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Am J Clin Nutr. 2015 May;101(5):1047-54. doi: 10.3945/ajcn.114.101857. Epub 2015 Mar 18.

Plasma phospholipid very-long-chain saturated fatty acids and incident diabetes in older adults: the Cardiovascular Health Study.

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From the Cardiovascular Health Research Unit (RNL, AMF, CMS, and NS), Departments of Medicine (RNL, CMS, and NS), Epidemiology (AMF), and Biostatistics (MLB and BM), University of Washington, Seattle, WA; the Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (KM); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (LD); New York Academy of Medicine, New York, NY (DSS); the Departments of Medicine and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (JRK); and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM).



Circulating saturated fatty acids (SFAs) are integrated biomarkers of diet and metabolism that may influence the pathogenesis of diabetes. In epidemiologic studies, circulating levels of palmitic acid (16:0) are associated with diabetes; however, very-long-chain SFAs (VLSFAs), with 20 or more carbons, differ from palmitic acid in their biological activities, and little is known of the association of circulating VLSFA with diabetes.


By using data from the Cardiovascular Health Study, we examined the associations of plasma phospholipid VLSFA levels measured at baseline with subsequent incident diabetes.


A total of 3179 older adults, with a mean age of 75 y at study baseline (1992-1993), were followed through 2011. We used multiple proportional hazards regression to examine the associations of arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with diabetes.


Baseline levels of each VLSFA were cross-sectionally associated with lower triglyceride levels and lower circulating palmitic acid. We identified 284 incident diabetes cases during follow-up. Compared with the lowest quartile, levels of arachidic acid in the highest quartile of the fatty acid distribution were associated with a 47% lower risk of diabetes (95% CI: 23%, 63%; P-trend: <0.001), after adjustment for demographics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of behenic and lignoceric acid were similarly associated with 33% (95% CI: 6%, 53%; P-trend: 0.02) and 37% (95% CI: 11%, 55%; P-trend: 0.01) lower diabetes risk, respectively. Adjustment for triglycerides and palmitic acid attenuated the associations toward the null, and only the association of arachidic acid remained statistically significant (32% lower risk for fourth vs. first quartile; P-trend: 0.04).


These results suggest that circulating VLSFAs are associated with a lower risk of diabetes, and these associations may be mediated by lower triglycerides and palmitic acid. The study highlights the need to distinguish the effects of different SFAs and to explore determinants of circulating VLSFAs. This trial was registered at as NCT00005133.


arachidic acid; behenic acid; diabetes; epidemiology; fatty acids; lignoceric acid; saturated

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