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Cheong L, Law LSC, Tan LYL, Amal AAA, Khoo CM, Eng PC. Medical Nutrition Therapy for Women with Gestational Diabetes: Current Practice and Future Perspectives. Nutrients 2025; 17:1210. [PMID: 40218968 PMCID: PMC11990351 DOI: 10.3390/nu17071210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2025] [Revised: 03/21/2025] [Accepted: 03/27/2025] [Indexed: 04/14/2025] Open
Abstract
Gestational diabetes mellitus (GDM) is a complication that affects 20% of pregnancies worldwide. It is associated with adverse short- and long-term cardiometabolic outcomes for both mother and infant. Effective management of GDM involves lifestyle modifications, including medical nutrition therapy (MNT) and physical activity (PA), with the addition of insulin or metformin if glycaemic control remains inadequate. However, substantial gaps persist in the determination of optimal medical nutrition therapy (MNT) for women with GDM. Challenges in MNT include individual variation in glucose tolerance and changing maternal physiology and dietary requirements during pregnancy. Achieving optimal glycaemic control depends on careful macronutrient balance, particularly the distribution and quality of carbohydrate intake and sufficient protein and fat intake. Additionally, micronutrient deficiencies, such as inadequate vitamin D, calcium, and essential minerals, may exacerbate oxidative stress, inflammation, and glycaemic dysregulation, further impacting foetal growth and development. Cultural beliefs and dietary practices among pregnant women can also hinder adherence to recommended nutritional guidelines. Conditions like hyperemesis gravidarum (HG) affect ~1% to 2% of pregnant women can result in unintended energy and nutrient deficits. This special issue explores the current evidence and major barriers to optimising dietary therapy for women with GDM. It also identifies future research priorities to advance clinical practice, improve maternal and foetal outcomes, and address gaps in personalised nutrition interventions.
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Affiliation(s)
- Louisa Cheong
- Division of Endocrinology, Department of Medicine, National University Hospital, Singapore 119074, Singapore; (L.C.); (L.S.-C.L.); (L.Y.L.T.); (C.M.K.)
| | - Lawrence Siu-Chun Law
- Division of Endocrinology, Department of Medicine, National University Hospital, Singapore 119074, Singapore; (L.C.); (L.S.-C.L.); (L.Y.L.T.); (C.M.K.)
| | - Li Ying Lyeann Tan
- Division of Endocrinology, Department of Medicine, National University Hospital, Singapore 119074, Singapore; (L.C.); (L.S.-C.L.); (L.Y.L.T.); (C.M.K.)
| | - Amal Al-Amri Amal
- Department of Internal Medicine, Nizwa Hospital, Nizwa P.O. Box 1222, Oman;
| | - Chin Meng Khoo
- Division of Endocrinology, Department of Medicine, National University Hospital, Singapore 119074, Singapore; (L.C.); (L.S.-C.L.); (L.Y.L.T.); (C.M.K.)
| | - Pei Chia Eng
- Division of Endocrinology, Department of Medicine, National University Hospital, Singapore 119074, Singapore; (L.C.); (L.S.-C.L.); (L.Y.L.T.); (C.M.K.)
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London W12 0NN, UK
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Gong J, Xu W, Chen Y, Chen S, Wu Y, Chen Y, Li Y, He Y, Yu H, Xie L. Maternal Gestational Diabetes Mellitus and High-Fat Diet Influenced Hepatic Polyunsaturated Fatty Acids Profile in the Offspring of C57BL/6J Mice. Mol Nutr Food Res 2024; 68:e2400386. [PMID: 39246092 DOI: 10.1002/mnfr.202400386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 08/04/2024] [Indexed: 09/10/2024]
Abstract
SCOPE This research examines the effects of maternal high-fat (HF) diet and gestational diabetes mellitus (GDM) on offspring lipid metabolism and polyunsaturated fatty acids (PUFA) profile. METHODS AND RESULTS GDM is induced using the insulin receptor antagonist S961. Weaning offspring are categorized into HF-GDM, HF-CON, NC-GDM, and NC-CON groups based on maternal diet or GDM. Adult offspring are then grouped into NC-CON-NC, NC-CON-HF, NC-GDM-NC, NC-GDM-HF, HF-CON-NC, HF-CON-HF, HF-GDM-NC, and HF-GDM-HF according to dietary patterns. Gas chromatography determines PUFA composition. Western blot assesses PI3K/Akt signaling pathway-related protein expression. Feeding a normal chow diet until adulthood improves the distribution of hepatic PUFA during weaning across the four groups. PI3K expression is upregulated during weaning in HF-CON and HF-GDM, particularly in HF-CON-NC and HF-GDM-NC, compared to NC-CON-NC during adulthood. Akt expression increases in NC-GDM-NC after weaning with a normal diet. The hepatic PUFA profile in HF-CON-HF significantly distinguishes among the maternal generation health groups. Maternal HF diet exacerbates the combined impact of maternal GDM and offspring HF diet on hepatic PUFA and PI3K/Akt signaling pathway-related proteins during adulthood. CONCLUSIONS Early exposure to HF diets and GDM affects hepatic PUFA profiles and PI3K/Akt signaling pathway protein expression in male offspring during weaning and adulthood.
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Affiliation(s)
- JiaYu Gong
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun City, Jilin Province, 130021, China
| | - WenHui Xu
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun City, Jilin Province, 130021, China
| | - YiFei Chen
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun City, Jilin Province, 130021, China
| | - ShuTong Chen
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun City, Jilin Province, 130021, China
| | - YanYan Wu
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun City, Jilin Province, 130021, China
| | - YiRu Chen
- Clinical Nutrition Department, Third Hospital of Jilin University, Changchun City, Jilin Province, 130032, China
| | - YueTing Li
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun City, Jilin Province, 130021, China
| | - Yuan He
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun City, Jilin Province, 130021, China
| | - HaiTao Yu
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun City, Jilin Province, 130021, China
| | - Lin Xie
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun City, Jilin Province, 130021, China
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Gaddy JA, Moore RE, Lochner JS, Rogers LM, Noble KN, Giri A, Aronoff DM, Cliffel D, Eastman AJ. Palmitate and group B Streptococcus synergistically and differentially induce IL-1β from human gestational membranes. Front Immunol 2024; 15:1409378. [PMID: 38855112 PMCID: PMC11158625 DOI: 10.3389/fimmu.2024.1409378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 05/10/2024] [Indexed: 06/11/2024] Open
Abstract
Introduction Rupture of the gestational membranes often precedes major pregnancy complications, including preterm labor and preterm birth. One major cause of inflammation in the gestational membranes, chorioamnionitis (CAM) is often a result of bacterial infection. The commensal bacterium Streptococcus agalactiae, or Group B Streptococcus (GBS) is a leading infectious cause of CAM. Obesity is on the rise worldwide and roughly 1 in 4 pregnancy complications is related to obesity, and individuals with obesity are also more likely to be colonized by GBS. The gestational membranes are comprised of several distinct cell layers which are, from outermost to innermost: maternally-derived decidual stromal cells (DSCs), fetal cytotrophoblasts (CTBs), fetal mesenchymal cells, and fetal amnion epithelial cells (AECs). In addition, the gestational membranes have several immune cell populations; macrophages are the most common phagocyte. Here we characterize the effects of palmitate, the most common long-chain saturated fatty acid, on the inflammatory response of each layer of the gestational membranes when infected with GBS, using human cell lines and primary human tissue. Results Palmitate itself slightly but significantly augments GBS proliferation. Palmitate and GBS co-stimulation synergized to induce many inflammatory proteins and cytokines, particularly IL-1β and matrix metalloproteinase 9 from DSCs, CTBs, and macrophages, but not from AECs. Many of these findings are recapitulated when treating cells with palmitate and a TLR2 or TLR4 agonist, suggesting broad applicability of palmitate-pathogen synergy. Co-culture of macrophages with DSCs or CTBs, upon co-stimulation with GBS and palmitate, resulted in increased inflammatory responses, contrary to previous work in the absence of palmitate. In whole gestational membrane biopsies, the amnion layer appeared to dampen immune responses from the DSC and CTB layers (the choriodecidua) to GBS and palmitate co-stimulation. Addition of the monounsaturated fatty acid oleate, the most abundant monounsaturated fatty acid in circulation, dampened the proinflammatory effect of palmitate. Discussion These studies reveal a complex interplay between the immunological response of the distinct layers of the gestational membrane to GBS infection and that such responses can be altered by exposure to long-chain saturated fatty acids. These data provide insight into how metabolic syndromes such as obesity might contribute to an increased risk for GBS disease during pregnancy.
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Affiliation(s)
- Jennifer A. Gaddy
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
- Tennessee Valley Healthcare Systems, Department of Veterans Affairs, Nashville, TN, United States
| | - Rebecca E. Moore
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
- Publications Division, American Chemical Society, Washington, DC, United States
| | - Jonathan S. Lochner
- Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC, United States
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Lisa M. Rogers
- Department Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Kristen N. Noble
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Ayush Giri
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
- Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, United States
| | - David M. Aronoff
- Department Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
| | - David Cliffel
- Department of Chemistry, Vanderbilt University, Nashville, TN, United States
| | - Alison J. Eastman
- Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, United States
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Houttu N, Vahlberg T, Miles EA, Calder PC, Laitinen K. The impact of fish oil and/or probiotics on serum fatty acids and the interaction with low-grade inflammation in pregnant women with overweight and obesity: secondary analysis of a randomised controlled trial. Br J Nutr 2024; 131:296-311. [PMID: 37642166 PMCID: PMC10751948 DOI: 10.1017/s0007114523001915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 08/10/2023] [Accepted: 08/20/2023] [Indexed: 08/31/2023]
Abstract
N-3 long-chain PUFA (LC-PUFA) and probiotics are generally considered to induce health benefits. The objective was to investigate (1) the impact of fish oil and/or probiotics on serum fatty acids (sFA), (2) the interaction of sFA with low-grade inflammation and (3) the relation of sFA to the onset of gestational diabetes mellitus (GDM). Pregnant women with overweight/obesity were allocated into intervention groups with fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo in early pregnancy (fish oil: 1·9 g DHA and 0·22 g EPA, probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 CFU, each daily). Blood samples were collected in early (n 431) and late pregnancy (n 361) for analysis of fatty acids in serum phosphatidylcholine (PC), cholesteryl esters (CE), TAG and NEFA with GC and high-sensitivity C-reactive protein and GlycA by immunoassay and NMR spectroscopy, respectively. GDM was diagnosed according to 2 h 75 g oral glucose tolerance test. EPA in PC, CE and TAG and DHA in PC, CE, TAG and NEFA were higher in fish oil and fish oil + probiotics groups compared with placebo. EPA in serum NEFA was lower in women receiving probiotics compared with women not receiving. Low-grade inflammation was inversely associated with n-3 LC-PUFA, which were related to an increased risk of GDM. Fish oil and fish oil + probiotics consumption increase serum n-3 LC-PUFA in pregnant women with overweight/obesity. Although these fatty acids were inversely related to inflammatory markers, n-3 LC-PUFA were linked with an increased risk for GDM.
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Affiliation(s)
- Noora Houttu
- Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520Turku, Finland
| | - Tero Vahlberg
- Department of Clinical Medicine, Biostatistics, University of Turku, 20520Turku, Finland
| | - Elizabeth A. Miles
- School of Human Development and Health, Faculty of Medicine, University of Southampton, SouthamptonSO16 6YD, UK
| | - Philip C. Calder
- School of Human Development and Health, Faculty of Medicine, University of Southampton, SouthamptonSO16 6YD, UK
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, SouthamptonSO16 6YD, UK
| | - Kirsi Laitinen
- Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520Turku, Finland
- Department of Obstetrics and Gynaecology, Turku University Hospital, 20500Turku, Finland
- Functional Foods Forum, University of Turku, Turku, Finland
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Joshi NP, Madiwale SD, Sundrani DP, Joshi SR. Fatty acids, inflammation and angiogenesis in women with gestational diabetes mellitus. Biochimie 2023; 212:31-40. [PMID: 37059350 DOI: 10.1016/j.biochi.2023.04.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 03/01/2023] [Accepted: 04/11/2023] [Indexed: 04/16/2023]
Abstract
Gestational diabetes mellitus (GDM) is a metabolic disorder in pregnancy whose prevalence is on the rise. Reports suggest a likely association between inflammation and maternal GDM. A balance between pro and anti-inflammatory cytokines is necessary for the regulation of maternal inflammation system throughout pregnancy. Along with various inflammatory markers, fatty acids also act as pro-inflammatory molecules. However, studies reporting the role of inflammatory markers in GDM are contradictory, suggesting the need of more studies to better understand the role of inflammation in pregnancies complicated by GDM. Inflammatory response can be regulated by angiopoietins suggesting a link between inflammation and angiogenesis. Placental angiogenesis is a normal physiological process which is tightly regulated during pregnancy. Various pro and anti-angiogenic factors influence the regulation of the feto-placental vascular development. Studies evaluating the levels of angiogenic markers in women with GDM are limited and the findings are inconsistent. This review summarizes the available literature on fatty acids, inflammatory markers and angiogenesis in women with GDM. We also discuss the possible link between them and their influence on placental development in GDM.
