ADA 2010: Is HDL too much of a good thing in type 1 diabetes?

Too much high-density lipoprotein (HDL) cholesterol could be harmful for women with type 1 diabetes. Men with type 1 diabetes, however, continue to experience cardioprotection with increasing HDL, said Tina Costacou, PhD.

Cardiovascular disease is increased markedly in patients with type 1 diabetes despite generally higher HDL concentrations compared with the general population. One hypothesis is that HDL particle structure and function might be altered in type 1 diabetes. To explore the relationship further, Costacou and colleagues assessed the relationship between HDL cholesterol and HDL subfractions with coronary artery disease (CAD) in 599 patients with childhood-onset type 1 diabetes (diagnosed before age 17) who were free of CAD and participated in the Epidemiology of Diabetes Complications Study. For this analysis, CAD was defined as angina, ischemic electrocardiographic changes, confirmed myocardial infarction, an angiographic stenosis of 50% or greater, revascularization, or CAD death.

Study participants were followed for 18 years, during which 29.6% of men and 25.5% of women had a CAD event. At baseline HDL levels of less than 47 mg/dL, CAD incidence was elevated in both genders compared with baseline HDL levels of 47 mg/dL or greater. The risk of a CAD event kept decreasing in men as HDL concentration increased, but in women, there was a U-shaped association such that the incidence of CAD increased with HDL cholesterol levels of 80 mg/dL or greater. In this group of women with HDL cholesterol of at least 80 mg/dL, the incidence of CAD was 36%, which was similar to the incidence of CAD in women with HDL cholesterol levels less than 47 mg/dL, said Costacou, assistant professor of epidemiology, University of Pittsburgh Graduate School of Public Health. This U-shaped association between HDL cholesterol and CAD events remained significant after adjusting for levels of apolipoprotein (apo) A1 and apo B.

The investigators also measured HDL subfractions, and “the loss of cardioprotection with high HDL cholesterol largely reflected the relationship between the smaller, denser HDL3 particles and incident events,” Costacou said.

“Very high (>80 mg/dL) HDL cholesterol does not appear to protect against CAD in type 1 diabetes,” Costacou continued. “While this relationship was observed only among women, gender specificity could not be determined as only 2 men had HDL greater than or equal to 80 mg/dL.”