Background: In the FIELD trial, a 5-year randomized double-blind placebo-controlled trial of fenofibrate vs. placebo in 9,795 adults with type 2 diabetes (T2D), the only standard lipid parameter correlating with microvascular (renal) events was triglycerides. Given the high prevalence of diabetic microangiopathy, we explored associations between lipoprotein subfractions and nephropathy, retinopathy, microvascular amputations (MiAmp) and neuropathy.
Methods: We performed ultracentrifugation using the vertical autoprofile (VAP, Atherotech) on plasma (baseline and after 6 weeks of fenofibrate). Analyses were performed using Cox proportional hazards and logistic regression for new on-study events. Results were adjusted for gender and fenofibrate or placebo allocation.
Results: HDL related analytes (HDL-C, HDL3-C, apo A1, apoA2) correlated with reduced risk for neuropathy, nephropathy, and MiAmp. Buoyant LDL (LDL1-C) and densest LDL (LDL4-C) correlated negatively with neuropathy and positively for MiAmp, respectively. Triglycerides and apo C3 increased neuropathy and nephropathy risk. VLDL species correlated with increased MiAmp and retinopathy risk.
Conclusions: VAP identifies multiple lipoprotein subclasses and VAP subclass/apoprotein ratios associated with diabetic microangiopathy. Many were improved with fenofibrate.
P.P. Toth: Consultant; Self; Amarin Corporation, Amgen Inc., AstraZeneca, Kowa Pharmaceutical Europe Co. Ltd., Novo Nordisk Inc. Speaker’s Bureau; Self; Amarin Corporation, Amgen Inc., Merck & Co., Inc., Novo Nordisk Inc., Regeneron Pharmaceuticals, Sanofi US. A.C. Keech: None. A.S. Januszewski: None. R.L. OConnell: None. L. Li: None. D. Sullivan: None. M. Taskinen: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Akcea Therapeutics, Chiesi USA, Inc. Research Support; Self; Amgen Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; Amgen Inc. P.L. Drury: None. G.F. Watts: None. J.D. Best: Consultant; Self; Abbott. J. Ansquer: Research Support; Self; Abbott, Mylan. S.R. Jones: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc.