Lipid variability and risk of microvascular complications in Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: A post hoc analysis

BACKGROUND: Greater lipid variability may cause adverse health events among diabetic patients. We aimed to examine the effect of lipid variability on the risk of diabetic microvascular outcomes among type 2 diabetes mellitus patients. METHODS: We assessed the association between visit‐to‐visit variability (measured by variability independent of mean) in high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein‐cholesterol (LDL), triglyceride, and remnant cholesterol (RC) measurements among participants involved in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and the risk of incident microvascular outcomes, including nephropathy, neuropathy, and retinopathy. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders. RESULTS: There were 2400, 2470, and 2468 cases of nephropathy, neuropathy, and retinopathy during a follow‐up period of 22 600, 21 542, and 26 701 person‐years, respectively. Higher levels of HDL, triglyceride, and RC variability were associated with an increased risk of incident nephropathy and neuropathy. Compared with the lowest quartile, the fully adjusted HRs (95% CI) for the highest quartile of HDL, triglyceride, and RC variability for nephropathy risk were 1.57 (1.22, 2.01), 1.50 (1.18, 1.92), and 1.40 (1.09, 1.80), respectively; and for neuropathy, the corresponding risks were 1.36 (1.05, 1.75), 1.47 (1.14, 1.91), and 1.35 (1.04, 1.74), respectively. Null association was observed between LDL variability and all microvascular complications. Additionally, all associations of variability in the other lipids with retinopathy risk were null. CONCLUSION: Among individuals with type 2 diabetes mellitus, HDL, triglyceride, and RC variability were associated with increased risks of nephropathy and neuropathy but not retinopathy. Trial registration: ClinicalTrials.gov., no. NCT00000620.