Oct. 16, 2012

Metabolic Syndrome Among People with Lupus

Clinical associations of the metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort
Parker B, Urowitz MB, Gladman DD, Lunt M, Bae SC, Sanchez-Guerrero J, Romero-Diaz J, Gordon C, Wallace DJ, Clarke AE, Bernatsky S, Ginzler EM, Isenberg DA, Rahman A, Merrill JT, Alarcón GS, Fessler BJ, Fortin PR, Hanly JG, Petri M, Steinsson K, Dooley MA, Manzi S, Khamashta MA, Ramsey-Goldman R, Zoma AA, Sturfelt GK, Nived O, Aranow C, Mackay M, Ramos-Casals M, van Vollenhoven RF, Kalunian KC, Ruiz-Irastorza G, Lim S, Kamen DL, Peschken CA, Inanc M, and Bruce IN. Annals of the Rheumatic Diseases 2012 Sept 22. doi: 10.1136/annrheumdis-2012-202106. [Epub ahead of print]

What is the topic?

Metabolic syndrome (see below) is associated with increased risk for the development of diabetes mellitus and hardening of the arteries in the general population. Patients with lupus are at increased risk of metabolic syndrome and are thus at increased risk of cardiovascular disease. Therefore, these patients are in need of more comprehensive cardiovascular disease screening.

What did the researchers hope to learn?

The researchers hoped to learn about the relationship between lupus and its treatments with the development of metabolic syndrome.

Who was studied?

Patients studied were those recruited into the Systemic Lupus International Collaborating Clinics (SLICC) cohort from 2000 to 2009 and were from one of the 30 participating centers distributed in 11 countries throughout North America, Europe, and Asia. They had a disease duration of up to 15 months at enrollment.

How was the study conducted?

Patients were evaluated according to a pre-specified protocol in order to document lupus disease activity, lupus treatments, lupus-related organ damage, cardiovascular disease risk factors, metabolic syndrome, active nephritis, and nephrotic syndrome.

Metabolic syndrome was defined according to the 2009 joint interim statement from the: International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and the International Association for the Study of Obesity. This definition requires the presence of at least three of the following criteria: a) elevated waist circumference using population/country-specific thresholds; b) elevated triglycerides (fats in the blood; > 150 mg/dl) or a regimen of drug therapy to treat it; c) reduced high-density lipoprotein (HDL) cholesterol (< 50 mg/dl); elevated blood pressure (130/85 mm Hg or greater) or a regimen of drug therapy to treat it; and d) elevated fasting glucose (> 100 mg/dl) or a regimen of drug therapy to treat it.

Lupus-related factors implicated in the risk of developing metabolic syndrome were pre-determined and included the following: inflammatory lupus disease activity, kidney involvement, low levels of complement or high levels of anti-double-stranded DNA antibodies, and a regimen of steroid treatment.

What did the researchers find?

A total of 1484 patients participated in the study. The participants were mostly women (89%), who were (on average) about 35 years of age, and who had lupus for about 18 months. About 44% of the participants were Caucasian, 16% were Hispanic, 15% were African-American or Afro-Caribbean, and 20% were Southeast Asian. The participants had, on average, moderate lupus disease activity, but about 20% had severe lupus disease activity.

Metabolic syndrome was present in 16% of the patients studied, and was significantly more common in men (22.2%) than in women (15.2%). Lupus patients having metabolic syndrome were more likely to be older and of Hispanic or Korean ethnicity than those without it.

Lupus-related factors significantly associated with the metabolic syndrome included: active nephritis, severe lupus disease activity (10 or greater on the SLEDAI-2K), low platelets, current oral or past intravenous steroid treatment, and current immunosuppressive treatment. Treatment with anti-malarial drugs was associated with a decreased risk of metabolic syndrome. Additional analyses revealed that factors independently associated with increased risk of metabolic syndrome included: increased oral daily dose of prednisone, older age at study entry, being of Korean or Hispanic ethnicity, having active nephritis, and current treatment with immunosuppressive drugs.

Additional analyses indicated that Korean patients had a significantly lower body mass index, levels of complement, and prevalence of obesity, but had significantly increased prevalence of high blood sugar levels and lipid (fat) abnormalities, and significantly more features of increased lupus disease activity (such as positive anti-double-stranded DNA antibodies) than patients from other ethnic groups. Over 95% of the Korean patients were taking oral steroids, but at lower doses than in the rest of the patients. Hispanic patients had significantly more active renal disease at study enrollment and were taking higher doses of oral steroids than patients from other ethnic groups.

What were the limitations of the study?

The study design was not ideal to examine the relationship among inflammation, steroid use, and the metabolic syndrome. Also, the relationship between the metabolic syndrome and adverse cardiovascular events was not examined.

What do the results mean for you?

This study reports that the metabolic syndrome is relatively common among young patients with lupus, even among those having moderate disease activity, although it is more common among those with greater disease activity and those using higher doses of steroids. It is emphasized that treating lupus with the lowest dose of steroids possible may be ideal in order to minimize the risk for cardiovascular disease and the metabolic syndrome. The ethnic variations observed in the prevalence of this syndrome may reflect genetic predisposition to its development, which remains to be elucidated.


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