Effect of daily consumption of probiotic yoghurt on insulin resistance in pregnant women: a randomized controlled trial

European Journal of Clinical Nutrition (2013) 67, 71–74& 2013 Macmillan Publishers Limited Effect of daily consumption of probiotic yoghurt on insulinresistance in pregnant women: a randomized controlled trial Z Asemi1, M Samimi2, Z Tabassi2, M Naghibi Rad1, A Rahimi Foroushani3, H Khorammian1 and A Esmaillzadeh4,5 BACKGROUND/OBJECTIVES: Owing to excess body weight and increased secretion of inflammatory cytokines primarily during thethird trimester, pregnancy is associated with elevated insulin resistance. To our knowledge, no report is available indicating theeffects of probiotic yoghurt consumption on serum insulin levels in pregnant women. This study was designed to determine theeffects of daily consumption of probiotic yoghurt on insulin resistance and serum insulin levels of Iranian pregnant women.
SUBJECTS/METHODS: In this randomized controlled clinical trial, 70 primigravida pregnant women with singleton pregnancy attheir third trimester were participated. We randomly assigned participants to consume 200 g per day of conventional (n ¼ 33) or theprobiotic group (n ¼ 37) for 9 weeks. The probiotic yoghurt was a commercially available product prepared with the starter culturesof Streptococcus thermophilus and Lactobacillus bulgaricus, enriched with probiotic culture of two strains of lactobacilli (Lactobacillusacidophilus LA5) and bifidobacteria (Bifidobacterium animalis BB12) with a total of min 1 Â 107 colony-forming units. Fasting bloodsamples were taken at baseline and after 9-week intervention to measure fasting plasma glucose and serum insulin levels.
Homeostatic model assessment of insulin resistance (HOMA-IR) was used to calculate insulin resistance score.
RESULTS: Although consumption of probiotic yogurt for 9 weeks did not affect serum insulin levels and HOMA-IR score, significantdifferences were found comparing changes in these variables between probiotic and conventional yogurts (changes from baselinein serum insulin levels: þ 1.2±1.2 vs þ 5.0±1.1 mIU/ml, respectively, P ¼ 0.02; and in HOMA-IR score: À 0.2±0.3 vs 0.7±0.2,respectively, P ¼ 0.01).
CONCLUSIONS: It is concluded that in contrast to conventional yogurt, daily consumption of probiotic yogurt for 9 weeksmaintains serum insulin levels and might help pregnant women prevent developing insulin resistance.
European Journal of Clinical Nutrition (2013) 67, 71–74; published online 28 November 2012 Keywords: probiotic yoghurt; insulin; insulin resistance; women; pregnancy fasting plasma glucose (FPG) as well as on improved insulin Owing to excess body weight, pregnancy is associated with Probiotics use glucose as their primary energy abnormal glucose homeostasis and insulin resistance particularly source. Therefore, they can influence blood glucose and insulin in the third trimester.Pregnancy is also associated with levels through their effects on decreased glucose absorption.
increased secretion of cytokines including leptin,resistin, Probiotics can also improve insulin resistance through their impact interleukin-6 (Senn et al) and tumor necrosis factor-aElevated on reduced inflammatory upregulated expression of levels of these adipocytokines along with increased levels of proglucagonsand decreased adiposity.
To the best of our knowledge, no report is available examining progesterone and estrogen have the potential to augment the the effects of probiotic yoghurt consumption on plasma glucose insulin Insulin resistant pregnant women are at and serum insulin levels of pregnant women. Therefore, the aim of increased risk of developing gestational diabetes The this study was to investigate the effects of daily consumption of incidence of gestational diabetes mellitus has been reported in 1– probiotic yoghurt on FPG, serum insulin levels and insulin 14% of all a higher incidence has been found in resistance status of pregnant Iranian women.
pregnant women with Asian Gestational diabetes isassociated with adverse pregnancy outcomes such as shoulderdystocia, This randomized single-blinded controlled clinical trial was carried out in the use of oral hypoglycemic agents (17) and Kashan, Iran, during October 2010 to March 2011. Pregnant women, insulin have been suggested for the management of primigravida, aged 18–30 years old who were carrying singleton insulin resistance during pregnancy. Recently, few studies in pregnancy at their third trimester were recruited in this study. Gestational animal models have shown the beneficial effects of probiotics on age was assessed from the date of last menstrual period and concurrent 1Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, . Iran; 2Department of Gynecology and Obstetrics, Schoolof Medicine, Kashan University of Medical Sciences, Kashan, Iran; 3Department of Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; 4FoodSecurity Research Center, Isfahan University of Medical Sciences, Isfahan, Iran and 5Department of Community Nutrition, School of Nutrition and Food Science, Isfahan Universityof Medical Sciences, Isfahan, Iran. Correspondence: Dr A Esmaillzadeh, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of MedicalSciences, Isfahan 81745-151, Iran.
