妊娠糖尿病发展成为2型糖尿病患者血清FGF-21变化的前瞻性研究

A prospective study of serum fibroblast growth factor 21 changes in type 2 diabetes mellitus developed from gestational diabetes mellitus

目的探讨成纤维细胞生长因子21(FGF-21)与妊娠糖尿病及2型糖尿病(T2DM)发生和发展之间的关系。方法通过对孕单胎24~28 w的妊娠妇女440例进行5年的随访,记录参与者一般临床资料,测定空腹及服糖后1 h、2 h胰高血糖素(PG)及胰岛素(INS)、C肽水平,并计算稳态模型胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)。采用酶联免疫吸附法(ELISA)测定基线及随访5年后血清FGF-21浓度水平。对比分析T2DM组与非T2DM组间FGF-21浓度水平差异。结果妊娠糖尿病的发生率10.2%,5年后妊娠糖尿病患者转变为T2DM的发生率44.4%。妊娠糖尿病组的空腹血糖(FPG)、1 h PG、2 h PG、空腹胰岛素(FINS)、HOMAIR,FGF-21水平均明显高于正常对照组,HOMA-β低于正常对照组,差异有统计学意义(P<0.05)。随访5年后,T2DM组的FPG、2h PG、FINS、FGF-21水平均明显高于非T2DM组,而HOMA-β均明显低于非T2DM组,差异均有统计学意义(均P<0.05)。T2DM组血清FGF-21浓度水平明显高于基线血清FGF-21浓度水平,差异有统计学意义(P<0.05);非T2DM组血清FGF-21浓度水平与基线血清FGF-21浓度水平接近,差异无统计学意义(P>0.05)。结论妊娠糖尿病及T2DM患者随着空腹血糖水平的升高,胰岛素抵抗进行性加重,胰岛β细胞功能下降,FGF-21水平逐渐升高。FGF-21的升高在妊娠糖尿病及T2DM的发生发展中起着重要作用。FGF-21未来可能成为妊娠糖尿病及T2DM早期诊断和评估的分子标记物。

Objective To investigate the prospective association of fibroblast growth factor 2l （ FGF - 21 ） with type 2 dia- betes mellitus developed from gestational diabetes mellitus development in a 5 - year prospective study. Methods By the five years follow - up among 440 pregnant women between 24 to 28 gestational weeks, the clinical data of subjects were re- corded. Fasting plasma glucose （FPG）, insulin and C peptide, 1 h,2 h. Plasma glucose, insulin and C peptide of different time points were soon measured. The homeostasis model assessment of insulin resistance（ HOMA -IR） and the HOMA of β -cell insulin secretion（ HOMA- β）were calculated . Serum FGF -21 levels at baseline and follow -up were measured using an enzyme - linked immunosorbent assay. Difference of the level of FGF -21 between T2DM group and non - T2DM group was compared. Results The incidence of gestational diabetes mellitus was 10. 2%. After five years,the incidence of type 2 diabetes mellitus developed from gestational diabetes mellitus was 44. 4%. Compared with normal control group, pa- tients with gestational diabetes mellitus had significantly increased levels of FPG, 1 hPG,2 hPG, FINS, HOMA - IR and FGF- 21, while, had significantly decreased levels of HOMA- β. At five years follow -up, compared with non -T2DM group, patients with T2DM had significantly increased levels of FPG,2 hPG, FINS, and FGF -21, while, had significantly decreased levels of HOMA-β. Serum FGF- 21 levels of T2DM group was significantly higher than that of non- T2DM. At follow- up,significant increase of FGF- 21 level was observed in those subjects who developed T2DM, but in non - T2DM group,there was no significant difference of FGF-21 level between baseline and follow-up. Conclusion The se- verity of FPG in gestational diabetes mellitus and type 2 diabetes mellitus may reflect the degree of their insulin resistance and their bete cell dysfunction. High FGF -21 levels play important role in development gestational diabetes mellitus and type 2 diabetes mellitus,it may be useful for early diagnosis and assessment of these diseases.