Serum homocysteine and lipid levels in the third trimester and their relationship with perinatal outcomes in diet-controlled gestational diabetes mellitus
Abstract
Objectives: This study investigates the relationship between serum homocysteine, blood lipids, and perinatal outcomes in patients with diet-controlled gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT).
Material and methods: A prospective cohort of 150 diet-controlled GDM patients and 150 pregnant women with NGT, all delivering at our hospital, were selected based on predefined criteria. Data on demographics, physical parameters, and perinatal outcomes were compiled. Blood samples for fasting plasma glucose (FPG), homocysteine (Hcy), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and apolipoprotein A1 (apoA1) were collected before delivery.
Results: GDM patients exhibited higher levels of FPG, Hcy, and the apoB/apoA1 ratio, but lower HDL-C and apoA1 levels compared to the NGT group. Adverse outcomes such as macrosomia, premature rupture of membranes, and postpartum hemorrhage were more prevalent in the GDM group. In GDM patients, neonatal birth weight positively correlated with FPG and TG levels. Stratified Hcy analysis in GDM showed no significant differences in perinatal outcomes. However, the third quartile of the apoB/apoA1 ratio had a lower incidence of macrosomia compared to the first quartile, and the second quartile showed a higher incidence of birth asphyxia.
Conclusions: GDM patients demonstrated increased levels of Hcy, FPG, and the apoB/apoA1 ratio, correlating with more adverse perinatal outcomes than healthy pregnant individuals. The relationships between Hcy, lipids, and these outcomes remain inconclusive, highlighting the need for further research.
Keywords: serum homocysteineHcygestational diabetes mellitusdiet-controlled GDMblood lipidsapoB/apoA1 ratiopregnancy outcomeperinatal outcome
References
- Szmuilowicz ED, Josefson JL, Metzger BE. Gestational diabetes mellitus. Endocrinol Metab Clin North Am. 2019; 48(3): 479–493.
- Gopalakrishnan V, Singh R, Pradeep Y, et al. Evaluation of the prevalence of gestational diabetes mellitus in North Indians using the International Association of Diabetes and Pregnancy Study groups (IADPSG) criteria. J Postgrad Med. 2015; 61(3): 155–158.
- Plows JF, Stanley JL, Baker PN, et al. The pathophysiology of gestational diabetes mellitus. Int J Mol Sci. 2018; 19(11).
- Samuel VT, Petersen KF, Shulman GI. Lipid-induced insulin resistance: unravelling the mechanism. Lancet. 2010; 375(9733): 2267–2277.
- Tessari P, Cecchet D, Vettore M, et al. Decreased homocysteine trans-sulfuration in hypertension with hyperhomocysteinemia: relationship with insulin resistance. J Clin Endocrinol Metab. 2018; 103(1): 56–63.
- Patterson S, Flatt PR, Brennan L, et al. Detrimental actions of metabolic syndrome risk factor, homocysteine, on pancreatic beta-cell glucose metabolism and insulin secretion. J Endocrinol. 2006; 189(2): 301–310.
- Lai JS, Pang WW, Cai S, et al. High folate and low vitamin B12 status during pregnancy is associated with gestational diabetes mellitus. Clin Nutr. 2018; 37(3): 940–947.
- Liu W, Huang Z, Tang S, et al. Changes of serum sex hormone-binding globulin, homocysteine, and hypersensitive CRP levels during pregnancy and their relationship with gestational diabetes mellitus. Gynecol Obstet Invest. 2021; 86(1–2): 193–199.
- Radzicka S, Ziolkowska K, Zaborowski MP, et al. Serum homocysteine and vitamin B12 levels in women with gestational diabetes mellitus. Ginekol Pol. 2019; 90(7): 381–387.
- Herrera E, Ortega-Senovilla H. Lipid metabolism during pregnancy and its implications for fetal growth. Curr Pharm Biotechnol. 2014; 15(1): 24–31.
- Li Y, Wang X, Jiang F, et al. Serum lipid levels in relation to clinical outcomes in pregnant women with gestational diabetes mellitus: an observational cohort study. Lipids Health Dis. 2021; 20(1): 125.
- Vahedian-Azimi A, Karimi L, Reiner Ž, et al. Effects of statins on preeclampsia: a systematic review. Pregnancy Hypertens. 2021; 23: 123–130.
- Kc K, Shakya S, Zhang H. Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab. 2015; 66 Suppl 2: 14–20.
- American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins — Obstetrics. Practice bulletin no. 172: premature rupture of membranes. Obstet Gynecol. 2016; 128(4): e165–e177.
- Evensen A, Anderson JM, Fontaine P. Postpartum hemorrhage: prevention and treatment. Am Fam Physician. 2017; 95(7): 442–449.
