Possible direct influence of complement 3 in decreasing insulin sensitivity in a cohort of overweight and obese subjects

A group of 608 apparently healthy patients, 136 men and 472 women, either overweight or obese, aged 18-69 years, were examined. BMI, waist circumference, fasting blood glucose (FBG), insulin, and complement 3 (C3) serum levels were measured; the homeostasis model assessment (HOMAIR) was used to evaluate insulin resistance; and physical activity was quantified by a questionnaire. Results: HOMAIR showed a positive correlation with BMI (r: 0.478, p < 0.001), waist circumference (r: 0.487, p < 0.001), and C3 (r: 0.445, p < 0.001). Moreover, it was significantly associated with gender (F Fisher = 22.12, p < 0.001), and the mean HOMAIR levels were significantly different among the three groups of physical activity, with the lowest level of insulin resistance at the highest level of physical activity (F=7,31, p < 0.001). A multiple regression analysis was carried out with HOMAIR as the dependent variable and gender, age, BMI, waist circumference, C3 and the level of physical activity as independent variables (fitted model: F = 41.24, P<0.001, R2 = 0.328). HOMAIR maintained an independent association with C3 (β = 0.678, P<0.001), sex (β = 0.189, P<0.001), BMI (β = 0.637, P<0.01), and age (β = -0.004, P<0.05). Conclusions: This study of a cohort of overweight and obese subjects has shown that insulin resistance (dependent variable) is positively associated with C3 serum levels, independently of age, gender, anthropometric parameters and physical activity, suggesting that higher C3 serum levels may directly increase insulin resistance in obesity.