Email: Received 18 June 2012; revised 13 October 2012; accepted 24 October 2012; published online 28 November 2012 clinical assessment.Individuals with the above-mentioned inclusion criteria were called for participation in the study from among those that Anthropometric measurements were assessed at baseline and after 9 attended maternity clinics affiliated to the Kashan University of Medical weeks of intervention. Body weight was measured in an overnight fasting Sciences, Kashan, Iran. Women with multiparity, maternal hypertension, status, without shoes and in a minimal clothing state by the use of a digital liver or renal disease and gestational diabetes mellitus were not included scale (Seca, Hamburg, Germany) to the nearest 0.1 kg. Height was measured using a non-stretched tape measure (Seca) to the nearest A total of 82 pregnant women were recruited in the study and were 0.1 cm. Body mass index was calculates as weight in kg divided by height randomly assigned to consume probiotic (n ¼ 42) or conventional yogurt (n ¼ 40) for 9 weeks. Among individuals in the probiotic yogurt group, fivewomen (gestational diabetes (n ¼ 2), preeclampsia (n ¼ 2) and bed rest(n ¼ 1) were excluded. The exclusions in conventional yogurt group was seven persons (gestational diabetes (n ¼ 3), preeclampsia (n ¼ 2) and bed The probiotic yoghurt was a commercially available product prepared with rest (n ¼ 2). Finally, 70 participants (probiotic yogurt (n ¼ 37) and the starter cultures of S. thermophilus and L. bulgaricus, enriched with conventional yogurt (n ¼ 33) completed the trial. The study was conducted probiotic culture of two strains of lactobacilli (L. acidophilus LA5) and according to the guidelines laid down in the Declaration of Helsinki. The bifidobacteria (B. animalis BB12) with a total of min 1 Â 107 c.f.u. The Ethical Committee of Tehran University of Medical Sciences approved the conventional yoghurt contained the starter cultures of S. thermophilus and study (no: 20402–89–7–18), and informed written consent was obtained L. bulgaricus. Both yogurts’ PH was in the range of 4.3–4.5 and their fat To obtain detailed information about the dietary intakes of study To ensure the normal distribution of variables, Histogram and Kolmogrov– participants, all women were entered into a 2-week run-in period; during Smirnov test were applied. Student’s t-test was used to detect differences which all subjects had to refrain from taking probiotic yoghurt or any other between groups. Po0.05 was considered as statistically significant. All probiotic food. At the end of run-in period, subjects were randomly statistical analyses were done using the Statistical Package for Social assigned to consume 200 g per day of conventional or probiotic yogurts Science version 17 (SPSS Inc., Chicago, IL, USA).
for 9 weeks. Participants were asked not to alter their routine physicalactivity or usual diets and not to consume any yogurt other than the oneprovided to them by the investigators. They were also asked to avoid consuming any other probiotic and fermented products. Conventional or Individuals in the conventional yoghurt group were slightly older probiotic yogurts were provided for participants every week. Compliance than those in the probiotic yogurt group (25.7±3.1 vs 24.2±3.3 with the yoghurt consumption was monitored once a week through phoneinterviews. The compliance was also double checked by the use of 3-day years, P ¼ 0.05). Comparing the two groups, baseline weight and dietary records completed throughout the study. To obtain nutrient body mass index were not significantly different. There was also intakes of participants based on these three-day food diaries, we used no significant difference in end-of-trial weight and body mass Nutritionist IV software (First Databank, San Bruno, CA, USA) modified for index between conventional and probiotic yogurt groups.
Consumption of probiotic yogurts was not associated with anyserious adverse reactions.
