妊娠期糖尿病对母婴脂代谢及胎盘脂质转运酶的影响

doi:10.12372/jcp.2025.24e0524

摘要/Abstract

摘要：

目的探讨妊娠期糖尿病（GDM）对不同孕周孕妇和新生儿脂代谢以及胎盘脂肪转运酶表达的影响。方法回顾性分析2022年1月至2022年12月住院分娩孕妇及其新生儿的临床资料，采集2023年8月至2023年10月分娩孕妇的胎盘。根据孕妇是否罹患GDM分为GDM组和对照组，比较两组间孕妇及其新生儿脂代谢指标差异；比较两组间胎盘组织内皮脂肪酶（EL）及脂蛋白脂肪酶（LPL）表达差异。结果纳入足月妊娠孕妇共541例，对照组418例、GDM组123例；早产孕妇共203例，GDM组110例、对照组93例。在足月妊娠孕妇中，与对照组比较，GDM组孕妇孕期增重更多、剖宫产率更高，差异存在统计学意义（P<0.05）；但早产孕妇中，GDM组孕妇较对照组分娩孕周更小、孕期增重也较少，差异有统计学意义（P<0.05）。在足月和早产孕妇中，GDM组分娩前三酰甘油（TG）均高于对照组，高密度脂蛋白胆固醇（HDL）均低于对照组，差异有统计学意义（P<0.05）。GDM组足月新生儿77例入住NICU，按照孕周及出生日期1︰1比例匹配77例入住NICU的新生儿作为对照组，其血总胆固醇（TC）、TG均高于对照组，HDL低于对照组，差异有统计学意义（P<0.05）。在足月妊娠孕妇的胎盘中，GDM组EL表达量较对照组升高，差异有统计学意义（P<0.05），但两组间LPL表达差异无统计学意义（P>0.05）；而早产分娩孕妇中，两组间EL和LPL表达差异均无统计学意义（P>0.05）。结论 GDM与母孕期脂代谢紊乱相关，但仅在足月新生儿中存在相关；胎盘EL可能参与了GDM孕妇所分娩的足月新生儿的脂代谢紊乱的发生。

关键词: 妊娠期糖尿病, 脂代谢, 胎盘转运, 新生儿

Abstract:

Objective To explore the impact of gestational diabetes mellitus (GDM) on lipid metabolism in pregnant women and neonates at different gestational weeks, as well as the expression of placental lipid transport enzymes. Methods A retrospective analysis was conducted on clinical data from pregnant women and their neonates who delivered between January 2022 and December 2022. Placentas were collected from women who delivered between August 2023 and October 2023. Participants were divided into a GDM group and a control group based on the presence or absence of GDM. The serum lipids were compared between the two groups for both pregnant women and neonates. Additionally, differences in the expression of endothelial lipase (EL) and lipoprotein lipase (LPL) in placental tissue were compared between the two groups. Results A total of 541 full-term pregnant women were included, with 123 in the GDM group and 418 in the control group. There were 203 pregnant women with premature delivery, with 110 in the GDM group and 93 in the control group. Among full-term pregnant women, compared with the control group, the GDM pregnancies had greater weight gain and a higher rate of cesarean section, and the differences were statistically significant (P<0.05). However, the premature pregnant women with GDM had a smaller gestational age at delivery and less weight gain during pregnancy than those in the control group (P<0.05). Both in full-term and premature pregnancies, compared with the control group, triacylglycerol (TG) was higher and high-density lipoprotein cholesterol (HDL) was lower in the GDM group before delivery, and the difference was statistically significant (P<0.05). In GDM group, 77 full-term newborns were admitted to NICU, and 77 newborns were matched according to gestation week and birth date at a 1:1 ratio as control group; Total cholesterol (TC) and TG in the GDM group were higher than those in the control group, while HDL was lower than that in the control group, and the difference was statistically significant (P<0.05). In the placentas of full-term pregnant women, the expression of EL in the GDM group was significantly increased (P<0.05), but there was no difference in LPL expression between the two groups (P>0.05). In pregnant women with premature delivery, both EL and LPL had no differences in expression between the two groups (P>0.05). Conclusions GDM was associated with lipid metabolism disorders during pregnancy, but only in full-term newborns. Placental EL may be involved in the occurrence of lipid metabolism disorders in full-term newborns delivered by GDM mothers.

Key words: gestational diabetes mellitus, lipid metabolism, placental transport, newborn

徐碟, 卢春霞, 李伟, 董文斌, 康兰, 雷小平. 妊娠期糖尿病对母婴脂代谢及胎盘脂质转运酶的影响[J]. 临床儿科杂志, 2025, 43(4): 251-256.

XU Die, LU Chunxia, LI Wei, DONG Wenbin, KANG Lan, LEI Xiaoping. Effect of gestational diabetes mellitus on maternal and fetal lipid metabolism and placental lipid transport enzymes[J]. Journal of Clinical Pediatrics, 2025, 43(4): 251-256.

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参考文献 34

[1]	Wang H, Li N, Chivese T, et al. IDF diabetes Atlas: estimation of global and regional gestational diabetes mellitus prevalence for 2021 by international association of diabetes in pregnancy study group's criteria[J]. Diabetes Res Clin Pract, 2022, 183: 109050.
[2]	Gao C, Sun X, Lu L, et al. Prevalence of gestational diabetes mellitus in mainland China: a systematic review and meta-analysis[J]. J Diabetes Investig, 2019, 10(1): 154-162.
[3]	Furse S, Fernandez-Twinn DS, Chiarugi D, et al. Lipid metabolism is dysregulated before, during and after pregnancy in a mouse model of gestational diabetes[J]. Int J Mol Sci, 2021, 22(14): 7452.
[4]	Bedell S, Hutson J, de Vrijer B, et al. Effects of maternal obesity and gestational diabetes mellitus on the placenta: current knowledge and targets for therapeutic interventions[J]. Curr Vasc Pharmacol, 2021, 19(2): 176-192.
[5]	Murray SR, Reynolds RM. Short- and long-term outcomes of gestational diabetes and its treatment on fetal development[J]. Prenat Diagn, 2020, 40(9): 1085-1091.
[6]	Schaefer-Graf UM, Meitzner K, Ortega-Senovilla H, et al. Differences in the implications of maternal lipids on fetal metabolism and growth between gestational diabetes mellitus and control pregnancies[J]. Diabet Med, 2011, 28(9): 1053-1059.
[7]	Farrar D, Tuffnell DJ, West J, et al. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes[J]. Cochrane Database Syst Rev, 2016, 2016(6): CD005542.
[8]	Duttaroy AK. Transport of fatty acids across the human placenta: a review[J]. Prog Lipid Res, 2009, 48(1): 52-61. doi: 10.1016/j.plipres.2008.11.001 pmid: 19041341
[9]	Hoffman DJ, Powell TL, Barrett ES, et al. Developmental origins of metabolic diseases[J]. Physiol Rev, 2021, 101(3): 739-795. doi: 10.1152/physrev.00002.2020 pmid: 33270534
[10]	Stein AD, Obrutu OE, Behere RV, et al. Developmental undernutrition, offspring obesity and type 2 diabetes[J]. Diabetologia, 2019, 62(10): 1773-1778. doi: 10.1007/s00125-019-4930-1 pmid: 31451877
[11]	Chiang AN, Yang ML, Hung JH, et al. Alterations of serum lipid levels and their biological relevances during and after pregnancy[J]. Life Sci, 1995, 56(26): 2367-2375. pmid: 7791523
[12]	Desoye G, Herrera E. Adipose tissue development and lipid metabolism in the human fetus: The 2020 perspective focusing on maternal diabetes and obesity[J]. Prog Lipid Res, 2021, 81: 101082.
[13]	Metzger BE, Coustan DR. Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee[J]. Diabetes Care, 1998, 21 (Suppl 2): B161-B167.
[14]	Sohlström A, Kabir N, Sadurskis A, et al. Body composition and fat distribution during the first 2 weeks of gestation in ad lib.-fed and energy-restricted rats[J]. Br J Nutr, 1994, 71(3): 317-333.
[15]	Chavan-Gautam P, Rani A, Freeman DJ. Distribution of fatty acids and lipids during pregnancy[J]. Adv Clin Chem, 2018, 84: 209-239. doi: S0065-2423(17)30083-5 pmid: 29478515
[16]	Ortega-Senovilla H, Schaefer-Graf U, Herrera E. Pregnant women with gestational diabetes and with well controlled glucose levels have decreased concentrations of individual fatty acids in maternal and cord serum[J]. Diabetologia, 2020, 63(4): 864-874. doi: 10.1007/s00125-019-05054-x pmid: 31832744
[17]	Kim SY, Lee YJ, An SM, et al. Dynamic regulation of lipid metabolism in the placenta of in vitro and in vivo models of gestational diabetes mellitus[J]. Biol Reprod, 2022, 107(5): 1311-1318. doi: 10.1093/biolre/ioac156 pmid: 35932454
[18]	Rahnemaei FA, Pakzad R, Amirian A, et al. Effect of gestational diabetes mellitus on lipid profile: A systematic review and meta-analysis[J]. Open Med (Wars), 2022, 17(1): 70-86.
[19]	Zeljković A, Ardalić D, Vekić J, et al. Effects of gestational diabetes mellitus on cholesterol metabolism in women with high-risk pregnancies: possible implications for neonatal outcome[J]. Metabolites, 2022, 12(10): 959.
[20]	Nasioudis D, Doulaveris G, Kanninen TT. Dyslipidemia in pregnancy and maternal-fetal outcome[J]. Minerva Ginecol, 2019, 71(2): 155-162. doi: 10.23736/S0026-4784.18.04330-7 pmid: 30318877
[21]	Gauster M, Desoye G, Tötsch M, et al. The placenta and gestational diabetes mellitus[J]. Curr Diab Rep, 2012, 12(1): 16-23.
[22]	Diamant YZ, Metzger BE, Freinkel N, et al. Placental lipid and glycogen content in human and experimental diabetes mellitus[J]. Am J Obstet Gynecol, 1982, 144(1): 5-11. doi: 10.1016/0002-9378(82)90385-4 pmid: 7051832
[23]	Song L, Wang N, Peng Y, et al. Placental lipid transport and content in response to maternal overweight and gestational diabetes mellitus in human term placenta[J]. Nutr Metab Cardiovasc Dis, 2022, 32(3): 692-702. doi: 10.1016/j.numecd.2021.12.018 pmid: 35109996
[24]	Gauster M, Hiden U, Blaschitz A, et al. Dysregulation of placental endothelial lipase and lipoprotein lipase in intrauterine growth-restricted pregnancies[J]. J Clin Endocrinol Metab, 2007, 92(6): 2256-2263.
[25]	崔双, 陈羽, 余颖. 孕中期血脂水平对妊娠期糖尿病孕妇妊娠期并发症及妊娠结局的影响[J]. 现代实用医学, 2023, 35(12): 1621-1624.
	Cui S, Chen Y, Yu Y, et al. Effect of second-trimester blood lipid levels on pregnancy complications and pregnancy outcomes in pregnant women with gestational diabetes[J]. Xiandai Shiyong Yixue, 2023, 35(12): 1621-1624.
[26]	周学欣, 吴昊, 徐先明, 等. 妊娠期糖尿病孕妇妊娠晚期血脂代谢特征及妊娠结局相关研究[J]. 哈尔滨医科大学学报, 2023, 57(5): 525-529.
	Zhou XX, Wu H, Xu XM, et al. Characteristics of lipid metabolism and pregnancy outcomes in pregnant women with gestational diabetes mellitus during the third trimester[J]. Haerbin Yike Daxue Xuebao, 2023, 57(5): 525-529.
[27]	袁二伟, 朱雷, 郭华贤, 等. 妊娠期糖尿病母亲新生儿血清蛋白质、血脂、免疫功能的变化及临床意义[J]. 广东医学, 2023, 44(3): 288-292.
	Yuan EW, Zhu L, Guo HX, et al. The clinical significance of serum protein, blood lipid and immune function in neonatal with maternal gestational diabetes mellitus[J]. Guangdong Yixue, 2023, 44(3): 288-292.
[28]	Alejandro EU, Mamerto TP, Chung G, et al. Gestational diabetes mellitus: a harbinger of the vicious cycle of diabetes[J]. Int J Mol Sci, 2020, 21(14): 5003.
[29]	Vogel JP, Chawanpaiboon S, Moller AB, et al. The global epidemiology of preterm birth[J]. Best Pract Res Clin Obstet Gynaecol, 2018, 52: 3-12. doi: S1521-6934(18)30079-8 pmid: 29779863
[30]	Walani SR. Global burden of preterm birth[J]. Int J Gynaecol Obstet, 2020, 150(1): 31-33. doi: 10.1002/ijgo.13195 pmid: 32524596
[31]	Gauster M, Hiden U, van Poppel M, et al. Dysregulation of placental endothelial lipase in obese women with gestational diabetes mellitus[J]. Diabetes, 2011, 60(10): 2457-2464. doi: 10.2337/db10-1434 pmid: 21852675
[32]	Ortega-Senovilla H, Alvino G, Taricco E, et al. Enhanced circulating retinol and non-esterified fatty acids in pregnancies complicated with intrauterine growth restriction[J]. Clin Sci (Lond), 2009, 118(5): 351-358. doi: 10.1042/CS20090292 pmid: 19656084
[33]	Desoye G, Cervar-Zivkovic M. Diabetes Mellitus, Obesity, and the Placenta[J]. Obstet Gynecol Clin North Am, 2020, 47(1): 65-79.
[34]	Lager S, Powell TL. Regulation of nutrient transport across the placenta[J]. J Pregnancy, 2012, 2012: 179-827.

项目	足月妊娠		统计量	P	早产妊娠		统计量	P
项目	GDM组(n=123)	对照组(n=418)	统计量	P	GDM组(n=110)	对照组(n=93)	统计量	P
孕期增重[M(P₂₅~P₇₅)]/kg	14.8(10.0~17.0)	12.0(10.0~15.0)	Z=3.54	<0.001	10.0(6.0~12.1)	10.0(8.0~15.0)	Z=2.29	0.022
孕次[n(%)]			χ²=0.40	0.528			χ²=0.01	0.976
1次	47(38.2)	173(41.4)			27(24.5)	23(24.7)
≥2次	76(61.8)	245(58.6)			83(75.5)	70(75.3)
产次[n(%)]			χ²=0.34	0.558			χ²=0.49	0.485
1次	78(63.4)	277(66.3)			42(38.2)	40(43.0)
≥2次	45(36.6)	141(33.7)			68(61.8)	53(57.0)
胎龄( x±s)/周	39.4±1.1	39.5±1.1	t=1.07	0.283	33.8±2.8	34.7±1.8	t=2.76	0.006
剖宫产[n(%)]	77(63.0)	209(50.0)	χ²=6.06	0.010	71(64.5)	58(62.3)	χ²=0.10	0.748
新生儿为男性[n(%)]	68(55.3)	221(52.9)	χ²=0.22	0.640	55(50.0)	50(53.8)	χ²=0.29	0.593

项目	足月妊娠孕妇		统计量	P	早产妊娠孕妇		统计量	P
项目	GDM组(n=123)	对照组(n=418)	统计量	P	GDM组(n=110)	对照组(n=93)	统计量	P
TC( x±s)/mmol·L^-1	6.3±1.5	6.2±1.3	t=0.64	0.525	6.3±2.2	6.3±1.3	t=0.11	0.914
TG[M(P₂₅~P₇₅)]/mmol·L^-1	4.1(3.3~5.0)	3.5(2.7~4.5)	Z=4.08	<0.001	3.9(2.8~4.9)	3.1(2.3~3.9)	Z=3.09	0.002
HDL( x±s)/mmol·L^-1	1.8±0.4	1.9±0.4	t=2.92	0.004	1.8±0.4	1.9±0.5	t=2.17	0.032
LDL[M(P₂₅~P₇₅)]/mmol·L^-1	3.2(2.5~4.1)	3.2(2.7~3.8)	Z=0.13	0.897	3.1(2.5~3.7)	3.4(2.8~4.1)	Z=2.39	0.017

项目	足月儿		统计量	P	早产儿		统计量	P
项目	GDM组(n=77)	对照组(n=77)	统计量	P	GDM组(n=110)	对照组(n=93)	统计量	P
TC( x±s)/mmol·L^-1	1.8±0.4	1.6±0.4	t=2.58	0.011	2.3±0.8	2.4±0.6	t=0.92	0.360
TG[M(P₂₅~P₇₅)]/mmol·L^-1	0.6(0.5~0.8)	0.5(0.4~0.7)	Z=2.06	0.040	0.2(0.2~0.3)	0.2(0.2~0.3)	Z=0.64	0.519
HDL( x±s)/mmol·L^-1	0.95±0.25	1.04±0.28	t=2.11	0.037	1.1±0.3	1.2±0.3	t=1.34	0.182
LDL[M(P₂₅~P₇₅)]/mmol·L^-1	0.6(0.5~0.7)	0.6(0.5~0.8)	Z=0.04	0.932	1.0(0.7~1.3)	1.0(0.8~1.3)	Z=0.41	0.680
APOA1( x±s)/g·L^-1	1.0±0.2	0.9±0.2	t=0.85	0.398	1.0±0.2	1.7±7.6	t=1.07	0.489
APOB( x±s)/g·L^-1	0.2±0.1	0.2±0.1	t=1.01	0.314	0.3±0.2	0.3±0.1	t=1.05	0.296

胎龄	组别	例数	TC( x±s)/ mmol·L^-1	TG[M(P₂₅~P₇₅)]/ mmol·L^-1	HDL( x±s)/ mmol·L^-1	LDL[M(P₂₅~P₇₅)]/ mmol·L^-1	APOA1( x±s)/ g·L^-1	APOB[M(P₂₅~P₇₅)]/ g·L^-1
35~37周	GDM组	63	2.3±0.7	0.2(0.2~0.3)	1.3±0.4	0.9(0.7~1.3)	1.0±0.2	0.3(0.2~0.4)
	对照组	73	2.4±0.6	0.2(0.2~0.3)	1.3±0.2	0.9(0.8~1.2)	1.0±0.2	0.3(0.2~0.4)
	统计量		t=0.83	Z=0.33	t=0.95	Z=1.09	t=0.99	Z=0.60
	P		0.410	0.743	0.345	0.276	0.326	0.550
32~34周	GDM组	22	2.5±0.8	0.2(0.1~0.3)	1.3±0.4	1.0(0.7~1.3)	1.0±0.1	0.3(0.2~0.4)
	对照组	13	2.7±0.8	0.2(0.1~0.3)	1.3±0.2	1.1(0.9~1.4)	1.0±0.2	0.3(0.3~0.4)
	统计量		t=1.04	Z=0.22	t=0.00	Z=1.19	t=0.40	Z=0.82
	P		0.309	0.824	1.000	0.232	0.694	0.412
<32周	GDM组	25	2.5±0.8	0.2(0.1~0.6)	1.0±0.3	1.3(0.9~1.7)	0.9±0.1	0.4(0.3~0.5)
<32周	对照组	7	2.4±0.4	0.2(0.1~0.4)	1.1±0.2	1.2(1.0~1.3)	0.7±0.3	0.4(0.3~0.4)
	统计量		t=0.64	Z=1.21	t=0.77	Z=0.84	t=1.77	Z=0.23
	P		0.528	0.227	0.459	0.399	0.121	0.819

妊娠类别	组别	例数	EL[M(P₂₅~P₇₅)]/ng·mL^-1	LPL[M(P₂₅~P₇₅)]/ng·mL^-1
足月妊娠	GDM组	10	2 850.1(2 328.7~4 358.8)	804.2(319.2~1 378.7)
	对照组	10	1 853.5(1 593.9~2 375.1)	517.3(333.3~830.4)
	Z值		2.50	0.61
	P		0.013	0.545
早产妊娠	GDM组	5	737.8(733.2~761.8)	243.7(215.6~771.4)
	对照组	5	753.0(559.7~782.1)	287.8(240.5~739.6)
	Z值		0.31	0.52
	P		0.754	0.602