Plasma phospholipid n-3 and n-6 polyunsaturated fatty acids in relation to cardiometabolic markers and gestational diabetes: A longitudinal study within the prospective NICHD Fetal Growth Studies

Autoři: Yeyi Zhu aff001;  Mengying Li aff003;  Mohammad L. Rahman aff004;  Stefanie N. Hinkle aff003;  Jing Wu aff005;  Natalie L. Weir aff006;  Yuan Lin aff007;  Huixia Yang aff008;  Michael Y. Tsai aff006;  Assiamira Ferrara aff001;  Cuilin Zhang aff003
Působiště autorů: Division of Research, Kaiser Permanente Northern California, Oakland, California, United States of America aff001;  Department of Epidemiology & Biostatistics, University of California, San Francisco, California, United States of America aff002;  Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States of America aff003;  Department of Population Medicine and Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, Massachusetts, United States of America aff004;  Glotech Inc., Bethesda, Maryland, United States of America aff005;  Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America aff006;  Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, United States of America aff007;  Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China aff008
Vyšlo v časopise: Plasma phospholipid n-3 and n-6 polyunsaturated fatty acids in relation to cardiometabolic markers and gestational diabetes: A longitudinal study within the prospective NICHD Fetal Growth Studies. PLoS Med 16(9): e32767. doi:10.1371/journal.pmed.1002910
Kategorie: Research Article
doi: 10.1371/journal.pmed.1002910



Despite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM).

Methods and findings

Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies–Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10–14, 15–26, 23–31, and 33–39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15–26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42–0.96; P = 0.042) and 33% (0.67; 95% CI 0.45–0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10–14 and DGLA at GWs 10–14 and 15–26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15–26 was associated with a 45% (0.55; 95% CI 0.37–0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low (<median) n-6 PUFAs levels had a 64% (95% CI 0.14–0.95; P value = 0.039) lower risk of GDM versus women with low n-3 and high n-6 PUFAs. Limitations include the inability to distinguish between exogenous and endogenous influences on circulating PUFA levels and the lack of causality inherent in observational studies.


Our findings may suggest a potential role of primarily endogenously metabolized plasma phospholipid n-6 PUFAs including GLA, DGLA, and DTA in early to midpregnancy in the development of GDM. Null findings on primarily diet-derived n-3 EPA and DHA and n-6 LA do not provide strong evidence to suggest a beneficial role in prevention of GDM, although not excluding the potential benefit of EPA and DHA on glucose–insulin homeostasis given the inverse associations with insulin-resistance markers. Our findings highlight the importance of assessing individual circulating PUFAs to investigate their distinct pathophysiologic roles in glucose homeostasis in pregnancy.

Klíčová slova:

Biology and life sciences – Biochemistry – Lipids – Phospholipids – Fatty acids – Metabolism – Carbohydrate metabolism – Glucose metabolism – Anatomy – Body fluids – Blood – Blood plasma – Physiology – Physiological processes – Homeostasis – Medicine and health sciences – Endocrinology – Endocrine disorders – Metabolic disorders – Women's health – Maternal health – Pregnancy – Obstetrics and gynecology


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