Horm Metab Res 2019; 51(10): 655-660
DOI: 10.1055/a-0945-0328
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Common Type 2 Diabetes Genetic Risk Variants Improve the Prediction of Gestational Diabetes

Violetta Dziedziejko
1   Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
,
Krzysztof Safranow
1   Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
,
Maciej Tarnowski
2   Department of Physiology, Pomeranian Medical University, Szczecin, Poland
,
Andrzej Pawlik
2   Department of Physiology, Pomeranian Medical University, Szczecin, Poland
› Author Affiliations
Further Information

Publication History

received 22 November 2018

accepted 21 May 2019

Publication Date:
12 July 2019 (online)

Abstract

Gestational diabetes mellitus (GDM) is a carbohydrate intolerance that occurs in women during pregnancy. The aims of this study were to develop a model to predict the risk of GDM development using common clinical parameters and selected genetic polymorphisms and to analyse the performance of the model using receiver operator characteristic (ROC) curves. ROC analysis was used to examine whether the evaluation of genetic polymorphisms may enhance the accuracy of GDM prediction in comparison to using common clinical risk factors only. This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75 g oral glucose tolerance test at 24–28 weeks gestation. The difference between the AUC of ROC curves for the model 1 including only age and BMI and the model 2 also including 8 genetic polymorphisms was highly significant (p=0.0001) in favour of model 2 (0.090±0.023). Moreover, the additional use of 8 genetic polymorphisms may increase both the sensitivity and specificity of GDM prediction by 10%. The results of this study indicate that the use of 8 genetic polymorphisms associated with carbohydrate and lipid metabolism and type 2 diabetes [PTGS2 (COX2) rs6681231, FADS1 rs174550, HNF1B rs4430796, ADIPOQ rs266729, IL18 rs187238, CCL2 rs1024611, HHEX rs5015480 and CDKN2A/2B rs10811661] together with clinical risk factors (BMI and age) may significantly improve the prediction of GDM.

 
  • References

  • 1 Kim C. Gestational diabetes: Risks, management, and treatment options. Int J Womens Health 2010; 2: 339-351
  • 2 Barbour LA, McCurdy CE, Hernandez TL. et al. Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes. Diabetes Care 2007; 30 (Suppl 2) S112-S119
  • 3 Olmos PR, Rigotti A, Busso D. et al. Maternal hypertriglyceridemia: A link between maternal overweight-obesity and macrosomia in gestational diabetes. Obesity (Silver Spring) 2014; 22: 2156-2163
  • 4 Sullivan SD, Umans JG, Ratner R. Gestational diabetes: Implications for cardiovascular health. Curr Diab Rep 2012; 12: 43-52
  • 5 Fugmann M, Uhl O, Hellmuth C. et al. Differences in the serum nonesterified Fatty Acid profile of young women associated with a recent history of gestational diabetes and overweight/obesity. PLoS One 2015; 10: e0128001
  • 6 Li G, Kong L, Zhang L. et al. Early pregnancy maternal lipid profiles and the risk of gestational diabetes mellitus stratified for body mass index. Reprod Sci 2015; 22: 712-717
  • 7 Korkmazer E, Solak N. Correlation between inflammatory markers and insulin resistance in pregnancy. J Obstet Gynaecol 2015; 35: 142-145
  • 8 Gomes JS, Minasi LB, da Cruz AD. et al. Identification of trends in scientific publications related to genetic polymorphisms in gestational diabetes mellitus. Genet Mol Res 2016; 15 doi:10.4238/gmr.15027672
  • 9 Zeggini E, Scott LJ, Saxena R. et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 2008; 40: 638-645
  • 10 Tarnowski M, Tkacz M, Dziedziejko V. et al. COX2 and NOS3 gene polymorphisms in women with gestational diabetes. J Gene Med 2017; 19 doi:10.1002/jgm.2959
  • 11 Tarnowski M, Malinowski D, Pawlak K. et al. GCK, GCKR, FADS1, DGKB/TMEM195 and CDKAL1 gene polymorphisms in women with gestational diabetes. Can J Diabetes 2017; 41: 372-379
  • 12 Tarnowski M, Malinowski D, Safranow K. et al. HNF1B, TSPAN8 and NOTCH2 gene polymorphisms in women with gestational diabetes. J Matern Fetal Neonatal Med 2017; 8: 1-6
  • 13 Pawlik A, Teler J, Maciejewska A. et al. Adiponectin and leptin gene polymorphisms in women with gestational diabetes mellitus. J Assist Reprod Genet 2017; 34: 511-516
  • 14 Tarnowski M, Wieczorek A, Dziedziejko V. et al. IL16 and IL18 gene polymorphisms in women with gestational diabetes. Ginekol Pol 2017; 88: 249-254
  • 15 Teler J, Tarnowski M, Safranow K. et al. CCL2, CCL5, IL4 and IL15 Gene polymorphisms in women with gestational diabetes mellitus. Horm Metab Res 2017; 49: 10-15
  • 16 Tarnowski M, Malinowski D, Safranow K. et al. Hematopoietically expressed homeobox (HHEX) gene polymorphism (rs5015480) is associated with increased risk of gestational diabetes mellitus. Clin Genet 2017; 91: 843-848
  • 17 Tarnowski M, Malinowski D, Safranow K. et al. CDC123/CAMK1D gene rs12779790 polymorphism and rs10811661 polymorphism upstream of the CDKN2A/2B gene in women with gestational diabetes. J Perinatol 2017; 37: 345-348
  • 18 Metzger BE, Gabbe SG, Persson B. et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010; 33: 676-682
  • 19 Hanley JA, Hajian-Tilaki KO. Sampling variability of nonparametric estimates of the areas under receiver operating characteristic curves: an update. Acad Radiol 1997; 4: 49-58
  • 20 Lauenborg J, Grarup N, Damm P. et al. Common type 2 diabetes risk gene variants associate with gestational diabetes. J Clin Endocrinol Metab 2009; 94: 145-150
  • 21 Cormier H, Vigneault J, Garneau V. et al. An explained variance-based genetic risk score associated with gestational diabetes antecedent and with progression to pre-diabetes and type 2 diabetes: a cohort study. BJOG 2015; 122: 411-419
  • 22 Kawai VK, Levinson RT, Adefurin A. et al. A genetic risk score that includes common type 2 diabetes risk variants is associated with gestational diabetes. Clin Endocrinol (Oxf) 2017; 87: 149-155
  • 23 Bort R, Martinez-Barbera JP, Beddington RS. et al. Hex homeobox gene-dependent tissue positioning is required for organogenesis of the ventral pancreas. Development 2004; 131: 797-806
  • 24 Pivovarova O, Nikiforova VJ, Pfeiffer AF. et al. The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort. Diabetes Metab Res Rev 2009; 25: 156-162
  • 25 Grarup N, Rose CS, Andersson EA. et al. Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: Validation and extension of genome-wide association studies. Diabetes 2007; 56: 3105-3111
  • 26 Pascoe L, Tura A, Patel SK. et al. Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function. Diabetes 2007; 56: 3101-3104