Exp Clin Endocrinol Diabetes 2014; 122 - P096
DOI: 10.1055/s-0034-1372113

Type 2 Diabetes mellitus genetic risk variant T in TCF7L2 rs7903146 in women is associated with an increased probability of insulin therapy in gestational diabetes mellitus (GDM)

L Potasso 1, N Perakakis 1, A Lamprinou 1, E Polyzou 2, D Kassanos 2, A Peter 3, R Rasenack 4, G Päth 1, J Seufert 1, K Laubner 1
  • 1University Hospital of Freiburg, Internal Medicine II, Endocrinology/Diabetology, Freiburg, Germany
  • 2University Hospital Attikon, 3 rd Department of Obstetrics and Gynaecology, Athens, Greece
  • 3University Hospital of Tübingen, Clin. Med. IV, Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Tübingen, Germany
  • 4University Hospital of Freiburg, Department of Obstetrics an Gynaecology, Freiburg, Germany

Objective: Single nucleotide polymorphisms (SNPs) within the transcription factor 7-like 2 (TCF7L2) gene are well known risk variants for type 2 diabetes (T2DM). The rs7903146 SNP is involved in glucose- and incretin-induced insulin secretion and in proinsulin conversion. The aim of this international multicentric retrospective analysis was to assess and compare the effect of the TCF7L2 rs7903146 T risk variant on the development and clinical course of gestational diabetes mellitus (GDM).

Research Design and Methods: We genotyped the C/T polymorphism of the TCF7L2 gene variant rs7903146 in 160 unrelated Caucasian women with a history of GDM and in 160 non-diabetic pregnant women as control. The enrolment took place in Germany and in Greece. The prevalence of non-risk CC and risk TT alleles in the two groups was compared. Moreover, in the GDM group we evaluated the impact of the T risk allele on clinical sequelae and outcomes, defined as need for therapy with insulin and macrosomy of the offspring.

Results: The TT variant was associated with increased risk of GDM (p = 0.021). Women carrying the T risk allele mutation had a lower BMI (mean 24.86 kg/m2 for TT vs. 26.06 kg/m2 for CC), and a higher probability of initiation of insulin therapy, both in homozygotes (p = 0.02) and heterozygotes (p = 0.001) for the mutation. No statistically significant effect of the T allele on the development of macrosomy was detected (p > 0.05).

Conclusions: The TT genotype of TCF7L2 rs7903146 is associated with an increased risk of GDM in Caucasian women. This confirms the hypothesis of a common genetic background between GDM and T2DM. Moreover, the T allele is associated with the risk of therapy with insulin in GDM, both in homozygotes as well as in heterozygotes, independently from BMI. These results suggest an independent effect of the T risk allele on the severity of GDM.