Fallucca Franco, Dalfrà Maria Grazia, Sciullo Ernesta, Masin Michela, Buongiorno Angela Maria, Napoli Angela, Fedele Domenico, Lapolla Annunziata
Dipartimento di Scienze Cliniche, Ospedale S. Andrea, II Facoltà di Medicina e Chirurgia, Università La Sapienza, Roma.
Metabolism. 2006 Nov;55(11):1451-6. doi: 10.1016/j.metabol.2006.06.004.
Gestational diabetes mellitus (GDM) is considered an important risk factor for the development of type 2 diabetes mellitus. We studied possible relations between GDM and both insulin receptor substrate 1 (IRS-1) (Gly972Arg) and beta3-adrenergic receptor (ADRB3 Trp64Arg, beta3-AR) gene mutations, considered potential modifying factors in the etiology of type 2 diabetes mellitus. We evaluated the 2 gene mutations in late gestation in 627 pregnant women, all studied using the glucose challenge test, followed (in positive tests) by the oral glucose tolerance test (100 g, Carpenter and Coustan [J Obstet Gynecol. 1982;144:768-773] criteria) We diagnosed 309 women with GDM, 41 with gestational impaired glucose tolerance and 277 normal pregnant women. Age, family history of diabetes, prepregnancy body mass index, weight gain during pregnancy, plasma glucose levels, hemoglobin A1c, islet autoantibody levels, and insulin treatment during pregnancy were all evaluated. All pregnant women were genotyped for IRS-1 (Gly972Arg) and beta3-AR (ADRB3 Trp64Arg) polymorphisms. The frequency of IRS-1 gene polymorphism was significantly higher in women with GDM than in women with a normal glucose tolerance (NGT) (P = .039), and there was a significant trend (P = .032) in the increasing frequency of mutant allele Arg from NGT > gestational impaired glucose tolerance > GDM. The search for beta3-AR gene polymorphism showed no significant differences between women with GDM and women with NGT. The X-Arg genotype of IRS-1 was significantly associated with a positive family history of diabetes in NGT (P = .006) and neared significance in GDM (P = .057). Moreover, we found that NGT carriers of both polymorphisms had a higher prepregnancy body mass index than carriers of the IRS-1 variant alone (P = .0034), the beta3-AR variant alone (P = .039), or neither (P = .048), suggesting a possible synergistic effect of the 2 gene polymorphisms. These results suggest that the IRS-1 genetic polymorphism is involved in the occurrence of gestational diabetes, as well as type 2 diabetes mellitus.
妊娠期糖尿病（GDM）被认为是2型糖尿病发生的重要危险因素。我们研究了GDM与胰岛素受体底物1（IRS-1）（Gly972Arg）和β3-肾上腺素能受体（ADRB3 Trp64Arg，β3-AR）基因突变之间的可能关系，这些基因被认为是2型糖尿病病因中的潜在修饰因素。我们评估了627名孕妇妊娠晚期的这两种基因突变情况，所有孕妇均采用葡萄糖耐量试验进行研究，阳性者随后进行口服葡萄糖耐量试验（100g，采用Carpenter和Coustan [《妇产科杂志》。1982年；144:768 - 773]标准）。我们诊断出309名患有GDM的女性、41名患有妊娠糖耐量受损的女性和277名正常孕妇。对年龄、糖尿病家族史、孕前体重指数、孕期体重增加、血糖水平、糖化血红蛋白A1c、胰岛自身抗体水平以及孕期胰岛素治疗情况均进行了评估。所有孕妇均对IRS-1（Gly972Arg）和β3-AR（ADRB3 Trp64Arg）多态性进行基因分型。GDM女性中IRS-1基因多态性的频率显著高于糖耐量正常（NGT）女性（P = 0.039），并且从NGT>妊娠糖耐量受损>GDM，突变等位基因Arg的频率呈显著上升趋势（P = 0.032）。对β3-AR基因多态性的研究表明，GDM女性与NGT女性之间无显著差异。IRS-1的X-Arg基因型在NGT中与糖尿病家族史阳性显著相关（P = 0.006），在GDM中接近显著水平（P = 0.057）。此外，我们发现两种多态性的NGT携带者孕前体重指数高于仅携带IRS-1变体的携带者（P = 0.0034）、仅携带β3-AR变体的携带者（P = 0.039）或两者均不携带的携带者（P = 0.048），提示这两种基因多态性可能存在协同效应。这些结果表明，IRS-1基因多态性与妊娠期糖尿病以及2型糖尿病的发生有关。
