Low-density lipoprotein particle size and coronary artery disease in a childhood-onset type 1 diabetes population

Abstract

Low-density lipoprotein (LDL) cholesterol has been widely recognized as a strong predictor of coronary artery disease (CAD). Recently, studies have examined the influence of LDL particle size (an integral part of the insulin resistance syndrome) on the development of CAD in the general population. This report examines the correlates of LDL particle size and its association with CAD in a type 1 diabetes population. We evaluated the interrelationships between LDL particle size and the presence of CAD in a cohort of childhood-onset type 1 diabetic subjects using the Pittsburgh Epidemiology of Diabetes Complications (EDC) study. LDL particle size was measured in 337 subjects (mean age, 35.6 years; mean diabetes duration, 27.2 years) who underwent the 8-year follow-up examination. LDL particle size was determined by vertical polyacrylamide gel (2% to 16%) electrophoresis. Subjects with the small dense LDL particle phenotype (<235.5 nmol/L) had a longer diabetes duration, higher cholesterol, triglyceride, LDL, fibrinogen, waist to hip ratio (WHR), and hemoglobin A₁ (HbA₁), and lower high-density lipoprotein (HDL) cholesterol compared with subjects with the large LDL particle phenotype (>257 nmol/L). Males were also more likely to have an increased body mass index (BMI) and CAD, while females were more likely to have hypertension and a family history of type 2 diabetes (a potential marker of insulin resistance and CAD risk). The odds ratio ([OR] 95% confidence, interval [CI]) using logistic regression analysis for LDL particle size in association with CAD was 0.79 (0.60 to 1.04). Multivariate modeling indicated that the duration of type 1 diabetes, depressive symptomatology, and triglycerides were independently associated with the presence of CAD. We conclude that although small dense LDL particle size is associated with CAD in our type 1 diabetes population, its borderline association can largely be explained by the triglyceride concentration. However, as in the general population, LDL particle size is associated with many elements of the insulin resistance syndrome, including a family history of type 2 diabetes, and is likely an important element in the contribution of insulin resistance to the development of CAD in type 1 diabetes.