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Affiliation(s)
- Nikita P Joshi
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, India
| | - Shweta D Madiwale
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, India
| | - Deepali P Sundrani
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, India
| | - Sadhana R Joshi
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, India.
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Sot J, García-Arribas AB, Abad B, Arranz S, Portune K, Andrade F, Martín-Nieto A, Velasco O, Arana E, Tueros I, Ferreri C, Gaztambide S, Goñi FM, Castaño L, Alonso A. Erythrocyte Membrane Nanomechanical Rigidity Is Decreased in Obese Patients. Int J Mol Sci 2022; 23:ijms23031920. [PMID: 35163842 PMCID: PMC8836476 DOI: 10.3390/ijms23031920] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 02/04/2022] [Accepted: 02/06/2022] [Indexed: 12/13/2022] Open
Abstract
This work intends to describe the physical properties of red blood cell (RBC) membranes in obese adults. The hypothesis driving this research is that obesity, in addition to increasing the amount of body fat, will also modify the lipid composition of membranes in cells other than adipocytes. Forty-nine control volunteers (16 male, 33 female, BMI 21.8 ± 5.6 and 21.5 ± 4.2 kg/m2, respectively) and 52 obese subjects (16 male and 36 female, BMI 38.2± 11.0 and 40.7 ± 8.7 kg/m2, respectively) were examined. The two physical techniques applied were atomic force microscopy (AFM) in the force spectroscopy mode, which allows the micromechanical measurement of penetration forces, and fluorescence anisotropy of trimethylammonium diphenylhexatriene (TMA-DPH), which provides information on lipid order at the membrane polar–nonpolar interface. These techniques, in combination with lipidomic studies, revealed a decreased rigidity in the interfacial region of the RBC membranes of obese as compared to control patients, related to parallel changes in lipid composition. Lipidomic data show an increase in the cholesterol/phospholipid mole ratio and a decrease in sphingomyelin contents in obese membranes. ω-3 fatty acids (e.g., docosahexaenoic acid) appear to be less prevalent in obese patient RBCs, and this is the case for both the global fatty acid distribution and for the individual major lipids in the membrane phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS). Moreover, some ω-6 fatty acids (e.g., arachidonic acid) are increased in obese patient RBCs. The switch from ω-3 to ω-6 lipids in obese subjects could be a major factor explaining the higher interfacial fluidity in obese patient RBC membranes.
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Affiliation(s)
- Jesús Sot
- Instituto BIOFISIKA (CSIC, UPV/EHU), Departamento de Bioquímica, Universidad del País Vasco, 48940 Leioa, Spain; (J.S.); (A.B.G.-A.); (F.M.G.)
| | - Aritz B. García-Arribas
- Instituto BIOFISIKA (CSIC, UPV/EHU), Departamento de Bioquímica, Universidad del País Vasco, 48940 Leioa, Spain; (J.S.); (A.B.G.-A.); (F.M.G.)
| | - Beatriz Abad
- SGIKER, Servicios Generales de Investigación (SGiker), Universidad del País Vasco, 48940 Leioa, Spain;
| | - Sara Arranz
- AZTI, Food Research, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Bizkaia, Astondo Bidea, Edificio 609, 48160 Derio, Spain; (S.A.); (K.P.); (I.T.)
| | - Kevin Portune
- AZTI, Food Research, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Bizkaia, Astondo Bidea, Edificio 609, 48160 Derio, Spain; (S.A.); (K.P.); (I.T.)
| | - Fernando Andrade
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Alicia Martín-Nieto
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Olaia Velasco
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Eunate Arana
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Itziar Tueros
- AZTI, Food Research, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Bizkaia, Astondo Bidea, Edificio 609, 48160 Derio, Spain; (S.A.); (K.P.); (I.T.)
| | - Carla Ferreri
- ISOF, Consiglio Nazionale delle Ricerche, Via Piero Gobetti, 101, 40129 Bologna, Italy;
| | - Sonia Gaztambide
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Félix M. Goñi
- Instituto BIOFISIKA (CSIC, UPV/EHU), Departamento de Bioquímica, Universidad del País Vasco, 48940 Leioa, Spain; (J.S.); (A.B.G.-A.); (F.M.G.)
| | - Luis Castaño
- Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, 48903 Barakaldo, Spain; (F.A.); (A.M.-N.); (O.V.); (E.A.); (S.G.); (L.C.)
| | - Alicia Alonso
- Instituto BIOFISIKA (CSIC, UPV/EHU), Departamento de Bioquímica, Universidad del País Vasco, 48940 Leioa, Spain; (J.S.); (A.B.G.-A.); (F.M.G.)
- Correspondence:
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Mauro AK, Rengarajan A, Albright C, Boeldt DS. Fatty acids in normal and pathological pregnancies. Mol Cell Endocrinol 2022; 539:111466. [PMID: 34610360 DOI: 10.1016/j.mce.2021.111466] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 09/26/2021] [Accepted: 09/28/2021] [Indexed: 12/26/2022]
Abstract
Long chain fatty acids, namely omega-3 and omega-6, are essential fatty acids and are necessary for proper pregnancy progression and fetal growth and development. Maternal fatty acid consumption and release of fatty acids from lipid stores provide increased availability of fatty acids for the placenta to transport to the growing fetus. Both omega-3 and omega-6 fatty acids are then utilized for generation of signaling molecules, such as eicosanoids, and for promoting of growth and developmental, most notably in the nervous system. Perturbations in fatty acid concentration and fatty acid signaling have been implicated in three major pregnancy complications - gestational diabetes, preeclampsia, and preterm birth. In this review we discuss the growing literature surrounding the role of fatty acids in normal and pathological pregnancies. Differences in maternal, placental, and fetal fatty acids and molecular regulation of fatty acid signaling and transport are presented. A look into novel fatty acid-based therapies for each of the highlighted disorders are discussed, and may present exciting bench to bedside alternatives to traditional pharmacological intervention.
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Affiliation(s)
- Amanda K Mauro
- Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin - Madison, School Medicine and Public Health, Madison, WI, 53715, USA
| | - Aishwarya Rengarajan
- Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin - Madison, School Medicine and Public Health, Madison, WI, 53715, USA
| | - Carly Albright
- Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin - Madison, School Medicine and Public Health, Madison, WI, 53715, USA
| | - Derek S Boeldt
- Perinatal Research Laboratories, Department of Obstetrics & Gynecology, University of Wisconsin - Madison, School Medicine and Public Health, Madison, WI, 53715, USA.
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Wang QY, You LH, Xiang LL, Zhu YT, Zeng Y. Current progress in metabolomics of gestational diabetes mellitus. World J Diabetes 2021; 12:1164-1186. [PMID: 34512885 PMCID: PMC8394228 DOI: 10.4239/wjd.v12.i8.1164] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 05/20/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders of pregnancy and can cause short- and long-term adverse effects in both pregnant women and their offspring. However, the etiology and pathogenesis of GDM are still unclear. As a metabolic disease, GDM is well suited to metabolomics study, which can monitor the changes in small molecular metabolites induced by maternal stimuli or perturbations in real time. The application of metabolomics in GDM can be used to discover diagnostic biomarkers, evaluate the prognosis of the disease, guide the application of diet or drugs, evaluate the curative effect, and explore the mechanism. This review provides comprehensive documentation of metabolomics research methods and techniques as well as the current progress in GDM research. We anticipate that the review will contribute to identifying gaps in the current knowledge or metabolomics technology, provide evidence-based information, and inform future research directions in GDM.
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Affiliation(s)
- Qian-Yi Wang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 21000, Jiangsu Province, China
| | - Liang-Hui You
- Nanjing Maternity and Child Health Care Institute, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
| | - Lan-Lan Xiang
- Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
| | - Yi-Tian Zhu
- Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
| | - Yu Zeng
- Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
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Hai-Tao Y, Zhi-Heng G, Yi-Ru C, Yue-Ting L, Hai-Ying Z, Ya-Juan L, Lin X. Gestational diabetes mellitus decreased umbilical cord blood polyunsaturated fatty acids: a meta-analysis of observational studies. Prostaglandins Leukot Essent Fatty Acids 2021; 171:102318. [PMID: 34246926 DOI: 10.1016/j.plefa.2021.102318] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 06/21/2021] [Accepted: 06/25/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Polyunsaturated fatty acid (PUFA) is important for the development of the fetal brain, and the retina. Gestational diabetes mellitus (GDM) may influence maternal and fetal fatty acid metabolism, in turn affecting fetal growth and development. In several studies, maternal and fetal PUFA metabolic differences have been reported between mothers with and without GDM, but not in other studies. Thus, the aim of this meta-analysis (registration number: CRD42020220448) was to compare levels of linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA), docosahexaenoic acid (DHA), and total n-3 and n-6 PUFA between mothers with and without GMD and their fetuses. METHODS We performed a meta-analysis of observational studies on maternal and fetal fatty acid metabolism, published until May 2021. In addition, we performed subgroup analysis depending on the analyzed tissues (plasma/serum, erythrocyte membrane, or placenta) and the expression modes of fatty acids (concentration or percentage). RESULTS We included 24 observational studies involving 4335 maternal datasets and 12 studies involving 1675 fetal datasets in the meta-analysis. Levels of AA, DHA, and n-6 and n-3 PUFA were lower in the cord blood of mothers with GDM than in controls (P < 0.05). Compared to that in controls, in erythrocyte membranes, the percentages of AA, DHA, and n-6 and n-3 PUFA in total fatty acid were lower in mothers with GDM (P < 0.05), but in plasma/serum, the percentages of AA, DHA, and n-6 PUFA in total fatty acid were higher in mothers with GDM (P < 0.05). CONCLUSIONS GDM appears to influence the transfer of PUFAs from mothers to fetuses. The percentage of PUFAs in maternal plasma/serum was higher, and that in erythrocyte membranes was lower in mothers with GDM compared to those with normal glucose tolerance.
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Affiliation(s)
- Yu Hai-Tao
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun,Jilin Province, 130021, China
| | - Guo Zhi-Heng
- Department of Obstetrics, The First Hospital of Jilin University, Changchun city, Jilin Province,130021, China
| | - Chen Yi-Ru
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun,Jilin Province, 130021, China
| | - Li Yue-Ting
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun,Jilin Province, 130021, China
| | - Zhang Hai-Ying
- Experimental Teaching Center for Radiation Medicine, School of Public Health, Jilin University, Changchun city, Jilin Province,130021, China
| | - Liu Ya-Juan
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun,Jilin Province, 130021, China
| | - Xie Lin
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun,Jilin Province, 130021, China.
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Meng X, Zhu B, Liu Y, Fang L, Yin B, Sun Y, Ma M, Huang Y, Zhu Y, Zhang Y. Unique Biomarker Characteristics in Gestational Diabetes Mellitus Identified by LC-MS-Based Metabolic Profiling. J Diabetes Res 2021; 2021:6689414. [PMID: 34212051 PMCID: PMC8211500 DOI: 10.1155/2021/6689414] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 02/18/2021] [Accepted: 05/15/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is a type of glucose intolerance disorder that first occurs during women's pregnancy. The main diagnostic method for GDM is based on the midpregnancy oral glucose tolerance test. The rise of metabolomics has expanded the opportunity to better identify early diagnostic biomarkers and explore possible pathogenesis. METHODS We collected blood serum from 34 GDM patients and 34 normal controls for a LC-MS-based metabolomics study. RESULTS 184 metabolites were increased and 86 metabolites were decreased in the positive ion mode, and 65 metabolites were increased and 71 were decreased in the negative ion mode. Also, it was found that the unsaturated fatty acid metabolism was disordered in GDM. Ten metabolites with the most significant differences were selected for follow-up studies. Since the diagnostic specificity and sensitivity of a single differential metabolite are not definitive, we combined these metabolites to prepare a ROC curve. We found a set of metabolite combination with the highest sensitivity and specificity, which included eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, arachidonic acid, citric acid, α-ketoglutaric acid, and genistein. The area under the curves (AUC) value of those metabolites was 0.984 between the GDM and control group. CONCLUSIONS Our results provide a direction for the mechanism of GDM research and demonstrate the feasibility of developing a diagnostic test that can distinguish between GDM and normal controls clearly. Our findings were helpful to develop novel biomarkers for precision or personalized diagnosis for GDM. In addition, we provide a critical insight into the pathological and biological mechanisms for GDM.
