Atorvastatin improves diabetic dyslipidemia and increases lipoprotein lipase activity in vivo

Schneider, Jochen G.; Eynatten, M. von; Parhofer, Klaus G.; Volkmer, Jan E; Schiekofer, Stephan; Hamann, Andreas; Nawroth, Peter P.; Dugi, Klaus A.

doi:10.1016/j.atherosclerosis.2004.04.003

Cited by 42 publications

(26 citation statements)

References 37 publications

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“…This major finding of our study is consistent with the recent report by Schneider et al (24) that atorvastatin treatment (40 mg daily) increased LPL activity in diabetic subjects. Increased postheparin LPL activity has also been seen in subjects with familial combined hyperlipidemia treated with 10-40 mg/day simvastatin (25), in CHD subjects treated with 10 mg/day simvastatin (26), and in highfat/high-cholesterol-fed rabbits administered atorvastatin or simvastatin at 3 mg/kg/day (21).…”

Section: Discussionsupporting

confidence: 83%

The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus

Isley

Miles

Patterson

et al. 2006

Journal of Lipid Research

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Statins decrease triglycerides (TGs) in addition to decreasing low density lipoprotein-cholesterol. Although the mechanism for the latter effect is well understood, it is still unclear how TG decrease is achieved with statin therapy. Because hypertriglyceridemia is common in obese patients with type 2 diabetes mellitus, we studied triglyceride-rich lipoprotein triglyceride (TRL-TG) turnover in 12 such subjects using stable isotopically labeled glycerol. The diabetic subjects were studied after 12 weeks of placebo and after a similar course of therapy with simvastatin (80 mg daily) in a single-blind design. The results were compared with those from six nonobese nondiabetic control subjects. Simvastatin therapy reduced serum TGs by 35% in the diabetic subjects. Compared with the control subjects, TRL-TG secretion was almost 2-fold higher in the diabetic subjects (45.4 6 4.9 vs. 24.4 6 1.9 mmol/min; P , 0.002) and was unaffected by simvastatin therapy. However, TRL-TG clearance was significantly increased in the diabetic subjects during simvastatin treatment compared with placebo (0.25 6 0.03 vs. 0.16 6 0.02 pools/h; P , 0.002). This change was accompanied by a 49% increase in preheparin plasma lipase activity (P , 0.03) and a 21% increase in postheparin LPL activity (P , 0.01). Together, these findings provide strong evidence that the effect of statins on serum TGs is related to an increase in LPL activity, resulting in accelerated delipidation of TRL particles. HMG-CoA reductase inhibitors, or statins, are widely used in diabetic patients and have been shown to decrease cardiovascular morbidity in individuals with type 2 diabetes (5, 6). The major effect of statins is a reduction in low density lipoprotein-cholesterol (LDL-C) concentrations, primarily mediated by inhibition of the rate-limiting step in cholesterol biosynthesis, resulting in an increase in LDL receptors in the liver (7). In addition, statins can reduce TGs and increase HDL-C (8, 9), all of which lead to a reduced risk for coronary heart disease (CHD) in patients with type 2 diabetes mellitus (5, 6, 10).The mechanism responsible for the TG-lowering effect of statins is poorly defined. In theory, it could be related to decreased VLDL production (presumably secondary to decreased availability of hepatic free cholesterol for particle assembly), increased clearance of VLDL through the LDL receptor (or other lipoprotein receptors), increased delipidation of VLDL particles via LPL, or a combination of these mechanisms. To address these questions, we determined triglyceride-rich lipoprotein triglyceride (TRL-TG, which is predominantly VLDL) production and clearance in subjects with type 2 diabetes mellitus and hypertriglyceridemia on placebo and high-dose simvastatin therapy (80 mg daily) for 12 weeks and in nondiabetic controls. RESEARCH DESIGN AND METHODS Study subjects

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Section: Discussionsupporting

confidence: 83%

The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus

Isley

Miles

Patterson

et al. 2006

Journal of Lipid Research

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“…We speculate that the effect of statin on lowering sd-LDL-C was not only by upregulating LDL receptors but also by decreasing hepatic VLDL synthesis and increasing LPL activities. In previous studies, statin reduced CETP levels 41) and increased LPL activity 21) . These factors may partially contribute to the reduction of sd-LDL-C levels.…”

Section: Discussionmentioning

confidence: 99%

“…The goal of this study was to assess the effects of statin therapy on sd-LDL-C and RLP-C levels in heterozygous FH. Furthermore, the comparative effects of two statins (pitavastatin and atorvastatin), both of which appeared to decrease TG levels [19][20][21] , were evaluated.…”

Section: Introductionmentioning

confidence: 99%

Effects of Statin on Small Dense Low-Density Lipoprotein Cholesterol and Remnant-Like Particle Cholesterol in Heterozygous Familial Hypercholesterolemia

Nozue

Michishita

Ito

et al. 2008

JAT

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Aim:The effects of statin on small dense low-density lipoprotein cholesterol (sd-LDL-C) and remnant-like particle cholesterol (RLP-C) levels in heterozygous familial hypercholesterolemia (FH) have not been examined. This study aimed to clarify the effects of statin on sd-LDL-C and RLP-C levels in heterozygous FH. Methods: Seventeen patients with heterozygous FH were randomly assigned to 2 mg/day pitavastatin or 10 mg/day atorvastatin. At baseline and 12 weeks after treatment with statin, we measured sd-LDL-C and RLP-C levels.

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“…21 Administration of the potent statins simvastatin or atorvastatin to humans with hyperlipidemia and/or diabetes led to increases in preheparin LPL mass or post-heparin LPL activity in three out of four studies. [22][23][24][25] The weaker statin fluvastatin did not alter LPL activity in dyslipidemic subjects. 26 Given this evidence of statin modulation of LPL activity, the LPL haplotypes we analyzed may affect lipid response to statin by altering the responsiveness of LPL expression or activity to statins.…”

Section: Discussionmentioning

confidence: 99%

Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts

et al. 2006

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Lipoprotein lipase (LPL) hydrolyzes circulating triglycerides (TGs). We previously showed that 3 0 -end haplotypes in the LPL gene influence atherosclerosis and insulin resistance. This study asked whether these LPL haplotypes influence response to lipid-lowering therapy among 829 subjects from the Post-Coronary Artery Bypass Graft trial. Lipid profiles were obtained at baseline and 4-5 years after treatment with lovastatin. Haplotypes were based on 12 SNPs. The fourth most frequent haplotype, 12-4, was associated with a decreased increment in high-density lipoprotein-cholesterol (HDL-C) following treatment. Haplotypes 12-6, 12-7 and 12-8 were each associated with increased HDL-C response to therapy, and haplotype 12-2 with decreased TG response. The most common haplotype, 12-1, was protective against graft worsening or occlusion. Haplotype 12-4 reduced HDL-C response to lovastatin, possibly consistent with our prior observations of this haplotype as predisposing to coronary artery disease. LPL may influence atherosclerosis risk through pleiotropic effects on each aspect of the metabolic syndrome.

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Atorvastatin improves diabetic dyslipidemia and increases lipoprotein lipase activity in vivo

Cited by 42 publications

References 37 publications

The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus

The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus

Effects of Statin on Small Dense Low-Density Lipoprotein Cholesterol and Remnant-Like Particle Cholesterol in Heterozygous Familial Hypercholesterolemia

Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts

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