Plasma epoxyeicosatrienoic acids and dihydroxyeicosatrieonic acids, insulin, glucose and risk of diabetes: The strong heart study.
Plasma epoxyeicosatrienoic acids and dihydroxyeicosatrieonic acids, insulin, glucose and risk of diabetes: The strong heart study.
- 2021
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. 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. FUNDING: US National Institutes of Health. Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved. 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. 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.
English
2352-3964
10.1016/j.ebiom.2021.103279 [doi] PMC8010619 [pmc] S2352-3964(21)00072-4 [pii]
*8,11,14-Eicosatrienoic Acid/bl [Blood]
*Biomarkers/bl [Blood]
*Blood Glucose
*Diabetes Mellitus, Type 2/et [Etiology]
*Diabetes Mellitus, Type 2/me [Metabolism]
*Insulin/bl [Blood]
8,11,14-Eicosatrienoic Acid/aa [Analogs & Derivatives]
Adolescent
Adult
Aged
Aged, 80 and over
Case-Control Studies
Cross-Sectional Studies
Diabetes Mellitus, Type 2/bl [Blood]
Diabetes Mellitus, Type 2/ep [Epidemiology]
Disease Susceptibility
Female
Glucose/me [Metabolism]
Humans
Male
Middle Aged
Risk Assessment
Risk Factors
Young Adult
MedStar Health Research Institute
Journal Article
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. 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. FUNDING: US National Institutes of Health. Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved. 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. 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.
English
2352-3964
10.1016/j.ebiom.2021.103279 [doi] PMC8010619 [pmc] S2352-3964(21)00072-4 [pii]
*8,11,14-Eicosatrienoic Acid/bl [Blood]
*Biomarkers/bl [Blood]
*Blood Glucose
*Diabetes Mellitus, Type 2/et [Etiology]
*Diabetes Mellitus, Type 2/me [Metabolism]
*Insulin/bl [Blood]
8,11,14-Eicosatrienoic Acid/aa [Analogs & Derivatives]
Adolescent
Adult
Aged
Aged, 80 and over
Case-Control Studies
Cross-Sectional Studies
Diabetes Mellitus, Type 2/bl [Blood]
Diabetes Mellitus, Type 2/ep [Epidemiology]
Disease Susceptibility
Female
Glucose/me [Metabolism]
Humans
Male
Middle Aged
Risk Assessment
Risk Factors
Young Adult
MedStar Health Research Institute
Journal Article