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Affiliation(s)
- Xingjun Meng
- Department of Clinical Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Institute of Laboratory Medicine, Zhejiang University, Hangzhou 310006, China
| | - Bo Zhu
- Department of Clinical Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Institute of Laboratory Medicine, Zhejiang University, Hangzhou 310006, China
| | - Yan Liu
- School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China
| | - Lei Fang
- Department of Clinical Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Institute of Laboratory Medicine, Zhejiang University, Hangzhou 310006, China
| | - Binbin Yin
- Department of Clinical Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Institute of Laboratory Medicine, Zhejiang University, Hangzhou 310006, China
| | - Yanni Sun
- Department of Clinical Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Institute of Laboratory Medicine, Zhejiang University, Hangzhou 310006, China
| | - Mengni Ma
- Department of Clinical Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Institute of Laboratory Medicine, Zhejiang University, Hangzhou 310006, China
| | - Yuli Huang
- Department of Cardiology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan 528300, China
| | - Yuning Zhu
- Department of Clinical Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Institute of Laboratory Medicine, Zhejiang University, Hangzhou 310006, China
| | - Yunlong Zhang
- Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China
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11
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Godhamgaonkar AA, Wadhwani NS, Joshi SR. Exploring the role of LC-PUFA metabolism in pregnancy complications. Prostaglandins Leukot Essent Fatty Acids 2020; 163:102203. [PMID: 33227645 DOI: 10.1016/j.plefa.2020.102203] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 10/09/2020] [Accepted: 11/07/2020] [Indexed: 12/14/2022]
Abstract
Maternal nutrition during pregnancy plays a significant role in growth and development of the placenta and influencing pregnancy outcome. Suboptimal nutritional status during early gestational period compromises the normal course of pregnancy leading to adverse maternal and fetal outcomes. Omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFA) are important for the growth and development of the placenta. Maternal fatty acids and their metabolites influence the normal course of pregnancy by regulating cell growth and development, cell signaling, regulate angiogenesis, modulate inflammatory responses and influence various structural and functional processes. Alterations in LC-PUFA and their metabolites may result in inadequate spiral artery remodeling or placental angiogenesis leading to structural and functional deficiency of the placenta which contributes to several pregnancy complications like preeclampsia, gestational diabetes mellitus, intrauterine growth restriction, and results in adverse birth outcomes. In this review, we summarize studies examining the role of fatty acids and their metabolites in pregnancy. We also discuss the possible molecular mechanisms through which LC-PUFA influences placental growth and development. Studies have demonstrated that omega-3 fatty acid supplementation lowers the incidence of preterm births, but its effect on reducing pregnancy complications are inconclusive.
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Affiliation(s)
- Aditi A Godhamgaonkar
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune-Satara Road, Pune 411043, India
| | - Nisha S Wadhwani
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune-Satara Road, Pune 411043, India
| | - Sadhana R Joshi
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune-Satara Road, Pune 411043, India.
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12
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Jadhav A, Khaire A, Joshi S. Exploring the role of oxidative stress, fatty acids and neurotrophins in gestational diabetes mellitus. Growth Factors 2020; 38:226-234. [PMID: 33703982 DOI: 10.1080/08977194.2021.1895143] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Gestational diabetes mellitus (GDM) constitutes an unfavorable intrauterine environment for embryonic and feto-placental development. Women with GDM are at higher risk for materno-fetal complications and placental abnormalities. The placenta acts as an interface between the maternal and fetal circulations and also plays an important role in protecting the fetus from adverse effects of maternal metabolic conditions. One of the earliest abnormalities observed in GDM pregnancies is increased oxidative stress in the placenta which affects fetal development. Imbalances in maternal nutrition particularly long-chain polyunsaturated fatty acid (LCPUFA) intake and/or metabolism lead to increased oxidative stress. Reports indicate that oxidative stress and LCPUFA such as docosahexaenoic acid affect the levels of neurotrophins. The present review aims to provide insights into a mechanistic link between oxidative stress, LCPUFA and neurotrophin in the placenta in women with GDM and its implications for neurodevelopmental outcomes in children.
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Affiliation(s)
- Anjali Jadhav
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Amrita Khaire
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Sadhana Joshi
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
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Abstract
INTRODUCTION The Diabetes Prevention Program study results indicated that metformin therapy was not as beneficial as a lifestyle modification for delaying the development of type 2 diabetes in individuals at high risk of the disease. A key feature in the etiology of type 2 diabetes mellitus, which appears in the prediabetic phase, is a significant deficiency, compared to healthy controls, in highly flexible poly-cis-unsaturated fatty acyl chains in membrane phospholipids. This deficiency lowers membrane flexibility, which in turn, reduces the amount of all functional Class I glucose transporters, and thereby reduces glucose-mediated ATP production. This leads to an increase in essentially saturated free fatty acid (FFA) levels for fatty-acid-mediated ATP production, which will set up a vicious cycle of raising the levels of essentially saturated FFAs and lowering the level of transmembrane glucose transport. Metformin suppresses hepatic gluconeogenesis, which reduces the plasma glucose concentration. CONCLUSION We hypothesize that chronic metformin treatment leads to an additional increase in essentially saturated FFAs, which causes an additional rise in membrane stiffness and hypoxia. So we propose that all these metformin-mediated activities accelerated the onset of type 2 diabetes in the participants of the metformin group in the Diabetes Prevention Program study, compared to the participants of the lifestyle-intervention group in this study. We propose that the biochemical reactions, involved in the fatty-acid-mediated ATP production, play an important part in the increase of the observed essentially saturated FFA concentrations. These statements should also extend to the metformin therapy of individuals with type 2 diabetes.
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Affiliation(s)
- Rob N M Weijers
- Teaching Hospital, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands
| | - Dick J Bekedam
- Department of Obstetrics and Gynecology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands
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14
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Zhu Y, Li M, Rahman ML, Hinkle SN, Wu J, Weir NL, Lin Y, Yang H, Tsai MY, Ferrara A, Zhang C. Plasma phospholipid n-3 and n-6 polyunsaturated fatty acids in relation to cardiometabolic markers and gestational diabetes: A longitudinal study within the prospective NICHD Fetal Growth Studies. PLoS Med 2019; 16:e1002910. [PMID: 31518348 PMCID: PMC6743768 DOI: 10.1371/journal.pmed.1002910] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 08/14/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Despite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM). METHODS AND FINDINGS Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15-26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42-0.96; P = 0.042) and 33% (0.67; 95% CI 0.45-0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10-14 and DGLA at GWs 10-14 and 15-26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15-26 was associated with a 45% (0.55; 95% CI 0.37-0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low (<median) n-6 PUFAs levels had a 64% (95% CI 0.14-0.95; P value = 0.039) lower risk of GDM versus women with low n-3 and high n-6 PUFAs. Limitations include the inability to distinguish between exogenous and endogenous influences on circulating PUFA levels and the lack of causality inherent in observational studies. CONCLUSIONS Our findings may suggest a potential role of primarily endogenously metabolized plasma phospholipid n-6 PUFAs including GLA, DGLA, and DTA in early to midpregnancy in the development of GDM. Null findings on primarily diet-derived n-3 EPA and DHA and n-6 LA do not provide strong evidence to suggest a beneficial role in prevention of GDM, although not excluding the potential benefit of EPA and DHA on glucose-insulin homeostasis given the inverse associations with insulin-resistance markers. Our findings highlight the importance of assessing individual circulating PUFAs to investigate their distinct pathophysiologic roles in glucose homeostasis in pregnancy.
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Affiliation(s)
- Yeyi Zhu
- Division of Research, Kaiser Permanente Northern California, Oakland, California, United States of America
- Department of Epidemiology & Biostatistics, University of California, San Francisco, California, United States of America
- * E-mail: (CZ); (YZ)
| | - Mengying Li
- Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States of America
| | - Mohammad L. Rahman
- Department of Population Medicine and Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Stefanie N. Hinkle
- Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States of America
| | - Jing Wu
- Glotech Inc., Bethesda, Maryland, United States of America
| | - Natalie L. Weir
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Yuan Lin
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, United States of America
| | - Huixia Yang
- Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China
| | - Michael Y. Tsai
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Assiamira Ferrara
- Division of Research, Kaiser Permanente Northern California, Oakland, California, United States of America
| | - Cuilin Zhang
- Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States of America
- * E-mail: (CZ); (YZ)
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Ferchaud-Roucher V, Barner K, Jansson T, Powell TL. Maternal obesity results in decreased syncytiotrophoblast synthesis of palmitoleic acid, a fatty acid with anti-inflammatory and insulin-sensitizing properties. FASEB J 2019; 33:6643-6654. [PMID: 30811959 PMCID: PMC6463919 DOI: 10.1096/fj.201802444r] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 01/28/2019] [Indexed: 12/16/2022]
Abstract
The fetus is dependent on delivery of fatty acids (FAs) by the syncytiotrophoblast, the transporting epithelium of the human placenta. Obese pregnant women have dyslipidemia; however, whether obesity impacts placental lipid transport and metabolism remains to be fully established. Palmitoleic acid (POA), an FA with anti-inflammatory and insulin-sensitizing properties, is synthesized from palmitic acid (PA) catalyzed by stearoyl-coenzyme A desaturase (SCD) activity. We hypothesized that the uptake and incorporation of FAs and POA synthesis are reduced in primary human trophoblasts (PHTs) isolated from pregnancies complicated by maternal obesity. Villous cytotrophoblasts were isolated from 7 placentas of obese [body mass index (BMI) = 37.5 ± 1.9] and 12 normal (BMI = 23.6 ± 0.6) mothers. FA uptake and incorporation were assessed using uniformly labeled (U[13C])-FA mixtures of PA, oleic acid (OA), linoleic acid, and docosahexaenoic acid. Cellular [13C] FAs were quantified both in total cellular lipids and in lipid classes by GC-MS. Uptake and incorporation of [13C] FAs in total cellular lipids were not different in PHTs isolated from obese mothers compared with normal mothers. Only the concentration of OA was increased in the triglyceride fraction (P < 0.05) if the mother was obese. We found an isotopic enrichment of POA after U[13C]-PA treatment, demonstrating SCD activity in PHT cells. Labeled POA content and the POA:PA ratio were significantly lower in PHTs isolated from placentas of obese mothers compared with normal, healthy controls. Decreased syncytiotrophoblast POA synthesis may contribute to insulin resistance and low-grade inflammation in the mother, placenta, or fetus (or a combination of the 3) in pregnancies complicated by obesity.-Ferchaud-Roucher, V., Barner, K., Jansson, T., Powell, T. L. Maternal obesity results in decreased syncytiotrophoblast synthesis of palmitoleic acid, a fatty acid with anti-inflammatory and insulin-sensitizing properties.
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Affiliation(s)
- Véronique Ferchaud-Roucher
- Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Kelsey Barner
- Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Thomas Jansson
- Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Theresa L. Powell
- Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Section of Neonatology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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16
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Elshani B, Kotori V, Daci A. Role of omega-3 polyunsaturated fatty acids in gestational diabetes, maternal and fetal insights: current use and future directions. J Matern Fetal Neonatal Med 2019; 34:124-136. [PMID: 30857450 DOI: 10.1080/14767058.2019.1593361] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
ω-3-Polyunsaturated fatty acids (ω-3 PUFAs) are widely used during pregnancy and gestational diabetes mellitus (GDM). ω-3 PUFAs are beneficial in the regulation of maternal and fetal metabolic function, inflammation, immunity, macrosomia (MAC), oxidative stress, preeclampsia, intrauterine growth, preterm birth, offspring metabolic function, and neurodevelopment. Dietary counseling is vital for improving therapeutic outcomes in patients with GDM. In maternal circulation, ω-3 PUFAs are transported via transporters, synthesis enzymes, and intracellular proteins, which activate nuclear receptors and play central roles in the cellular metabolic processes of placental trophoblasts. In patients with GDM, this process is compromised due to abnormal functioning of the placenta, which disrupts the normal mother to fetus transport. This results in reduced fetal levels of ω-3 PUFAs, which contributes negatively to fetal growth, metabolic function, and development. Dietary counseling and nutritional assessment remain challenging in the prevention and alleviation of GDM. Therefore, personalized approaches, including measurement of the ω-3 index, pharmacogenetic implementation strategies, and appropriate supplementation with ω-3 PUFAs are used to achieve sufficient distribution in the maternal and fetal fluids during the entire pregnancy period. Developing new dosing guidelines and personalized approaches, determining the mechanisms of ω-3 PUFAs in the placenta, and examining the pharmacodynamic and pharmacokinetics interactions involving ω-3 PUFAs will lead to better management and increase the quality of life of patients with GDM and their offspring. Moreover, different strategies for supplementing with ω-3 PUFAs, improving their placental transport, and pharmacological exploration of the maternal-fetal interactions will help to further elucidate the role of ω-3 PUFAs in women with GDM. In this review, we summarize the current information on the potential therapeutic benefits and clinical applicability of ω-3 PUFAs in patients with GDM and their offspring, highlighting recent progress and future perspectives in this field. Studies investigating the mechanisms of ω-3 PUFA transport to targeted tissues have spurred an interest in personalized treatment strategies for patients with GDM and their offspring. To implement such therapies, we need to clarify the index/ratio of ω-3 PUFAs in maternal and fetal fluids, delineate the ω-3 PUFA transport pathways, and establish the guidelines for FA profiling prepregnancy and during pregnancy-associated weight gain. Such therapies also need to take into account the gender of the fetus, and whether the patient is obese.
