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Inflammation in Pregnant Women with Obesity and Gestational Diabetes Mellitus

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Obesity, Diabetes and Inflammation

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

Pregnant women with obesity and/or gestational diabetes mellitus (GDM) represent a unique patient population with specific maternal and fetal health risks. This chapter explores the complex metabolic milieu and dynamic adaptive mechanisms of the maternal and placental immune response, the role of inflammation specific to obesity and GDM, and concepts of fetal programming and concludes with clinical and research considerations.

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Abbreviations

ACOG:

American College of Obstetricians and Gynecologists

ADA:

American Diabetes Association

AT:

Adipose tissue

BMI:

Body mass index

BPA:

Bisphenol A

DASH:

Dietary Approaches to Stop Hypertension

DC:

Dendritic cell

DM:

Diabetes mellitus

EDC:

Endocrine-disrupting chemicals

EPA:

Eicosapentaenoic acid

EPOCH:

Exploring Perinatal Outcomes among Children

FA:

Folic acid

FDA:

Food and Drug Administration

FPG:

Fasting plasma glucose

FSH:

Follicle-stimulating hormone

GD:

Grave’s disease

GDM:

Gestational diabetes mellitus

GWG:

Gestational weight gain

HAPO:

Hyperglycemia and Adverse Pregnancy Outcome

HbA1c:

Hemoglobin A1c

HT:

Hashimoto’s thyroiditis

IFN:

Interferon

IL:

Interleukin

IOM:

Institute of Medicine

LGA:

Large-for-gestational-age

M:

Macrophage

M1:

M1 macrophages

M2:

M2 macrophages

MG:

Myasthenia gravis

MI:

Myo-inositol

MMP:

Matrix metalloproteinases

MMR:

Maternal mortality rate

MO:

Maternal obesity

Mono:

Monocytes

MP:

Macrophage

MS:

Multiple sclerosis

NF:

Nuclear factor

NIH:

National Institutes of Health

NK:

Natural killer

NP:

Neutrophils

NTD:

Neural tube defect

OGTT:

Oral glucose tolerance test

PPT:

Postpartum thyroiditis

PRIMS:

Pregnancy in multiple sclerosis

RA:

Rheumatoid arthritis

RCT:

Randomized control trial

RPG:

Random plasma glucose

SGA:

Small-for-gestational-age

SPRING:

Study of PRobiotics IN Gestation

T2DM:

Type 2 diabetes mellitus

TGFβ:

Transforming growth factor-beta

Th:

T helper cell type

TNF:

Tumor necrosis factor

TNFα:

Tumor necrosis factor-alpha

Treg:

Regulatory T-cell

TSH:

Thyroid stimulating hormone

WAT:

White adipose tissue

WHO:

World Health Organization

References

  1. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–7.

    CAS  Google Scholar 

  2. Rohm TV, Meier DT, Olefsky JM, Donath MY. Inflammation in obesity, diabetes, and related disorders. Immunity. 2022;55:31–55.

    CAS  PubMed Central  Google Scholar 

  3. Baeten JM, Bukusi EA, Lambe M. Pregnancy complications and outcomes among overweight and obese nulliparous women. Am J Public Health. 2001;91:436–40.

    CAS  PubMed Central  Google Scholar 

  4. Sebire NJ, Jolly M, Harris JP, et al. Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London. Int J Obes Relat Metab Disord. 2001;25:1175–82.

    CAS  Google Scholar 

  5. Ehrenberg HM, Mercer BM, Catalano PM. The influence of obesity and diabetes on the prevalence of macrosomia. Am J Obstet Gynecol. 2004;191:964–8.

    CAS  Google Scholar 

  6. Hartling L, Dryden DM, Guthrie A, Muise M, Vandermeer B, Donovan L. Diagnostic thresholds for gestational diabetes and their impact on pregnancy outcomes: a systematic review. Diabet Med. 2014;31:319–31.

    CAS  Google Scholar 

  7. Lowe WL Jr, Scholtens DM, Lowe LP, et al. Association of gestational diabetes with Maternal disorders of glucose metabolism and childhood adiposity. JAMA. 2018;320:1005–16.

    CAS  PubMed Central  Google Scholar 

  8. Driscoll AK, Gregory ECW. Increases in prepregnancy obesity: United States, 2016–2019. NCHS Data Brief; 2020.

    Google Scholar 

  9. Casagrande SS, Linder B, Cowie CC. Prevalence of gestational diabetes and subsequent type 2 diabetes among U.S. women. Diabetes Res Clin Pract. 2018;141:200–8.

    Google Scholar 

  10. Thornton P, Abrams R, Briller J, Geller S. Illinois maternal morbidity and mortality report October 2018. University of Illinois at Chicago; 2020.

    Google Scholar 

  11. Frey HA, Ashmead R, Farmer A, et al. Association of Prepregnancy Body Mass Index with Risk of severe maternal morbidity and mortality among medicaid beneficiaries. JAMA Netw Open. 2022;5:e2218986-e.

    Google Scholar 

  12. Blomberg M. Maternal obesity, mode of delivery, and neonatal outcome. Obstet Gynecol. 2013;122:50–5.

    Google Scholar 

  13. Bodnar LM, Siminerio LL, Himes KP, et al. Maternal obesity and gestational weight gain are risk factors for infant death. Obesity (Silver Spring). 2016;24:490–8.

    Google Scholar 

  14. Chen A, Feresu SA, Fernandez C, Rogan WJ. Maternal obesity and the risk of infant death in the United States. Epidemiology. 2009;20:74–81.

    PubMed Central  Google Scholar 

  15. Tavera G, Dongarwar D, Salemi JL, et al. Diabetes in pregnancy and risk of near-miss, maternal mortality and foetal outcomes in the USA: a retrospective cross-sectional analysis. J Public Health. 2021;44:549–57.

    Google Scholar 

  16. Murray SR, Reynolds RM. Short- and long-term outcomes of gestational diabetes and its treatment on fetal development. Prenat Diagn. 2020;40:1085–91.

    CAS  Google Scholar 

  17. Kaseva N, Vääräsmäki M, Sundvall J, et al. Gestational diabetes but not Prepregnancy overweight predicts for cardiometabolic markers in offspring twenty years later. J Clin Endocrinol Metabol. 2019;104:2785–95.

    Google Scholar 

  18. Rahier J, Wallon J, Henquin JC. Cell populations in the endocrine pancreas of human neonates and infants. Diabetologia. 1981;20:540–6.

    CAS  Google Scholar 

  19. Wellmann KF, Volk BW. The islets of infants of diabetic mothers. In: Volk BW, Wellmann KF, editors. The diabetic pancreas. Boston, MA: Springer; 1977. p. 365–80.

    Google Scholar 

  20. Holemans K, Aerts L, Van Assche FA. Lifetime consequences of abnormal fetal pancreatic development. J Physiol. 2003;547:11–20.

    CAS  PubMed Central  Google Scholar 

  21. Ozanne SE, Hales CN. Early programming of glucose–insulin metabolism. Trends Endocrinol Metabol. 2002;13:368–73.

    CAS  Google Scholar 

  22. Barker DJ, Osmond C, Kajantie E, Eriksson JG. Growth and chronic disease: findings in the Helsinki Birth Cohort. Ann Hum Biol. 2009;36:445–58.

    Google Scholar 

  23. Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992;35:595–601.

    CAS  Google Scholar 

  24. Hales CN, Barker DJP. The thrifty phenotype hypothesis: type 2 diabetes. Br Med Bull. 2001;60:5–20.

    CAS  Google Scholar 

  25. Ignacio RM, Kim CS, Kim SK. Immunological profiling of obesity. J Lifestyle Med. 2014;4:1–7.

    PubMed Central  Google Scholar 

  26. Esposito K, Pontillo A, Giugliano F, et al. Association of low Interleukin-10 levels with the metabolic syndrome in obese women. J Clin Endocrinol Metabol. 2003;88:1055–8.

    CAS  Google Scholar 

  27. McElwain CJ, McCarthy FP, McCarthy CM. Gestational diabetes mellitus and maternal immune dysregulation: what we know so far. Int J Mol Sci. 2021;22:4261.

    CAS  PubMed Central  Google Scholar 

  28. Mor G, Cardenas I, Abrahams V, Guller S. Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci. 2011;1221:80–7.

    CAS  PubMed Central  Google Scholar 

  29. Meyyazhagan A, Kuchi Bhotla H, Pappuswamy M, Tsibizova V, Al Qasem M, Di Renzo GC. Cytokine see-saw across pregnancy, its related complexities and consequences. Int J Gynaecol Obstet. 2023;160(2):516–25.

