Circulating Docosahexaenoic Acid Levels Are Associated with Fetal Insulin Sensitivity

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.

Effects of polyunsaturated fatty acid intake and status during pregnancy, lactation, and early childhood on cardiometabolic health: A systematic review

“…In the first study, cord blood levels of the n-6 FA 319 GLA, but not ARA, LA, DHA, or EPA were inversely associated with 320 fasting insulin and HOMA-IR at 7 y [57]. In the second study, cord 321 blood DGLA was inversely associated with the glucose/insulin ratio 322 and DHA and ALA levels were inversely associated with proinsulin 323 levels [68]. A higher PUFA/SFA intake ratio during pregnancy was Parameter estimate from mentioned statistical model, +, positive value (increase in outcome); À, negative value (decrease in outcome); null, no association.…”

“…Only six studies examined the associations between PUFAs in 414 early life and measures of insulin sensitivity. The results of these 415 studies suggest a beneficial effect of PUFAs: DHA supplementation 416 in pregnancy led to lower insulin levels in cord blood in a trial in 417 47 women [37], and observational studies reported inverse associ-418 ations between DHA, ALA, and DGLA levels with proinsulin in cord 419 blood[68]; between GLA levels in cord blood and HOMA-IR at 7 y 420[57]; and between maternal PUFA intake and infant insulin levels421 [48]. This potential beneficial effect on insulin sensitivity was not 422 observed in a meta-analysis of n-3 FA intervention studies in adults 423 [89].…”

Effects of dietary fat subtypes on glucose homeostasis during pregnancy in rats

“…These PUFAs must come from the diet of the mother and their amount and the n-3/n-6 balance may well be one of the “stressors” that drives the pathogenesis of GDM [7, 8]. There is already a good deal of evidence from non-pregnant humans and experimental animal models showing that dietary fatty acid composition strongly influences both insulin secretion and sensitivity [9–11].…”

The maternal diabetes mellitus and consequences for newborn

“…Kolejne badanie kliniczne wykazało, iż obniżenie stężenia estrogenów, obserwowane u ciężarnych z cukrzycą, może stanowić przyczynę niedoborów omega-3. Estrogeny stymulują bowiem konwersję kwasu alfa linolenowego do DHA i EPA [15]. Przeprowadzone do tej pory badania pozwalają na wysunięcie wniosku, iż być może odpowiednia suplementacja kwasów omega-3 u kobiet ciężarnych pozwoli na ograniczenie u dzieci zjawiska powstawania insulinooporności, a co za tym idzie -zmniejszy ryzyko rozwoju cukrzycy typu 2 w wieku dorosłym.…”