Effect of rosuvastatin on insulin sensitivity in patients with familial combined hyperlipidaemia.
BACKGROUND
By influencing the mevalonate pathway, statins may have multiple effects besides lipid lowering. This study was designed to evaluate the effect of rosuvastatin on serum lipids and insulin sensitivity in nondiabetic subjects with familial combined hyperlipidaemia (FCH), a population characterized by decreased insulin sensitivity.


METHODS
In a double-blind randomized crossover study, 18 subjects with FCH (without evident cardiovascular disease, mean age 54 +/- 7 years) were randomized to rosuvastatin 40 mg day(-1) or placebo for 12 weeks. Blood samples were taken at baseline and after 4, 8 and 12 weeks of both treatment periods. Insulin sensitivity was determined with euglycaemic-hyperinsulinaemic clamp after 12 weeks of both treatment periods.


RESULTS
Serum lipids and lipoproteins improved significantly. Mean total cholesterol after the rosuvastatin treatment period was 44% lower compared to the placebo treatment period (triglycerides -28%; LDL-c -50%; VLDL-c -56%, VLDL-TG -39%) and both parameters of low-grade inflammation (as measured by hsCRP, -16%) and oxidative stress (as measured by plasma-oxLDL, -55%) decreased markedly after rosuvastatin therapy as compared to placebo. However, the insulin sensitivity index was unchanged (41.7 +/- 17.4 vs. 40.6 +/- 11.1 L kg(-1) min(-1), placebo vs. rosuvastatin, P = 0.71).


CONCLUSIONS
Despite marked improvements in lipid and lipoprotein values, low-grade inflammation and oxidative stress, a relatively high dose of rosuvastatin did not change insulin sensitivity in subjects with FCH.
ter Avest
E
E
Department of Medicine, Radboud University Nijmegen, Medical Centre, The Netherlands.
Abbink
E J
EJ
de Graaf
J
J
Tack
C J
CJ
Stalenhoef
A F H
AF
D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
D001786:Blood Glucose; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium