ArticlesEffect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study*
Introduction
Atherosclerosis is the most common complication of diabetes, particularly type 2 diabetes.1 Studies suggest that if hyperglycaemia is a risk factor for atherosclerosis in diabetes, its effect is weak.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 By contrast, lipoprotein abnormalities do increase the risk of coronary-artery disease in diabetes.13, 14
The Diabetes Atherosclerosis Intervention Study (DAIS) was developed and conducted in collaboration with the WHO to find out whether correction of the dyslipoproteinaemias seen in type 2 diabetes would decrease the rate of angiographic progression of coronary-artery disease. In previous lipid intervention trials, only post-hoc subgroup analyses of people with diabetes have been presented.
The most common lipoprotein abnormality in diabetes is an increase in the triglyceride-rich lipoproteins and a decrease in HDL cholesterol.15 The DAIS planning committee therefore developed a double-blind randomised placebo-controlled protocol with micronized fenofibrate as the active study drug. So that the required population would be smaller and the study duration shorter, DAIS was designed as an angiographic study and was not powered to seek differences in clinical endpoints. The protocol, the baseline characteristics of the study population, the angiographic methods, and the biochemical laboratory methods have been described elsewhere.16, 17 This paper reports the first study results.
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Patients
DAIS took place in 11 clinical centres in Canada, Finland, France, and Sweden. Eligible patients were men and women with type 2 diabetes aged 40–65 years, with or without previous coronary intervention. The lipid and diabetes eligibility characteristics were assessed during an 8-week dietary (American Heart Association/National Cholesterol Education Program step 1 diet) baseline period while the participant was off all lipid-lowering medications. The same diet was maintained throughout the
Results
731 patients were screened for inclusion, and 418 were found to meet the metabolic or cardiac entry criteria (figure 2). There were no differences between those who were and those who were not eligible for entry. Overall, the study participants had good glycaemic control and mild hypertriglyceridaemia (table 1). The placebo group had slightly higher HDL-cholesterol and fasting glucose concentrations than the fenofibrate group. Half of the participants had a clinical history of coronary disease.
Discussion
Coronary-artery disease is a very important cause of both death and disability in diabetes, so any possible preventive measures are vital. The UK Prospective Diabetes Study demonstrated the critical role of glycaemic control in preventing the microvascular complications of type 2 diabetes.10 That study also showed, however, that glycaemic control had little effect on macrovascular disease. Thus, the effects of correcting other coronary risk factors need to be examined. Lipoprotein abnormalities
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Study organisation given at the end of the paper