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
Abstract
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.
Keywords: gestational diabetesmacrosomiamaternal outcomeneonatal outcomeprediabetes
References
- Weinert LS, Metzger BE, Gabbe SG, et al. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010; 33(3): 676–682.
- Coustan DR, Lowe LP, Metzger BE, et al. The HAPO Study: Paving the Way For New Diagnostic Criteria For GDM. Am J Obstet Gynecol . 2010; 202(6): 654–656.
- Ben-Haroush A, Yogev Y, Hod M. Epidemiology of gestational diabetes mellitus and its association with Type 2 diabetes. Diabet Med. 2004; 21(2): 103–113.
- Carr DB, Utzschneider KM, Hull RL, et al. Gestational diabetes mellitus increases the risk of cardiovascular disease in women with a family history of type 2 diabetes. Diabetes Care. 2006; 29(9): 2078–2083.
- Brewster S, Zinman B, Retnakaran R, et al. Cardiometabolic consequences of gestational dysglycemia. J Am Coll Cardiol. 2013; 62(8): 677–684.
- Zhang C, Bao W, Rong Y, et al. Genetic variants and the risk of gestational diabetes mellitus: a systematic review. Hum Reprod Update. 2013; 19(4): 376–390.
- Ekelund M, Shaat N, Almgren P, et al. Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus. Diabetes Res Clin Pract. 2012; 97(3): 394–398.
- Tarquini F, Picchiassi E, Centra M, et al. Body mass index associated to rs2021966 ENPP1 polymorphism increases the risk for gestational diabetes mellitus. Gynecol Endocrinol. 2015; 31(1): 83–86.
- Michalak-Wojnowska M, Gorczyca-Siudak D, Gorczyca T, et al. Association between rs7901695 and rs7903146 polymorphisms of the TCF7L2 gene and gestational diabetes in the population of Southern Poland. Ginekol Pol. 2016; 87(11): 745–750.
- Tarnowski M, Wieczorek A, Dziedziejko V, et al. IL16 and IL18 gene polymorphisms in women with gestational diabetes. Ginekol Pol. 2017; 88(5): 249–254.
- Widén E, Lehto M, Kanninen T, et al. Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns. N Engl J Med. 1995; 333(6): 348–351.
- Bhatti JS, Bhatti GK, Mastana SS, et al. ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes in North Indians. Mol Cell Biochem. 2010; 345(1-2): 249–257.
- Hod M, Kapur A, Sacks DA, et al. The International Federation of Gynecology and Obstetrics (FIGO) Initiative on gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and care. Int J Gynaecol Obstet. 2015; 131 Suppl 3: S173–S211.
- Wender-Ożegowska E, Bomba-Opoń D, Brązert J, et al. Standards of Polish Society of Gynecologists and Obstetricians in management of women with diabetes. Ginekol Pol. 2018; 89(6): 341–350.
- Lambrinoudaki I, Vlachou SA, Creatsas G. Genetics in gestational diabetes mellitus: association with incidence, severity, pregnancy outcome and response to treatment. Curr Diabetes Rev. 2010; 6(6): 393–399.
- Tok EC, Ertunc D, Bilgin O, et al. Association of insulin receptor substrate-1 G972R variant with baseline characteristics of the patients with gestational diabetes mellitus. Am J Obstet Gynecol. 2006; 194(3): 868–872.
- Schmitz-Peiffer C, Whitehead JP. IRS-1 regulation in health and disease. IUBMB Life. 2003; 55(7): 367–374.
- Bacci S, De Cosmo S, Prudente S, et al. ENPP1 gene, insulin resistance and related clinical outcomes. Curr Opin Clin Nutr Metab Care. 2007; 10(4): 403–409.
- Abate N, Chandalia M, Di Paola R, et al. Mechanisms of disease: Ectonucleotide pyrophosphatase phosphodiesterase 1 as a 'gatekeeper' of insulin receptors. Nat Clin Pract Endocrinol Metab. 2006; 2(12): 694–701.
- Kautzky-Willer A, Harreiter J, Pacini G. Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus. Endocr Rev. 2016; 37(3): 278–316.
- Wakabayashi I. Age-dependent influence of gender on the association between obesity and a cluster of cardiometabolic risk factors. Gend Med. 2012; 9(4): 267–277.
- Chen J, Meng Y, Zhou J, et al. Identifying Candidate Genes for Type 2 Diabetes Mellitus and Obesity through Gene Expression Profiling in Multiple Tissues or Cells. Journal of Diabetes Research. 2013; 2013: 1–9.