Dimethylglycine Deficiency and the Development of Diabetes mellitus.
Magnusson, Martin LU
; Wang, Thomas J
; Clish, Clary
; Engström, Gunnar
LU
; Nilsson, Peter
LU
; Gerszten, Robert E
and Melander, Olle
LU
(2015)
In Diabetes
64(8).
p.3010-3016
- Abstract
- Experimental studies have suggested possible protective effects of dimethylglycine (DMG) on glucose metabolism. DMG is degraded to glycine through a DMG-dehydrogenase (DMGDH)-catalyzed reaction and this is the only known pathway for the breakdown of DMG in mammals. In this study we aimed to identify the strongest genetic determinant of circulating DMG concentration and to investigate its associations with metabolic traits and incident diabetes. In the cohort with full metabolomics data (n=709), low plasma levels of DMG were significantly associated with higher blood glucose levels (p=3.9E-4). In the genome-wide association study (GWAS) of the discovery cohort (n=5,205) the strongest genetic signal of plasma DMG was conferred by rs2431332... (More)
- Experimental studies have suggested possible protective effects of dimethylglycine (DMG) on glucose metabolism. DMG is degraded to glycine through a DMG-dehydrogenase (DMGDH)-catalyzed reaction and this is the only known pathway for the breakdown of DMG in mammals. In this study we aimed to identify the strongest genetic determinant of circulating DMG concentration and to investigate its associations with metabolic traits and incident diabetes. In the cohort with full metabolomics data (n=709), low plasma levels of DMG were significantly associated with higher blood glucose levels (p=3.9E-4). In the genome-wide association study (GWAS) of the discovery cohort (n=5,205) the strongest genetic signal of plasma DMG was conferred by rs2431332 at the DMGDH-locus where the major allele was associated with lower DMG levels (p=2.5E-15). The same genetic variant (major allele of rs2431332), was also significantly associated with higher plasma insulin (p=0.019), increased insulin resistance (HOMA-IR) (p=0.019), as well as increased risk of incident diabetes (p=0.001) in the pooled analysis of the discovery cohort together with the two replication cohorts ((n=20,698) and (N=7,995). These data are consistent with a possible causal role of DMG deficiency in diabetes development and encourages for future studies examining if inhibition of DMG-dehydrogenase, or alternatively supplementation of DMG, might prove useful for the treatment/prevention of diabetes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5257955
- author
- Magnusson, Martin
LU
; Wang, Thomas J
; Clish, Clary
; Engström, Gunnar
LU
; Nilsson, Peter
LU
; Gerszten, Robert E
and Melander, Olle
LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 64
- issue
- 8
- pages
- 3010 - 3016
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- pmid:25795213
- wos:000358671300038
- scopus:84943184774
- ISSN
- 1939-327X
- DOI
- 10.2337/db14-1863
- project
- The use of Genomics and Proteomics for the Detection and Prevention of Cardiometabolic Disease
- language
- English
- LU publication?
- yes
- id
- 209e125f-9557-4fa9-916b-6ccfbc8cb2d6 (old id 5257955)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25795213?dopt=Abstract
- date added to LUP
- 2016-04-01 10:54:15
- date last changed
- 2024-01-07 03:54:06
@article{209e125f-9557-4fa9-916b-6ccfbc8cb2d6,
abstract = {{Experimental studies have suggested possible protective effects of dimethylglycine (DMG) on glucose metabolism. DMG is degraded to glycine through a DMG-dehydrogenase (DMGDH)-catalyzed reaction and this is the only known pathway for the breakdown of DMG in mammals. In this study we aimed to identify the strongest genetic determinant of circulating DMG concentration and to investigate its associations with metabolic traits and incident diabetes. In the cohort with full metabolomics data (n=709), low plasma levels of DMG were significantly associated with higher blood glucose levels (p=3.9E-4). In the genome-wide association study (GWAS) of the discovery cohort (n=5,205) the strongest genetic signal of plasma DMG was conferred by rs2431332 at the DMGDH-locus where the major allele was associated with lower DMG levels (p=2.5E-15). The same genetic variant (major allele of rs2431332), was also significantly associated with higher plasma insulin (p=0.019), increased insulin resistance (HOMA-IR) (p=0.019), as well as increased risk of incident diabetes (p=0.001) in the pooled analysis of the discovery cohort together with the two replication cohorts ((n=20,698) and (N=7,995). These data are consistent with a possible causal role of DMG deficiency in diabetes development and encourages for future studies examining if inhibition of DMG-dehydrogenase, or alternatively supplementation of DMG, might prove useful for the treatment/prevention of diabetes.}},
author = {{Magnusson, Martin and Wang, Thomas J and Clish, Clary and Engström, Gunnar and Nilsson, Peter and Gerszten, Robert E and Melander, Olle}},
issn = {{1939-327X}},
language = {{eng}},
number = {{8}},
pages = {{3010--3016}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{Dimethylglycine Deficiency and the Development of Diabetes mellitus.}},
url = {{http://dx.doi.org/10.2337/db14-1863}},
doi = {{10.2337/db14-1863}},
volume = {{64}},
year = {{2015}},
}