Insulin action and insulinemia are closely related to the fasting complement C3, but not acylation stimulating protein concentration.
OBJECTIVE
An elevated C3 concentration has been reported in people with obesity, type 2 diabetes, hypertension, and dyslipidemia, and has been proposed to play a role in the development of atherosclerosis. We hypothesized that an elevated C3 concentration might be linked to insulin resistance and/or hyperinsulinemia, abnormalities commonly observed in association with the above conditions.


METHODS
Fasting concentrations of C3 and acylation stimulating protein (ASP, C3adesarg), a cleavage product of C3 recently found to stimulate glucose uptake in vitro, were measured in 33 healthy nondiabetic Pima Indians (14 women and 19 men; age 27 +/- 1 and body fat 33 +/- 1%, means +/- SEM). Subjects were characterized for body composition dual-energy X-ray absorptiometry, insulin action (insulin-stimulated glucose disposal [M], hyperinsulinemic glucose clamp), and glucose tolerance (75-g oral glucose 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 body fat (r = 0.77), M (r = -0.75), and fasting insulin concentration (r = 0.72) (all P < 0.0001). Fasting C3 concentrations remained significantly related to M and fasting insulin after adjusting for percent body fat (partial r = -0.53 and 0.33, both P < 0.05). In subjects with impaired glucose tolerance, fasting C3 concentrations were higher than in those with normal glucose tolerance--a difference that remained after adjustment for percent body fat and M. We found that fasting ASP concentrations were significantly related to percent body fat (r = 0.37, P < 0.05), but not to M or fasting insulin.


CONCLUSIONS
In Pima Indians, fasting C3 concentration is closely related to adiposity, insulin action, and fasting insulin levels and may thus be a mediator for the postulated link between obesity, insulin resistance, hyperinsulinemia, and possibly atherosclerosis.
Weyer
C
C
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA. cweyer@phx.niddk.nih.gov
Tataranni
P A
PA
Pratley
R E
RE
D015502:Absorptiometry, Photon; D000328:Adult; D001130:Arizona; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism*; D001823:Body Composition; D003176:Complement C3 / Q000032:analysis / Q000378:metabolism*; D015926:Complement C3a / Q000031:analogs & derivatives*; D005215:Fasting; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007198:Indians, North American; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D012016:Reference Values; D012044:Regression Analysis
D001786:Blood Glucose; D001798:Blood Proteins; D003176:Complement C3; D007328:Insulin; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a