title: Atorvastatin improves diabetic dyslipidemia and increases lipoprotein lipase activity in vivo.
abstract: A major factor contributing to cardiovascular mortality in type 2 diabetes is dyslipidemia, characterized by low HDL cholesterol and high triglycerides, rather than elevated LDL cholesterol. Lipoprotein lipase (LPL) is the rate-limiting enzyme of triglyceride removal from plasma and has been implicated in atherosclerosis. Since treatment with statins significantly reduces cardiovascular morbidity in diabetes, we analyzed the lipid profile and LPL activities in 61 patients with type 2 diabetes before and 8 weeks after initiation of atorvastatin (40 mg) or placebo treatment. Lipid parameters and LPL activity were unchanged under treatment with placebo. Atorvastatin treatment resulted in a 30% reduction of total and a 45% reduction of LDL cholesterol (6.06 +/- 1.39 mmol/L versus 4.14 +/- 1.27 mmol/L and 4.11 +/- 1.13 mmol/L versus 2.27 +/- 0.89 mmol/L, both P < 0.0001). Triglycerides and VLDL cholesterol were also significantly reduced by statin therapy (2.24 +/- 2.11 mmol/L versus 1.82 +/- 1.46 mmol/L and 1.08 +/- 1.56 mmol/L versus 0.67 +/- 0.66 mmol/L, both P < 0.05). HDL cholesterol was not different between the atorvastatin and the placebo group. Compared to baseline, LPL activity was increased by 25% after atorvastatin treatment (213.0 +/- 28.1 nmol/mL/min versus 171.9 +/- 17.7 nmol/mL/min, P < 0.01). Our data demonstrate that atorvastatin induces a significant improvement of diabetic dyslipidemia and a significant increase of LPL activity. Since low LPL activity indicates an increased cardiovascular risk, the statin-mediated increase in LPL activity may help to explain the reduction of CAD in diabetic patients treated with statins.
authors.affiliation: Department of Internal Medicine I (Endocrinology & Metabolism), University of Heidelberg, Germany. jochen.schneider@mailhost-js.de
authors.forename: Jochen G
authors.initials: JG
authors.lastname: Schneider
authors.forename: Max
authors.initials: M
authors.lastname: von Eynatten
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Parhofer
authors.forename: Jan E
authors.initials: JE
authors.lastname: Volkmer
authors.forename: Stephan
authors.initials: S
authors.lastname: Schiekofer
authors.forename: Andreas
authors.initials: A
authors.lastname: Hamann
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Dugi
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology*; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008071:Lipoprotein Lipase / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin; D008071:Lipoprotein Lipase