title: Insulin action and insulinemia are closely related to the fasting complement C3, but not acylation stimulating protein concentration.
abstract: 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.
authors.affiliation: 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
authors.forename: C
authors.initials: C
authors.lastname: Weyer
authors.forename: P A
authors.initials: PA
authors.lastname: Tataranni
authors.forename: R E
authors.initials: RE
authors.lastname: Pratley
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D001798:Blood Proteins; D003176:Complement C3; D007328:Insulin; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a