Abstract 1596: High Levels of Oxidized Low Density Lipoprotein-Immune Complexes Are Associated With Increased Odds to Develop Nephropathy in Type 1 Diabetes
A subgroup of patients of the DCCT/EDIC cohort followed longitudinally for more than 20 years was selected to study the role of oxLDL-immune complexes (oxLDL-IC) in the development of nephropathy in type 1 diabetes. Participants with normal (<40mg/24h) albumin excretion rate (AER) at DCCT baseline were deemed resistant to diabetic nephropathy if their AER remained normal up to EDIC year 9. Those considered prone to diabetic nephropathy had at least two AER greater than 60mg/24h over the same period of time. Selection for this sub-study was not random (prone subjects were oversampled). To address this directly, subjects were stratified into deciles according to DCCT baseline AER. Conditional logistic regression was used to estimate the change in the log-odds for the development of nephropathy for the main effect of baseline natural-log-transformed ox-LDL-IC levels after conditioning out the AER decile effect and adjusting for DCCT treatment, retinopathy and HbA1c at DCCT baseline. Ox-LDL was measured in the antigen moiety of IC isolated from patients’ sera using a capture assay. A total of 384 DCCT/EDIC patients, 302 of which remained free of diabetic nephropathy through EDIC year 9, were included in this study. OxLDL-IC levels at DCCT baseline were higher in the nephropathy prone than the resistant group (5.1 (0.8) vs. 4.6 (0.9), p<0.01). In unadjusted conditional logistic analysis, an increase of 0.9 (1SD) in the log-transformed oxLDL-IC increased the odds of subsequent development of nephropathy by a factor of 2 (OR=2.0, p<0.01). This point estimate remained stable and highly significant with the addition of the three adjustment variables (OR=1.8, p<0.01). A trend towards a significant interaction of the DCCT treatment group and oxLDL-IC levels was observed (p=0.19). With the interaction included in the model, the 1 SD increase in oxLDL-IC yielded a significant increase for the odds of nephropathy in the group on conventional diabetes therapy (OR=2.0, 95% CI: 1.3 to 3.0, p<0.01), but the intensive treatment group had a non-significant increase for the same increase (OR=1.2, 95% CI: 0.7 to 2.3, p=0.49). In conclusion, higher baseline oxLDL-IC levels led to increased odds to develop diabetic nephropathy. Intensive therapy during DCCT may moderate this effect.