Rationale: Previous studies have associated low circulating IGFBP-2 with diastolic BP in a cross-sectional population. We examined 1) the relation between IGFBP-2 and long term trends in blood pressure in a population with type 2DM and 2) the relation between blood pressure and SNPs from the IGFBP-2 and IGF2 receptor (IGF2R) gene.

583 individuals with T2DM (58.5% male; n=341) had repeated yearly cardiometabolic assessments between 2002 and 2009. We used a commercial ELISA (RayBio Inc) platform for IGFBP-2 measurement. Haplotype tagging SNPs (8 from IGF2 gene, 12 from IGF2R gene and 2 from IGFBP2 gene) were selected.

Results: High baseline IGFBP-2 (ß = −1.52 95% CI: −2.56, −0.49, p=0.004) was associated with a longitudinal decrease in diastolic BP over 8 years, adjusted for age, gender, diabetes duration, time effects, as well as IGF-I, IGF-II, IGFBP-1, IGFBP-3 and anti-hypertensive use. There was no association in a similar model using systolic BP. In mixed-effects regression models the SNP rs2014620 from the IGF2R gene (encoding the IGF-II receptor which degrades IGF-II) was associated with decreased diastolic BP over the 8-year period adjusted for age and gender (ß = −0.252, 95% CI −0.14 to −0.298, p=0.003). Significance remained after gene-wise Bonferroni adjustment. This SNP rs2014620 was also nominally associated with higher baseline IGFBP-2 adjusted for age and gender (ß = 0.119, p=0.011).

Conclusion: We suggest that SNPs in the IGF2R gene may influence IGF-II bioavailability independently of IGF-II degradation, with the possibility that variations in this gene directly modulate longitudinal diastolic blood pressure trends.