Abstract
Aims
Fetal sex has recently emerged as a new factor that is related to maternal glucose homeostasis during pregnancy. The present study aimed to investigate the effect of fetal sex on maternal glucose metabolism in women with normal glucose tolerance (NGT) during pregnancy in the Chinese population.
Methods
A total of 877 pregnant women with NGT were recruited at 24–28 weeks of gestation and underwent a 75-g oral glucose tolerance test (OGTT). Pregnant women were divided into two groups according to fetal sex. Physical examinations and laboratory tests were performed. Pancreatic β-cell function and insulin sensitivity were evaluated using OGTT-derived indices.
Results
Compared with women bearing female fetuses, women who delivered male fetuses had higher fasting plasma glucose (FPG) concentrations [4.5 (4.2–4.8) vs. 4.4 (4.2–4.7) mmol/L, P < 0.05], but lower HOMA-β [161.9 (118.2–238.8) vs. 181.0 (131.7–260.9), P < 0.05] and Stumvoll first phase of insulin secretion [1230.2 (1077.9–1433.7) vs. 1290.9 (1134.0–1493.2), P < 0.05]. Multiple linear regression analysis indicated that the sex of the fetus was independently associated with maternal FPG and HOMA-β. Further binary logistic regression analyses revealed that the presence of a male fetus was significantly associated with elevated FPG [odds ratio (OR) 1.50; 95% confidence interval (CI) 1.12–2.00; P = 0.006] and lower HOMA-β (OR 0.70; 95% CI 0.52-0.94; P = 0.018) even after adjustment for potential confounders.
Conclusions
This study provided evidence that maternal glucose metabolism could be affected by fetal sex even in NGT pregnant women. Our results suggest that the presence of male fetuses was independently associated with maternal elevated FPG and lower basal β-cell function.
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References
Coustan DR (2013) Gestational diabetes mellitus. Clin Chem 59(9):1310–1321
Noctor E, Crowe C, Carmody LA et al (2015) ATLANTIC-DIP: prevalence of metabolic syndrome and insulin resistance in women with previous gestational diabetes mellitus by international association of diabetes in pregnancy study groups criteria. Acta Diabetol 52(1):153–160
Kohler M, Ziegler AG, Beyerlein A (2016) Development of a simple tool to predict the risk of postpartum diabetes in women with gestational diabetes mellitus. Acta Diabetol 53(3):433–437
Zhao C, Wang F, Wang P et al (2015) Early second-trimester plasma protein profiling using multiplexed isobaric tandem mass tag (TMT) labeling predicts gestational diabetes mellitus. Acta Diabetol 52(6):1103–1112
Wagner R, Fritsche L, Heni M et al (2016) A novel insulin sensitivity index particularly suitable to measure insulin sensitivity during gestation. Acta Diabetol 53(6):1037–1044
Wangler MF, Chang AS, Moley KH et al (2005) Factors associated with preterm delivery in mothers of children with Beckwith–Wiedemann syndrome: a case cohort study from the BWS registry. Am J Med Genet A 134A(2):187–191
Krishnaveni GV, Veena SR, Hill JC et al (2010) Intrauterine exposure to maternal diabetes is associated with higher adiposity and insulin resistance and clustering of cardiovascular risk markers in Indian children. Diabetes Care 33(2):402–404
Catalano PM, Presley L, Minium J et al (2009) Fetuses of obese mothers develop insulin resistance in utero. Diabetes Care 32(6):1076–1080
Walsh JM, Segurado R, Mahony RM et al (2015) The effects of fetal gender on maternal and fetal insulin resistance. PLoS ONE 10(9):e0137215
Hocher B, Chen YP, Schlemm L et al (2009) Fetal sex determines the impact of maternal PROGINS progesterone receptor polymorphism on maternal physiology during pregnancy. Pharmacogenet Genomics 19(9):710–718
Al Mamun A, O’Callaghan MJ, Williams GM et al (2015) Breastfeeding is protective to diabetes risk in young adults: a longitudinal study. Acta Diabetol 52(5):837–844
Sheiner E (2007) The relationship between fetal gender and pregnancy outcome. Arch Gynecol Obstet 275(5):317–319
Aibar L, Puertas A, Valverde M et al (2012) Fetal sex and perinatal outcomes. J Perinat Med 40(3):271–276
Khalil MM, Alzahra E (2013) Fetal gender and pregnancy outcomes in Libya: a retrospective study. Libyan J Med 8:20008
Jaskolka D, Retnakaran R, Zinman B et al (2015) Sex of the baby and risk of gestational diabetes mellitus in the mother: a systematic review and meta-analysis. Diabetologia 58(11):2469–2475
Ehrlich SF, Eskenazi B, Hedderson MM et al (2012) Sex ratio variations among the offspring of women with diabetes in pregnancy. Diabet Med 29(9):e273–e278
Retnakaran R, Kramer CK, Ye C et al (2015) Fetal sex and maternal risk of gestational diabetes mellitus: the impact of having a boy. Diabetes Care 38(5):844–851
International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE et al (2010) International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 33(3):676–682
Group HSCR, Metzger BE, Lowe LP et al (2008) Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 358(19):1991–2002
Sesmilo G, Meler E, Perea V et al (2017) Maternal fasting glycemia and adverse pregnancy outcomes in a Mediterranean population. Acta Diabetol 54(3):293–299
Lim WY, Kwek K, Chong YS et al (2014) Maternal adiposity and blood pressure in pregnancy: varying relations by ethnicity and gestational diabetes. J Hypertens 32(4):857–864
Khoo CM, Sairazi S, Taslim S et al (2011) Ethnicity modifies the relationships of insulin resistance, inflammation, and adiponectin with obesity in a multiethnic Asian population. Diabetes Care 34(5):1120–1126
Xiao L, Zhao JP, Nuyt AM et al (2014) Female fetus is associated with greater maternal insulin resistance in pregnancy. Diabet Med 31(12):1696–1701
