The T risk allele of TCF7L2 rs 7903146 is associated with impaired insulin secretion rather than insulin resistance: A clinical pilot study in women with a history of gestational diabetes (GDM)

Background:

In several studies, a strong association of the T risk-allele of the rs 7903146 polymorphism within the TCF7L2 gene with diabetes mellitus type 2 (T2DM), and also gestational diabetes (GDM) has been demonstrated in various ethnicities. Whether this association is due to increased insulin resistance or impaired insulin secretion remains unclear.

Materials and methods:

We performed 75 g oral glucose tolerance tests in 38 women with a history of GDM, collected data about age, BMI, glycaemia, insulin and genotyped the TCF7L2 rs 7903146 polymorphism. Indices of insulin resistance (Matsuda index, HOMA-IR, QUICKI and glucose insulin ratio basal) and impaired insulin production (HOMA-S; insulinogenic index) were stratified according to the genotype (19 wild type CC, 14 CT and 5 TT).

Results:

Women were comparable for age and BMI (p > 0.5 and p > 0.2). None had diabetes mellitus. There were no significant differences in indices of insulin resistance, with women with at least one T risk-allele showing slightly higher insulin sensitivity (Matsuda index: 4.14 vs. 3.46; HOMA-IR: 2.30 vs. 2.38; glu/ins basal 8.4 vs. 7.16; QUICKI 0.34 vs. 0.34). However, there was a common tendency towards lower pancreatic beta cell reserve in T-risk allele women when calculating the insulinogenic index (1.16 vs. 1.50) and the HOMA-S Index (150 vs. 209.1), especially in homozygous genotypes (TT vs. CC: 116.7 vs. 209.1; p 0.06).

Conclusion:

Women carrying the T risk allele of the TCF7L2 rs 7903146 polymorphism demonstrate a tendency to impaired insulin secretion rather than insulin resistance as compared to wild-type genotypes.