CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects

OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk ofcardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent theinsulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypasssurgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies onthe regulation of inflammatory markers.DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects.SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m2 were studied prior to and6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery.MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well asmarkers of glucose and lipid metabolism.RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRPcorrelated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, whencorrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m2 and lowered CRP, SAA and IL-6 levels by 82, 57 and50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the changein body weight (r=-0.36, P=0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA o 4(insulin sensitive) and HOMA49 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended toparallel the changes in CRP, but were less informative.CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers andimproves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulinresistantpatients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather thanenergy supply.