Hyperinsulinemia, Insulin Resistance, and Circulating Oxidized Low Density Lipoprotein in Women with Systemic Lupus Erythematosus

MASOUD EL MAGADMI, YASMEEN AHMAD, WAJDI TURKIE, ALLEN P. YATES, NASEEM SHEIKH, ROBERT M. BERNSTEIN, PAUL N. DURRINGTON, IAN LAING, and IAN N. BRUCE

ABSTRACT.

Objective. Women with systemic lupus erythematosus (SLE) have increased risk of coronary heart disease (CHD) that is not fully explained by the classic CHD risk factors. Insulin resistance is an established risk factor for CHD in the general population. We compared insulin secretion and sensitivity in patients with SLE and healthy controls, and assessed the prevalence of the metabolic syndrome in women with SLE and its relation to circulating oxidized low density lipoprotein (ox-LDL).

Methods. Fasting insulin, glucose, and lipid profiles were measured in nondiabetic women with SLE (≥ 4 revised 1997 criteria) not undergoing antimalarial therapy (n = 44), and in age matched controls recruited from the hospital staff and the local community (n = 45). Using the Homeostatic Model Assessment equations, insulin sensitivity (HOMA-S) and pancreatic beta cell function (HOMA-B) were calculated from fasting insulin and glucose. The metabolic syndrome, defined according to the Adult Treatment Panel (ATP III) criteria, was determined in a consecutive series of 61 women with SLE.

Results. Patients with SLE had significantly higher fasting insulin [median (range) 10 (2.8–38) vs 6.6 (3.1–26) mU/l; p < 0.01], higher pancreatic beta cell function (HOMA-B) [165 (54–1567) vs 111 (28–653); p < 0.01], and lower insulin sensitivity (HOMA-S) [0.46 (0.09–1.9) vs 0.73 (0.16–1.3); p < 0.01]. SLE patients also had significantly higher triglycerides (p < 0.01) and lower high density lipoprotein cholesterol (p < 0.01) than controls. HOMA-S did not correlate with disease activity or steroid therapy, but was associated with components of the insulin resistance syndrome. HOMA-S showed a significant negative correlation with levels of ox-LDL in patients, but not in controls. Eleven (18%) patients had the metabolic syndrome. Again, this was not related to current steroid therapy. SLE patients with the metabolic syndrome had no difference in LDL, but had significantly higher levels of ox-LDL.

Conclusion. Nondiabetic patients with SLE have evidence of significant decrease in sensitivity to insulin, and overall this population has a high prevalence of the metabolic syndrome (18%). Insulin resistance in the context of SLE was not strongly related to current or recent steroid therapy; it was, however, associated with higher levels of ox-LDL. Insulin resistance may therefore represent an additional CHD risk factor in patients with SLE. (J Rheumatol 2006;33:50-6)

Key Indexing Terms:

HYPERINSULINEMIA
INSULIN RESISTANCE
WOMEN
OXIDIZED LOW DENSITY LIPOPROTEIN
SYSTEMIC LUPUS ERYTHEMATOSUS

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From the ARC Epidemiology Unit, Rheumatism Research Centre, University of Manchester; and Departments of Clinical Biochemistry, Medicine, and Cardiology, Manchester Royal Infirmary, Manchester, UK.

M. El Magadmi, MB, PhD, Clinical Research Fellow, ARC Epidemiology Unit; Y. Ahmad, MB, MRCP, Clinical Research Fellow, ARC Epidemiology Unit, Rheumatism Research Centre; W. Turkie, MRCP, MD, Senior Clinical Fellow, Department of Cardiology, Manchester Royal Infirmary; A.P. Yates, PhD, Principal Clinical Scientist; N. Sheikh, MSc, Biomedical Scientist; I. Laing, PhD, Consultant Clinical Scientist, Department of Clinical Biochemistry, Manchester Royal Infirmary; R.M. Bernstein, MA, MD, FRCP, Consultant Rheumatologist, Rheumatism Research Centre; P.N. Durrington, MD, FMedSci, Professor of Medicine, Department of Medicine, Manchester Royal Infirmary; I.N. Bruce, MD, FRCP, Senior Lecturer and Consultant in Rheumatology, ARC Epidemiology Unit, and Rheumatism Research Centre.

Address reprint requests to Dr I.N. Bruce, ARC Epidemiology Unit, Stopford Building, Oxford Road, Manchester, M13 9PT, UK. E-mail: ian.bruce@manchester.ac.uk

Accepted for publication August 29, 2005.

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