Changes of serum Gremlin1 level in pregnant women in the second and third trimester of pregnancy and its relation with gestational diabetes mellitus

doi:10.3969/j.issn.1004-583X.2022.03.011

Abstract

Abstract:

Objective To explore the changes of serum Gremlin1 level in pregnant women in the second and third trimester of pregnancy and its relation with gestational diabetes mellitus (GDM). Methods From September to November 2020, a total of 175 pregnant women received pregnancy test in the First Affiliated Hospital of Anhui Medical University were enrolled, the patients had finished the oral glucose tolerance test (OGTT) during 24 to 28 weeks of pregnancy. They were divided into GDM group and normal glucose metabolism group (NGT group) by the OGTT results. The interclass clinical data including general data, Gremlin1 level and other biochemical indicators were collected, the differences of clinical data between the two groups were analyzed. Results The pre- and post-pregnancy body weight, pre-pregnancy body mass index (BMI), post-pregnancy BMI, fasting blood glucose (FBG), 1 h blood glucose (1 hBG), 2 h blood glucose (2 hBG), fasting insulin (FINS), 1 h insulin (1 hINS), 2 h insulin (2 hINS), fasting C protein (FCP), 1 h C peptide (1 hCP), 2 h C peptide (2 hCP), homeostasis model assessment of insulin resistance (HOMA-IR), area under curve of glucose (AUC-G), area under the curve for insulin (AUC-I) were higher in GDM group than in NGT group; homeostasis model assessment for beta-cell function index (HOMA-β) and insulin sensitivity index (ISI) in GDM group were lower than those in NGT group (all P<0.05). Serum Gremlin1 level in GDM group was higher than that in NGT group (P<0.05). Pearson correlation analysis showed that serum Gremlin1 level was positively correlated with post-pregnancy BMI, FBG, 1 hBG, 1 hINS, 2 hBG, 2 hINS, 2 hCP, HOMA-IR, AUG-G, AUC-I, and negatively correlated with HOMA-β, ISI (all P<0.05). Multivariate Logistic regression analysis showed that the independent risk factor for GDM was serum Gremlin1 (OR=8.922, 95%CI 1.863-42.736, P<0.05). Conclusion There is a positively correlated between increased serum Gremlin1 with insulin resistance in GDM patients, participating in the glucose metabolism of GDM.

Key words: diabetes,gestational, insulin resistance, Gremlin1

CLC Number:

R714.256

Qi Qi, Jiang Lichen, Sun Rong, Hu Honglin, Zhang Qiu. Changes of serum Gremlin1 level in pregnant women in the second and third trimester of pregnancy and its relation with gestational diabetes mellitus[J]. Clinical Focus, 2022, 37(3): 257-261.

Add to citation manager EndNote|Ris|BibTeX

URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2022.03.011

https://huicui.hebmu.edu.cn/EN/Y2022/V37/I3/257

Figures/Tables 5

References 17

[1]	Leng J, Shao P, Zhang C, et al. Prevalence of gestational diabetes mellitus and its risk factors in Chinese pregnant women: A prospective population-based study in Tianjin, China[J]. PLoS One, 2015, 10(3):e0121029.
[2]	Buchanan TA, Xiang AH. Gestational diabetes mellitus[J]. J Clin Invest, 2005, 115(3):485-491. pmid: 15765129
[3]	Hsu DR, Economides AN, Wang X, et al. The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities[J]. Mol Cell, 1998, 1(5):673-683. pmid: 9660951
[4]	Hedjazifar S, Khatib Shahidi R, Hammarstedt A, et al. The novel adipokine Gremlin1 antagonizes insulin action and is increased in type 2 diabetes and NAFLD/NASH[J]. Diabetes, 2020, 69(3):331-341. doi: 10.2337/db19-0701 pmid: 31882566
[5]	Koroglu N, Aydogan Mathyk B, Tola EN, et al. Gremlin-1 and gremlin-2 levels in polycystic ovary syndrome and their clinical correlations[J]. Gynecol Endocrinol, 2019, 35(7):604-607. doi: 10.1080/09513590.2019.1566452 pmid: 30712421
[6]	International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy[J]. Diabetes Care, 2010, 33(3):676-682. doi: 10.2337/dc09-1848 pmid: 20190296
[7]	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. doi: 10.1111/jdi.2019.10.issue-1 URL
[8]	HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcomes[J]. N Engl J Med, 2008, 358(19):1991-2002. doi: 10.1056/NEJMoa0707943 URL
[9]	Wu L, Han L, Zhan Y, et al. Prevalence of gestational diabetes mellitus and associated risk factors in pregnant Chinese women: A cross-sectional study in Huangdao, Qingdao, China[J]. Asia Pac J Clin Nutr, 2018, 27(2):383-388.
[10]	Abel ED, Peroni O, Kim JK, et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver[J]. Nature, 2001, 409(6821):729-733. doi: 10.1038/35055575 URL
[11]	Abhimanyu G. Regional adiposity and insulin resistance[J]. J Clin Endocrinol Metab, 2004,(9):4206-4210.
[12]	Zhang C, Ning Y. Effect of dietary and lifestyle factors on the risk of gestational diabetes: Review of epidemiologic evidence[J]. Am J Clin Nutr, 2011, 94(6 Suppl):1975S-1979S. doi: 10.3945/ajcn.110.001032 URL
[13]	Durnwald C. Gestational diabetes: Linking epidemiology, excessive gestational weight gain, adverse pregnancy outcomes, and future metabolic syndrome[J]. Semin Perinatol, 2015, 39(4):254-258. doi: 10.1053/j.semperi.2015.05.002 pmid: 26093518
[14]	Sun J, Zhuang FF, Mullersman JE, et al. BMP4 activation and secretion are negatively regulated by an intracellular gremlin-BMP4 interaction[J]. J Biol Chem, 2006, 281(39):29349-29356. doi: 10.1074/jbc.M603833200 URL
[15]	Hammarstedt A, Hedjazifar S, Jenndahl L, et al. WISP2 regulates preadipocyte commitment and PPARγ activation by BMP4[J]. Proc Natl Acad Sci U S A, 2013, 110(7):2563-2568. doi: 10.1073/pnas.1211255110 pmid: 23359679
[16]	Shao M, Ishibashi J, Kusminski C, et al. Zfp423 maintains white adipocyte identity through suppression of the beige cell thermogenic gene program[J]. Cell Metab, 2016, 23(6):1167-1184. doi: 10.1016/j.cmet.2016.04.023 URL
[17]	Gustafson B, Hammarstedt A, Hedjazifar S, et al. BMP4 and BMP antagonists regulate human white and beige adipogenesis[J]. Diabetes, 2015, 64(5):1670-1681. doi: 10.2337/db14-1127 pmid: 25605802

组别	例数	年龄 (岁)	孕周 (周)	身高 (cm)	妊娠前体重 (kg)	妊娠后体重 (kg)	妊娠前BMI (kg/m²)	妊娠后BMI (kg/m²)	妊娠期增加体重(kg)
NGT组	88	29.73±4.04	24.90±1.37	161.96±4.32	53.67±7.76	61.08±8.09	20.45±2.79	23.27±2.81	7.41±3.39
GDM组	87	30.72±4.17	24.75±1.42	160.79±5.13	57.66±9.57	65.07±9.47	22.27±3.32	25.13±3.15	7.41±3.29
t值		1.606	-0.714	-1.637	3.033	3.004	3.930	4.132	0.009
P值		0.110	0.476	0.103	<0.05	<0.05	<0.05	<0.05	0.993

组别	例数	年龄 (岁)	孕周 (周)	身高 (cm)	妊娠前体重 (kg)	妊娠后体重 (kg)	妊娠前BMI (kg/m²)	妊娠后BMI (kg/m²)	妊娠期增加体重(kg)
NGT组	88	29.73±4.04	24.90±1.37	161.96±4.32	53.67±7.76	61.08±8.09	20.45±2.79	23.27±2.81	7.41±3.39
GDM组	87	30.72±4.17	24.75±1.42	160.79±5.13	57.66±9.57	65.07±9.47	22.27±3.32	25.13±3.15	7.41±3.29
t值		1.606	-0.714	-1.637	3.033	3.004	3.930	4.132	0.009
P值		0.110	0.476	0.103	<0.05	<0.05	<0.05	<0.05	0.993

组别	例数		FBG (mmol/l)		FINS (mU/L)		FCP (μg/L)		1 hBG (mmol/L)		1 hINS (mU/L)		1 hCP (μg/L)		2 hBG (mmol/L)		2 hINS (mU/L)
NGT组	88		4.62±0.26		8.65±3.70		1.03±0.29		7.09±1.33		69.22±40.62		5.69±2.03		6.44±1.09		63.93±37.92
GDM组	87		5.27±0.53		11.65±4.83		1.34±0.63		9.52±1.84		92.81±49.76		6.46±2.23		8.13±1.48		95.37±55.29
t值			10.346		4.618		4.188		10.049		3.437		2.405		8.566		4.391
P值			0.000		0.000		0.000		0.000		0.001		0.017		0.000		0.000
组别		例数		2 hCP (μg/L)		HOMA-IR		HOMA-β		ISI		AUG-G		AUC-I		Gremlin1
NGT组		88		5.49±2.15		1.79±0.82		159.35±66.48		0.03±0.01		12.62±1.73		55.08±5.87		4.54±0.71
GDM组		87		7.29±3.11		2.76±1.25		138.48±60.16		0.02±0.01		16.22±2.38		146.32±73.93		5.33±0.80
t值				4.458		6.117		-2.176		-4.926		11.458		4.144		6.950
P值				0.000		0.000		0.031		0.000		0.000		0.000		0.000

组别	例数		FBG (mmol/l)		FINS (mU/L)		FCP (μg/L)		1 hBG (mmol/L)		1 hINS (mU/L)		1 hCP (μg/L)		2 hBG (mmol/L)		2 hINS (mU/L)
NGT组	88		4.62±0.26		8.65±3.70		1.03±0.29		7.09±1.33		69.22±40.62		5.69±2.03		6.44±1.09		63.93±37.92
GDM组	87		5.27±0.53		11.65±4.83		1.34±0.63		9.52±1.84		92.81±49.76		6.46±2.23		8.13±1.48		95.37±55.29
t值			10.346		4.618		4.188		10.049		3.437		2.405		8.566		4.391
P值			0.000		0.000		0.000		0.000		0.001		0.017		0.000		0.000
组别		例数		2 hCP (μg/L)		HOMA-IR		HOMA-β		ISI		AUG-G		AUC-I		Gremlin1
NGT组		88		5.49±2.15		1.79±0.82		159.35±66.48		0.03±0.01		12.62±1.73		55.08±5.87		4.54±0.71
GDM组		87		7.29±3.11		2.76±1.25		138.48±60.16		0.02±0.01		16.22±2.38		146.32±73.93		5.33±0.80
t值				4.458		6.117		-2.176		-4.926		11.458		4.144		6.950
P值				0.000		0.000		0.031		0.000		0.000		0.000		0.000

	年龄	孕周	身高	妊娠后体重	妊娠前体重	妊娠后 BMI	妊娠前 BMI	妊娠期增加体重	FBG	FINS	FCP
r值	-0.005	0.068	-0.138	0.1	0.05	0.168	0.105	0.136	0.369	0.127	0.032
P值	0.949	0.375	0.069	0.188	0.511	<0.05	0.168	0.072	<0.05	0.095	0.678
	1 hBG	1 hINS	1 hCP	2 hBG	2 hINS	2 hCP	HOMA-IR	HOMA-β	ISI	AUG-G	AUC-I
r值	0.321	0.209	0.139	0.274	0.215	0.220	0.191	-0.143	-0.200	0.347	0.226
P值	<0.05	<0.05	0.066	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05