Date Published: September 13, 2019
Publisher: Public Library of Science
Author(s): Yeyi Zhu, Mengying Li, Mohammad L. Rahman, Stefanie N. Hinkle, Jing Wu, Natalie L. Weir, Yuan Lin, Huixia Yang, Michael Y. Tsai, Assiamira Ferrara, Cuilin Zhang, Fumiaki Imamura
Abstract: BackgroundDespite 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 findingsWithin 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 (
Partial Text: Gestational diabetes mellitus (GDM) has emerged as the most common metabolic complication, affecting 7%–25% of pregnancies worldwide [1,2], forming a growing, urgent public health concern . Nutritional perturbations have been implicated in the programming of glucose homeostasis , with carbohydrate metabolism conceivably serving as a key component given its impact on postprandial glucose and insulin responses . Notably, emerging experimental data have linked altered fatty acids composition to exacerbation of insulin resistance and β-cell dysfunction [6–8], suggesting additional pathways underlying the etiology of hyperglycemia.
Compared to non-GDM controls, women with GDM were more likely to have a family history of diabetes and be overweight or obese before pregnancy (Table 1). Among all PUFAs, LA (18:2n-6) was the most abundant form and accounted for 21%–22% of the total plasma phospholipid fatty acids level, followed by AA 20:4n-6 for 10%–11%, DHA for 4%, and DGLA 20:3n-6 for 3%–4%, whereas other individual PUFAs contributed less than 1%, with the lowest concentration observed for GLA (0.07%–0.08%) at gestational weeks 10–14 and 15–26 (Table 2). Compared to non-GDM controls, women with GDM had significantly lower levels of DHA at weeks 10–14, EPA at weeks 15–26, total n-3 PUFAs at both weeks 10–14 and 15–26, and EDA and DTA at weeks 15–26, whereas they had significantly higher levels of GLA at weeks 10–14 and DGLA at weeks 10–14 and 15–26. Among PUFA ratios, Δ6-desaturase at weeks 10–14 and DGLA/LA at both gestational periods were significantly higher, whereas Δ5-desaturase was significantly lower among GDM women compared to non-GDM controls.
In this longitudinal study within the prospective NICHD Fetal Growth Studies–Singleton Cohort, we provide, to our knowledge, the most extensive evaluation to date of the longitudinal profile of 11 individual plasma phospholipid PUFAs and three PUFA product-to-precursor ratios across gestation and their associations in early to midpregnancy with subsequent risk of GDM. Overall, primarily diet-derived plasma phospholipid PUFAs including n-3 EPA and DHA and n-6 LA in early to midpregnancy were not significantly associated with GDM risk; however, EPA and DHA were inversely correlated with insulin-resistance markers. Among primarily endogenous PUFAs, n-6 GLA at weeks 10–14 and DGLA at both weeks 10–14 and 15–26 were positively associated with GDM risk, whereas DTA at weeks 15–26 was inversely related to GDM risk. For PUFA ratios, Δ6-desaturase at weeks 10–14 and DGLA/LA at both gestational periods were positively associated whereas Δ5-desaturase at both gestational periods was inversely associated with GDM risk.