Background/Purpose: Traditional risk factors for cardiovascular disease do not fully account for the increase in atherosclerosis in SLE.  Insulin resistance (IR) and other metabolic derangements are considered a harbinger of cardiovascular disease   Specific factors related to SLE including immune dysregulation and chronic inflammation are also important and may, in part, be mediated by adipocytokines. The relationship between body composition and cardiometabolic risk factors is not well characterized in children with chronic illness including pediatric SLE.  The study’s objective was to evaluate the association of body composition measures, inflammation, and insulin resistance a cohort of pediatric SLE.

Methods: This cross sectional study examined metabolic parameters, including adiponectin, leptin and hsCRP, and body composition, using dual x-ray absorptiometry to measure whole body lean and fat mass, in 33 children with SLE and 27 healthy controls.  All SLE subjects met ACR criteria for diagnosis.  Sex- specific BMI z scores (BMIZ), fat mass index (FMIZ) and lean mass index z scores (LMIZ) relative to age were calculated using national reference data. Multi-variable linear regression was used to determine the relationship of IR and SLE and predictors of IR within the SLE subjects.  

Results:  FMIZ (0.5 vs -0.6; p=0.001) was significantly greater in SLE, with no difference in LMIZ.  High sensitivity-c reactive protein (hs-CRP) (4.4 vs 1.1; p=0.04), homeostasis model assessment of insulin resistance (HOMA-IR) (6.4 vs 3.5; p=0.006), measured leptin (40.8 vs 12.9; p=0.0001), and leptin/kg of body fat (1.5 vs 0.7; p<0.001) were significantly greater in SLE.  While there was no difference in measured adiponectin, the adiponectin/leptin ratio was greater in controls compared to SLE (2.7 vs 1.1; p=0.03).  After adjustment for age, gender, ethnicity and tanner stage, hs-CRP (β=3.9 (1.3-6.4); p=0.004) was significantly associated with IR in SLE.  FMIZ (β=1.1 (0.2-2.1); p=0.02), was the significant body composition measure, and leptin/kg of body fat (β=2.3 (0.2-4.4); p=0.03), the most significant metabolic parameter, associated with IR in SLE.  Cumulative prednisone dose was not associated with IR.

Conclusion:  In this cohort, SLE subjects demonstrated cardiometabolic risk factors with elevated leptin and leptin/kg of body fat and decreased adiponectin/leptin ratio. IR was more common in SLE with adiposity, leptin, and inflammation as the crucial determinants of this association.  Further studies are needed to evaluate the use of adipocytokines as biomarkers of cardiovascular disease in this vulnerable population.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/adiposity-and-adipokines-are-associated-with-insulin-resistance-in-pediatric-systemic-lupus-erythematosus/