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Affiliation(s)
- Brikene Elshani
- Department of Gynecology and Obstetrics, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo
| | - Vjosa Kotori
- Department of Endocrinology, Pediatric Clinic, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo
| | - Armond Daci
- Department of Pharmacy, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo
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Andersson-Hall U, Carlsson NG, Sandberg AS, Holmäng A. Circulating Linoleic Acid is Associated with Improved Glucose Tolerance in Women after Gestational Diabetes. Nutrients 2018; 10:nu10111629. [PMID: 30400149 PMCID: PMC6266712 DOI: 10.3390/nu10111629] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 10/23/2018] [Accepted: 10/24/2018] [Indexed: 02/06/2023] Open
Abstract
Women with previously diagnosed gestational diabetes mellitus (GDM) are at increased risk of type-2-diabetes mellitus (T2D). We aimed to establish links between glucose tolerance (GT) and serum fatty acid (FA) profile in the transition from GDM to T2D. Six years after GDM, 221 women were grouped as having normal GT (NGT), impaired GT (IGT), or T2D based on oral GT test results. Fasting serum FAs were profiled, anthropometric measures taken, and dietary intake determined. Linoleic acid (LA) was significantly higher in NGT women (p < 0.001) compared with IGT and T2D, and emerged as a strong predictor of low glucose and insulin levels, independently of BMI. Self-reported vegetable oil consumption correlated with LA serum levels and glucose levels. Delta-6-, delta-9-, and stearoyl-CoA-desaturase activities were associated with decreased GT, and delta-5-desaturase activities with increased GT. In a subgroup of women at high risk of diabetes, low LA and high palmitic acid levels were seen in those that developed T2D, with no differences in other FAs or metabolic measurements. Results suggest that proportions of LA and palmitic acid are of particular interest in the transition from GDM to T2D. Interconversions between individual FAs regulated by desaturases appear to be relevant to glucose metabolism.
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Affiliation(s)
- Ulrika Andersson-Hall
- Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
| | - Nils-Gunnar Carlsson
- Division of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
| | - Ann-Sofie Sandberg
- Division of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
| | - Agneta Holmäng
- Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
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Thota RN, Ferguson JJA, Abbott KA, Dias CB, Garg ML. Science behind the cardio-metabolic benefits of omega-3 polyunsaturated fatty acids: biochemical effects vs. clinical outcomes. Food Funct 2018; 9:3576-3596. [PMID: 29904777 DOI: 10.1039/c8fo00348c] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Lower incidence of cardiovascular disease (CVD) in the Greenland Inuit, Northern Canada and Japan has been attributed to their consumption of seafood rich in long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA). While a large majority of pre-clinical and intervention trials have demonstrated heart health benefits of LCn-3PUFA, some studies have shown no effects or even negative effects. LCn-3PUFA have been shown to favourably modulate blood lipid levels, particularly a reduction in circulating levels of triglycerides. High density lipoprotein-cholesterol (HDL-C) levels are elevated following dietary supplementation with LCn-3PUFA. Although LCn-3PUFA have been shown to increase low-density lipoprotein-cholesterol (LDL-C) levels, the increase is primarily in the large-buoyant particles that are less atherogenic than small-dense LDL particles. The anti-inflammatory effects of LCn-3PUFA have been clearly outlined with inhibition of NFkB mediated cytokine production being the main mechanism. In addition, reduction in adhesion molecules (intercellular adhesion molecule, ICAM and vascular cell adhesion molecule 1, VCAM-1) and leukotriene production have also been demonstrated following LCn-3PUFA supplementation. Anti-aggregatory effects of LCn-3PUFA have been a subject of controversy, however, recent studies showing sex-specific effects on platelet aggregation have helped resolve the effects on hyperactive platelets. Improvements in endothelium function, blood flow and blood pressure after LCn-3PUFA supplementation add to the mechanistic explanation on their cardio-protective effects. Modulation of adipose tissue secretions including pro-inflammatory mediators and adipokines by LCn-3PUFA has re-ignited interest in their cardiovascular health benefits. The aim of this narrative review is to filter out the reasons for possible disparity between cohort, mechanistic, pre-clinical and clinical studies. The focus of the article is to provide possible explanation for the observed controversies surrounding heart health benefits of LCn-3PUFA.
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Affiliation(s)
- Rohith N Thota
- Nutraceuticals Research Program, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia.
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Bukowiecka-Matusiak M, Burzynska-Pedziwiatr I, Sansone A, Malachowska B, Zurawska-Klis M, Ferreri C, Chatgilialoglu C, Ochedalski T, Cypryk K, Wozniak LA. Lipid profile changes in erythrocyte membranes of women with diagnosed GDM. PLoS One 2018; 13:e0203799. [PMID: 30216387 PMCID: PMC6138398 DOI: 10.1371/journal.pone.0203799] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Accepted: 08/09/2018] [Indexed: 12/30/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is a glucose intolerance that begins or is first recognized during pregnancy. It is currently a growing health problem worldwide affecting from 1% to 14% of all pregnant women depending on racial and ethnic group as well as the diagnostic and screening criteria. Our preliminary study aimed at investigating the erythrocyte membrane fatty acid profiles of pregnant women, in particular with diagnosed with gestational diabetes mellitus (GDM), and with normal glucose tolerant (NGT) pregnant women as a control group. The study group comprised 43 pregnant women, 32 of whom were diagnosed with GDM according to the WHO criteria, and 11 with normal glucose tolerance. The erythrocyte membrane phospholipids were obtained according to the Folch extraction procedure. Fatty acids (FA) were analyzed by gas chromatography (GC) as the corresponding fatty acid methyl esters (FAME). A cluster of 14 fatty acids identified contained >98% of the recognized peaks in the GC analysis. The analysis of fatty acids from erythrocytes revealed important differences between GDM and NGT women in the third trimester, and the results were correlated with biochemical data. Among the 14 measured FA representing the membrane lipidomic profile, the levels of three saturated FA (myristic, palmitic, stearic acids) tended to decrease in GDM patients, with the percentage content of stearic acid significantly changed. The relative content of monounsaturated fatty acids (MUFA) tended to increase, in particular the oleic acid and vaccenic acid contents were significantly increased in erythrocyte membranes of the GDM group in comparison with the NGT group. The GDM group demonstrated higher sapienic acid levels (+29%) but this change was not statistically significant. This study revealed association between an impaired cis-vaccenic acid concentration in erythrocytes membrane and GDM development. No significant changes of polyunsaturated fatty acids (PUFA) were observed in GDM and NGT erythrocytes. We postulate, basing on the differences between the GDM and NGT lipidomic profiles, that stearic and cis-vaccenic acids can be considered as dual biomarkers of specific SFA-MUFA conversion pathway, involving the coupling of delta-9 desaturase and elongase enzymes. Our results indicate that the SFA-MUFA families may be involved in the pathophysiology of metabolic diseases such as GDM, but the further studies are needed to confirm our hypothesis. In conclusion, the erythrocyte membranes of GDM women undergo remodeling resulting in abnormal fatty acid profiles, which are reflection of the long-term status of organism and can have great impact on both the mother and her offspring.
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Affiliation(s)
| | | | - Anna Sansone
- Consiglio Nazionale delle Ricerche, Institute for the Organic Synthesis and Photoreactivity, Bologna, Italy
| | - Beata Malachowska
- Medical University of Lodz, Department of Biostatistics and Translational Medicine, Lodz, Poland
| | - Monika Zurawska-Klis
- Medical University of Lodz, Department of Nursing and Obstetrics, Department of Clinic Nursing, Department of Diabetology and Metabolic Diseases Lodz, Poland
| | - Carla Ferreri
- Consiglio Nazionale delle Ricerche, Institute for the Organic Synthesis and Photoreactivity, Bologna, Italy
| | | | - Tomasz Ochedalski
- Medical University of Lodz, Department of Comparative Endocrinology, Lodz, Poland
| | - Katarzyna Cypryk
- Medical University of Lodz, Department of Nursing and Obstetrics, Department of Clinic Nursing, Department of Diabetology and Metabolic Diseases Lodz, Poland
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Wadhwani N, Patil V, Joshi S. Maternal long chain polyunsaturated fatty acid status and pregnancy complications. Prostaglandins Leukot Essent Fatty Acids 2018; 136:143-152. [PMID: 28888333 DOI: 10.1016/j.plefa.2017.08.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Revised: 07/06/2017] [Accepted: 08/09/2017] [Indexed: 12/18/2022]
Abstract
Maternal nutrition plays a crucial role in influencing fetal growth and birth outcome. Any nutritional insult starting several weeks before pregnancy and during critical periods of gestation is known to influence fetal development and increase the risk for diseases during later life. Literature suggests that chronic adult diseases may have their origin during early life - a concept referred to as Developmental Origins of Health and Disease (DOHaD) which states that adverse exposures early in life "program" risks for later chronic disorders. Long chain polyunsaturated fatty acids (LCPUFA), mainly omega-6 and omega-3 fatty acids are known to have an effect on fetal programming. The placental supply of optimal levels of LCPUFA to the fetus during early life is extremely important for the normal growth and development of both placenta and fetus. Any alteration in placental development will result in adverse pregnancy outcome such as gestational diabetes mellitus (GDM), preeclampsia, and intrauterine growth restriction (IUGR). A disturbed materno-fetal LCPUFA supply is known to be linked with each of these pathologies. Further, a disturbed LCPUFA metabolism is reported to be associated with a number of metabolic disorders. It is likely that LCPUFA supplementation during early pregnancy may be beneficial in improving the health of the mother, improving birth outcome and thereby reducing the risk of diseases in later life.
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Affiliation(s)
- Nisha Wadhwani
- Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune Satara Road, Pune 411043, India
| | - Vidya Patil
- Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune Satara Road, Pune 411043, India
| | - Sadhana Joshi
- Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune Satara Road, Pune 411043, India.
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21
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22
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Randomized Controlled Trial of DHA Supplementation during Pregnancy: Child Adiposity Outcomes. Nutrients 2017; 9:nu9060566. [PMID: 28574453 PMCID: PMC5490545 DOI: 10.3390/nu9060566] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 05/10/2017] [Accepted: 05/30/2017] [Indexed: 12/12/2022] Open
Abstract
Investigating safe and effective interventions in pregnancy that lower offspring adiposity is important given the burden of obesity and subsequent metabolic derangements. Our objective was to determine if docosahexaenoic acid (DHA) given during pregnancy to obese mothers results in lower offspring adiposity. This study was a long-term follow-up of a randomized trial of mothers with gestational diabetes or obesity who were randomized to receive DHA supplementation at 800 mg/day or placebo (corn/soy oil) starting at 25-29 weeks gestation. Anthropometric measures were collected at birth and maternal erythrocyte DHA and arachidonic (AA) levels were measured at 26 and 36 weeks gestation. At two- and four-year follow-up time points, offspring adiposity measures along with a diet recall were assessed. A significant increase in erythrocyte DHA levels was observed at 36 weeks gestation in the supplemented group (p < 0.001). While no significant differences by measures of adiposity were noted at birth, two or four years by randomization group, duration of breastfeeding (p < 0.001), and DHA level at 36 weeks (p = 0.002) were associated with body mass index z-score. Our data suggest that DHA supplementation during pregnancy in obese mothers may have long-lasting effects on offspring measures of adiposity.
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23
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Taschereau-Charron A, Da Silva MS, Bilodeau JF, Morisset AS, Julien P, Rudkowska I. Alterations of fatty acid profiles in gestational diabetes and influence of the diet. Maturitas 2017; 99:98-104. [PMID: 28364876 DOI: 10.1016/j.maturitas.2017.01.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 01/26/2017] [Indexed: 12/30/2022]
Abstract
Gestational diabetes mellitus (GDM) is a pregnancy-induced complication with increased prevalence, especially in overweight women. Fatty acid (FA) composition in tissues can reflect dietary fat intake, especially essential FA intake. Moreover, it has been shown that FA profiles in blood lipid fractions are altered in diabetic patients. Consequently, women with GDM may also have a distinctive FA profile. The objective of this review is compare FA profiles in different blood lipid fractions and the influence of dietary fat intake in women with GDM or normoglycemic pregnancies. Results show that women with GDM have more saturated and less polyunsaturated FA (PUFA) in their red blood cell (RBC) membranes than normoglycemic pregnant women. Moreover, some studies reported that women with GDM have a greater energy intake from total fat and saturated FA, along with a lower energy intake from PUFA, when compared to normoglycemic pregnancies. Clinical trials showed that omega-3 PUFA levels in RBC membranes of GDM women can be restored by a dietary intervention. Further research is required to determine whether FA profiles are altered prior to the diagnosis of GDM and can be prevented by diet.
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Affiliation(s)
- Andréa Taschereau-Charron
- Endocrinology and Nephrology Unit, Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, Canada
| | - Marine S Da Silva
- Endocrinology and Nephrology Unit, Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, Canada
| | - Jean-François Bilodeau
- Endocrinology and Nephrology Unit, Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, Canada
| | - Anne-Sophie Morisset
- Endocrinology and Nephrology Unit, Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, Canada
| | - Pierre Julien
- Endocrinology and Nephrology Unit, Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, Canada
| | - Iwona Rudkowska
- Endocrinology and Nephrology Unit, Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, Canada.
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Zhao JP, Levy E, Shatenstein B, Fraser WD, Julien P, Montoudis A, Spahis S, Xiao L, Nuyt AM, Luo ZC. Longitudinal circulating concentrations of long-chain polyunsaturated fatty acids in the third trimester of pregnancy in gestational diabetes. Diabet Med 2016; 33:939-46. [PMID: 26433139 DOI: 10.1111/dme.12978] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/29/2015] [Indexed: 11/28/2022]
Abstract
AIM Gestational diabetes mellitus is a common complication of pregnancy. Long-chain polyunsaturated fatty acids (LCPUFA) are essential for fetal neurodevelopment. Docosahexaenoic acid (DHA) is the predominant n-3 LCPUFA in the brain and retina. Circulating absolute concentrations of total n-3 and n-6 LCPUFAs rise during normal pregnancy. It remains unclear whether gestational diabetes may affect the normal rise in circulating concentrations of LCPUFAs in the third trimester of pregnancy - a period of rapid fetal neurodevelopment. This study aimed to address this question. METHODS In a prospective singleton pregnancy cohort, fatty acids in fasting plasma total lipids were measured at 24-28 and 32-35 weeks of gestation in women with (n = 24) and without gestational diabetes mellitus (n = 116). Fatty acid desaturase activity indices were estimated by relevant product-to-precursor fatty acid ratios. Dietary nutrient intakes were estimated by a food frequency questionnaire. RESULTS Plasma absolute concentrations of total n-6 LCPUFAs rose significantly between 24-28 and 32-35 weeks of gestation in women with or without gestational diabetes, whereas total n-3 LCPUFAs and DHA concentrations rose significantly only in women without gestational diabetes (all P < 0.01). Delta-5 desaturase indices (20:4n-6/20:3n-6) were similar, but delta-6 desaturase indices (18:3n-6/18:2n-6) were significantly lower in women with gestational diabetes at 32-35 weeks of gestation. Dietary intakes of all fatty acids were comparable. CONCLUSION The normal rise in circulating absolute concentrations of DHA and total n-3 LCPUFAs in the third trimester of pregnancy may be compromised in gestational diabetes, probably due to impaired synthesis or mobilization rather than dietary intake difference.
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Affiliation(s)
- J P Zhao
- Department of Obstetrics and Gynecology, Sainte Justine Hospital Research Centre, University of Montreal, Canada
| | - E Levy
- Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
| | - B Shatenstein
- Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
| | - W D Fraser
- Department of Obstetrics and Gynecology, Sainte Justine Hospital Research Centre, University of Montreal, Canada
- Department of Obstetrics and Gynecology, University of Sherbrooke, Sherbrooke, Quebec, Canada
| | - P Julien
- Molecular and Oncologic Endocrinology and Human Genomics Research Center, University Hospital Research Center, Laval University, Quebec City, Canada
| | - A Montoudis
- Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
| | - S Spahis
- Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
| | - L Xiao
- Department of Obstetrics and Gynecology, Sainte Justine Hospital Research Centre, University of Montreal, Canada
| | - A M Nuyt
- Department of Pediatrics, Sainte Justine Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada
| | - Z C Luo
- Department of Obstetrics and Gynecology, Sainte Justine Hospital Research Centre, University of Montreal, Canada
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
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Min Y, Djahanbakhch O, Hutchinson J, Eram S, Bhullar AS, Namugere I, Ghebremeskel K. Efficacy of docosahexaenoic acid-enriched formula to enhance maternal and fetal blood docosahexaenoic acid levels: Randomized double-blinded placebo-controlled trial of pregnant women with gestational diabetes mellitus. Clin Nutr 2015; 35:608-14. [PMID: 26091965 DOI: 10.1016/j.clnu.2015.05.020] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 05/15/2015] [Accepted: 05/31/2015] [Indexed: 11/28/2022]
Abstract
BACKGROUND & AIMS Gestational diabetes mellitus (GDM) compromises the level of docosahexaenoic acid (DHA) in phospholipids of maternal and fetal red blood cells and fetal plasma. This is of some concern because of the importance of DHA for fetal neuro-visual development. We have investigated whether this abnormality could be rectified by supplementation with DHA-enriched formula. METHODS Women with GDM (n = 138) recruited from Newham University Hospital, London received two capsules of DHA-enriched formula (active-group) or high oleic acid sunflower seed oil (placebo-group) from diagnosis until delivery. Maternal (baseline and delivery) and fetal (cord blood) red blood cell and plasma phospholipid fatty acid composition, and neonatal anthropometry were assessed. RESULTS One hundred and fourteen women (58 active, 56 placebo) completed the trial. The active-group compared with the placebo-group had significantly enhanced level of DHA in plasma phosphatidylcholine (4.5% vs 3.8%, P = 0.011), red blood cell phosphatidylcholine (2.7% vs 2.2%, P = 0.022) and phosphatidylethoanolamine (9.5% vs 7.6%, P = 0.002). There was no difference in cord plasma and red blood cell phospholipid DHA between the two groups. The neonates of the two groups of women had comparable anthropometric measurements at birth. CONCLUSION Daily supplementation of 600 mg DHA enhances maternal but not fetal DHA status in pregnancy complicated by GDM. The inefficacy of the supplement to improve fetal status suggests that the transfer of DHA across the placenta maybe impaired in women with the condition. Regardless of the mechanisms responsible for the impairment of the transfer, the finding has implications for the management of neonates of women with GDM because they are born with a reduced level of DHA and the condition is thought to be associated with a risk of neuro-developmental deficits. We suggest that babies of women with GDM, particularly those not suckling, similar to the babies born prematurely require formula milk fortified with a higher level of DHA.
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Affiliation(s)
- Yoeju Min
- Lipidomics and Nutrition Research Centre, Faculty of Life Sciences and Computing, London Metropolitan University, London, UK.
| | - Ovrang Djahanbakhch
- Newham University Hospital National Health Service Trust, London, UK; Academic Department of Women's Health, Queen Mary's School of Medicine, University of London, London, UK
| | - Joanne Hutchinson
- Newham University Hospital National Health Service Trust, London, UK; Lipidomics and Nutrition Research Centre, Faculty of Life Sciences and Computing, London Metropolitan University, London, UK
| | - Sofia Eram
- Lipidomics and Nutrition Research Centre, Faculty of Life Sciences and Computing, London Metropolitan University, London, UK
| | - Amritpal S Bhullar
- Lipidomics and Nutrition Research Centre, Faculty of Life Sciences and Computing, London Metropolitan University, London, UK
| | - Irene Namugere
- Newham University Hospital National Health Service Trust, London, UK
| | - Kebreab Ghebremeskel
- Lipidomics and Nutrition Research Centre, Faculty of Life Sciences and Computing, London Metropolitan University, London, UK
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26
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Weijers RNM. Unsaturation index and type 2 diabetes: Unknown, unloved. World J Meta-Anal 2015; 3:89-92. [DOI: 10.13105/wjma.v3.i2.89] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2014] [Revised: 01/28/2015] [Accepted: 04/07/2015] [Indexed: 02/05/2023] Open
Abstract
A useful parameter for interpreting analyses of membrane fatty-acid composition is the unsaturation index (UI), a measure of unsaturation that is calculated as the mean number of cis double bonds per fatty-acid residue multiplied by 100. The UI is a fundamental parameter that contains information about many membrane biophysical properties and behavior. UI is a crucial index for type 2 diabetes (T2D) and other disorders, yet it is not properly considered in the scientific community. The goal of the present editorial is to familiarize the scientific T2D community with the UI. The idea of early systemic cell-membrane disease necessitates new thinking and suggests that UI should feature prominently on the research agenda.
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Larqué E, Pagán A, Prieto MT, Blanco JE, Gil-Sánchez A, Zornoza-Moreno M, Ruiz-Palacios M, Gázquez A, Demmelmair H, Parrilla JJ, Koletzko B. Placental fatty acid transfer: a key factor in fetal growth. ANNALS OF NUTRITION AND METABOLISM 2014; 64:247-53. [PMID: 25300267 DOI: 10.1159/000365028] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The functionality of the placenta may affect neonatal adiposity and fetal levels of key nutrients such as long-chain polyunsaturated fatty acids. Fetal macrosomia and its complications may occur even in adequately controlled gestational diabetic (GDM) mothers, suggesting that maternal glycemia is not the only determinant of fetal glycemic status and wellbeing. We studied in vivo the placental transfer of fatty acids (FA) labeled with stable isotopes administered to 11 control and 9 GDM pregnant women (6 treated with insulin). Subjects received orally ¹³C-palmitic, ¹³C-oleic, and ¹³C-linoleic acids and ¹³C-docosahexaenoic acid (¹³C-DHA) 12 h before an elective caesarean section. FA were quantified by gas chromatography and ¹³C enrichments by gas chromatography-isotope ratio mass spectrometry. The ¹³C-FA concentration was higher in total lipids of maternal plasma in GDM patients versus controls, except for ¹³C-DHA. Moreover, ¹³C-DHA showed a lower placenta/maternal plasma ratio in GDM patients versus controls and a significantly lower cord/maternal plasma ratio. Other FA ratios studied were not different between GDM and controls. A disturbed ¹³C-DHA placental uptake occurred in GDM patients treated with diet or insulin, while the latter also had lower ¹³C-DHA levels in the venous cord. The tracer study pointed towards an impaired placental DHA uptake as a critical step, while the transfer of other ¹³C-FA was less affected. Patients with GDM treated with insulin could also have a greater fetal fat storage, which may have contributed to the reduced ¹³C-DHA in the venous cord observed. The DHA transfer to the fetus was reduced in GDM pregnancies compared to controls. This might have an influence on fetal neurodevelopment and long-term consequences for the child.
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Affiliation(s)
- Elvira Larqué
- Department of Physiology, University of Murcia, Murcia, Spain
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Koehrer P, Saab S, Berdeaux O, Isaïco R, Grégoire S, Cabaret S, Bron AM, Creuzot-Garcher CP, Bretillon L, Acar N. Erythrocyte phospholipid and polyunsaturated fatty acid composition in diabetic retinopathy. PLoS One 2014; 9:e106912. [PMID: 25188352 PMCID: PMC4154797 DOI: 10.1371/journal.pone.0106912] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Accepted: 08/04/2014] [Indexed: 12/16/2022] Open
Abstract
Background Long chain polyunsaturated fatty acids (LCPUFAs) including docosahexaenoic acid and arachidonic acid are suspected to play a key role in the pathogenesis of diabetes. LCPUFAs are known to be preferentially concentrated in specific phospholipids termed as plasmalogens. This study was aimed to highlight potential changes in the metabolism of phospholipids, and particularly plasmalogens, and LCPUFAs at various stages of diabetic retinopathy in humans. Methodology and Principal Findings We performed lipidomic analyses on red blood cell membranes from controls and mainly type 2 diabetes mellitus patients with or without retinopathy. The fatty acid composition of erythrocytes was determined by gas chromatography and the phospholipid structure was determined by liquid chromatography equipped with an electrospray ionisation source and coupled with a tandem mass spectrometer (LC-ESI-MS/MS). A significant decrease in levels of docosahexaenoic acid and arachidonic acid in erythrocytes of diabetic patients with or without retinopathy was observed. The origin of this decrease was a loss of phosphatidyl-ethanolamine phospholipids esterified with these LCPUFAs. In diabetic patients without retinopathy, this change was balanced by an increase in the levels of several phosphatidyl-choline species. No influence of diabetes nor of diabetic retinopathy was observed on the concentrations of plasmalogen-type phospholipids. Conclusions and Significance Diabetes and diabetic retinopathy were associated with a reduction of erythrocyte LCPUFAs in phosphatidyl-ethanolamines. The increase of the amounts of phosphatidyl-choline species in erythrocytes of diabetic patients without diabetic retinopathy might be a compensatory mechanism for the loss of LC-PUFA-rich phosphatidyl-ethanolamines.
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Affiliation(s)
| | - Sarah Saab
- INRA, UMR1324 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- CNRS, UMR6265 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- Université de Bourgogne, UMR Centre des Sciences du Goût et de l’Alimentation, Dijon, France
| | - Olivier Berdeaux
- INRA, UMR1324 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- CNRS, UMR6265 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- Université de Bourgogne, UMR Centre des Sciences du Goût et de l’Alimentation, Dijon, France
| | - Rodica Isaïco
- Department of Ophthalmology, University Hospital, Dijon, France
| | - Stéphane Grégoire
- INRA, UMR1324 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- CNRS, UMR6265 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- Université de Bourgogne, UMR Centre des Sciences du Goût et de l’Alimentation, Dijon, France
| | - Stéphanie Cabaret
- INRA, UMR1324 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- CNRS, UMR6265 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- Université de Bourgogne, UMR Centre des Sciences du Goût et de l’Alimentation, Dijon, France
| | - Alain M. Bron
- Department of Ophthalmology, University Hospital, Dijon, France
- INRA, UMR1324 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- CNRS, UMR6265 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- Université de Bourgogne, UMR Centre des Sciences du Goût et de l’Alimentation, Dijon, France
| | - Catherine P. Creuzot-Garcher
- Department of Ophthalmology, University Hospital, Dijon, France
- INRA, UMR1324 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- CNRS, UMR6265 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- Université de Bourgogne, UMR Centre des Sciences du Goût et de l’Alimentation, Dijon, France
| | - Lionel Bretillon
- INRA, UMR1324 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- CNRS, UMR6265 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- Université de Bourgogne, UMR Centre des Sciences du Goût et de l’Alimentation, Dijon, France
| | - Niyazi Acar
- INRA, UMR1324 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- CNRS, UMR6265 Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- Université de Bourgogne, UMR Centre des Sciences du Goût et de l’Alimentation, Dijon, France
- * E-mail:
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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; 9:e85054. [PMID: 24454790 PMCID: PMC3890289 DOI: 10.1371/journal.pone.0085054] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Accepted: 11/21/2013] [Indexed: 01/22/2023] Open
Abstract
Background Arachidonic 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 Findings In 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. Conclusion Low 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.
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Affiliation(s)
- Jin-Ping Zhao
- Department of Obstetrics and Gynecology, University of Montreal, Montreal, Quebec, Canada
| | - Emile Levy
- Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
| | - William D. Fraser
- Department of Obstetrics and Gynecology, University of Montreal, Montreal, Quebec, Canada
| | - Pierre Julien
- Endocrinology and Nephrology, Laval University Hospital Research Centre, and Department of Medicine, Laval University, Quebec City, Quebec, Canada
| | - Edgard Delvin
- Department of Biochemistry, University of Montreal, Montreal, Quebec, Canada
| | - Alain Montoudis
- Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
| | - Schohraya Spahis
- Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
| | - Carole Garofalo
- Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
| | - Anne Monique Nuyt
- Department of Pediatrics, Sainte-Justine Hospital Research Center, University of Montreal, Montreal, Quebec, Canada
| | - Zhong-Cheng Luo
- Department of Obstetrics and Gynecology, University of Montreal, Montreal, Quebec, Canada
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
- * E-mail:
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Pagán A, Prieto-Sánchez MT, Blanco-Carnero JE, Gil-Sánchez A, Parrilla JJ, Demmelmair H, Koletzko B, Larqué E. Materno-fetal transfer of docosahexaenoic acid is impaired by gestational diabetes mellitus. Am J Physiol Endocrinol Metab 2013; 305:E826-33. [PMID: 23921142 DOI: 10.1152/ajpendo.00291.2013] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Better knowledge on the disturbed mechanisms implicated in materno-fetal long-chain polyunsaturated fatty acid (LC-PUFA) transfer in pregnancies with gestational diabetes mellitus (GDM) may have potentially high implications for later on in effective LC-PUFA supplementation. We studied in vivo placental transfer of fatty acids (FA) using stable isotope tracers administrated to 11 control and 9 GDM pregnant women (6 treated with insulin). Subjects received orally [(13)C]palmitic, [(13)C]oleic and [(13)C]linoleic acids, and [(13)C]docosahexaenoic acid ((13)C-DHA) 12 h before elective caesarean section. Maternal blood samples were collected at -12, -3, -2, and -1 h, delivery, and +1 h. Placental tissue and venous cord blood were also collected. FA were quantified by gas chromatography (GC) and (13)C enrichments by GC-isotope ratio mass spectrometry. [(13)C]FA concentration was higher in total lipids of maternal plasma in GDM vs. controls, except for [(13)C]DHA. Moreover, [(13)C]DHA showed lower placenta/maternal plasma ratio in GDM vs. controls and significantly lower cord/maternal plasma ratio. For the other studied FA, ratios were not different between GDM and controls. Disturbed [(13)C]DHA placental uptake occurs in both GDM treated with diet or insulin, whereas the last ones also have lower [(13)C]DHA in venous cord. The tracer study pointed toward impaired placental DHA uptake as critical step, whereas the transfer of the rest of [(13)C]FA was less affected. GDM under insulin treatment could also have higher fetal fat storage, contributing to reduce [(13)C]DHA in venous cord. DHA transfer to the fetus was reduced in GDM pregnancies compared with controls, which might affect the programming of neurodevelopment in their neonates.
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Affiliation(s)
- Ana Pagán
- Physiology Department, Faculty of Biology, University of Murcia, Murcia, Spain
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31
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Berberovic E, Ivanisevic M, Juras J, Horvaticek M, Delas I, Djelmis J. Arachidonic and docosahexaenoic acid in the blood of a mother and umbilical vein in diabetic pregnant women. J Matern Fetal Neonatal Med 2013; 26:1287-91. [DOI: 10.3109/14767058.2013.783800] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Weijers RNM. Lipid composition of cell membranes and its relevance in type 2 diabetes mellitus. Curr Diabetes Rev 2012; 8:390-400. [PMID: 22698081 PMCID: PMC3474953 DOI: 10.2174/157339912802083531] [Citation(s) in RCA: 116] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2012] [Revised: 05/30/2012] [Accepted: 05/31/2012] [Indexed: 01/10/2023]
Abstract
Identifying the causative relationship between the fatty acid composition of cell membranes and type 2 diabetes mellitus fundamentally contributes to the understanding of the basic pathophysiological mechanisms of the disease. Important outcomes of the reviewed studies appear to support the hypotheses that the flexibility of a membrane determined by the ratio of (poly)unsaturated to saturated fatty acyl chains of its phospholipids influences the effectiveness of glucose transport by insulin-independent glucose transporters (GLUTs) and the insulin-dependent GLUT4, and from the prediabetic stage on a shift from unsaturated towards saturated fatty acyl chains of membrane phospholipids directly induces a decrease in glucose effectiveness and insulin sensitivity. In addition, it has become evident that a concomitant increase in stiffness of both plasma and erythrocyte membranes may decrease the microcirculatory flow, leading ultimately to tissue hypoxia, insufficient tissue nutrition, and diabetes-specific microvascular pathology. As to the etiology of type 2 diabetes mellitus, a revised hypothesis that attempts to accommodate the reviewed findings is presented.
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Affiliation(s)
- Rob N M Weijers
- Teaching Hospital, Onze Lieve Vrouwe Gasthuis, Oosterparkstraat 9, PO Box 95500, 1090 HM Amsterdam, The Netherlands.
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33
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Novel methodologies for assessing omega-3 fatty acid status - a systematic review. Br J Nutr 2012; 107 Suppl 2:S53-63. [PMID: 22591903 DOI: 10.1017/s0007114512001468] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Over the last few decades n-3 long chain polyunsaturated fatty acid status became of special interest for scientists. Biochemical measures on the n-3 fatty acid status vary depending on body compartment assessed and measures chosen. Plasma phospholipids and red blood cell membrane phospholipids are mainly used as n-3 fatty acid status marker. The conventional analysis of phospholipid fatty acids involves lipid extraction and consecutive chromatographic separation of phospholipids from other lipid fractions, which is time-consuming and costly. In recent years, different investigators have tried to overcome these limitations by using other biological markers or by modifying the analytical procedures used to assess n-3 fatty acid status. The aim of this systematic review was to provide an overview on these novel analytical methods developed for the fatty acid quantification by gas chromatography, highlights the methodological limitations, and discusses advantages or disadvantages of the biological markers used. Seventeen papers were identified that fulfilled the inclusion criteria. New opportunities arise from sensitive and precise high-throughput methodologies for assessment of plasma total lipid and plasma glycerophospholipid fatty acids, as well as cheek cell fatty acid composition.
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Abstract
PURPOSE OF REVIEW The amount and activity of placental enzymes, receptors, and transport proteins will determine the extent of lipid transfer to the fetus that strongly contributes to fetal fat accretion. RECENT FINDINGS Several studies have shown an association between the percentage of maternal plasma docosahexaenoic acid during gestation and the development of cognitive functions in the neonate. The functionality of the placenta could affect neonatal adiposity and fetal levels of long-chain polyunsaturated fatty acids in the offspring. SUMMARY Both in-vitro and human in-vivo studies using labeled fatty acids (FAs) reported a preferential placental-fetal transfer of long-chain polyunsaturated fatty acids, although the mechanisms are still uncertain. The placenta uptakes the maternal circulating nonesterified fatty acids (NEFAs) and FAs released by maternal lipoprotein lipase and endothelial lipase. These NEFAs enter the cell through passive diffusion or by membrane carrier proteins. NEFAs bind to cytosolic fatty-acid-binding proteins to interact with subcellular organelles, including the endoplasmic reticulum, mitochondria, lipid droplets and peroxisomes. Knowledge about FA metabolism and adaptations in response to obesity or diabetes in human placenta is more limited, and contradictory results are available in their influence on placental lipases and carriers.
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Affiliation(s)
- Alfonso Gil-Sánchez
- Service of Gynecology and Obstetrics, Virgen de la Arrixaca Hospital, Murcia, Spain
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35
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Min Y, Lowy C, Islam S, Khan FS, Swaminathan R. Relationship between red cell membrane fatty acids and adipokines in individuals with varying insulin sensitivity. Eur J Clin Nutr 2011; 65:690-5. [DOI: 10.1038/ejcn.2011.19] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Min Y, Ghebremeskel K, Geppert J, Khalil F. Effect of storage temperature and length on fatty acid composition of fingertip blood collected on filter paper. Prostaglandins Leukot Essent Fatty Acids 2011; 84:13-8. [PMID: 21093236 DOI: 10.1016/j.plefa.2010.10.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2010] [Revised: 09/24/2010] [Accepted: 10/25/2010] [Indexed: 11/23/2022]
Abstract
We have compared the fatty acids of the capillary and venous whole blood samples collected on the commercially developed blood collection paper and standard grade filter paper extracted by either the direct methylation or conventional method (including various blood lipids fractions). Also, reproducibility of fatty acids extracted from dried blood on the filter paper after storing at room temperature up to 2 months and at 4°C up to 6 months was assessed. In conclusion, the direct methylation of fingertip blood collected on both brand of papers produced fatty acids that reflected venous blood fatty acids extracted by the conventional method. Of the eight fatty acids evaluated, capillary DHA showed the strongest correlation with DHA of the venous whole lipids as well as various lipid fractions of the plasma and red cells. However, a prolonged storage of blood samples at 4°C had deleterious effect on the qualitative value of fatty acids, especially DHA.
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Affiliation(s)
- Yoeju Min
- Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, 166-220 Holloway Road, London N7 8DB, UK.