    CAS  Google Scholar 

  30. Brown MB, von Chamier M, Allam AB, Reyes L. M1/M2 macrophage polarity in normal and complicated pregnancy. Front Immunol. 2014;5:606.

    PubMed Central  Google Scholar 

  31. Zhang YH, He M, Wang Y, Liao AH. Modulators of the balance between M1 and M2 macrophages during pregnancy. Front Immunol. 2017;8:120.

    PubMed Central  Google Scholar 

  32. Lindström TM, Bennett PR. The role of nuclear factor kappa B in human labour. Reproduction (Cambridge, England). 2005;130:569–81.

    Google Scholar 

  33. Chen J, Khalil RA. Matrix metalloproteinases in normal pregnancy and preeclampsia. Prog Mol Biol Transl Sci. 2017;148:87–165.

    CAS  PubMed Central  Google Scholar 

  34. Shimaoka Y, Hidaka Y, Tada H, et al. Changes in cytokine production during and after normal pregnancy. Am J Reprod Immunol. 2000;44:143–7.

    CAS  Google Scholar 

  35. Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT. Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset. Immunology. 2004;112:38–43.

    CAS  PubMed Central  Google Scholar 

  36. Elenkov IJ, Wilder RL, Bakalov VK, et al. IL-12, TNF-α, and hormonal changes during late pregnancy and early postpartum: implications for autoimmune disease activity during these times. J Clin Endocrinol Metabol. 2001;86:4933–8.

    CAS  Google Scholar 

  37. Gaberšček S, Zaletel K. Thyroid physiology and autoimmunity in pregnancy and after delivery. Expert Rev Clin Immunol. 2011;7:697–707.

    Google Scholar 

  38. Vukusic S, Hutchinson M, Hours M, et al. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain J Neurol. 2004;127:1353–60.

    Google Scholar 

  39. Al-Shammri S, Rawoot P, Azizieh F, et al. Th1/Th2 cytokine patterns and clinical profiles during and after pregnancy in women with multiple sclerosis. J Neurol Sci. 2004;222:21–7.

    CAS  Google Scholar 

  40. Szpunar MJ, Malaktaris A, Baca SA, Hauger RL, Lang AJ. Are alterations in estradiol, cortisol, and inflammatory cytokines associated with depression during pregnancy and postpartum? An exploratory study. Brain, Behav Immun Health. 2021;16:100309.

    CAS  Google Scholar 

  41. Osborne LM, Yenokyan G, Fei K, et al. Innate immune activation and depressive and anxious symptoms across the peripartum: an exploratory study. Psychoneuroendocrinology. 2019;99:80–6.

    Google Scholar 

  42. Vesco KK, Dietz PM, Rizzo J, et al. Excessive gestational weight gain and postpartum weight retention among obese women. Obstet Gynecol. 2009;114:1069.

    Google Scholar 

  43. Rooney BL, Schauberger CW. Excess pregnancy weight gain and long-term obesity: one decade later. Obstet Gynecol. 2002;100:245–52.

    Google Scholar 

  44. Institute of Medicine, National Research Council Committee to Reexamine IOMPWG. The National Academies Collection: reports funded by National Institutes of Health. In: Rasmussen KM, Yaktine AL, editors. Weight gain during pregnancy: reexamining the guidelines. Washington, DC: National Academies Press (US), National Academy of Sciences; 2009.

    Google Scholar 

  45. Institute of Medicine Committee on Nutritional Status During Pregnancy and Lactation. Nutrition during pregnancy: part I weight gain: part II nutrient supplements. Washington, DC: National Academies Press (US) 1990 by the National Academy of Sciences; 1990.

    Google Scholar 

  46. Institute of Medicine. Weight gain during pregnancy: reexamining the guidelines. Report Brief; 2009.

    Google Scholar 

  47. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995;95:2409–15.

    CAS  PubMed Central  Google Scholar 

  48. Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T. Tumor necrosis factor-α in sera of obese patients: fall with weight loss. J Clin Endocrinol Metabol. 1998;83:2907–10.

    CAS  Google Scholar 

  49. Challier JC, Basu S, Bintein T, et al. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta. 2008;29:274–81.

    CAS  PubMed Central  Google Scholar 

  50. Saben J, Lindsey F, Zhong Y, et al. Maternal obesity is associated with a lipotoxic placental environment. Placenta. 2014;35:171–7.

