Insulin resistance may enhance statin response
MedWire News: Insulin resistance is associated with an enhanced response to statin therapy, research suggests.
The superior lipid-lowering response in insulin-resistant individuals is most likely due to differences in cholesterol metabolism, say Michel Hoenig (University of Queensland Centre for Clinical Research, Australia) and Frank Selke (Rhode Island Hospital and Brown Medical School, USA).
Their study, which appears in the journal Atherosclerosis, involved 66 high-risk patients with vascular disease eligible for lipid-lowering therapy. They were started on atorvastatin 80 mg/day for 6 weeks and blood was analyzed for changes in lipids and insulin resistance.
At the end of the treatment period, the average reduction in low-density lipoprotein (LDL) cholesterol was 57%.
Insulin sensitivity was assessed using the QUantitative Insulin sensitivity ChecK Index (QUICKI). In univariate analysis, QUICKI was the only significant determinant of the percent reduction in LDL cholesterol, with an r-value of –0.258.
Furthermore, in regression analysis, QUICKI explained 6.7% of the variation in percent LDL cholesterol reduction; this figure compares favorably with the approximately 5% variation in statin response explained by pharmacogenomics, remark Hoenig et al.
Next, participants were divided into tertiles of QUICKI and those in the lowest tertile (ie, insulin-resistant) were compared with those in the highest tertile (ie, insulin-sensitive).
Insulin-resistant patients had a significantly greater average reduction in LDL cholesterol in response to atorvastatin therapy than insulin-sensitive patients, at 60.9% versus 52.6%.
Insulin-resistant patients also had higher plasma markers of cholesterol synthesis and lower plasma markers of cholesterol absorption; after adjusting for these differences, the correlation between percent LDL cholesterol reduction and QUICKI ceased to be significant.
“These findings suggest that variations in cholesterol metabolism explain the enhanced LDL cholesterol response to statins in insulin-resistant individuals,” the authors remark.
They add: “Given our limited sample size, these findings require replication in a larger cohort.”
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By Joanna Lyford