Dimethylglycine Deficiency and the Development of Diabetes

DSpace/Manakin Repository

Dimethylglycine Deficiency and the Development of Diabetes

Citable link to this page

 

 
Title: Dimethylglycine Deficiency and the Development of Diabetes
Author: Magnusson, Martin; Wang, Thomas J.; Clish, Clary; Engström, Gunnar; Nilsson, Peter; Gerszten, Robert E.; Melander, Olle

Note: Order does not necessarily reflect citation order of authors.

Citation: Magnusson, Martin, Thomas J. Wang, Clary Clish, Gunnar Engström, Peter Nilsson, Robert E. Gerszten, and Olle Melander. 2015. “Dimethylglycine Deficiency and the Development of Diabetes.” Diabetes 64 (8): 3010-3016. doi:10.2337/db14-1863. http://dx.doi.org/10.2337/db14-1863.
Full Text & Related Files:
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 HOMA insulin resistance (P = 0.019), and an 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 encourage future studies examining if inhibition of DMGDH, or alternatively, supplementation of DMG, might prove useful for the treatment/prevention of diabetes.
Published Version: doi:10.2337/db14-1863
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512219/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29002540
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters