An observational study of the risk of neonatal macrosomia, and early gestational diabetes associated with selected candidate genes for type 2 diabetes mellitus polymorphisms in women with gestational diabetes mellitus.

OBJECTIVES

1. to analyse the prevalence of selected candidate genes for type 2 diabetes mellitus polymorphisms (IRS1 G972R; ENPP1 K121Q; ADRB3 W64R) among women with gestational diabetes; and 2) to investigate any association between variants of these genes and risk of neonatal macrosomia.

MATERIAL AND METHODS

We conducted a prospective observational study of a group of women (N = 140) in singleton pregnancies who delivered at term. Characteristics of the study group at enrolment: age: 32.0 ± 4.9 years; GA: 26.6 ± 7.5 weeks; HbA1c: 5.6 ± 0.6%; fasting blood glucose: 102.3 ± 16.3 mg/dL; insulin treatment (G2DM): 65.7%; chronic hypertension: 11.4%; gestational hypertension: 17.9%; preeclampsia: 1.4%; birth weight: 3590 ± 540 g; birth weight ≥ 4000 g (macrosomia): 18.6%; caesarean section: 44.3%; and female newborns: 57.1%.

RESULTS

The maternal metabolic characteristics at the time of booking did not differ between polymorphisms. Macrosomia was insignificantly more frequent in females (22.5%) than in males (13.3%) (p = 0.193). Only maternal height and body weight at the time of booking significantly predicted birth weight (R = 0.27, p = 0.007; R = 0.25, p = 0.005, respectively). IRS1 G972R GR and ENPP1 K121Q KQ polymorphisms were associated with an insignificantly increased risk for macrosomia. Carriers of the heterozygotic variant of the IRS 1 gene were significantly more likely to be diagnosed with GDM/DiP in the first trimester: OR 5.2, 95% CI: 1.4; 19.2; p = 0.014.

CONCLUSIONS

1. having similar metabolic characteristics, carriers of specific variants of T2DM candidate genes might be at increased risk of delivery of macrosomic newborns; 2) any association between genetic variants and macrosomia in this population might be gender-specific; and 3) allelic variation in the IRS1 gene is associated with early GDM/DiP.