Dietary intakes of study participants during the run-in period and throughout the study have been presented in We Fasting blood samples (10 ml) were taken at baseline and after 9-week found no statistically significant difference between the two intervention at Kashan reference laboratory in an early morning after an groups in terms of dietary intakes during the run-in period. Lack of overnight fast. Blood samples, collected into tubes containing 0.1% EDTA, significant between-group differences in dietary intakes of energy, were taken in a sitting position according to a standard protocol and fat, protein, carbohydrate, dietary fiber and soluble fiber was also centrifuged within 30–45 min of collection. The samples were centrifuged to separate plasma from buffy coat and red blood cells. All measurements Although consumption of probiotic yogurt for 9 weeks did not were done on the day of blood collection. Plasma glucose levels were affect serum insulin levels and homeostatic model assessment of quantified by the use of glucose oxidase/peroxidase method withcommercially available kits (Parsazmun Co., Tehran, Iran). Serum insulin insulin resistance score, significant differences were found levels were assayed by enzyme-linked immunoassay kits (Demeditec, Kiel- comparing changes in these variables between probiotic and Wellsee, Germany). To assess insulin resistance, we used homeostatic conventional yogurts (changes from baseline in serum insulin model assessment of insulin resistance.
levels: þ 1.2±1.2 vs þ 5.0±1.1 mIU/ml, respectively, P ¼ 0.02; and Dietary intakes of study participants at run-in period and throughout the studya aData are mean±s.d. bObtained from independent t-test.
European Journal of Clinical Nutrition (2013) 71 – 74 Probiotic yoghurt and insulin resistanceZ Asemi et al Means (±s.e.) of FPG, serum insulin and insulin resistance at baseline and after the intervention Abbreviations: DBP, diastolic blood pressure; FPG, fasting plasma glucose; SBP, systolic blood pressure aIndicates between group differences (independentsamples t-test).
in homeostatic model assessment of insulin resistance score: insulin resistance and glucose intolerance was also seen with À 0.2±0.3 vs 0.7±0.2, respectively, P ¼ 0.01; Consump- consumption of Lactobacillus casei 0.05% for 4 weeks in mice.
tion of probiotic yogurt did not influence FPG compared with Such findings has also been reached by consumption of conventional yogurt. Systolic and diastolic blood pressures were Bifidobacterium breve B-3 at 108 or 109 c.f.u. per day for 8 weeks in mice fed a high-fat As is clear from the above-mentionedstudies, most studies have been done on animals and limited dataare available among humans. Furthermore, despite the effect of probiotics on maintenance of serum insulin levels in this study, we In this randomized controlled clinical trial, we found that did not find any significant difference between probiotic yogurt compared with conventional yogurt, consumption of probiotic and conventional yogurt in terms of their effect on FPG. However, yogurt for 9 weeks in the third trimester of pregnancy prevented within-group comparisons revealed the beneficial effect of both the increase in serum insulin levels and the development of yogurts on FPG. Lack of finding a significant difference between insulin resistance. This product could not significantly affect FPG, the two yogurts in this regard might be explained by the different systolic and diastolic blood pressures compared with the situation of the studied population, particularly the physiological conventional yogurt. To the best of our knowledge, this study is mechanisms occurring during the pregnancy. Furthermore, the the first examining the effect of probiotics on serum insulin levels discrepancy in probiotic strains and also the dosage used in and insulin resistance in pregnant women.
different studies might provide some reasons.
Pregnant women are very susceptible to increased insulin We did not find any significant effect of probiotics on blood resistance, particularly in the third trimester. Elevated insulin pressure. This finding is in contrast to previous studies that have resistance during pregnancy has been linked with adverse shown the reducing effect of blood pressure by pregnancy outcomes.Although probiotics has primarily been The beneficial effects of probiotics on blood pressure in earlier investigated in relation to gastrointestinal health, recent evidence studies have been attributed to its releasing effect of bioactive has indicated the probiotics as a role having factor in metabolic peptides, such as the angiotensin converting enzyme-inhibitory conditions. Based on the findings of this study, consumption of This mechanism has been confirmed with the probiotic yogurt during the third trimester of pregnancy might consumption of both Bifidobacterium longum and L. acidophilus.
reduce the risk of adverse pregnancy outcomes through its Furthermore, angiotensin converting enzyme-inhibitory peptides preventive effect on developing insulin resistance. Insulin have been found in yogurt, cheese and milk fermented with L.
resistance normally develops during the last trimester in casei ssp. rhamnosus, L. acidophilus and Bifidobacteria strains.
pregnant women. Therefore, the changes we observed in the Lack of significant effect of probiotics on blood pressure in this group receiving the conventional yogurt are normal. The study might be explained by the normal blood pressure levels of interesting aspect of our findings is the absence of these changes in the group received probiotic yogurt.
