Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans

Eugene P. Rhee, Susan Cheng, Martin G. Larson, Geoffrey A. Walford, Gregory D. Lewis, Elizabeth McCabe, Elaine Yang, Laurie Farrell, Caroline S. Fox, Christopher J. O'Donnell, Steven A. Carr, Ramachandran S. Vasan, Jose C. Florez, Clary B. Clish, Thomas J. Wang, Robert E. Gerszten

Research output: Contribution to journalArticle

Abstract

Dyslipidemia is an independent risk factor for type 2 diabetes, although exactly which of the many plasma lipids contribute to this remains unclear. We therefore investigated whether lipid profiling can inform diabetes prediction by performing liquid chromatography/mass spectrometry - based lipid profiling in 189 individuals who developed type 2 diabetes and 189 matched disease-free individuals, with over 12 years of follow up in the Framingham Heart Study. We found that lipids of lower carbon number and double bond content were associated with an increased risk of diabetes, whereas lipids of higher carbon number and double bond content were associated with decreased risk. This pattern was strongest for triacylglycerols (TAGs) and persisted after multivariable adjustment for age, sex, BMI, fasting glucose, fasting insulin, total triglycerides, and HDL cholesterol. A combination of 2 TAGs further improved diabetes prediction. To explore potential mechanisms that modulate the distribution of plasma lipids, we performed lipid profiling during oral glucose tolerance testing, pharmacologic interventions, and acute exercise testing. Levels of TAGs associated with increased risk for diabetes decreased in response to insulin action and were elevated in the setting of insulin resistance. Conversely, levels of TAGs associated with decreased diabetes risk rose in response to insulin and were poorly correlated with insulin resistance. These studies identify a relationship between lipid acyl chain content and diabetes risk and demonstrate how lipid profiling could aid in clinical risk assessment.

Original languageEnglish (US)
Pages (from-to)1402-1411
Number of pages10
JournalJournal of Clinical Investigation
Volume121
Issue number4
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans'. Together they form a unique fingerprint.

  • Cite this

    Rhee, E. P., Cheng, S., Larson, M. G., Walford, G. A., Lewis, G. D., McCabe, E., Yang, E., Farrell, L., Fox, C. S., O'Donnell, C. J., Carr, S. A., Vasan, R. S., Florez, J. C., Clish, C. B., Wang, T. J., & Gerszten, R. E. (2011). Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans. Journal of Clinical Investigation, 121(4), 1402-1411. https://doi.org/10.1172/JCI44442