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Objective: To determine the effects of statin treatment and omega-3 polyunsaturated fatty acid supplementation on plasma plant sterol concentrations and cholesterol synthesis in patients with type 2 diabetes. Methods: Plant sterol concentrations and lanosterol (a marker of cholesterol synthesis) were measured using a high sensitivity assay to assess the effect of double-blind daily treatment for 4 months with atorvastatin 20. mg or placebo and, in a 2 × 2 factorial design, omega-3 ethyl esters 90 2. g or placebo. Results: 658 patients were included in a per protocol analysis. The 4 treatment groups had similar mean [SD] age (63.5 years [11.7]), HbA1c (6.9% [1.1]) and diabetes duration (median 4 years [inter-quartile range 2, 8]). Atorvastatin treatment alone reduced low density lipoprotein (LDL) cholesterol by 1.4mmol/l (44%, p<0.001), triglycerides by 0.3mmol/l (20%, p<0.0001) and lanosterol by 0.36μmol/l (72%, p<0.001). There was no significant placebo adjusted change in median [95% confidence intervals] total plant sterol concentrations (-0.77μmol/l [inter-quartile range -2.13, 0.59]), although they were increased significantly with omega-3-acid EE90 treatment (3.23μmol/l [1.28, 5.17]). There was a 27% smaller reduction in LDL cholesterol with atorvastatin treatment in low cholesterol synthesisers with high absorption, defined by changes at or above the median lanosterol and campesterol levels, respectively, compared with the obverse group (difference 0.42mmol/l [0.21, 0.62]). Conclusion: Treatment with atorvastatin in type 2 diabetes did not change median total plasma plant sterol concentrations, but LDL cholesterol was reduced most efficaciously in high cholesterol synthesisers with low intestinal cholesterol absorption. Clinical trial registration information: Current controlled trials number ISRCTN: 76737502 (http://isrctn.org). © 2010 Elsevier Ireland Ltd.

Original publication

DOI

10.1016/j.atherosclerosis.2010.09.013

Type

Journal

Atherosclerosis

Publication Date

01/12/2010

Volume

213

Pages

512 - 517