Background-Plasma C-reactive protein (CRP) concentrations are increased in obese and/or hyperinsulinemic individuals.The goal of this study was to determine if the relation between insulin resistance and CRP was independent of obesity. Methods and Results-Plasma CRP concentrations were measured before and after 3 months of calorie restriction in 38 healthy, obese women. Steady-state plasma glucose (SSPG) concentration during a 180-minute infusion of octreotide, glucose, and insulin was used to stratify participants into insulin-resistant (IR, nϭ20) or insulin-sensitive (nϭ18) groups, similar in terms of mean age (46Ϯ2 versus 44Ϯ2 years), body mass index (32.0Ϯ0.4 versus 31.4Ϯ0.3 kg/m 2 ), and waist circumference (96Ϯ2 versus 95Ϯ2 cm). Mean CRP (0.39Ϯ0.08 versus 0.12Ϯ0.03 mg/dL, Pϭ0.003) concentrations were higher in the IR group, as were day-long plasma glucose and insulin responses (PϽ0.001). There was a significant correlation at baseline between CRP and day-long plasma integrated insulin response (rϭ0.47, Pϭ0.001) but not between CRP and body mass index (rϭ0.14) or waist circumference (rϭ0.10). Weight loss was similar in the two groups (8.7Ϯ0.9 versus 8.4Ϯ0.8 kg) but was associated with significant (PϽ0.001) decreases in SSPG and CRP concentrations in the IR group only. Regression analysis showed that SSPG and day-long plasma insulin response were the only significant predictors of CRP concentration. Conclusions-CRP concentrations are elevated predominantly in obese individuals who are also insulin resistant and fall in parallel with weight loss-associated improvements in insulin resistance. The relation between CRP concentrations and insulin resistance is independent of obesity.

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