Abstract
This study was performed to evaluate the effects of omega-3 fatty acids from flaxseed oil on genetic and metabolic profiles in patients with gestational diabetes mellitus (GDM). This randomized, double-blind, placebo-controlled clinical trial was performed in 60 women with GDM. Participants were randomly divided into two groups to intake either 2 x 1,000 mg/day omega-3 fatty acids from flaxseed oil containing 400 mg α-linolenic acid in each capsule (n=30) or placebo (n=30) for 6 weeks. Omega-3 fatty acids intake upregulated peroxisome proliferator-activated receptor gamma (P<0.001) and low-density lipoprotein receptor (P=0.004), and downregulated gene expression of interleukin-1 (P=0.002) and tumor necrosis factor alpha (P=0.001) in peripheral blood mononuclear cells of subjects with GDM. In addition, omega-3 fatty acids supplementation reduced fasting plasma glucose (P=0.001), insulin levels (P=0.001) and insulin resistance (P<0.001), and increased insulin sensitivity (P=0.005) when compared with the placebo. Additionally, omega-3 fatty acids supplementation was associated with a decrease in triglycerides (P<0.001), VLDL-cholesterol (P<0.001), total cholesterol (P=0.01) and total-/HDL-cholesterol ratio (P=0.01) when compared with placebo. Omega-3 fatty acids administration was also associated with a significant reduction in high sensitivity C-reactive protein (P=0.006) and malondialdehyde (P<0.001), and an increase in total nitrite (P<0.001) and total glutathione levels (P=0.006) when compared with the placebo. Omega-3 fatty acids supplementation for 6 weeks to women with GDM had beneficial effects on gene expression related to insulin, lipid and inflammation, glycemic control, lipids, inflammatory markers and oxidative stress.
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Key Points
Gestational diabetes mellitus (GDM) is a condition in which glucose intolerance occurs in pregnant women without previously diagnosed diabetes mellitus. Both pre-existing maternal obesity and gestational diabetes are associated with decreased expression of transcription factors involved in carbohydrate and lipid metabolism such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element binding protein 1c and increased gene expression levels of adipokines, tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and leptin in adipose tissue. A previous study indicated that a 6-week supplementation with 1,000 mg fish oil enhanced gene expression of the PPAR-γ, low-density lipoprotein receptor (LDLR), TNF-α and IL-6. Other studies investigated the effects of omega-3 fatty acids supplementation on gene expression levels in different metabolic conditions. The aim of this study to evaluate the effect of a 6-week supplementation with 2 g/day flaxseed oil on glycemic control, lipid profile, parameters of inflammation and oxidative stress and gene expression related to metabolic profiles.
Omega-3 fatty acids supplementation during 6 weeks to women with GDM had beneficial effects on gene expression related to insulin, lipids, glycemic control, inflammatory markers and oxidative stress. A significant improvement in PPAR-γ and LDLR mRNA expression as well as parameters of glycemic control, triglycerides, VLDL-cholesterol, total cholesterol and total-/HDL-cholesterol ratio were found.
Omega-3 fatty acids supplementation increases β-oxidation of fatty acids, reduces lipogenesis, improves antioxidant functions and facilitates insulin action. This study showed that the ingestion of flaxseed oil by women with GDM caused a significant decrease in TNF-α and IL-1 expression. It was also effective in improving hs-CRP, NO, GSH and MDA, but did not affect TAC values and gene expression of TGF-β and VEGF. In this study, beneficial effects on cardio-metabolic markers may be due to the type of omega-3 fatty acids used and baseline levels of biochemical variables. As there are multiple metabolic disorders such as insulin resistance, dyslipidemia, increased inflammatory markers and oxidative stress which occur during pregnancy, especially in women with GDM, omega-3 fatty acids may have better effects than in other metabolic diseases. Studies with longer duration of the intervention are needed to confirm these findings.