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The randomized controlled trial (RCT) recruits pregnant women with de novo diagnosis of gestational diabetes. Women bearing a singleton pregnancy are randomized into four arms: DHA, oat, oat plus DHA, and placebo. The primary outcomes are cord blood leptin concentration in the newborns and maternal fasting glucose levels at 8 weeks post-intervention.
DHA is a long-chain fatty acid that has been shown to increase insulin sensitivity in basic science studies. Some studies have reported that oat (β-glucan) intake in patients with type 2 diabetes may improve glycaemic control. Evidence is emerging that gut microbiota may play an important role in energy homeostasis and glucose metabolism. This RCT aims to test the hypothesis that DHA and/or oat intake may improve glycemic control in women with gestational diabetes mellitus (GDM), and may impact metabolic health in fetuses/infants as indicated by cord blood leptin level. Changes in microbiota may be linked to these effects.
Growing evidence suggests that epigenetic changes may occur during fetal development in response to an adverse in utero environment, and this may "program" the risk of metabolic syndrome and type 2 diabetes in adulthood. GDM's offspring are programmed to be at substantially elevated risk of metabolic syndrome and type 2 diabetes in adulthood. We will explore whether the intervention may affect epigenetic profile in placental DNA in GDM.
Pregnant women bearing a singleton fetus without any evidence of malformation and with a de novo diagnosis of GDM at 22-28 weeks of gestation will be randomized into four arms: DHA, oat, oat plus DHA, and placebo. We will collect maternal blood and stool specimens on recruitment and 8-weeks post-intervention, cord blood and placenta specimens at delivery. The primary outcomes are cord blood leptin concentration in the baby, and fasting blood glucose at the 8 weeks post-intervention in the mother.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| nutritional guidance | No Intervention | routine care (all arms with nutritional guidance per routine care) | |
| oat grains | Active Comparator | 90 mg oat, per day. |
|
| oat grains and DHA tablets | Experimental | 90 mg oat and 500 mg DHA oral tablets, per day. |
|
| DHA tablets | Active Comparator | 500 mg DHA oral tablets, per day. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DHA | Dietary Supplement | 500 mg DHA tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| neonatal leptin | cord blood leptin concentration | at birth/delivery |
| Measure | Description | Time Frame |
|---|---|---|
| maternal fasting plasma glucose concentration | fasting plasma glucose concentration | 8 weeks post-intervention |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wen-Juan Wang, Master | Contact | 18621823005 | wangwe.njuan@163.com | |
| Dan-Li Zhang, Master | Contact | 13162215826 | zhangdanli1232@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Yexuan Tao, Doctor | Xinhua Hospital, Shanghai Jiao Tong University School of Medicine | Study Director |
| Zhongcheng Luo, Doctor | Xinhua Hospital, Shanghai Jiao Tong University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Xinhua Hospital Affliated to Shanghai Jiao Tong University School of Medicine; | Recruiting | Shanghai | Shanghai Municipality | 200052 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23748438 | Background | Vandorsten JP, Dodson WC, Espeland MA, Grobman WA, Guise JM, Mercer BM, Minkoff HL, Poindexter B, Prosser LA, Sawaya GF, Scott JR, Silver RM, Smith L, Thomas A, Tita AT. NIH consensus development conference: diagnosing gestational diabetes mellitus. NIH Consens State Sci Statements. 2013 Mar 6;29(1):1-31. | |
| 15821725 | Background |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Sep 28, 2022 | |
| Reset | Aug 17, 2023 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Sep 28, 2022 | Aug 17, 2023 |
| ID | Term |
|---|---|
| D016640 | Diabetes, Gestational |
| D015799 | Gyrate Atrophy |
| ID | Term |
|---|---|
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D003920 | Diabetes Mellitus |
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| ID | Term |
|---|---|
| D004281 | Docosahexaenoic Acids |
| ID | Term |
|---|---|
| D015525 | Fatty Acids, Omega-3 |
| D004042 | Dietary Fats, Unsaturated |
| D004041 | Dietary Fats |
| D005223 | Fats |
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| oat grains | Dietary Supplement | 90 mg oat, containing 4.05 mg β-glucan |
|
