Predictive value of fibroblast growth factor 19 subgroup in early pregnancy on gestational diabetes mellitus

doi:10.3969/j.issn.1674-8115.2022.07.008

Abstract

Abstract: Objective

·To investigate the relationship between serum levels of fibroblast growth factor 19 subgroup (FGF19, 21 and 23) and the risk of gestational diabetes mellitus (GDM) in early pregnancy.

Methods

·The levels of fasting blood glucose (FPG), blood lipid, FGF19, FGF21 and FGF23 of women in the early pregnancy (8-12 weeks) who underwent obstetric examination in Taizhou People's Hospital from October 2019 to October 2020 were collected. According to the results of 75 g oral glucose tolerance test at 24-28 weeks of pregnancy, they were divided into GDM group and NGT group. The levels of FGF19, FGF21 and FGF23 were compared between the two groups, and their relationship with GDM were analyzed.

Results

·A total of 180 pregnant women were followed up, including 27 cases in the GDM group and 153 cases in the NGT group. Compared with the NGT group, FGF21 levels in the GDM group were significantly higher, while the levels of FGF19 and FGF23 were significantly lower (P<0.05, respectively). Correlation analysis showed that FPG was negatively correlated with FGF19 (r=-0.283, P<0.01), and positively correlated with LogFGF21 (r=0.160, P<0.05), and had no significant correlation with LogFGF23 (P>0.05). Single factor regression analysis showed that FGF19, FGF21, FGF23 and FPG were influencing factors of GDM (P<0.05, respectively). Multivariate Logistic regression analysis showed that FGF21 and FPG were risk factors for GDM (OR=1.196, P=0.000; OR=2.280, P=0.010). The areas under the ROC curve of FGF21, FPG and their combined prediction of GDM were 0.707, 0.646 and 0.847.

Conclusion

·The levels of FGF21 and FPG increase, while the levels of FGF19 and FGF23 decrease in GDM pregnancies in early pregnancy. FGF21 and FPG are risk factors of GDM. The FGF21- and FPG- combined prediction of GDM has greater diagnostic efficiency.

Key words: fibroblast growth factor 19, fibroblast growth factor 21, fibroblast growth factor 23, blood glucose, gestational diabetes mellitus, early pregnancy

CLC Number:

R714.25

GAO Fei, LU Yu, DONG Shuqin, YANG Liu, WU Shaohua, WEI Jing. Predictive value of fibroblast growth factor 19 subgroup in early pregnancy on gestational diabetes mellitus[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(7): 898-903.

Figures/Tables 5

TrendMD

References 21

1	GAO C, SUN X, LU L, et al. Prevalence of gestational diabetes mellitus in mainland China: a systematic review and meta-analysis [J]. Diabet Investig, 2019, 10(1):154-162.
2	JOHNS E C, DENISON F C, NORMAN J E, et al. Gestational diabetes mellitus: mechanisms, treatment, and complications[J]. Trends Endocrinol Metab, 2018, 29(11): 743-754.
3	DEGIROLAMO C, SABBÀ C, MOSCHETTA A. Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF₂₃[J]. Nat Rev Drug Discov, 2016, 15(1): 51-69.
4	赵月婷, 徐一娇, 徐书杭, 等. 成纤维细胞生长因子19亚家族因子在相关代谢性疾病中的临床研究进展[J]. 医学综述, 2018, 24(1): 51-56.
	ZHAO Y T, XU Y J, XU S H, et al. Clinical research progress of fibroblast growth factor 19 subfamily in metabolic diseases[J]. Med Recapitul, 2018, 24(1): 51-56.
5	中华医学会妇产科学分会产科学组, 中华医学会围产医学分会妊娠合并糖尿病协作组. 妊娠合并糖尿病诊治指南(2014)[J]. 中华妇产科杂志, 2014, 49(8): 561-569.
	Obstetrics Group, Obstetrics and Gynecology Branch of Chinese Medical Association,Pregnancy with Diabetes Collaborative Group, Perinatal Medicine Branch of Chinese Medical Association. Guidelines for the diagnosis and treatment of diabetes mellitus in pregnancy (2014)[J]. Chin J Obstetr Gynecol, 2014, 49(8): 561-569.
6	FEGHALI M N, SCIFRES C M. Novel therapies for diabetes mellitus in pregnancy[J]. BMJ Clin Res Ed, 2018, 362: k2034.
7	LIU B, CAI J, XU Y, et al. Early diagnosed gestational diabetes mellitus is associated with adverse pregnancy outcomes: a prospective cohort study[J]. J Clin Endocrinol Metab, 2020, 105(12): e4264-e4274.
8	XIE T, SO W Y, LI X Y, et al. Fibroblast growth factor 21 protects against lipotoxicity-induced pancreatic β‑cell dysfunction via regulation of AMPK signaling and lipid metabolism[J]. Clin Sci, 2019, 133(19): 2029-2044.
9	WATANABE H, MIYAHISA M, CHIKAMATSU M, et al. Development of a long acting FGF21 analogue-albumin fusion protein and its anti-diabetic effects[J]. J Control Release, 2020, 324: 522-531.
10	葛李娜, 杨进, 洪天配. 成纤维细胞生长因子21在血糖调节中的作用及其治疗学意义[J]. 中华糖尿病杂志, 2018, 10(6): 434-437.
	GE L N, YANG J, HONG T P. The role of fibroblast growth factor 21 in blood glucose regulation and its therapeutic significance[J]. Chin J Diabet Mellit, 2018, 10(6): 434-437.
11	吴佳铭. 白色脂肪中FGF21抵抗对妊娠期糖尿病发病的功能及分子机制研究[D]. 广州: 广东药科大学, 2019.
	WU J M. Fibroblast growth factor 21 (FGF21) resistance in adipose tissue is associated with the pathogenesis of gestational diabetes mellitus in humans[D]. Guangzhou: Guangdong Pharmaceutical University, 2019.
12	BONAKDARAN S, KHORASANI Z M, JAFARZADEH F. Increased serum level of fgf21 in gestational diabetes mellitus[J]. Acta Endocrinol (Buchar), 2017, 13(3): 278-281.
13	WANG Z H, YUAN M, XU C J, et al. FGF21 serum levels in the early second trimester are positively correlated with the risk of subsequent gestational diabetes mellitus: a propensity-matched nested case-control study[J]. Front Endocrinol, 2021, 12: 630287.
14	GADALETA R M, MOSCHETTA A. Metabolic messengers: fibroblast growth factor 15/19[J]. Nat Metab, 2019, 1(6): 588-594.
15	TANG M J, SU J B, XU T L, et al. Serum fibroblast growth factor 19 and endogenous islet beta cell function in type 2 diabetic patients [J]. Diabetol Metab Syndr, 2019, 11: 79.
16	WANG D Y, XU S Q, DING W J, et al. Decreased placental and muscular expression of the fibroblast growth factor 19 in gestational diabetes mellitus[J]. J Diabet Investig, 2019, 10(1): 171-181.
17	ZHOU M, LEARNED R M, ROSSI S J, et al. Engineered FGF19 eliminates bile acid toxicity and lipotoxicity leading to resolution of steatohepatitis and fibrosis in mice[J]. Hepatol Commun, 2017, 1(10): 1024-1042.
18	WANG D, ZHU W, LI J, et al. Serum concentrations of fibroblast growth factors 19 and 21 in women with gestational diabetes mellitus: association with insulin resistance, adiponectin, and polycystic ovary syndrome history[J]. PLoS One, 2013, 8(11): e81190.
19	URSEM S R, VERVLOET M G, BÜTTLER R M, et al. The interrelation between FGF23 and glucose metabolism in humans[J]. J Diabetes Complicat, 2018, 32(9): 845-850.
20	BÄR L, FEGER M, FAJOL A, et al. Insulin suppresses the production of fibroblast growth factor 23 (FGF₂₃)[J]. PNAS, 2018, 115(22): 5804-5809.
21	MOSAVAT M, OMAR S Z, STHANSHEWAR P. Serum FGF-21 and FGF-23 in association with gestational diabetes: a longitudinal case-control study[J]. Horm Mol Biol Clin Investig, 2020, 41(2). DOI:1515/hmbci-2019-0060.

Index	GDM group （n=27）	NGT group （n=153）	F/Z value	P value
Age/year	29 （26， 31）	27 （25， 30）	-1.420	0.156
BMI/（kg·m^-2）	22.1 （20.31， 26.04）	22.43 （20.69， 24.28）	-0.540	0.995
SBP/mmHg	118.15±15.05	113.41±10.96	1.167	0.070
DBP/mmHg	72.44±9.48	70.02±8.16	1.068	0.190
FPG/（mmoL·L^-1）	4.86±0.53	4.58±0.34	9.555	0.001
HbA1c/%	5.4 （5.2， 5.7）	5.3 （5.1， 5.5）	-1.650	0.099
TC/（mmoL·L^-1）	4.57±0.60	4.40±0.75	0.528	0.270
TAG/（mmoL·L^-1）	1.47 （1.22， 2.25）	1.34 （1.14， 1.80）	-1.380	0.167
HDL-C/（mmoL·L^-1）	1.60 （1.43， 1.86）	1.56 （1.40， 1.87）	-0.570	0.568
LDL-C/（mmoL·L^-1）	2.55 （2.27， 2.83）	2.35 （2.17， 2.85）	-1.320	0.187
FIns	58.52±20.05	46.16±26.05	0.003	0.008
HOMA-IR	1.81±0.66	1.37±0.75	0.043	0.001
HOMA-β	119.82 （94.33， 178.91）	108.02 （81.70， 149.32）	-1.537	0.124
FGF19/（pg·mL^-1）	56.27±19.74	66.36±28.87	12.090	0.027
FGF21/（pg·mL^-1）	56.26 （45.43， 67.30）	41.73 （32.16， 59.63）	3.330	0.001
FGF23/（pg·mL^-1）	57.83 （43.31， 76.08）	69.81 （57.61， 109.59）	0.975	0.030

Index	GDM group （n=27）	NGT group （n=153）	F/Z value	P value
Age/year	29 （26， 31）	27 （25， 30）	-1.420	0.156
BMI/（kg·m^-2）	22.1 （20.31， 26.04）	22.43 （20.69， 24.28）	-0.540	0.995
SBP/mmHg	118.15±15.05	113.41±10.96	1.167	0.070
DBP/mmHg	72.44±9.48	70.02±8.16	1.068	0.190
FPG/（mmoL·L^-1）	4.86±0.53	4.58±0.34	9.555	0.001
HbA1c/%	5.4 （5.2， 5.7）	5.3 （5.1， 5.5）	-1.650	0.099
TC/（mmoL·L^-1）	4.57±0.60	4.40±0.75	0.528	0.270
TAG/（mmoL·L^-1）	1.47 （1.22， 2.25）	1.34 （1.14， 1.80）	-1.380	0.167
HDL-C/（mmoL·L^-1）	1.60 （1.43， 1.86）	1.56 （1.40， 1.87）	-0.570	0.568
LDL-C/（mmoL·L^-1）	2.55 （2.27， 2.83）	2.35 （2.17， 2.85）	-1.320	0.187
FIns	58.52±20.05	46.16±26.05	0.003	0.008
HOMA-IR	1.81±0.66	1.37±0.75	0.043	0.001
HOMA-β	119.82 （94.33， 178.91）	108.02 （81.70， 149.32）	-1.537	0.124
FGF19/（pg·mL^-1）	56.27±19.74	66.36±28.87	12.090	0.027
FGF21/（pg·mL^-1）	56.26 （45.43， 67.30）	41.73 （32.16， 59.63）	3.330	0.001
FGF23/（pg·mL^-1）	57.83 （43.31， 76.08）	69.81 （57.61， 109.59）	0.975	0.030

Model	FGF19		LogFGF21		LogFGF23
Model	r value	P value	r value	P value	r value	P value
Model 1	-0.283	0.002	0.160	0.013	-0.037	0.688
Model 2	-0.224	0.014	0.194	0.035	-0.155	0.693
Model 3	-0.215	0.019	0.192	0.037	-0.147	0.744
Model 4	-0.207	0.029	0.186	0.039	-0.140	0.740

Model	FGF19		LogFGF21		LogFGF23
Model	r value	P value	r value	P value	r value	P value
Model 1	-0.283	0.002	0.160	0.013	-0.037	0.688
Model 2	-0.224	0.014	0.194	0.035	-0.155	0.693
Model 3	-0.215	0.019	0.192	0.037	-0.147	0.744
Model 4	-0.207	0.029	0.186	0.039	-0.140	0.740

Variables	B	SE	OR value	95%CI	P value
FPG	1.417	0.654	2.124	0.144‒6.869	0.001
FGF19	-0.043	0.024	0.958	0.914‒1.004	0.027
FGF21	0.183	0.035	1.201	1.121‒1.286	0.001
FGF23	-0.031	0.024	0.970	0.925‒1.016	0.030
Age	0.175	0.073	1.191	1.032‒1.376	0.156
BMI	-0.041	0.081	0.960	0.820‒1.124	0.995
SBP	0.015	0.030	1.015	0.957‒1.076	0.070
DBP	0.012	0.037	1.012	0.942‒1.088	0.190