The exact mechanisms by which probiotics might affect serum The beneficial effects of probiotics on serum insulin levels and insulin levels and insulin resistance are unknown. Owing to the insulin resistance have previously been reported. Andreasen use of glucose as the primary energy source by probiotics, their et al.in a randomized trial among type 2 diabetic patients effect on serum insulin levels might be mediated through have reported that intake of L. acidophilus for 4 weeks preserved influencing blood glucose levels. Decreased absorption of glucose insulin sensitivity compared with the placebo group. Such effects by probiotics might also be explained by their effect on changing have also been reported in experimental Several the intestinal environment,host gene expression and gut strains of bacteria, such as Lactobacilli and Bifidobacterium, have permeability.However, the effect of probiotics on FPG cannot also been shown to improve glucose tolerance and insulin be regarded as the single explanation for maintenance of serum resistance in animal models.In a study by Cani et al.
insulin levels because FPG has also decreased in conventional yogurt group. Therefore, other mechanisms might be involved in secretion was seen with the consumption of Bifidobacterium spp.
the beneficial effect of probiotics in these pregnant women.
in diabetic mice fed high-fat diet. Consumption of Lactobacillus Consumption of probiotics might affect the signaling line of rhamnosus GG for 4 weeks in streptozotocin-induced diabetic rats insulin secretion. In an earlier study, consumption of VSL#3 has also been resulted in improved glucose tolerance and insulin probiotics in mice has been resulted in improved insulin resistance Beside individual probiotics, combination of their due to increasing the hepatic natural killer T cells and reducing the strains has also been reported to be advantageous in reducing the inflammatory Our previous study in this group of onset of insulin resistance and diabetes in animals. Consumption pregnant women indicated the reduced levels of inflammation by probiotic Therefore, the beneficial effects of probiotic Bifidobacteria, Lactobacilli and S. thermophilus) for 4 weeks in yogurt on serum insulin levels might be mediated through their diabetic mice improved hepatic insulin resistance.Improved effects on high-sensitivity C-reactive protein, a surrogate measure European Journal of Clinical Nutrition (2013) 71 – 74 of inflammation. Reduced activity of Jun N-terminal kinase, a 10 Kirwan JP, Hauguel-De Mouzon S, Lepercq J, Challier JC, Huston-Presley L et al.
tumor necrosis factor-regulated kinase that promotes insulin TNF-alpha is a predictor of insulin resistance in human pregnancy. Diabetes 2002; resistance, and decreased DNA-binding activity of nuclear factor- kB by probiotics have also been suggested as other mechanisms 11 McGarry JD. Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 2002; 51: 7–18.
Our study had some limitations. First, we used single-blind 12 Ismail NA, Aris NM, Mahdy ZA, Ahmad S, Naim NM, Siraj HH et al. Gestational randomized trial instead of double-blind method. This might diabetes mellitus in primigravidae: a mild disease. Acta Medica 2011; 54: 21–24.
13 Seshiah V, Balaji V, Balaji MS, Paneerselvam A, Arthi T, Thamizharasi M et al.
affect our findings. Second, we were unable to administer the Gestational diabetes mellitus manifests in all trimesters of pregnancy. Diabetes yogurts for 49 weeks due to budget limitations. Third, we were unable to measure FPG and serum insulin levels repeatedly.
14 Cheung NW. The management of gestational diabetes. Vasc Health Risk Manag Fourth, the pregnant women we studied were all at their third trimester. Therefore, we cannot extrapolate our findings to the 15 Sunsaneevithayakul P, Kanokpongsakdi S, Sutanthavibul A, Ruangvutilert P, Boriboohirunsarn D, Keawprasit T et al. Result of ambulatory diet therapy in In conclusion, we found evidence indicating that in contrast to gestational diabetes mellitus. J Med Assoc Thai 2006; 89: 8–12.
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The authors declare no conflict of interest.
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