| Nicholson JK, Holmes E, Wilson ID. Gut microorganisms, mammalian metabolism and personalized health care. Nat Rev Microbiol. 2005 May;3(5):431-8. doi: 10.1038/nrmicro1152. |
| 21677749 | Background | Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011 Jun 15;474(7351):327-36. doi: 10.1038/nature10213. |
| 24631413 | Background | Cani PD, Geurts L, Matamoros S, Plovier H, Duparc T. Glucose metabolism: focus on gut microbiota, the endocannabinoid system and beyond. Diabetes Metab. 2014 Sep;40(4):246-57. doi: 10.1016/j.diabet.2014.02.004. Epub 2014 Mar 14. |
| 22863002 | Background | Koren O, Goodrich JK, Cullender TC, Spor A, Laitinen K, Backhed HK, Gonzalez A, Werner JJ, Angenent LT, Knight R, Backhed F, Isolauri E, Salminen S, Ley RE. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012 Aug 3;150(3):470-80. doi: 10.1016/j.cell.2012.07.008. |
| 21945359 | Background | Plagemann A. Maternal diabetes and perinatal programming. Early Hum Dev. 2011 Nov;87(11):743-7. doi: 10.1016/j.earlhumdev.2011.08.018. Epub 2011 Sep 23. |
| 23515667 | Background | Lehnen H, Zechner U, Haaf T. Epigenetics of gestational diabetes mellitus and offspring health: the time for action is in early stages of life. Mol Hum Reprod. 2013 Jul;19(7):415-22. doi: 10.1093/molehr/gat020. Epub 2013 Mar 20. |
| 22396200 | Background | Bouchard L, Hivert MF, Guay SP, St-Pierre J, Perron P, Brisson D. Placental adiponectin gene DNA methylation levels are associated with mothers' blood glucose concentration. Diabetes. 2012 May;61(5):1272-80. doi: 10.2337/db11-1160. Epub 2012 Mar 6. |
| 23209187 | Background | El Hajj N, Pliushch G, Schneider E, Dittrich M, Muller T, Korenkov M, Aretz M, Zechner U, Lehnen H, Haaf T. Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus. Diabetes. 2013 Apr;62(4):1320-8. doi: 10.2337/db12-0289. Epub 2012 Dec 3. |
| 24811788 | Background | Desgagne V, Hivert MF, St-Pierre J, Guay SP, Baillargeon JP, Perron P, Gaudet D, Brisson D, Bouchard L. Epigenetic dysregulation of the IGF system in placenta of newborns exposed to maternal impaired glucose tolerance. Epigenomics. 2014 Apr;6(2):193-207. doi: 10.2217/epi.14.3. |
| 12672596 | Background | Laine R, Salminen S, Benno Y, Ouwehand AC. Performance of bifidobacteria in oat-based media. Int J Food Microbiol. 2003 May 25;83(1):105-9. doi: 10.1016/s0168-1605(02)00318-5. |
| 24454790 | Background | Zhao JP, Levy E, Fraser WD, Julien P, Delvin E, Montoudis A, Spahis S, Garofalo C, Nuyt AM, Luo ZC. Circulating docosahexaenoic acid levels are associated with fetal insulin sensitivity. PLoS One. 2014 Jan 13;9(1):e85054. doi: 10.1371/journal.pone.0085054. eCollection 2014. |
| 23205866 | Background | Lindsay KL, Walsh CA, Brennan L, McAuliffe FM. Probiotics in pregnancy and maternal outcomes: a systematic review. J Matern Fetal Neonatal Med. 2013 May;26(8):772-8. doi: 10.3109/14767058.2012.755166. Epub 2013 Jan 11. |
| 24646819 | Background | Lindsay KL, Kennelly M, Culliton M, Smith T, Maguire OC, Shanahan F, Brennan L, McAuliffe FM. Probiotics in obese pregnancy do not reduce maternal fasting glucose: a double-blind, placebo-controlled, randomized trial (Probiotics in Pregnancy Study). Am J Clin Nutr. 2014 Jun;99(6):1432-9. doi: 10.3945/ajcn.113.079723. Epub 2014 Mar 19. |
| 26771637 | Result | Shen XL, Zhao T, Zhou Y, Shi X, Zou Y, Zhao G. Effect of Oat beta-Glucan Intake on Glycaemic Control and Insulin Sensitivity of Diabetic Patients: A Meta-Analysis of Randomized Controlled Trials. Nutrients. 2016 Jan 13;8(1):39. doi: 10.3390/nu8010039. |
| 25687568 | Result | Lindsay KL, Brennan L, Kennelly MA, Maguire OC, Smith T, Curran S, Coffey M, Foley ME, Hatunic M, Shanahan F, McAuliffe FM. Impact of probiotics in women with gestational diabetes mellitus on metabolic health: a randomized controlled trial. Am J Obstet Gynecol. 2015 Apr;212(4):496.e1-11. doi: 10.1016/j.ajog.2015.02.008. Epub 2015 Feb 14. |
| 37020805 | Derived | Xu YJ, Wang WJ, Zhang QY, Yang MN, Zhang L, He H, Dong Y, Ouyang F, Gao Y, Zhang J, Zheng T, Luo ZC. Docosahexaenoic acid supplementation in gestational diabetes mellitus and neonatal metabolic health biomarkers. Front Nutr. 2023 Mar 20;10:1089131. doi: 10.3389/fnut.2023.1089131. eCollection 2023. |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D015785 | Eye Diseases, Hereditary |
| D005128 | Eye Diseases |
| D015862 | Choroid Diseases |
| D014603 | Uveal Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008055 |
| Lipids |
| D005231 | Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D005395 | Fish Oils |
| D009821 | Oils |