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Herrera E, Ortega-Senovilla H. Disturbances in lipid metabolism in diabetic pregnancy - Are these the cause of the problem? Best Pract Res Clin Endocrinol Metab 2010; 24:515-25. [PMID: 20832733 DOI: 10.1016/j.beem.2010.05.006] [Citation(s) in RCA: 156] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The most common neonatal complication of gestational diabetes (GDM) is macrosomia. During early pregnancy an accumulation of maternal fat depots occurs followed by increased adipose tissue lipolysis and subsequent hyperlipidaemia, which mainly corresponds to increased triglycerides (TG) in all circulating lipoproteins. In GDM women, the enhanced insulin resistance and decreased oestrogens are responsible for the reported wide range of dyslipidaemic conditions. In GDM, decreased proportion of long chain polyunsaturated fatty acids in fetus plasma could result from decreased supply, impaired placental transfer or even altered intrauterine metabolism. A positive correlation between maternal TG and neonatal body weight or fat mass has been found in GDM. Augmented oxidative stress and altered adipokines have also been found, with an adverse outcome even in normoglycaemic conditions. Thus, although additional studies are required, overall these findings indicate that altered maternal lipid metabolism rather than hyperglycaemia constitutes a risk for macrosomia in GDM.
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Affiliation(s)
- Emilio Herrera
- Universidad San Pablo CEU, Boadilla del Monte, Madrid, Spain.
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Long-term effects of gestational diabetes on offspring health are more pronounced in skeletal growth than body composition and glucose tolerance. Br J Nutr 2010; 104:1641-9. [PMID: 20615268 DOI: 10.1017/s0007114510002631] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Infants of diabetic mothers may have low arachidonic acid (AA) and develop obesity and insulin resistance in adulthood. The present study tested the effect of maternal diabetes and AA supplementation on offspring body composition, bone mass and glucose tolerance from 4 to 12 weeks. Rat dams were randomised into six groups using a 3 × 2 design. The rat dams were treated using the following treatments: saline-placebo, streptozotocin-induced diabetes (STZ) with glucose controlled at < 13 mmol/l (STZ/GC) or poorly controlled at 13-20 mmol/l (STZ/PC) using insulin, and fed either a control or an AA (0.5 % of fat) diet throughout reproduction. Weaned offspring were fed regular chow. Measurements included offspring body composition, bone and oral glucose tolerance testing (OGTT) plus liver fatty acids of dam and offspring. Comparable to saline-placebo offspring, the STZ/GC offspring had greater (P < 0.03) whole body and regional bone area than STZ/PC offspring. Maternal glucose negatively correlated (P < 0.05) with offspring whole body bone area and mineral content at 4 weeks in all offspring, and with tibia area in males at 12 weeks. Maternal liver DHA negatively (P < 0.03) correlated with femur and tibia mineral content and tibia mineral density of female offspring at 12 weeks. Offspring from AA-supplemented dams had higher (P = 0.004) liver AA at 4 weeks. Liver AA at 4 weeks positively (P = 0.05) correlated with lumbar spine mineral density in males. OGTT was not affected by maternal treatment or diet. These results suggest that maternal glucose control has long-term consequences to bone health of adult offspring. Skeletal growth appears more sensitive to maternal hyperglycaemia than glucose tolerance.
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Muskiet F. Pathophysiology and Evolutionary Aspects of Dietary Fats and Long-Chain Polyunsaturated Fatty Acids across the Life Cycle. Front Neurosci 2009. [DOI: 10.1201/9781420067767-c2] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
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40
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Hanebutt FL, Demmelmair H, Schiessl B, Larqué E, Koletzko B. Long-chain polyunsaturated fatty acid (LC-PUFA) transfer across the placenta. Clin Nutr 2008; 27:685-93. [PMID: 18639956 DOI: 10.1016/j.clnu.2008.05.010] [Citation(s) in RCA: 122] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2008] [Accepted: 05/30/2008] [Indexed: 10/21/2022]
Abstract
Fetal long-chain polyunsaturated fatty acid (LC-PUFA) supply during pregnancy is of major importance, particularly with respect to docosahexaenoic acid (DHA) that is an important component of the nervous system cell membranes. Growing evidence points to direct effects of DHA status on visual and cognitive outcomes in the offspring. Furthermore, DHA supply in pregnancy reduces the risk of preterm delivery. Because of limited fetal capacity to synthesize LC-PUFA, the fetus depends on LC-PUFA transfer across the placenta. Molecular mechanisms of placental LC-PUFA uptake and transport are not fully understood, but it has been clearly demonstrated that there is a preferential DHA transfer. Thus, the placenta is of pivotal importance for the selective channeling of DHA from maternal diet and body stores to the fetus. Several studies have associated various fatty acid transport and binding proteins (FATP) with the preferential DHA transfer, but also the importance of the different lipolytic enzymes has been shown. Although the exact mechanisms and the interaction of these factors remains elusive, recent studies have shed more light on the processes involved, and this review summarizes the current understanding of molecular mechanisms of LC-PUFA transport across the placenta and the impact on pregnancy outcome and fetal development.
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Affiliation(s)
- Fabienne L Hanebutt
- Division of Metabolic Diseases and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University of Munich, Lindwurmstrasse 4, 80337 Munich, Germany
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41
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Gorjão R, Cury-Boaventura MF, de Lima TM, Curi R. Regulation of human lymphocyte proliferation by fatty acids. Cell Biochem Funct 2007; 25:305-15. [PMID: 17195961 DOI: 10.1002/cbf.1388] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
In the present study, the effect of increasing concentrations of palmitic (PA, C16:0), stearic (SA, C18:0), oleic (OA, C18:1, n-9), linoleic (LA, C18:2n-6), docosahexaenoic (DHA, C22:6 n-3) and eicosapentaenoic (EPA, C20:5 n-3) acids on lymphocyte proliferation was investigated. The maximal non-toxic concentrations of these fatty acids for human lymphocytes in vitro were determined. It was also evaluated whether these fatty acids at non-toxic concentrations affect IL-2 induced lymphocyte proliferation and cell cycle progression. OA and LA at 25 microM increased lymphocyte proliferation and at higher concentrations (75 microM and 100 microM) inhibited it. Both fatty acids promoted cell death at 200 microM concentration. PA and SA decreased lymphocyte proliferation at 50 microM and promoted cell death at concentrations of 100 microM and above. EPA and DHA decreased lymphocyte proliferation at 25 and 50 microM being toxic at 50 and 100 microM, respectively. PA, SA, DHA and EPA decreased the stimulatory effect of IL-2 on lymphocyte proliferation, increasing the percentage of cells in G1 phase and decreasing the proportion of cells in S and G2/M phases. OA and LA caused an even greater pronounced effect. The treatment with all fatty acids increased neutral lipid accumulation in the cells but the effect was more pronounced with PA and DHA. In conclusion, PA, SA, DHA and EPA decreased lymphocyte proliferation, whereas OA and LA stimulated it at non-toxic concentrations.
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Affiliation(s)
- Renata Gorjão
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
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Weijers RNM, Bekedam DJ. Relationship between Gestational Diabetes Mellitus and Type 2 Diabetes: Evidence of Mitochondrial Dysfunction. Clin Chem 2007; 53:377-83. [PMID: 17327503 DOI: 10.1373/clinchem.2006.077636] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Abstract
Background: We examined the pathogenesis of gestational diabetes mellitus (GDM) in a large Dutch multiethnic cohort.
Methods: We used a 2-step testing procedure to stratify 2031 consecutive pregnant women into 4 groups according to American Diabetes Association criteria: (a) normal glucose tolerance (NGT), (b) mild gestational hyperglycemia (MGH), (c) GDM without early postpartum diabetes within 6 months of delivery (GDM1), and (d) GDM with early postpartum diabetes (GDM2). Antepartum and postpartum clinical characteristics and measures of glucose tolerance were documented.
Results: Overall, 1627 women had NGT, 237 had MGH, 156 had GDM1, and 11 had GDM2. Prepregnancy body mass index values progressively increased from NGT to MGH to GDM1. The fasting plasma glucose concentration, the 100-g oral glucose tolerance test (OGTT) area under the curve, and the mean glucose concentration during the OGTT all increased progressively among the 4 groups. The fasting C-peptide concentration displayed an inverted-U pattern, with a maximum at a mean plasma glucose concentration during the OGTT of 9.6 mmol/L in the transition from GDM1 to GDM2. The fasting C-peptide/glucose concentration ratio decreased by 42% in GDM patients compared with NGT patients, whereas the ratios in MGH and NGT women were similar.
Conclusions: Progressive metabolic derangement of glucose tolerance 1st detected during pregnancy mimics the pathogenesis of type 2 diabetes. In addition, our results imply an impaired basal glucose effectiveness in the early prediabetic state. To explain the parallel in both metabolic derangements, we postulate that GDM, like type 2 diabetes, is attributable to the same inherited mitochondrial dysfunction.
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Affiliation(s)
- Rob N M Weijers
- Department of Clinical Chemistry and Haematology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
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Rasic-Milutinovic Z, Perunicic G, Pljesa S, Gluvic Z, Sobajic S, Djuric I, Ristic D. Effects of N-3 PUFAs supplementation on insulin resistance and inflammatory biomarkers in hemodialysis patients. Ren Fail 2007; 29:321-329. [PMID: 17497447 DOI: 10.1080/08860220601184092] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
AIMS/HYPOTHESIS It was suggested that polyunsaturated n-3 fatty acids (n-3 PUFAs) could improve insulin sensitivity and have an anti-inflammatory effects in overall population. This study investigates a possible effect of n-3 PUFAs supplementation on the insulin sensitivity and some inflammatory markers; hence, patients with chronic renal failure (CRF) on maintenance hemodialysis (MHD) are presented with insulin resistance. METHODS This study explored the ratio between red blood cells (RBC) phospholipid long chain fatty acids (LC FAs) and components of metabolic syndrome (MeS) in 35 patients (mean age 54.50 +/- 11.99 years) with CRF on MHD. Furthermore, the effects of omega-3 FA eight-week's supplementation (EPA+DHA, 2.4 g/d) on the MeS features and inflammatory markers TNF-alpha, IL 6, and hsCRP were examined. RESULTS Supplementation increased EPA and DHA levels in RBCs (p = 0.009 for EPA and p = 0.002 for DHA). Total n-6 PUFAs: n-3 PUFAs ratio tended to be lower after supplementation (p = 0.31), but not significantly. Data revealed a significant decrease of saturated FAs (SFA) (p = 0.01) as well as total SFA: n-3 PUFAs ratio during the treatment (p = 0.04). The values of serum insulin and calculated IR index-IR HOMA were reduced after supplementation (p = 0.001 for both). There was a significant decrease in the levels of all inflammatory markers (p = 0.01 for TNF alpha, p = 0.001 for IL 6, p = 0.001 for hsCRP, and p = 0.01 for ferritin). In multivariate regression analysis, only the changes in n-6 PUFAs: n-3 PUFAs ratio independently contributed to 40% of the variance in IR HOMA. The impact of changes in PUFAs level in RBCs membrane phospholipid fatty acids on inflammation markers was also registered. The changes in n-6: n-3 PUFAs ratio independently contributed to 18% of the variance in TNF alpha. CONCLUSION It was concluded that the EPA and DHA moderate dose administration in the patients with CRF on MHD had a beneficial effect on insulin resistance decrease. The anti-inflammatory effects of the supplemented PUFAs were also presented.
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Peet M. The metabolic syndrome, omega-3 fatty acids and inflammatory processes in relation to schizophrenia. Prostaglandins Leukot Essent Fatty Acids 2006; 75:323-7. [PMID: 16934964 DOI: 10.1016/j.plefa.2006.07.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Although schizophrenia is normally regarded as a brain disease, there is clear evidence that schizophrenia is strongly associated with a variety of physical conditions. These include an increased rate of the metabolic syndrome and its physical complications including diabetes and coronary heart disease, and a reduced rate of rheumatoid arthritis. It is argued that these associations may point to a commonality of some aetiological factors. Evidence implicating omega-3 fatty acids in all of these disorders is presented. The associations may derive either from genetic or from environmental factors, including nutrition. Further investigation of these associations may give important clues regarding the aetiology of schizophrenia.
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Affiliation(s)
- Malcolm Peet
- Doncaster and South Humber Healthcare NHS Trust, Rotherham Services, Early Intervention Service, Swallownest, Sheffield, S26 4TH, UK.
