Change search
ReferencesLink to record
Permanent link

Direct link
Effect of insulin resistance on monounsaturated fatty acid levels: a multi-cohort non-targeted metabolomics and mendelian randomization study
Show others and affiliations
Number of Authors: 22
2016 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, no 10, e1006379Article in journal (Refereed) Published
Abstract [en]

Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or β-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.

Place, publisher, year, edition, pages
2016. Vol. 12, no 10, e1006379
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
URN: urn:nbn:se:du-23279DOI: 10.1371/journal.pgen.1006379ISI: 000386683300041PubMedID: 27768686OAI: oai:DiVA.org:du-23279DiVA: diva2:1039801
Available from: 2016-10-25 Created: 2016-10-25 Last updated: 2016-12-01Bibliographically approved

Open Access in DiVA

fulltext(2322 kB)12 downloads
File information
File name FULLTEXT01.pdfFile size 2322 kBChecksum SHA-512
dc7e0899f72880f62357d6f936530ce459192802c1cf04451f380c5f7cd3085c3950791ba57e4783a83c2593c4f0bbd74cad6296a9db377740f0d0e0510d3474
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Ärnlöv, Johan
By organisation
Medical Science
In the same journal
PLoS Genetics
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 12 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 52 hits
ReferencesLink to record
Permanent link

Direct link