Elevated C-Reactive Protein Levels Do Not Correspond to Autoimmunity in Type 1 Diabetes

A large body of data now supports that high normal or elevated C-reactive protein (CRP) levels are a marker of ongoing low-grade chronic inflammatory process and may predict a higher risk for cardiovascular disease. Type 1 diabetes is a T-cell-mediated disease (1), and autoantibodies (2) are considered to be the surrogate markers for the autoimmune process and have been used for disease prediction (3). However, little is known about the relationship between diabetes autoimmunity and the acute-phase response. We studied the relationship of islet cell autoimmunity in type 1 diabetes as reflected by the presence of GAD65 and ICA512 autoantibodies and CRP titers. We analyzed the following five groups of individuals: pre-diabetic (n = 10), new-onset (n = 29), long-term type 1 diabetic (n = 16), and long-term type 2 diabetic (n = 55) patients and healthy subjects (n = 50). CRP levels were significantly higher in long-term type 1 diabetic patients (0.11 mg/dl [range 0.014–1.39]) than in either new-onset type 1 diabetic patients (0.061 mg/dl [0.012–1.12], P = 0.04) or healthy control subjects (0.06 mg/dl [0.007–1.33], P = 0.02). Long-term type 2 diabetic patients have higher CRP levels (0.24 mg/dl [0.03–4.41]) than healthy control subjects (P = 0.04). We could not find any correlation between CRP levels and any combination or titer of autoantibodies in pre-diabetic, new-onset, and long-term type 1 diabetic patients.

The lack of elevated CRP in the pre-diabetic and recently diagnosed patients with type 1 diabetes is consistent with the notion that chronic localized autoimmune inflammation does not result in appreciable changes in the CRP levels, thus making it unsuitable as a marker of type 1 diabetic autoimmunity. The difference in CRP levels in long-term and new-onset type 1 diabetic patients may be related in part to the vanish of the intrinsic physiologically secreted insulin once extending the honeymoon period in type 1 diabetes. Insulin has been shown to have anti-inflammatory properties, including downregulation of acute-phase protein production of the liver (4); thus, it may lead to lower CRP levels.

The underlying mechanisms behind elevated CRP levels in long-term type 1 and type 2 diabetic patients might be different, as elevated glucose levels as well as insulin resistance are contributing factors to the inflammatory process. Prolonged elevated blood glucose levels are implicated in chronic inflammatory changes in the tissues in both type 1 and type 2 diabetic patients and reflected by the elevated CRP values. However, in type 2 diabetes, insulin resistance is also likely to be a major factor (5), as elevated CRP values have been found in near-normoglycemic pre-diabetic type 2 diabetic and metabolic syndrome patients.