Circulating Docosahexaenoic Acid Levels Are Associated with Fetal Insulin Sensitivity

Jin-Ping Zhao,Zhong-Cheng Luo,Edgard Delvin,Carole Garofalo,William D Fraser,Schohraya Spahis,Anne Monique Nuyt,Alain Montoudis,Pierre Julien,Emile Levy,Victor Sanchez-Margalet

doi:10.1371/journal.pone.0085054

Abstract

BackgroundArachidonic acid (AA; C20∶4 n-6) and docosahexaenoic acid (DHA; C22∶6 n-3) are important long-chain polyunsaturated fatty acids (LC-PUFA) in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally “programming” this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies.Methods and Principal FindingsIn a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation) and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration) and beta-cell function (proinsulin-to-insulin ratio) in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids) were lower comparing newborns of gestational diabetic (n = 24) vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01). Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = −0.37, P <0.0001). The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity.ConclusionLow circulating DHA levels are associated with compromised fetal insulin sensitivity, and may be involved in perinatally “programming” the susceptibility to type 2 diabetes in the offspring of gestational diabetic mothers.

Highlights

Gestational diabetes is a common pregnancy complication affecting 3.5% to 7.2% of pregnancies [1]
Low circulating docosahexaenoic acid (DHA) levels are associated with compromised fetal insulin sensitivity, and may be involved in perinatally ‘‘programming’’ the susceptibility to type 2 diabetes in the offspring of gestational diabetic mothers
We explored whether circulating levels of other fatty acids are associated with fetal insulin sensitivity, and whether there are differences in circulating levels of fatty acids correlated to fetal insulin sensitivity comparing gestational vs. non-diabetic pregnancies

Summary

Introduction

Gestational diabetes is a common pregnancy complication affecting 3.5% to 7.2% of pregnancies [1]. Levels of plasma and tissue fatty acids have been associated with insulin resistance [13,15,16] It remains unknown whether DHA and AA may affect insulin sensitivity or beta-cell function during fetal life, and whether low circulating DHA or AA levels may be involved in perinatally ‘‘programming’’ the susceptibility to type 2 diabetes in the offspring of gestational diabetic mothers. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies

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