Plasma epoxyeicosatrienoic acids and dihydroxyeicosatrieonic acids, insulin, glucose and risk of diabetes: The strong heart study

• Published in: EBioMedicine Vol. 66; p. 103279
• Main Authors: Lemaitre, Rozenn N., Jensen, Paul N, Zeigler, Maxwell, Denham, Julie, Fretts, Amanda M., Umans, Jason G., Howard, Barbara V., Sitlani, Colleen M., McKnight, Barbara, Gharib, Sina A., King, Irena B., Siscovick, David S., Psaty, Bruce M, Sotoodehnia, Nona, Totah, Rheem A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-04-2021; Elsevier
• Subjects: 8,11,14-Eicosatrienoic Acid - analogs & derivatives; 8,11,14-Eicosatrienoic Acid - blood; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers - blood; Blood Glucose; Case-Control Studies; Cross-Sectional Studies; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - etiology; Diabetes Mellitus, Type 2 - metabolism; Dihydroxyeicosatrieonic acids; Disease Susceptibility; Epidemiology; Epoxyeicosatrienoic acids; Female; Glucose; Glucose - metabolism; Humans; Insulin; Insulin - blood; Male; Middle Aged; Research paper; Risk Assessment; Risk Factors; Young Adult; Epoxyeicosatrienoic acids; Diabetes; Glucose; Epidemiology; Insulin; Dihydroxyeicosatrieonic acids
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2021.103279

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.
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.
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.
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.
US National Institutes of Health