High insulin levels and increased low‐density lipoprotein oxidizability in pediatric patients with systemic lupus erythematosus

Abstract

Objective. To examine low-density lipoprotein (LDL) size, LDL susceptibility to oxidation, and plasma insulin levels in children with systemic lupus erythematosus (SLE).Methods. Fifty-nine SLE patients and 59 healthy, age-matched control subjects were studied. LDL size was determined by gradient gel electrophoresis. LDL oxidizability was assessed by lag time for conjugated diene formation during copper incubation. Plasma levels of fasting insulin, glucose, lipids, lipoproteins, apolipoproteins B and A-I, and fatty acids were also measured.Results. Compared with control subjects, SLE patients showed significantly higher plasma insulin levels and increased susceptibility of LDLs to oxidation. Patients with active disease were more likely than patients with inactive disease or control subjects to have the following lipid characteristics: small, dense LDL subclass, elevated total cholesterol levels, elevated LDL cholesterol levels, elevated triglyceride levels, and low levels of high-density lipoprotein cholesterol (HDL-C). Statistically significant direct correlations were observed between disease activity and triglyceride levels and between disease activity and lag time, whereas significant inverse correlations were found between disease activity and HDL-C levels and between disease activity and LDL size. Prednisone dosage explained only 15.6% of the variance in insulin levels.Conclusion. SLE patients have higher plasma insulin levels and increased LDL oxidizability compared with healthy control subjects. These abnormalities may contribute to the accelerated atherosclerosis observed in patients with SLE.

The complex nature of the interaction between disease activity and therapy on the lipid profile in patients with pediatric systemic lupus erythematosus

“…The percentage of patients with abnormal levels was only slightly higher at time of presentation than at other times and remained relatively constant in subsequent years. Our results contrast with those of most of the previous crosssectional pediatric studies in smaller cohorts, which have shown that mean total cholesterol levels tended to be similar to those in age-matched controls (6,16,25,27). Total cholesterol levels were higher when patients were taking high-dose prednisone as compared with when they had active SLE but were taking low-dose prednisone, but were not higher than at the time of diagnosis of SLE.…”

“…Cross-sectional studies of patients with differing degrees of disease activity and steroid dosages have generally demonstrated elevated mean triglyceride levels, while total cholesterol levels have been either normal or elevated. Similar variability in low-density lipoprotein (LDL) cholesterol and HDL cholesterol levels have been seen (13,16,23,24,27,(31)(32)(33). None of the studies published thus far have reported longitudinal data on lipid levels at fixed time points or evaluated large numbers of pediatric patients at presentation and at times of differing disease activity in order to better differentiate the effects of disease activity and steroid treatment.…”

“…Although both traditional and nontraditional factors are important in the development of premature atherosclerosis in patients with SLE, dyslipoproteinemia, which is present in 30-73% of adult patients with SLE, plays a role in the development of atherosclerosis (2,10,(17)(18)(19)(20)(21)(22)(23)(24). To date, there have been few comprehensive lipid studies in pediatric patients with SLE (5,6,16,(25)(26)(27).…”

Recent corticosteroid use and recent disease activity: Independent determinants of coronary heart disease risk factors in systemic lupus erythematosus?

“…Some previous studies reported positive associations between corticosteroid use and traditional coronary risk factors, such as total plasma cholesterol (7-9,12,13,17,31), systolic BP (7), triglycerides (12)(13)(14)17,32,33), LDL cholesterol (13,14,31), Apo B (10), and hyperinsulinemia (33). However, most of these studies did not adjust for disease activity, which in our cohort was correlated both with corticosteroid dose (r ϭ 0.32) and with most CHD risk factors, and therefore may act as a confounder.…”

Prevalence and etiology of low bone mineral density in juvenile systemic lupus erythematosus

“…Despite the more severe disease course of juvenile SLE, however, there has been significant improvement in long-term mortality. Therefore, more studies have focused on long-term morbidities, specifically, premature atherosclerosis and osteoporosis leading to insufficiency fractures (2)(3)(4).…”