Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Olle Melander

Principal investigator

Default user image.

Dimethylglycine Deficiency and the Development of Diabetes mellitus.

Author

  • Martin Magnusson
  • Thomas J Wang
  • Clary Clish
  • Gunnar Engström
  • Peter Nilsson
  • Robert E Gerszten
  • Olle Melander

Summary, in English

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.

Department/s

  • Cardiovascular Research - Hypertension
  • Cardiovascular Research - Epidemiology
  • Internal Medicine - Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2015

Language

English

Pages

3010-3016

Publication/Series

Diabetes

Volume

64

Issue

8

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Project

  • The use of Genomics and Proteomics for the Detection and Prevention of Cardiometabolic Disease

Research group

  • Cardiovascular Research - Hypertension
  • Cardiovascular Research - Epidemiology
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1939-327X