The Effect of Aggressive Versus Standard Lipid Lowering by Atorvastatin on Diabetic Dyslipidemia

Abstract

The DALI Study: a double-blind, randomized, placebo-controlled trial in patients with type 2 diabetes and diabetic dyslipidemia THE DIABETES ATORVASTATIN LIPID INTERVENTION (DALI) STUDY GROUPOBJECTIVE -In patients with type 2 diabetes, intensive glucose regulation, although effective for microangiopathy, has not been shown to have unambiguous preventive effects on the occurrence of cardiovascular disease. Patients with diabetes show a characteristic dyslipidemia (high triglyceride level, low HDL cholesterol level). Aggressive reduction of triglycerides might be an effective method to reduce the cardiovascular risk in these patients. RESEARCH DESIGN AND METHODS-A double-blind, placebo-controlled, randomized study to assess the effect of 30 weeks of administration of atorvastatin 10 and 80 mg on plasma triglyceride levels in 217 patients with type 2 diabetes and fasting triglyceride levels between 1.5 and 6.0 mmol/l.RESULTS -Administration of atorvastatin 10 and 80 mg resulted in significant reductions (25 and 35%, respectively) of plasma triglyceride levels (both P Ͻ 0.001). The difference between 10 and 80 mg was not statistically significant (P Ͼ 0.5). Atorvastatin 10 mg provided significant reductions from baseline in total cholesterol (Ϫ30%, P Ͻ 0.001), LDL cholesterol (Ϫ40%, P Ͻ 0.001), and apolipoprotein B (Ϫ31%, P Ͻ 0.001), and significantly increased HDL cholesterol from baseline by 6% (P Ͻ 0.005). Atorvastatin 80 mg had a similar effect on HDL cholesterol (ϩ5.2%, P Ͻ 0.005) but significantly decreased total cholesterol (Ϫ40%, P Ͻ 0.001), LDL cholesterol (Ϫ52%, P Ͻ 0.001), and apolipoprotein B (Ϫ40%, P Ͻ 0.001) more than atorvastatin 10 mg (P Ͻ 0.005). The side effects of atorvastatin 10 and 80 mg were similar and did not differ from the patients receiving placebo.CONCLUSIONS -Administration of 10-and 80-mg doses of atorvastatin provides similar, significant reductions from baseline in triglyceride levels in patients with type 2 diabetes. A higher dose of atorvastatin improves cholesterol-related parameters. Both doses were well tolerated in this patient population. Diabetes Care 24:1335-1341, 2001P atients with type 2 diabetes have a two-to fourfold increased risk for cardiovascular morbidity and mortality (1-5). Intensive glucose regulation in type 2 diabetes, although effective for microangiopathy, has not been shown to have unambiguous preventive effects on the occurrence of coronary heart disease, stroke, and peripheral artery disease (6). Besides hypertension, dyslipidemia has emerged as a prevalent and modifiable atherogenic risk factor in patients with type 2 diabetes. LDL cholesterol-lowering strategies, with the use of hydroxymethylglutaryl (HMG)-CoA reductase inhibitors, have shown at least equal benefits for subgroups of patients with diabetes in large secondary prevention trials (7-9). In primary prevention trials, the diabetic subgroups were too small to show significant results (10,11). However, these were all post-hoc analyses, and patients with diabetes included in these studies did not h...

Are post-treatment low-density lipoprotein subclass pattern analyses potentially misleading?

“…In a larger, placebo-controlled study of 217 dyslipidemic patients with type 2 diabetes mellitus, using polyacrylamide gradient gel electrophoresis, atorvastatin 10 mg and 80 mg significantly lowered LDL-C levels, significantly reduced apo B, and produced no significant effects upon LDL particle size. However, similar to this report, atorvastatin produced a numerical increase in the proportion of patients with Pattern B (21.3%, 21.4%, and 22.2% for placebo, atorvastatin 10 mg, and atorvastatin 80 mg, respectively)[27]. …”

Atorvastatin helps preserve pancreatic β cell function in obese C57BL/6 J mice and the effect is related to increased pancreas proliferation and amelioration of endoplasmic-reticulum stress

“…Meanwhile, antioxidant and anti-inflammation benefits of atorvastatin 80 mg were also observed in MIRACL and ASAP trails [38,39]. Besides, the aggressive (80 mg/d) and moderate (10 mg/d) lipid-lowering therapy with atorvastatin was compared in the DALI trail [40]. Consequently, Fasting TG was reduced by 35% with aggressive therapy and by 25% with moderate therapy.…”

A review of the potential therapeutic role of statins in the treatment of Alzheimer’s disease: current research and opinion

“…Carlsson et al86 conducted a study in a population with an incremented risk of AD (siblings of diagnosed patients) and found a slight improvement in some neuropsychological tasks (verbal fluency and working memory) but no effect on cerebrospinal fluid amyloid (42 fraction). Some additional small studies found some beneficial effects on cognition in statins users 90–92. In the DALI study,90,92 a 24% improvement in a verbal memory test was observed in a group of diabetic patients treated with atorvastatin for 30 weeks.…”