    CAS  PubMed Central  Google Scholar 

  51. Basu S, Haghiac M, Surace P, et al. Pregravid obesity associates with increased maternal endotoxemia and metabolic inflammation. Obesity (Silver Spring). 2011;19:476–82.

    CAS  Google Scholar 

  52. Reynolds RM, Osmond C, Phillips DIW, Godfrey KM. Maternal BMI, parity, and pregnancy weight gain: influences on offspring adiposity in young adulthood. J Clin Endocrinol Metabol. 2010;95:5365–9.

    CAS  Google Scholar 

  53. Neri C, Edlow AG. Effects of maternal obesity on fetal programming: molecular approaches. Cold Spring Harb Perspect Med. 2015;6:a026591.

    Google Scholar 

  54. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The pathophysiology of gestational diabetes mellitus. Int J Mol Sci. 2018;19:19.

    Google Scholar 

  55. Metzger BE, Buchanan TA, Coustan DR, et al. Summary and recommendations of the fifth international workshop-conference on gestational diabetes mellitus. Diabetes Care. 2007;30:S251–S60.

    CAS  Google Scholar 

  56. Coustan DR, Lowe LP, Metzger BE, Dyer AR. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus. Am J Obstet Gynecol. 2010;202(654):e1–6.

    Google Scholar 

  57. Lowe LP, Metzger BE, Dyer AR, et al. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: associations of maternal A1C and glucose with pregnancy outcomes. Diabetes Care. 2012;35:574–80.

    CAS  PubMed Central  Google Scholar 

  58. Solomon CG, Willett WC, Carey VJ, et al. A prospective study of Pregravid determinants of gestational diabetes mellitus. JAMA. 1997;278:1078–83.

    CAS  Google Scholar 

  59. Ehrlich S, Lambers D, Baccarelli A, Khoury J, Macaluso M, Ho S-M. Endocrine disruptors: a potential risk factor for gestational diabetes mellitus. Am J Perinatol. 2016;33:1313–8.

    Google Scholar 

  60. Wolf M, Sauk J, Shah A, et al. Inflammation and glucose intolerance: a prospective study of gestational diabetes mellitus. Diabetes Care. 2004;27:21–7.

    Google Scholar 

  61. Marseille-Tremblay C, Ethier-Chiasson M, Forest J-C, et al. Impact of maternal circulating cholesterol and gestational diabetes mellitus on lipid metabolism in human term. Placenta. 2008;75:1054–62.

    CAS  Google Scholar 

  62. Lappas M, Mitton A, Permezel M. In response to oxidative stress, the expression of inflammatory cytokines and antioxidant enzymes are impaired in placenta, but not adipose tissue, of women with gestational diabetes. J Endocrinol. 2010;204:75–84.

    CAS  Google Scholar 

  63. Kim SY, Sharma AJ, Callaghan WM. Gestational diabetes and childhood obesity: what is the link? Curr Opin Obstet Gynecol. 2012;24:376–81.

    PubMed Central  Google Scholar 

  64. Yang IV, Zhang W, Davidson EJ, Fingerlin TE, Kechris K, Dabelea D. Epigenetic marks of in utero exposure to gestational diabetes and childhood adiposity outcomes: the EPOCH study. Diabet Med. 2018;35:612–20.

    CAS  PubMed Central  Google Scholar 

  65. Silva L, Plösch T, Toledo F, Faas MM, Sobrevia L. Adenosine kinase and cardiovascular fetal programming in gestational diabetes mellitus. Biochim Biophys Acta (BBA) - Mol Basis Dis. 2020;1866:165397.

    CAS  Google Scholar 

  66. Dodd JM, Turnbull D, McPhee AJ, et al. Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial. BMJ. 2014;348:g1285.

    PubMed Central  Google Scholar 

  67. Vesco KK, Karanja N, King JC, et al. Efficacy of a group-based dietary intervention for limiting gestational weight gain among obese women: a randomized trial. Obesity (Silver Spring). 2014;22:1989–96.

    CAS  Google Scholar 

  68. Du M-C, Ouyang Y-Q, Nie X-F, Huang Y, Redding SR. Effects of physical exercise during pregnancy on maternal and infant outcomes in overweight and obese pregnant women: a meta-analysis. Birth. 2019;46:211–21.

    Google Scholar 

  69. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008;358:2003–15.

    CAS  Google Scholar 

  70. Balani J, Hyer SL, Rodin DA, Shehata H. Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case–control study. Diabet Med. 2009;26:798–802.

