Determinants of Vascular Impairment in Type 1 Diabetes; Impact of Sex and Connexin 37 Gene Polymorphism, Cross-sectional study.

Abstract

Background Predictors of cardiovascular complications are well established in type 2 diabetes but not in type 1 diabetes (T1D). We analyzed the association between traditional and novel cardiovascular risk factors and macro- and microvascular parameters in T1D patients and modification of these associations by sex and genetic factors. Methods In a cross-sectional study we analyzed in T1D patients younger than 65 years the association of wide range of cardiovascular risk factors with vascular parameters represented by ankle brachial index (ABI), toe brachial index (TBI), by duplex ultrasound measured presence of plaques in carotid and femoral arteries (Belcaro score) and intima media thickness of carotid arteries (CIMT), by photoplethysmography measured interbranch index expressed as Oliva/Roztocil index (ORI), and renal parameters represented by urine albumin/creatinine ratio (uACR) and cystatin C filtration rate. We evaluated these associations by multivariate regression analysis including interactions with sex and gene for connexin 37 (cx37) polymorphism (rs1764391). Results In 235 men and 227 women (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years) pulse pressure was the strongest predictor of unfavorable values of most of vascular parameters under study (ABI, TBI, Belcaro scores, uACR and ORI) while plasma lipids represented by remnant cholesterol (cholesterol – LDL-HDL cholesterol), atherogenic index of plasma (log (triglycerides/HDL cholesterol) and Lp(a) were associated mainly with renal impairment (uACR, cystatin C clearance and lipoprotein (a)). Plasma non-HDL cholesterol (total – HDL cholesterol) was not associated with any vascular parameter under study. In contrast to the pulse pressure, the associations of lipid parameters with renal and vascular parameters were modified by sex and cx37 gene. Conclusion Pulse pressure was the strongest determinant for macro- and microvascular parameters in T1D and was not influenced by sex and genetic factors while lipid parameters were associated mostly with renal impairment and were modified by sex and genetic factors.