Impact of Weight Loss on Inflammatory Proteins and Their Association With the Insulin Resistance Syndrome in Morbidly Obese Patients

Abstract

Objective— Obesity is closely linked to the insulin resistance syndrome (IRS), type 2 diabetes, and cardiovascular disease, the primary cause of morbidity and mortality in these patients. Elevated levels of C-reactive protein (CRP) and interleukin-6 (IL-6), indicating chronic subclinical inflammation, have been associated with features of the IRS and incident cardiovascular disease. Methods and Results— We studied the cross-sectional and longitudinal relation of CRP, IL-6, and tumor necrosis factor-α (TNF-α) with features of the IRS in 37 morbidly obese patients with different stages of glucose tolerance before and 14 months after gastric surgery. Weight loss after gastric surgery induced a significant shift from diabetes (37% vs 3%) to impaired glucose tolerance (40% vs 33%) and normal glucose tolerance (23% vs 64%). The baseline concentration of IL-6 was correlated with TNF-α ( r =0.59, P <0.01) and CRP ( r =0.44, P <0.05) levels. TNF-α, IL-6, and CRP were significantly correlated with insulin resistance estimated by the homeostatic model assessment ( r =0.48, P <0.05; r =0.56, P <0.01; and r =0.35, P <0.05, respectively). Concentrations of CRP and IL-6 decreased after weight loss (median, 8.6 and interquartile range, 2.7/14.5 vs 2.5 and 1.2/4.1 mg/L; P <0.006, and 5.13 and 2.72/12.15 vs 3.95 and 1.97/5.64 pg/mL, P <0.02, respectively), whereas serum levels of TNF-α remained unchanged (8.6 and 6.3/18.8 vs 11.7 and 5.8/17.2 pg/mL; NS.). Multiple regression analysis revealed that the decrease in insulin resistance remained independently and significantly correlated with the decrease in IL-6 concentrations ( P <0.01) and the decrease in body mass index with the decrease in CRP ( P <0.05), respectively. Conclusions— Weight loss in morbidly obese patients induces a significant decrease of CRP and IL-6 concentrations in association with an improvement of the IRS.