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document
Effects of 20 mg rosuvastatin on VLDL1- , VLDL2- , IDL- and LDL-ApoB kinetics in type 2 diabetes . AIMS/HYPOTHESIS In addition to its efficacy in reducing LDL-cholesterol , rosuvastatin has been shown to significantly decrease plasma triacylglycerol . The use of rosuvastatin may be beneficial in patients with type 2 diabetes , who usually have increased triacylglycerol levels . However , its effects on the metabolism of triacylglycerol-rich lipoproteins in type 2 diabetic patients remains unknown . METHODS We performed a randomised double-blind crossover trial of 6-week treatment with placebo or rosuvastatin 20 mg in eight patients with type 2 diabetes who were being treated with oral glucose-lowering agents . In each patient , an in vivo kinetic study of apolipoprotein B ( ApoB ) -containing lipoproteins with [ 13C ] leucine was performed at the end of each treatment period . A central randomisation centre used computer-generated tables to allocate treatments . Participants , caregivers and those assessing the outcomes were blinded to group assignment . RESULTS Rosuvastatin 20 mg significantly reduced plasma LDL-cholesterol , triacylglycerol and total ApoB . It also significantly reduced ApoB pool sizes of larger triacylglycerol-rich VLDL particles ( VLDL1 ; p = 0.011 ) , smaller VLDL particles ( VLDL2 ; p = 0.011 ) , intermediate density lipoprotein ( IDL ; p = 0.011 ) and LDL ( p = 0.011 ) . This reduction was associated with a significant increase in the total fractional catabolic rate of VLDL1-ApoB ( 6.70 +/- 3.24 vs 4.52 +/- 2.34 pool/day , p = 0.049 ) , VLDL2-ApoB ( 8.72 +/- 3.37 vs 5.36 +/- 2.64 , p = 0.011 ) , IDL-ApoB ( 7.06 +/- 1.68 vs 4.21 +/- 1.51 , p = 0.011 ) and LDL-ApoB ( 1.02 +/- 0.27 vs 0.59 +/- 0.13 , p = 0.011 ) . Rosuvastatin did not change the production rates of VLDL2- , IDL- or LDL- , but did reduce VLDL1-ApoB production rate ( 12.4 +/- 4.5 vs 19.5 +/- 8.4 mg kg ( -1 ) day ( -1 ) , p = 0.035 ) . No side effects of rosuvastatin were observed during the study . CONCLUSIONS/INTERPRETATION In type 2 diabetic patients rosuvastatin 20 mg not only induces a significant increase of LDL-ApoB catabolism ( 73 % ) , but also has favourable effects on the catabolism of triacylglycerol-rich lipoproteins , e.g . a significant increase in the catabolism of VLDL1-ApoB ( 48 % ) , VLDL2-ApoB ( 63 % ) and IDL-ApoB ( 68 % ) , and a reduction in the production rate of VLDL1-ApoB ( -36 % ) . The effects of rosuvastatin on the metabolism of triacylglycerol-rich lipoproteins may be beneficial for prevention of atherosclerosis in type 2 diabetic patients .
35863
Intervention_Pharmacological
rosuvastatin
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Intervention_Pharmacological
rosuvastatin
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Intervention_Pharmacological
rosuvastatin
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Intervention_Control
placebo
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Intervention_Pharmacological
rosuvastatin 20 mg
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Intervention_Pharmacological
Rosuvastatin
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Intervention_Pharmacological
Rosuvastatin
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Intervention_Pharmacological
rosuvastatin
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Intervention_Pharmacological
rosuvastatin
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Outcome_Physical
LDL-cholesterol
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Outcome_Physical
plasma triacylglycerol
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Outcome_Physical
triacylglycerol levels .
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Outcome_Physical
plasma LDL-cholesterol , triacylglycerol and total ApoB .
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Outcome_Physical
ApoB pool sizes of larger triacylglycerol-rich VLDL particles
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Outcome_Physical
smaller VLDL particles
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Outcome_Physical
intermediate density lipoprotein
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Outcome_Physical
total fractional catabolic rate of VLDL1-ApoB
35880
Outcome_Physical
production rates of VLDL2-
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Outcome_Physical
IDL-
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Outcome_Physical
LDL-
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Outcome_Physical
VLDL1-ApoB production rate
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Outcome_Adverse-effects
side effects
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Outcome_Physical
LDL-ApoB catabolism
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Outcome_Physical
catabolism of triacylglycerol-rich lipoproteins
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Outcome_Physical
catabolism of VLDL1-ApoB
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Outcome_Physical
VLDL2-ApoB
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Outcome_Physical
IDL-ApoB
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Outcome_Physical
VLDL1-ApoB
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Participant_Condition
type 2 diabetes
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Participant_Condition
type 2 diabetes
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Participant_Condition
type 2 diabetic
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Participant_Sample-size
eight
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Participant_Condition
type 2 diabetes
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Participant_Condition
type 2 diabetic
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Participant_Condition
atherosclerosis
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Participant_Condition
type 2 diabetic