Clinical Nutrition xxx (2014) 1e6
Contents lists available at ScienceDirect
Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu
Randomized control trials
Effects of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles in gestational diabetes: Randomized, double-blind, placebo-controlled trial Mansooreh Samimi a, Mehri Jamilian b, Zatollah Asemi c, *, Ahmad Esmaillzadeh d, e a
Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran Department of Gynecology and Obstetrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran d Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran e Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran b c
a r t i c l e i n f o
s u m m a r y
Article history: Received 2 May 2014 Accepted 11 June 2014
Background & aims: We are aware of no study that examined the effects of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles in gestational diabetes (GDM). This study was designed to assess the effects of omega-3 fatty acid supplementation on insulin concentrations and lipid profiles among pregnant women with GDM. Methods: This randomized, double-blind, placebo-controlled clinical trial was performed among 56 women with GDM. Subjects were randomly assigned to receive either 1000 mg omega-3 fatty acid supplements containing 180 mg eicosapentaenoic acid and 120 mg docosahexanoic acid (n ¼ 28) or placebo (n ¼ 28) for 6 weeks. Fasting blood samples were taken at study baseline and after 6 weeks of intervention to quantify biochemical variables. Results: Although omega-3 fatty acid supplementation did not led to a significant change in serum insulin levels and HOMA-IR in omega-3 fatty acid group, we found a significant difference in changes in serum insulin levels (change from baseline: 1.5 ± 7.5 vs. þ3.5 ± 8.5 mIU/mL, P ¼ 0.02) and HOMA-IR (0.4 ± 2.1 vs. þ1.1 ± 2.4, P ¼ 0.02) comparing the two groups. Furthermore, a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) levels was seen after omega-3 fatty acid supplementation compared with placebo (236.3 ± 1541.9 vs. 898.6 ± 2292.7 ng/mL, P ¼ 0.03). Omega-3 fatty acid supplementation did not influence fasting plasma glucose, homeostatic model assessment-Beta cell function (HOMA-B), quantitative insulin sensitivity check index (QUICKI) and lipid profiles. Conclusions: Omega-3 fatty acid supplementation in GDM women had beneficial effects on insulin resistance, however, it did not affect plasma glucose, HOMA-B, QUICKI and lipid profiles. Clinical registration number: www.irct.ir as IRCT201312265623N16. © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Keywords: Omega-3 fatty acid Supplementation Gestational diabetes Pregnant women
1. Introduction Gestational diabetes mellitus (GDM) is one of the most common complications that occur in pregnancy, it affects 3e8% of all pregnancies with an increasing prevalence worldwide. [1] GDM is associated with insulin resistance and increased lipid profiles [2]. GDM is associated with undesirable long-term maternal outcomes,
* Corresponding author. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Ravandi, Kashan, Iran. Tel.: þ98 361 4463378; fax: þ98 361 4463377. E-mail addresses: [email protected], [email protected] (Z. Asemi).
increased perinatal morbidity (e.g. macrosomia, birth trauma and pre-eclampsia) and long-term sequelae in the offspring [3]. Abnormal maternal lipid profiles in GDM patients might detrimentally influence the fetus by increasing the rate of aortic fatty streaks [4]. Furthermore, it can lead to increased risk of cardiovascular diseases (CVD) in later life of the mother and the offspring [5]. Several strategies including the use of low-glycemic index diet [6], consumption of the dietary approaches to stop hypertension (DASH) eating plan [7], the use of Oral Hypoglycemic Agents (OHAs) [8] and insulin therapy [9] have been suggested for management of insulin resistance in GDM patients. Some studies have reported significant differences in blood omega-3 fatty acid levels
http://dx.doi.org/10.1016/j.clnu.2014.06.005 0261-5614/© 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Please cite this article in press as: Samimi M, et al., Effects of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles in gestational diabetes: Randomized, double-blind, placebo-controlled trial, Clinical Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2014.06.005
2
M. Samimi et al. / Clinical Nutrition xxx (2014) 1e6
between women with and those without GDM [10,11]. Epidemiologic studies examining the association between omega-3 fatty acid intake and risk of GDM have shown conflicting findings [12,13]. In a recent study [14], administration of 4 omega-3 fatty acid capsules daily in women with polycystic ovary syndrome (PCOS) for 12 weeks decreased fasting plasma glucose (FPG), insulin resistance and lipid profiles [14]. However, low dose intake of fish oil did not significantly affect insulin resistance and lipid profiles in HIVinfected patients on antiretroviral therapy [15]. Omega-3 fatty acid supplementation might affect insulin metabolism and lipid profiles via their effects on increased activation of AMP-activated protein kinase (AMPK) [16], improved LDL receptor activity in the liver, reduced LDL-cholesterol synthesis and increased fractional rate of catabolism of LDL-cholesterol [17]. Despite the increasing body of evidence suggesting a potential effect of omega-3 fatty acid supplements in enhancing insulin function [18], improving glucose tolerance and lipid profiles [14,19], we are aware of no randomized controlled trial that investigated the effect of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles in GDM patients. The current study was, therefore, done to investigate the effects of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles of pregnant women with GDM. 2. Subjects and methods 2.1. Participants This randomized, double-blind, placebo-controlled trial was conducted in Kashan, Iran, during January 2014eMarch 2014. For estimating sample size, we considered type one (a) and type two errors (b) of 0.05 and 0.20 (power ¼ 80%), respectively, and homeostasis model of assessment-insulin resistance (HOMA-IR) score as a key variable. Based on a previous study [14], standard deviation (SD) of HOMA-IR was 0.8 and the difference in mean (d) of HOMAIR was 0.6. We reached the sample size of 24 subjects for each group using the suggested formula for parallel clinical trials. In the current study, we included pregnant women aged 18e40 years that have been diagnosed with GDM by “one-step” 2-h 75-g oral glucose tolerance test (OGTT) at 24e28 weeks' gestation. Gestational age was assessed from the date of last menstrual period and concurrent clinical assessment. Pregnant women without a previous diagnosis of glucose intolerance were screened. Diagnosis of GDM was based on the criteria as set by the American Diabetes Association [20]: those whose plasma glucose met one of the following criteria were considered as having GDM: fasting 92 mg/dL, 1-h 180 mg/dL and 2-h 153 mg/dL. A total of 1000 pregnant women attending maternity clinics affiliated to Kashan University of Medical Sciences, Kashan, Iran, were screened for GDM. Finally, 56 pregnant women met the inclusion criteria (934 women were excluded due to not having GDM and 10 women were excluded because of the diagnosis of GDM class A2 that needed insulin therapy: FPG >105 and BS 2h postprandial >120 mg/dL). Subjects with premature preterm rupture of membrane (PPROM), placenta abruption, pre-eclampsia, eclampsia, chronic hypertension, hypothyroidism, urinary tract infection, smokers and those with kidney or liver diseases or those taking estrogen therapy were not included in the current study. We excluded those who required commencing insulin therapy during intervention. A total of 56 pregnant women at 24e28 weeks of gestation were recruited in the current study and after stratification for pre-intervention BMI (
Contents lists available at ScienceDirect
Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu
Randomized control trials
Effects of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles in gestational diabetes: Randomized, double-blind, placebo-controlled trial Mansooreh Samimi a, Mehri Jamilian b, Zatollah Asemi c, *, Ahmad Esmaillzadeh d, e a
Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran Department of Gynecology and Obstetrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran d Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran e Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran b c
a r t i c l e i n f o
s u m m a r y
Article history: Received 2 May 2014 Accepted 11 June 2014
Background & aims: We are aware of no study that examined the effects of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles in gestational diabetes (GDM). This study was designed to assess the effects of omega-3 fatty acid supplementation on insulin concentrations and lipid profiles among pregnant women with GDM. Methods: This randomized, double-blind, placebo-controlled clinical trial was performed among 56 women with GDM. Subjects were randomly assigned to receive either 1000 mg omega-3 fatty acid supplements containing 180 mg eicosapentaenoic acid and 120 mg docosahexanoic acid (n ¼ 28) or placebo (n ¼ 28) for 6 weeks. Fasting blood samples were taken at study baseline and after 6 weeks of intervention to quantify biochemical variables. Results: Although omega-3 fatty acid supplementation did not led to a significant change in serum insulin levels and HOMA-IR in omega-3 fatty acid group, we found a significant difference in changes in serum insulin levels (change from baseline: 1.5 ± 7.5 vs. þ3.5 ± 8.5 mIU/mL, P ¼ 0.02) and HOMA-IR (0.4 ± 2.1 vs. þ1.1 ± 2.4, P ¼ 0.02) comparing the two groups. Furthermore, a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) levels was seen after omega-3 fatty acid supplementation compared with placebo (236.3 ± 1541.9 vs. 898.6 ± 2292.7 ng/mL, P ¼ 0.03). Omega-3 fatty acid supplementation did not influence fasting plasma glucose, homeostatic model assessment-Beta cell function (HOMA-B), quantitative insulin sensitivity check index (QUICKI) and lipid profiles. Conclusions: Omega-3 fatty acid supplementation in GDM women had beneficial effects on insulin resistance, however, it did not affect plasma glucose, HOMA-B, QUICKI and lipid profiles. Clinical registration number: www.irct.ir as IRCT201312265623N16. © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Keywords: Omega-3 fatty acid Supplementation Gestational diabetes Pregnant women
1. Introduction Gestational diabetes mellitus (GDM) is one of the most common complications that occur in pregnancy, it affects 3e8% of all pregnancies with an increasing prevalence worldwide. [1] GDM is associated with insulin resistance and increased lipid profiles [2]. GDM is associated with undesirable long-term maternal outcomes,
* Corresponding author. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Ravandi, Kashan, Iran. Tel.: þ98 361 4463378; fax: þ98 361 4463377. E-mail addresses: [email protected], [email protected] (Z. Asemi).
increased perinatal morbidity (e.g. macrosomia, birth trauma and pre-eclampsia) and long-term sequelae in the offspring [3]. Abnormal maternal lipid profiles in GDM patients might detrimentally influence the fetus by increasing the rate of aortic fatty streaks [4]. Furthermore, it can lead to increased risk of cardiovascular diseases (CVD) in later life of the mother and the offspring [5]. Several strategies including the use of low-glycemic index diet [6], consumption of the dietary approaches to stop hypertension (DASH) eating plan [7], the use of Oral Hypoglycemic Agents (OHAs) [8] and insulin therapy [9] have been suggested for management of insulin resistance in GDM patients. Some studies have reported significant differences in blood omega-3 fatty acid levels
http://dx.doi.org/10.1016/j.clnu.2014.06.005 0261-5614/© 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Please cite this article in press as: Samimi M, et al., Effects of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles in gestational diabetes: Randomized, double-blind, placebo-controlled trial, Clinical Nutrition (2014), http://dx.doi.org/10.1016/j.clnu.2014.06.005
2
M. Samimi et al. / Clinical Nutrition xxx (2014) 1e6
between women with and those without GDM [10,11]. Epidemiologic studies examining the association between omega-3 fatty acid intake and risk of GDM have shown conflicting findings [12,13]. In a recent study [14], administration of 4 omega-3 fatty acid capsules daily in women with polycystic ovary syndrome (PCOS) for 12 weeks decreased fasting plasma glucose (FPG), insulin resistance and lipid profiles [14]. However, low dose intake of fish oil did not significantly affect insulin resistance and lipid profiles in HIVinfected patients on antiretroviral therapy [15]. Omega-3 fatty acid supplementation might affect insulin metabolism and lipid profiles via their effects on increased activation of AMP-activated protein kinase (AMPK) [16], improved LDL receptor activity in the liver, reduced LDL-cholesterol synthesis and increased fractional rate of catabolism of LDL-cholesterol [17]. Despite the increasing body of evidence suggesting a potential effect of omega-3 fatty acid supplements in enhancing insulin function [18], improving glucose tolerance and lipid profiles [14,19], we are aware of no randomized controlled trial that investigated the effect of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles in GDM patients. The current study was, therefore, done to investigate the effects of omega-3 fatty acid supplementation on insulin metabolism and lipid profiles of pregnant women with GDM. 2. Subjects and methods 2.1. Participants This randomized, double-blind, placebo-controlled trial was conducted in Kashan, Iran, during January 2014eMarch 2014. For estimating sample size, we considered type one (a) and type two errors (b) of 0.05 and 0.20 (power ¼ 80%), respectively, and homeostasis model of assessment-insulin resistance (HOMA-IR) score as a key variable. Based on a previous study [14], standard deviation (SD) of HOMA-IR was 0.8 and the difference in mean (d) of HOMAIR was 0.6. We reached the sample size of 24 subjects for each group using the suggested formula for parallel clinical trials. In the current study, we included pregnant women aged 18e40 years that have been diagnosed with GDM by “one-step” 2-h 75-g oral glucose tolerance test (OGTT) at 24e28 weeks' gestation. Gestational age was assessed from the date of last menstrual period and concurrent clinical assessment. Pregnant women without a previous diagnosis of glucose intolerance were screened. Diagnosis of GDM was based on the criteria as set by the American Diabetes Association [20]: those whose plasma glucose met one of the following criteria were considered as having GDM: fasting 92 mg/dL, 1-h 180 mg/dL and 2-h 153 mg/dL. A total of 1000 pregnant women attending maternity clinics affiliated to Kashan University of Medical Sciences, Kashan, Iran, were screened for GDM. Finally, 56 pregnant women met the inclusion criteria (934 women were excluded due to not having GDM and 10 women were excluded because of the diagnosis of GDM class A2 that needed insulin therapy: FPG >105 and BS 2h postprandial >120 mg/dL). Subjects with premature preterm rupture of membrane (PPROM), placenta abruption, pre-eclampsia, eclampsia, chronic hypertension, hypothyroidism, urinary tract infection, smokers and those with kidney or liver diseases or those taking estrogen therapy were not included in the current study. We excluded those who required commencing insulin therapy during intervention. A total of 56 pregnant women at 24e28 weeks of gestation were recruited in the current study and after stratification for pre-intervention BMI (
