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

Abstract

OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk of cardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent the insulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypass surgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies on the 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/m 2 were studied prior to and 6 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 as markers of glucose and lipid metabolism. RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRP correlated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, when corrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m 2 and lowered CRP, SAA and IL-6 levels by 82, 57 and 50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the change in body weight (r ¼ À0.36, P ¼ 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 to parallel the changes in CRP, but were less informative. CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers and improves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulinresistant patients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather than energy supply.

Obesity, endothelial function and inflammation: the effects of weight loss after bariatric surgery

“…Our investigation corroborates preliminary studies (18,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) as it shows that obesity is a state of chronic low-grade inflammation and the weight reduction resulting from bariatric surgery significantly improves the inflammatory state. This amelioration relies on the continuous reduction in hs-CRP and IL-6 concentrations, associated with a parallel decrease in BMI.…”

“…Previous studies have demonstrated that surgically induced weight loss is accompanied by an improvement of the endothelial function (18,19,21) and the proinflammatory state (18,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). However, few studies have studied endothelial function and proinflammatory state together, and have considered different time-points to determine postsurgical changes.…”

Association between serum amyloid A and obesity: a meta-analysis and systematic review

“…One prospective study was excluded for the same reason, and four others were excluded for the unsuccessful weight loss intervention, which was defined as no significant difference (P [ 0.05) in BMI levels before and after intervention. The final meta-analysis was carried out with the remaining 11 cross-sectional studies [12][13][14][15][16][17][18][19][20][21][22] and 10 prospective studies with successful interventions through gastric surgery [23][24][25][26][27] or diet and exercise [17,[28][29][30][31] as only these met the respective inclusion criteria (Fig. 1).…”

“…Therefore, it appears that heterogeneity of the studies may be due to a combination of other unknown factors and not simply a single one. Ten prospective studies comprising 353 participants who underwent weight loss by gastric surgery [23][24][25][26][27], or diet and/or exercise [17,[28][29][30][31] showed a significant decrease in SAA levels with weight loss represented by the pooled standardized mean difference of -0.480 (-0.678 to -0.283, P \ 0.0005) (Fig. 3).…”

Metabolic surgery and cancer

“…[73][74][75][76][77] Multiple regression analysis reveals that the decrease in postoperative insulin resistance after surgery is independently associated with a decrease in interleukin-6 concentrations. 77 At 6 months after surgery, there is also an increase in the production of interferongamma, IL-12, and IL-18 that is associated with a rise in natural killer (NK) cell activity.…”