Matthews DR, Hosker JP, Rudenski AS et al (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419
Stumvoll M, Van Haeften T, Fritsche A et al (2001) Oral glucose tolerance test indexes for insulin sensitivity and secretion based on various availabilities of sampling times. Diabetes Care 24(4):796–797
Seltzer HS, Allen EW, Herron AL Jr et al (1967) Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest 46(3):323–335
Cohen O, Epstein GS, Weisz B et al (2006) Longitudinal assessment of insulin sensitivity in pregnancy. Validation of the homeostasis model assessment. Clin Endocrinol (Oxf) 64(6):640–644
Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22(9):1462–1470
Jensen CC, Cnop M, Hull RL et al (2002) Beta-cell function is a major contributor to oral glucose tolerance in high-risk relatives of four ethnic groups in the U.S. Diabetes 51(7):2170–2178
Moosazadeh M, Asemi Z, Lankarani KB et al (2016) Family history of diabetes and the risk of gestational diabetes mellitus in Iran: a systematic review and meta-analysis. Diabetes Metab Syndr. doi:10.1016/j.dsx.2016.12.016
Zhu WW, Yang HX, Wang C et al (2017) High prevalence of gestational diabetes mellitus in Beijing: effect of maternal birth weight and other risk factors. Chin Med J (Engl) 130(9):1019–1025
Yang SJ, Kim TN, Baik SH et al (2013) Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance. Korean J Intern Med 28(3):306–313
Mamabolo RL, Alberts M, Levitt NS et al (2007) Prevalence of gestational diabetes mellitus and the effect of weight on measures of insulin secretion and insulin resistance in third-trimester pregnant rural women residing in the central region of Limpopo province, South Africa. Diabet Med 24(3):233–239
Cersosimo E, Solis-Herrera C, Trautmann ME et al (2014) Assessment of pancreatic beta-cell function: review of methods and clinical applications. Curr Diabetes Rev 10(1):2–42
Wallace TM, Levy JC, Matthews DR (2004) Use and abuse of HOMA modeling. Diabetes Care 27(6):1487–1495
Morkrid K, Jenum AK, Sletner L et al (2012) Failure to increase insulin secretory capacity during pregnancy-induced insulin resistance is associated with ethnicity and gestational diabetes. Eur J Endocrinol 167(4):579–588
Wang X, Li W, Ma L et al (2017) Investigation of miRNA-binding site variants and risk of gestational diabetes mellitus in Chinese pregnant women. Acta Diabetol 54(3):309–316
Huang Y, Fang C, Ma Z et al (2016) Betatrophin levels were increased in pregnant women with or without gestational diabetes mellitus and associated with beta cell function. Rev Bras Ginecol Obstet 38(6):287–292
Moller N, Jorgensen JO (2009) Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev 30(2):152–177
Huang C, Snider F, Cross JC (2009) Prolactin receptor is required for normal glucose homeostasis and modulation of beta-cell mass during pregnancy. Endocrinology 150(4):1618–1626
Nielsen JH, Galsgaard ED, Moldrup A et al (2001) Regulation of beta-cell mass by hormones and growth factors. Diabetes 50(Suppl 1):S25–S29
dos Santos Silva CM, Barbosa FR, Lima GA et al (2011) BMI and metabolic profile in patients with prolactinoma before and after treatment with dopamine agonists. Obesity (Silver Spring) 19(4):800–805
Scheinman EJ, Damouni R, Caspi A et al (2015) The beneficial effect of growth hormone treatment on islet mass in streptozotocin-treated mice. Diabetes Metab Res Rev 31(5):492–499
Gonzalez FA, Hobel CJ, Buster JE (1987) Fetal gender effects on maternal serum prolactin levels. J Reprod Med 32(1):21–24
Chellakooty M, Skibsted L, Skouby SO et al (2002) Longitudinal study of serum placental GH in 455 normal pregnancies: correlation to gestational age, fetal gender, and weight. J Clin Endocrinol Metab 87(6):2734–2739
Acknowledgements
The authors thank The Metabolic Diseases Biobank of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital for collecting data and offering help.
Funding
The work was financially supported by funding from National Key R&D Program of China (Grant No. 2017YFC0906903), National Natural Science Foundation of China (Grant No. 81570808), Program of Shanghai Subject Chief Scientist (Grant No. 2017BR045), the Innovation Foundation of Translational Medicine of Shanghai Jiao Tong University School of Medicine–Project of Precision Medicine (Grant No. 15ZH4006) and National Human Genetic Resources Sharing Service Platform (Grant No. YCZYPT[2017]02).
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MT, CW and WJ contributed to the planning of the study. XG, LG and YZ wrote the manuscript, analyzed and interpreted data. HL, YS, RC and PF performed the research. All authors reviewed the manuscript and approved the final draft.
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The authors declare that they have no conflict of interest.
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This study was approved by the institutional review board of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital.
Human and animal rights
All procedures were in accordance with the principles of the Declaration of Helsinki of 1975, as revised in 2008.
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Informed consent was obtained from all patients included in the study.
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Geng, X., Geng, L., Zhang, Y. et al. Fetal sex influences maternal fasting plasma glucose levels and basal β-cell function in pregnant women with normal glucose tolerance. Acta Diabetol 54, 1131–1138 (2017). https://doi.org/10.1007/s00592-017-1055-1
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DOI: https://doi.org/10.1007/s00592-017-1055-1