, replicable associations between three metabolites, DMGU, 7MG, and HTML, and future risk of T2DM. These findings warrant additional studies to investigate a potential functional connection between these metabolites and the onset of T2DM.
(Less)
- author
- Ottosson, Filip
LU
; Smith, Einar
LU
; Gallo, Widet
LU
; Fernandez, Céline
LU
and Melander, Olle
LU
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Journal of clinical endocrinology and metabolism
- volume
- 104
- issue
- 10
- pages
- 10 pages
- publisher
- Oxford University Press
- external identifiers
-
- scopus:85071986631
- pmid:31502646
- ISSN
- 1945-7197
- DOI
- 10.1210/jc.2019-00822
- language
- English
- LU publication?
- yes
- id
- 710d0220-fbb9-47bc-aa10-5487016d0dc3
- date added to LUP
- 2019-09-16 13:08:23
- date last changed
- 2024-06-27 04:53:45
@article{710d0220-fbb9-47bc-aa10-5487016d0dc3,
abstract = {{<p>CONTEXT: Metabolomics has the potential to generate biomarkers that can facilitate understanding relevant pathways in the pathophysiology of type 2 diabetes (T2DM). METHODS: Nontargeted metabolomics was performed, via liquid chromatography-mass spectrometry, in a discovery case-cohort study from the Malmö Preventive Project (MPP), which consisted of 698 metabolically healthy participants, of whom 202 developed T2DM within a follow-up time of 6.3 years. Metabolites that were significantly associated with T2DM were replicated in the population-based Malmö Diet and Cancer-Cardiovascular Cohort (MDC-CC) (N = 3423), of whom 402 participants developed T2DM within a follow-up time of 18.2 years. RESULTS: Using nontargeted metabolomics, we observed alterations in nine metabolite classes to be related to incident T2DM, including 11 identified metabolites. N2,N2-dimethylguanosine (DMGU) (OR = 1.94; P = 4.9e-10; 95% CI, 1.57 to 2.39) was the metabolite most strongly associated with an increased risk, and beta-carotene (OR = 0.60; P = 1.8e-4; 95% CI, 0.45 to 0.78) was the metabolite most strongly associated with a decreased risk. Identified T2DM-associated metabolites were replicated in MDC-CC. Four metabolites were significantly associated with incident T2DM in both the MPP and the replication cohort MDC-CC, after adjustments for traditional diabetes risk factors. These included associations between three metabolites, DMGU, 7-methylguanine (7MG), and 3-hydroxytrimethyllysine (HTML), and incident T2DM. CONCLUSIONS: We used nontargeted metabolomics in two Swedish prospective cohorts comprising >4000 study participants and identified independent, replicable associations between three metabolites, DMGU, 7MG, and HTML, and future risk of T2DM. These findings warrant additional studies to investigate a potential functional connection between these metabolites and the onset of T2DM.</p>}},
author = {{Ottosson, Filip and Smith, Einar and Gallo, Widet and Fernandez, Céline and Melander, Olle}},
issn = {{1945-7197}},
language = {{eng}},
number = {{10}},
pages = {{4921--4930}},
publisher = {{Oxford University Press}},
series = {{The Journal of clinical endocrinology and metabolism}},
title = {{Purine Metabolites and Carnitine Biosynthesis Intermediates Are Biomarkers for Incident Type 2 Diabetes}},
url = {{http://dx.doi.org/10.1210/jc.2019-00822}},
doi = {{10.1210/jc.2019-00822}},
volume = {{104}},
year = {{2019}},
}