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45
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Min Y, Nam JH, Ghebremeskel K, Kim A, Crawford M. A distinctive fatty acid profile in circulating lipids of Korean gestational diabetics: a pilot study. Diabetes Res Clin Pract 2006; 73:178-83. [PMID: 16455150 DOI: 10.1016/j.diabres.2006.01.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2005] [Accepted: 01/04/2006] [Indexed: 11/27/2022]
Abstract
Gestational diabetes mellitus (GDM) is a transient metabolic disorder that is a strong predictor of type 2 diabetes and cardiovascular disease. Previously, GDM was associated with reduced red cell long-chain omega-6 and omega-3 fatty acids in population (British) with high intake of total and saturated fat. The aim of the study was to examine blood fatty acids status of GDM patients (n=12) and normoglycaemic women (control, n=12) from South Korea where typical diet retains high omega-3 fat with low total fat intake. Subjects were matched for BMI and gestation week. Blood obtained at delivery were analyzed for plasma triacylglycerols (TG), phosphatidylcholine (PC), sphingomyelin (SM), and red cell PC, phosphatidylethanolamine (PE) and SM fatty acids. GDM patients had lower total saturated fatty acids (SFA) in the plasma TG (p<0.05) and PC (p<0.0001), and higher omega-6 and omega-3 metabolites in the plasma PC (p<0.05) than the controls. Conversely, the red cell PC and PE of the GDM contained higher proportions of palmitic (p<0.05) and SFA (p<0.05) but lower arachidonic (p<0.05) and docosahexaenoic (p>0.05) acids compared with the controls. Interestingly, red cell PC arachidonic acid level was comparable between Korean and British women whereas docosahexaenoic acid level decreased in the order of Korean control (5.5+/-0.9)>Korean GDM (3.5+/-2.1)=British control (3.9+/-2.9)>British GDM (2.8+/-2.3) (p<0.05). The similarity in the plasma and red cell fatty acids profile between Korean and British cohort suggests that the reduced membrane arachidonic and docosahexaenoic acids in GDM might be attributed to the effect of the disease itself regardless of ethnicity, obesity, or diet.
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Affiliation(s)
- Yoeju Min
- Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, 166-220 Holloway Road, London N7 8DB, UK.
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Thomas B, Ghebremeskel K, Lowy C, Crawford M, Offley-Shore B. Nutrient intake of women with and without gestational diabetes with a specific focus on fatty acids. Nutrition 2006; 22:230-6. [PMID: 16500549 DOI: 10.1016/j.nut.2005.07.017] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2005] [Accepted: 07/15/2005] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Diet therapy is the cornerstone for the management of gestational diabetes mellitus (GDM). Women with GDM are commonly given dietary advice that broadly focuses on a reduction of total energy and fat consumption. We compared nutrient intake and specifically fatty acids of women with GDM who had received individualized nutritional counseling with those of non-diabetic women who did not. METHOD Women with GDM (n=44) and healthy pregnant women (n=44) with uncomplicated singleton pregnancies were recruited during the third trimester. Women with GDM were given consultation on diet, health, and macronutrient content of foods commonly consumed by the individual. The non-diabetic group did not receive any dietary advice. Both groups were asked to keep a detailed record of all of foods and fluid consumed over a 4-d period. RESULTS After dietary counseling, the GDM group had lower intakes of energy (P<0.05), refined sugar (P<0.0001), total and saturated fats (P<0.0001), and monounsaturated (P<0.01) and trans (P<0.0001) fatty acids and higher levels of docosahexaenoic acid and fiber (P<0.05) compared with the non-diabetic group. CONCLUSIONS Individualized dietary advice was associated with a lower consumption of the target nutrients in women with GDM. Another benefit of the advice was a slight increase in intake of eicosapentaenoic and docosahexaenoic acids, although consumption of omega-3 fatty acids by both groups was well below the recommendations for pregnancy. There is evidence that docosahexaenoic acid modulates insulin resistance and that it is vital for neurovisual development. We suggest that dietary management for women with GDM should foster the current recommendations for essential fatty acids in pregnancy.
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Affiliation(s)
- Beverley Thomas
- Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, and Endocrine and Diabetic Day Centre, Guy's and St. Thomas' Hospital Trust, London, United Kingdom.
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Bitsanis D, Ghebremeskel K, Moodley T, Crawford MA, Djahanbakhch O. Gestational diabetes mellitus enhances arachidonic and docosahexaenoic acids in placental phospholipids. Lipids 2006; 41:341-6. [PMID: 16808147 DOI: 10.1007/s11745-006-5104-8] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
In previous studies, we reported that neonates of women with gestational diabetes mellitus (GDM) have reduced blood levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) that were unrelated to maternal status. Since both AA and DHA are selectively transferred from maternal to fetal circulation by the placenta, we have investigated whether the FA composition of the placenta is altered by GDM. Thirty-six women, 11 with and 25 without GDM, were recruited from Newham General Hospital, London. The women with GDM had higher levels of di-homo-gamma-linolenic (P < 0.05), docosatetraenoic (n-6 DTA; P< 0.0001), docosapentaenoic n-6 (P< 0.005), total n-6 (P < 0.005), docosapentaenoic (n-3 DPA; P < 0.005), and total n-3 (P < 0.01) FA, as well as higher levels of AA (P < 0.05) and DHA (P < 0.01), in placental choline phosphoglycerides (CPG) compared with the healthy women who served as controls. Similarly, the women with GDM had elevated n-6 DTA (P < 0.005), AA, total n-6 metabolites (P < 0.05), DHA, total n-3 metabolites, and total n-3 FA (P < 0.005) in ethanolamine phosphoglycerides (EPG). In contrast to CPG and EPG, the placental TG of the women with GDM had higher linoleic acid (P< 0.05) and lower AA, n-6 metabolites, and n-3 DPA (P < 0.01). The placenta is devoid of desaturase activity, and it is thought to be reliant on maternal circulation for both AA and DHA. Hence, the enhanced levels of the two FA in the placenta of the GDM group suggests that these FA are taken up from the maternal circulation and retained after esterification into phosphoglycerides instead of being transferred to the fetus. Further study is needed to elucidate the mechanism involved and the effect of the phenomenon on postnatal growth and development of the offspring.
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Affiliation(s)
- Demetris Bitsanis
- Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, United Kingdom.
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48
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Min Y, Lowy C, Ghebremeskel K, Thomas B, Offley-Shore B, Crawford M. Unfavorable effect of type 1 and type 2 diabetes on maternal and fetal essential fatty acid status: a potential marker of fetal insulin resistance. Am J Clin Nutr 2005; 82:1162-8. [PMID: 16332647 DOI: 10.1093/ajcn/82.6.1162] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Pregestational maternal diabetes increases obesity and diabetes risks in the offspring. Both conditions are characterized by insulin resistance, and diabetes is associated with low membrane arachidonic (AA) and docosahexaenoic (DHA) acids. OBJECTIVE We investigated whether type 1 and type 2 diabetes in pregnancy compromise maternal and fetal membrane essential fatty acids (FAs). DESIGN We studied 39 nondiabetic (control subjects), 32 type 1 diabetic, and 17 type 2 diabetic pregnant women and the infants they delivered. Maternal and cord blood samples were obtained at midgestation and at delivery, respectively. Plasma triacylglycerols and choline phosphoglycerides and red blood cell (RBC) choline and ethanolamine phosphoglyceride FAs were assessed. RESULTS The difference in maternal plasma triacylglycerol FAs between groups was not significant. However, the type 1 diabetes group had lower plasma choline phosphoglyceride DHA (3.7 +/- 0.9%; P < 0.01) than did the control group (5.2 +/- 1.6%). Likewise, RBC DHA was lower in the type 1 [choline: 3.4 +/- 1.5% (P < 0.01); ethanolamine: 5.9 +/- 2.5% (P < 0.05)] and type 2 [choline: 3.5 +/- 1.6% (P < 0.05)] diabetes groups than in the control group (choline: 5.5 +/- 2.2%; ethanolamine: 7.5 +/- 2.5%). Cord AA and DHA were lower in the plasma (type 1: P < 0.01) and RBC (type 2: P < 0.05) choline phosphoglycerides of the diabetics than of the control subjects, and cord RBC ethanolamine phosphoglycerides were lower in DHA (P < 0.05) in both diabetes groups than in the control group. CONCLUSIONS Diabetes (either type) compromises maternal RBC DHA and cord plasma and RBC AA and DHA. The association of these 2 FAs with insulin sensitivity may mean that the current finding explains the higher incidence of insulin resistance and diabetes in the offspring of diabetic women.
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MESH Headings
- Adult
- Arachidonic Acid/analysis
- Arachidonic Acid/blood
- Biomarkers/blood
- Case-Control Studies
- Diabetes Mellitus, Type 1/blood
- Diabetes Mellitus, Type 1/metabolism
- Diabetes Mellitus, Type 2/blood
- Diabetes Mellitus, Type 2/metabolism
- Docosahexaenoic Acids/analysis
- Docosahexaenoic Acids/blood
- Erythrocyte Membrane/chemistry
- Erythrocyte Membrane/metabolism
- Fatty Acids, Essential/analysis
- Fatty Acids, Essential/blood
- Fatty Acids, Essential/metabolism
- Female
- Fetal Blood/chemistry
- Fetal Blood/metabolism
- Glycerylphosphorylcholine/chemistry
- Humans
- Insulin Resistance/physiology
- Maternal-Fetal Exchange
- Phosphatidylethanolamines/chemistry
- Pregnancy
- Pregnancy Trimester, Second/blood
- Pregnancy Trimester, Second/metabolism
- Pregnancy Trimester, Third/blood
- Pregnancy Trimester, Third/metabolism
- Pregnancy in Diabetics/blood
- Pregnancy in Diabetics/metabolism
- Triglycerides/blood
- Triglycerides/chemistry
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Affiliation(s)
- Yoeju Min
- Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, London, United Kingdom.
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Bitsanis D, Crawford MA, Moodley T, Holmsen H, Ghebremeskel K, Djahanbakhch O. Arachidonic acid predominates in the membrane phosphoglycerides of the early and term human placenta. J Nutr 2005; 135:2566-71. [PMID: 16251612 DOI: 10.1093/jn/135.11.2566] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
The aim of this study was to determine whether the high concentration of arachidonic acid (AA) in term placentae accumulates during pregnancy or is an inherent characteristic of placental lipids. We investigated the lipid content and fatty acid composition of the human placental phospholipids at 2 gestational periods, early in pregnancy (8-14 wk, n = 48) and at term (38-41 wk of gestation, n = 19). The subjects were healthy, normotensive, and free of medical and obstetric complications. The lipid concentration of placentae increased from 0.8% in early gestation to 1.4% at term (P < 0.0001). The mean proportions of AA were lower in the choline (P < 0.05), inositol (P < 0.0001), and ethanolamine (P < 0.0001) phosphoglycerides of the term compared with the early placenta. In contrast, the proportions of the immediate precursor of AA, dihomo-gamma-linolenic acid (DGLA), were higher in the term placenta, particularly in the inositol and serine phosphoglycerides (P < 0.0001). In sphingomyelin, the percentage of lignoceric acid was increased and that of nervonic acid was reduced at term (P < 0.01). The dominance of AA, particularly in the early placenta, suggests that it has an important role for placental development, i.e., organogenesis and vascularization. There was no evidence of an accumulation of AA in the placenta toward term, which might be a trigger for parturition. In contrast, the increased proportion of DGLA (precursor of the vasorelaxant and anticoagulant prostaglandin E(1)) at term is more consistent with a profile favoring optimal blood flow to nourish the fetal growth spurt.
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Affiliation(s)
- Demetris Bitsanis
- Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, London, UK.
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Dijck-Brouwer DAJ, Hadders-Algra M, Bouwstra H, Decsi T, Boehm G, Martini IA, Rudy Boersma E, Muskiet FAJ. Impaired maternal glucose homeostasis during pregnancy is associated with low status of long-chain polyunsaturated fatty acids (LCP) and essential fatty acids (EFA) in the fetus. Prostaglandins Leukot Essent Fatty Acids 2005; 73:85-7. [PMID: 16006109 DOI: 10.1016/j.plefa.2005.05.022] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2005] [Revised: 03/16/2005] [Accepted: 05/15/2005] [Indexed: 11/21/2022]
Abstract
Low status of long-chain polyunsaturated fatty acids (LCP) and essential fatty acids (EFA) in the fetus is associated with less favorable neonatal neurological condition. A 'relative', rather than 'absolute' EFA deficiency might explain this finding. A relative EFA deficiency may derive from impaired maternal glucose homeostasis. We measured fatty acids in umbilical vessels of infants born to 7 mothers with (gestational) diabetes mellitus and of 258 infants born to healthy mothers. Umbilical veins of infants of diabetic mothers had higher omega7 and omega9 fatty acids and DHA deficiency index and lower 20:4omega6 and EFA index. Their umbilical arteries had higher omega7 and omega9 fatty acids, and lower 20:4omega6, LCP and EFA index. We conclude that children born to mothers with poor glucose homeostasis have lower EFA and LCP status, which is consistent with a 'relative deficiency' deriving from augmented de novo fatty acid synthesis from the abundant glucose.
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Affiliation(s)
- D A Janneke Dijck-Brouwer
- Pathology and Laboratory Medicine, Room Y1.165, Groningen University Hospital, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
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