Complement-mediated chronic inflammation is associated with diabetic microvascular complication
Article first published online: 11 MAR 2013
Copyright © 2012 John Wiley & Sons, Ltd.
Diabetes/Metabolism Research and Reviews
Volume 29, Issue 3, pages 220–226, March 2013
How to Cite
Fujita, T., Hemmi, S., Kajiwara, M., Yabuki, M., Fuke, Y., Satomura, A. and Soma, M. (2013), Complement-mediated chronic inflammation is associated with diabetic microvascular complication. Diabetes Metab. Res. Rev., 29: 220–226. doi: 10.1002/dmrr.2380
- Issue published online: 11 MAR 2013
- Article first published online: 11 MAR 2013
- Accepted manuscript online: 27 DEC 2012 05:21AM EST
- Manuscript Accepted: 15 NOV 2012
- Manuscript Revised: 20 OCT 2012
- Manuscript Received: 28 JAN 2012
- acylation stimulating protein;
- membrane attack complex;
- diabetic microvascular complication;
- chronic inflammation;
- complement activation
Chronic inflammation is characteristic of type 2 diabetes mellitus (T2DM). Obesity-activated adipocytes release adipocytokines, which induce the secretion of proinflammatory cytokines, resulting in vascular endothelial dysfunction and organ injury. C3a is a candidate to induce tissue inflammation.
We investigated the association between diabetic microangiopathy and complement-mediated inflammation in 32 obese T2DM patients and 32 normal donors. Plasma levels of complement components and their activation intermediates were examined and related to the level of complication. An incubation study of post-prandial serum was carried out to measure the in vitro production of acylation stimulating protein (ASP/C3a desArg) by chylomicron.
Plasma levels of C3, C4, factor B, iC3b, Bb, and ASP were significantly increased in T2DM patients. Levels of C4d and membrane attack complex (C5b-9) were not significantly elevated. The activation rate of these factors indicated that only the early phase of alternative complement pathway was excessively activated. A statistical study revealed close correlation between ASP, body mass index, and highly sensitive C-reactive protein. Plasma ASP was significantly increased in the macroalbuminuric and proliferative retinopathy patient groups. An incubation study revealed that ASP was produced after the in vitro incubation of post-prandial serum from a T2DM patient with hyperchylomicronaemia.
Activation of the alternative complement pathway occurs in obese T2DM patients and is enhanced in the post-prandial hyperchylomicronic condition, which induces overproduction of ASP and C3a-mediated tissue inflammation. Therefore, complement-mediated inflammation may contribute to the acceleration of diabetic microangiopathy in addition to the development of macroangiopathy. Copyright © 2012 John Wiley & Sons, Ltd.