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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:
author
organization
publishing date
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
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
2015-04-05 14:05:32
date last changed
2017-10-01 03:25:56
@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},
  volume       = {64},
  year         = {2015},
}