Plasma epoxyeicosatrienoic acids and dihydroxyeicosatrieonic acids, insulin, glucose and risk of diabetes: The strong heart study
Rozenn N. Lemaitre,
Paul N Jensen,
Maxwell Zeigler,
Julie Denham,
Amanda M. Fretts,
Jason G. Umans,
Barbara V. Howard,
Colleen M. Sitlani,
Barbara McKnight,
Sina A. Gharib,
Irena B. King,
David S. Siscovick,
Bruce M Psaty,
Nona Sotoodehnia,
Rheem A. Totah
Affiliations
Rozenn N. Lemaitre
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Corresponding author.
Paul N Jensen
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
Maxwell Zeigler
Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA
Julie Denham
Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA
Amanda M. Fretts
Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, WA, USA
Jason G. Umans
MedStar Health Research Institute, Hyattsville, MD, USA
Barbara V. Howard
MedStar Health Research Institute, Hyattsville, MD, USA; Georgetown and Howard Universities Center for Translational Science, Washington DC, USA
Colleen M. Sitlani
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
Barbara McKnight
Department of Biostatistics, University of Washington, Seattle, WA, USA
Sina A. Gharib
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA
Irena B. King
Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA
David S. Siscovick
New York Academy of Medicine, New York, NY, USA
Bruce M Psaty
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, WA, USA; Kaiser Permanente Washington Health Research Institute, Seattle, WA
Nona Sotoodehnia
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA
Rheem A. Totah
Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA
Background: Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid with multiple biological functions. Rodent experiments suggest EETs play a role in insulin sensitivity and diabetes, but evidence in humans is limited. To address this knowledge gap, we conducted a case-cohort study in the Strong Heart Family Study, a prospective cohort among American Indians. Methods: We measured 4 EET species and 4 species of corresponding downstream metabolites, dihydroxyeicosatrieonic acids (DHETs), in plasma samples from 1161 participants, including 310 with type 2 diabetes. We estimated the associations of total (esterified and free) EETs and DHETs with incident diabetes risk, adjusting for known risk factors. We also examined cross-sectional associations with plasma fasting insulin and glucose in the case-cohort and in 271 participants without diabetes from the older Strong Heart Study cohort, and meta-analyzed the results from the 2 cohorts. Findings: We observed no significant association of total EET or DHET levels with incident diabetes. In addition, plasma EETs were not associated with plasma insulin or plasma glucose. However, higher plasma 14,15-DHET was associated with lower plasma insulin and lower plasma glucose. Interpretation: In this first prospective study of EETs and diabetes, we found no evidence for a role of total plasma EETs in diabetes. The novel associations of 14,15-DHET with insulin and glucose warrant replication and exploration of possible mechanisms. Funding: US National Institutes of Health
