Serum Amyloid A Truncations in Type 2 Diabetes Mellitus

Serum Amyloid A (SAA) is an acute phase protein complex consisting of several abundant isoforms. The N-terminus of SAA is critical to its function in amyloid formation. SAA is frequently truncated, either missing an arginine or an arginine-serine dipeptide, resulting in isoforms that may influence the capacity to form amyloid. However, the relative abundance of truncated SAA in diabetes and chronic kidney disease is not known. Methods Using mass spectrometric immunoassay, the abundance of SAA truncations relative to the native variants was examined in plasma of 91 participants with type 2 diabetes and chronic kidney disease and 69 participants without diabetes. Results The ratio of SAA 1.1 (missing N-terminal arginine) to native SAA 1.1 was lower in diabetics compared to non-diabetics (p = 0.004), and in males compared to females (p<0.001). This ratio was negatively correlated with glycated hemoglobin (r = -0.32, p<0.001) and triglyceride concentrations (r = -0.37, p<0.001), and positively correlated with HDL cholesterol concentrations (r = 0.32, p<0.001). Conclusion The relative abundance of the N-terminal arginine truncation of SAA1.1 is significantly decreased in diabetes and negatively correlates with measures of glycemic and lipid control.