Insulin action and insulinemia are closely related to the fasting complement C3, hot not acylation stimulating protein concentration

OBJECTIVE - An elevated C3 concentration has been reported in people with o besity type 2 diabetes, hypertension, and dyslipidemia, and has been propos ed to play a role in the development of atherosclerosis. We hypothesized th at an elevated C3 concentration might be linked to insulin resistance and/o r hyperinsulinemia, abnormalities commonly observed in association with the above conditions. RESEARCH DESIGN AND METHODS - Fasting concentrations of C3 and acylation st imulating protein (ASP, C3adesarg), a cleavage product of C3 recently found to stimulate glucose uptake in vitro, were measured in 33 healthy nondiabe tic Pima Indians (14 women and 19 men; age 27 +/- 1 and body fat 33 +/- 1%, means +/- SEM). Subjects were characterized for body composition dual-ener gy X-ray absorptiometry insulin action (insulin-stimulated glucose disposal [M], hyperinsulinemic glucose clamp), and glucose tolerance (75-g oral glu cose tolerance test). RESULTS - Fasting C3 and ASP concentrations were positively correlated (r = 0.43, P < 0.05). Fasting C3 concentration was closely related to percent b ody fat (r = 0.77), M (r = -0.75), and lasting insulin concentration (r = 0 .72) (all P < 0.0001). Fasting C3 concentrations remained significantly rel ated to M and lasting insulin after adjusting for percent body fat (partial r = -0.53 and 0.33, both P < 0.05). In subjects with impaired glucose tole rance, fasting C3 concentrations were higher than in those with normal gluc ose tolerance-a difference that remained after adjustment for percent body fat and M. We found that fasting ASP concentrations were significantly rela ted to percent body fat (r = 0.37. P < 0.05), but not to M or fasting insul in. CONCLUSIONS - In Pima Indians, fasting C3 concentration is closely related to adiposity insulin action, and lasting insulin levels and may thus be a m ediator for the postulated link between obesity insulin resistance, hyperin sulinemia, and possibly atherosclerosis.