    CAS  Google Scholar 

  71. Dodd JM, Grivell RM, Deussen AR, Hague WM. Metformin for women who are overweight or obese during pregnancy for improving maternal and infant outcomes. Cochrane Database Syst Rev. 2018;2018:CD010564.

    PubMed Central  Google Scholar 

  72. Johansson K, Cnattingius S, Näslund I, et al. Outcomes of pregnancy after bariatric. Surgery. 2015;372:814–24.

    CAS  Google Scholar 

  73. Lesko J, Peaceman A. Pregnancy outcomes in women after bariatric surgery compared with obese and morbidly obese controls. Obstet Gynecol. 2012;119:547–54.

    Google Scholar 

  74. Haghiac M, Yang X-h, Presley L, et al. Dietary Omega-3 fatty acid supplementation reduces inflammation in obese pregnant women: a randomized double-blind controlled clinical trial. PLoS One. 2015;10:e0137309.

    PubMed Central  Google Scholar 

  75. van der Windt M, Schoenmakers S, van Rijn B, Galjaard S, Steegers-Theunissen R, van Rossem L. Epidemiology and (patho)physiology of folic acid supplement use in obese women before and during pregnancy. Nutrients. 2021;13:331.

    PubMed Central  Google Scholar 

  76. Keating E, Martel F, Araújo J. Folic acid and gestational diabetes: foundations for further studies. In: Nutrition and diet in maternal diabetes; 2018. p. 465–77.

    Google Scholar 

  77. Voevodskaya O, Poulakis K, Sundgren P, et al. Brain myoinositol as a potential marker of amyloid-related pathology. Neurology. 2019;92:e395.

    CAS  PubMed Central  Google Scholar 

  78. Unfer V, Carlomagno G, Papaleo E, Vailati S, Candiani M, Baillargeon J-P. Hyperinsulinemia alters myoinositol to d-chiroinositol ratio in the follicular fluid of patients with PCOS. Reprod Sci. 2014;21:854–8.

    CAS  Google Scholar 

  79. Chhetri DR. Myo-inositol and its derivatives: their emerging role in the treatment of human diseases. Front Pharmacol. 2019;10:1172.

    CAS  PubMed Central  Google Scholar 

  80. Unfer V, Facchinetti F, Orrù B, Giordani B, Nestler J. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Endocr Connect. 2017;6:647–58.

    CAS  PubMed Central  Google Scholar 

  81. D’Anna R, Santamaria A. Myo-inositol supplementation in gestational diabetes. In: Rajendram R, Preedy VR, Patel VB, editors. Nutrition and diet in maternal diabetes: an evidence-based approach. Cham: Springer; 2018. p. 229–35.

    Google Scholar 

  82. Mashayekh-Amiri S, Mohammad-Alizadeh-Charandabi S, Abdolalipour S, Mirghafourvand M. Myo-inositol supplementation for prevention of gestational diabetes mellitus in overweight and obese pregnant women: a systematic review and meta-analysis. Diabetol Metab Syndr. 2022;14:93.

    CAS  PubMed Central  Google Scholar 

  83. Zhang Y, Gong Y, Xue H, Xiong J, Cheng G. Vitamin D and gestational diabetes mellitus: a systematic review based on data free of Hawthorne effect. BJOG. 2018;125:784–93.

    CAS  Google Scholar 

  84. Koren O, Goodrich Julia K, Cullender Tyler C, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012;150:470–80.

    CAS  PubMed Central  Google Scholar 

  85. Callaway LK, McIntyre HD, Barrett HL, et al. Probiotics for the prevention of gestational diabetes mellitus in overweight and obese women: findings from the SPRING double-blind randomized controlled trial. Diabetes Care. 2019;42:364–71.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA

    Tara S. Kim

  2. Department of Internal Medicine, Division of Endocrinology, Lenox Hill Hospital, New York, NY, USA

    Tara S. Kim

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  1. Tara S. Kim
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Editors and Affiliations

  1. Friedman Diabetes Institute, Lenox Hill Hospital, New York, NY, USA

    Dimiter Avtanski

  2. Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA

    Leonid Poretsky

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Kim, T.S. (2023). Inflammation in Pregnant Women with Obesity and Gestational Diabetes Mellitus. In: Avtanski, D., Poretsky, L. (eds) Obesity, Diabetes and Inflammation. Contemporary Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-031-39721-9_9

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