- Berezowsky A, Ashwal E, Hiersch L, et al. Transient isolated polyhydramnios and perinatal outcomes. Ultraschall Med. 2019; 40(6): 749–756.
- Goldenberg RL, Culhane JF, Iams JD, et al. Epidemiology and causes of preterm birth. Lancet. 2008; 371(9606): 75–84.
- Locatelli A, Lambicchi L, Incerti M, et al. Is perinatal asphyxia predictable? BMC Pregnancy Childbirth. 2020; 20(1): 186.
- Voormolen DN, de Wit L, van Rijn BB, et al. Neonatal hypoglycemia following diet-controlled and insulin-treated gestational diabetes mellitus. Diabetes Care. 2018; 41(7): 1385–1390.
- Jiang XC, Liang ZD, Chen DL, et al. Correlation of homocysteine, AHSG, CRP with insulin resistance,25-(OH)2-VitD, blood lipids in gestational diabetes patients. Clin Lab. 2021; 67(2).
- Walker MC, Smith GN, Perkins SL, et al. Changes in homocysteine levels during normal pregnancy. Am J Obstet Gynecol. 1999; 180(3 Pt 1): 660–664.
- Aubard Y, Darodes N, Cantaloube M. Hyperhomocysteinemia and pregnancy--review of our present understanding and therapeutic implications. Eur J Obstet Gynecol Reprod Biol. 2000; 93(2): 157–165.
- Wu X, Zhang L, Miao Y, et al. Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic reticulum redox homeostasis. Redox Biol. 2019; 20: 46–59.
- Chaudhry SH, Taljaard M, MacFarlane AJ, et al. The role of maternal homocysteine concentration in placenta-mediated complications: findings from the Ottawa and Kingston birth cohort. BMC Pregnancy Childbirth. 2019; 19(1): 75.
- Cho NH, Lim S, Jang HC, et al. Elevated homocysteine as a risk factor for the development of diabetes in women with a previous history of gestational diabetes mellitus: a 4-year prospective study. Diabetes Care. 2005; 28(11): 2750–2755.
- Pasternak Y, Biron-Shental T, Ohana M, et al. Gestational diabetes type 2: variation in high-density lipoproteins composition and function. Int J Mol Sci. 2020; 21(17): 6281.
- Tennant P, Doxford-Hook E, Flynn L, et al. Fasting plasma glucose, diagnosis of gestational diabetes and the risk of large for gestational age: a regression discontinuity analysis of routine data. BJOG. 2022; 129(1): 82–89.
- Rao C, Ping F. Second-trimester maternal lipid profiles rather than glucose levels predict the occurrence of neonatal macrosomia regardless of glucose tolerance status: a matched cohort study in Beijing. J Diabetes Complications. 2021; 35(8): 107948.
- Osei-Hwedieh DO, Amar M, Sviridov D, et al. Apolipoprotein mimetic peptides: Mechanisms of action as anti-atherogenic agents. Pharmacol Ther. 2011; 130(1): 83–91.
- Ference BA, Kastelein JJP, Catapano AL. Lipids and Lipoproteins in 2020. JAMA. 2020; 324(6): 595–596.
- Yue CY, Ying CM. Epidemiological analysis of maternal lipid levels during the second trimester in pregnancy and the risk of adverse pregnancy outcome adjusted by pregnancy BMI. J Clin Lab Anal. 2018; 32(8): e22568.
- Alahakoon TI, Medbury HJ, Williams H, et al. Lipid profiling in maternal and fetal circulations in preeclampsia and fetal growth restriction-a prospective case control observational study. BMC Pregnancy Childbirth. 2020; 20(1): 61.
- Wang J, Li Z, Lin Li. Maternal lipid profiles in women with and without gestational diabetes mellitus. Medicine (Baltimore). 2019; 98(16): e15320.
- Stock J. Triglycerides and cardiovascular risk: Apolipoprotein B holds the key. Atherosclerosis. 2019; 284: 221–222.
- Ryoo JH, Park SK, Hong HP, et al. Clinical significance of serum apolipoproteins as a predictor of coronary heart disease risk in Korean men. Clin Endocrinol (Oxf). 2016; 84(1): 63–71.
- Charlton-Menys V, Betteridge DJ, Colhoun H, et al. Apolipoproteins, cardiovascular risk and statin response in type 2 diabetes: the Collaborative Atorvastatin Diabetes Study (CARDS). [published correction appears in Diabetologia. 2009 Mar;52 (3):556]. Diabetologia. 2009; 52(2): 218–225.
- Lekva T, Michelsen AE, Bollerslev J, et al. Low circulating pentraxin 3 levels in pregnancy is associated with gestational diabetes and increased apoB/apoA ratio: a 5-year follow-up study. Cardiovasc Diabetol. 2016; 15: 23.