http://repub.eur.nl/res/aut/11993/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/30694/ 2003-02-12T00:00:00Z It has been estimated that in the year 2010 there will be more than 220 million patients with diabetes mellitus worldwide. About 90% of these patients will have diabetes mellitus type 2. In the Netherlands, it is expected that the number of patients will have doubled to 500.000 patients. Type 2 diabetes is associated with high morbidity and mortality from macro- and microvascular complications. Atherosclerosis is the cause of death in 75-80% of adults with type 2 diabetes. At diagnosis, 30% of the patients have already some evidence of established coronary heart disease. Diabetes itself is a strong, independent risk factor for death from cardiovascular disease, and besides hyperglycemia, specific diabetic risk factors like endothelial dysfunction, glycation of proteins, and coa,oulation abnormalities may contribut. Several other atherosclerotic risk factors are combined in type 2 diabetes, like dyslipidemia, hypertension and obesity. http://repub.eur.nl/res/pub/10080/ 2003-01-01T00:00:00Z 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.