Background: The American Heart Association (AHA) and the American Diabetes Association (ADA) recommend at least two servings of oily fish a week to promote cardiovascular health. Oily fish is rich in the long-chain omega-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). These, along with the vegetable-derived omega-3 PUFA alpha-linolenic acid (ALA), play major roles in normal physiological processes. The aim of this dissertation was to consider associations of fish, fish-derived omega-3 PUFAs DHA and EPA, and vegetable-derived omega-3 PUFA ALA with cardiovascular and glycemia outcomes, presented in three related manuscripts. Methods: All analyses utilized data from the Atherosclerosis Risk in Communities (ARIC) Study, a multi-center prospective study designed to investigate the etiology and natural history of cardiovascular disease. There have been five visits: the baseline in 1987–89 (visit 1) and four follow-up visits in 1990–92, 1993–95, 1996–98 and 2011–13. Data from visits 1 through 4 were used in this dissertation. Dietary data were collected at visits 1 and 3 via food frequency questionnaire (FFQ). Paper 1: We studied the association of consumption of seafood, EPA, DHA, and ALA with fasting blood glucose (FBG) (n=13,173), HbA1c (n=11,575), and incident type 2 diabetes (T2D) (n=11,874). FBG and HbA1c were obtained using blood samples collected during study visits and diabetes status was identified through self-report and lab values. To estimate differences across exposure categories, linear regression was used for continuous outcomes (FBG, HbA1c), adjusting for repeated measures as appropriate; Cox proportional hazards regression with time varying covariates was used for the incident T2D outcome. Paper 2: We studied the association of consumption of seafood, EPA, DHA, and ALA with J-point height and heart rate-corrected (QTc) interval (n = 12,611). QTc interval and J-point height were measured using ECGs obtained during study visits. To estimate differences across exposure categories, generalized estimating equations were used to estimate odds ratios of prolonged QTc and J-point elevation and differences in continuous measures of QTc interval and J-point height. Paper 3: One ARIC field center collected plasma biomarker values from participants at visit 1, and these data were used to augment self-report dietary data obtained via FFQ. We imputed biomarker values for other participants using multiple imputation for chained equations and investigated the associations of plasma phospholipid measures of ALA, DHA, and EPA with prolonged QTc, HbA1c, and incident T2D. Results: Paper 1: In multivariable analyses, intake of seafood and DHA+EPA was favorably associated with FBG and HbA1c in non-diabetic participants, although the magnitude of the associations was small. ALA was not associated with FBG or HbA1c in non-diabetic participants. Among diabetic participants, intake of seafood, DHA+EPA, and ALA were adversely associated with FBG and HbA1c, with differential effects for seafood by sex and race. Finally, higher intake of ALA was associated with higher risk of incident T2D in normoglycemics, while seafood and DHA+EPA were not. Paper 2: Higher intakes of ALA+DHA+EPA and ALA were associated with a shorter QTc interval. None of the exposures were associated with prolonged QTc, J-point elevation, or J-point height. Paper 3: In the full cohort (imputed) and the Minnesota (observed) populations, none of the exposures was significantly associated with prolonged QTc, HbA1c, or incident T2D. Point estimates in both populations were similar across different covariate adjustments, and confidence intervals were narrower in the full cohort population than in the observed plasma population. Conclusions: Considering the dietary recommendations of the ADA and AHA, this dissertation examined the associations of dietary omega-3 PUFAs with cardiovascular and glycemia outcomes while also considering the implications of measurement error in the exposure of interest. Taken together, these results suggest that consumption of omega-3 PUFAs are not associated with certain cardiovascular outcomes in healthy individuals, and may be associated with deleterious glucose homeostasis in those with diabetes.
University of Minnesota Ph.D. dissertation. September 2017. Major: Epidemiology. Advisors: Alvaro Alonso, Pamela Schreiner. 1 computer file (PDF); xv, 182 pages.
Intake of Omega-3 Polyunsaturated Fatty Acids and Associations with Cardiometabolic Risk Factors.
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