Atorvastatin dose-dependently decreases hepatic lipase activity in type 2 diabetes: effect of sex and the LIPC promoter variant
OBJECTIVE: Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and may contribute to the atherogenic lipid profile in type 2 diabetes. Little is known about the effect of cholesterol synthesis inhibitors on HL activity in relation to sex and the hepatic lipase gene, the LIPC promoter variant in type 2 diabetes. Therefore, we studied the effect of atorvastatin 10 mg (A10) and 80 mg (A80) on HL activity in 198 patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients (aged 45-75 years, without manifest coronary artery disease, total cholesterol 4.0-8.0 mmol/l, and fasting triglycerides [TG] 1.5-6.0 mmol/l) were included in a double-blind, randomized, placebo-controlled trial for 30 weeks (Diabetes Atorvastatin Lipid Intervention study). RESULTS: HL activity at baseline was significantly higher in our population compared with an age-matched control group without type 2 diabetes (406 +/- 150 vs. 357 +/- 118 units/l). HL activity in men versus women (443 +/- 158 vs. 358 +/- 127 units/l), in carriers of the LIPC C/C allele versus carriers of the T/T allele (444 +/- 142 vs. 227 +/- 96 units/l), and in Caucasians versus blacks (415 +/- 150 vs. 260 +/- 127 units/l) all differed significantly (P < 0.001). Atorvastatin dose-dependently decreased HL (A10, -11%; A80, -22%; both P < 0.001). Neither sex nor the LIPC C-->T variation influenced the effect of atorvastatin on HL activity. CONCLUSIONS: Sex, LIPC promoter variant, and ethnicity significantly contribute to the baseline variance in HL activity. Atorvastatin treatment in diabetic dyslipidemia results in a significant dose-dependent decrease in HL activity, regardless of sex or the LIPC promoter variant.
|Keywords||African Continental Ancestry Group, Aged, Alleles, Diabetes Mellitus, Type 2/*drug therapy/*enzymology/ethnology/genetics, Dose-Response Relationship, Drug, Double-Blind Method, Enzyme Inhibitors/*administration & dosage, European Continental Ancestry Group, Female, Heptanoic Acids/*administration & dosage, Heterozygote, Humans, Hyperlipidemia/etiology, Lipase/*antagonists & inhibitors/genetics/metabolism, Liver/*enzymology, Male, Middle aged, Polymorphism, Genetic, Promoter Regions (Genetics), Pyrroles/*administration & dosage, Research Support, Non-U.S. Gov't, Sex Characteristics, Variation (Genetics)|
Berk-Planken, I.I.L., Hoogerbrugge, N., Stolk, R.P., Bootsma, A.H., & Jansen, H.. (2003). Atorvastatin dose-dependently decreases hepatic lipase activity in type 2 diabetes: effect of sex and the LIPC promoter variant. Diabetes Care. Retrieved from http://hdl.handle.net/1765/10080