Should C-reactive protein be measured in a fasting state to diagnose type 1 diabetes mellitus?

C-Reactive Protein Testing for Type 1 Diabetes Diagnosis

C-reactive protein (CRP) does not require fasting when used in the diagnostic evaluation of type 1 diabetes mellitus. 1

Role of CRP in Type 1 Diabetes

• CRP is an inflammatory marker that may be elevated in the development of type 1 diabetes, suggesting an immunoinflammatory component to the disease process 2
• Elevated CRP levels have been observed in patients with type 1 diabetes without clinical macroangiopathy, indicating a chronic inflammatory response that correlates with markers of endothelial dysfunction 3
• While CRP may provide additional information about inflammatory status, it is not a primary diagnostic test for type 1 diabetes 1

CRP Testing Guidelines

• According to the CDC/AHA guidelines, CRP measurements can be performed in either a fasting or non-fasting state 1
• When obtaining CRP concentrations in metabolically stable patients, two measurements (fasting or non-fasting) should be made approximately two weeks apart and the results averaged 1
• CRP results should be expressed in milligrams per liter (mg/L) to one decimal point 1

Primary Diagnostic Tests for Type 1 Diabetes

The diagnosis of type 1 diabetes relies primarily on the following tests:

• A1C ≥ 6.5% (performed in a laboratory using NGSP certified method) 1
• Fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L) 1
• 2-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during OGTT 1
• Random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) with classic symptoms of hyperglycemia 1

C-peptide in Type 1 Diabetes Diagnosis

• C-peptide measurements may help distinguish type 1 from type 2 diabetes in ambiguous cases, such as individuals with type 2 phenotype who present in ketoacidosis 1
• When measuring C-peptide for diagnostic purposes, it should be done in the fasting state when simultaneous fasting plasma glucose is ≤220 mg/dL (12.5 mmol/L) 1
• In long-standing type 1 diabetes, stimulated C-peptide testing may detect residual beta cell function in approximately 10% more individuals compared to fasting C-peptide alone 4

Important Considerations and Pitfalls

• CRP levels may be affected by various conditions unrelated to diabetes, including inflammatory bowel disease, rheumatoid arthritis, and alcoholism 1
• If CRP level is ≥10 mg/L, the test should be repeated and the patient examined for sources of infection or inflammation 1
• While CRP may provide information about inflammatory status in diabetes, routine testing for insulin or proinsulin is not recommended for most people with diabetes or at risk for diabetes 1
• A1C testing has advantages over glucose-based tests, including not requiring fasting, greater preanalytical stability, and less day-to-day perturbations during stress and illness 1

Conclusion for Clinical Practice

When evaluating for type 1 diabetes:

• Focus on standard diagnostic criteria (A1C, fasting glucose, OGTT, or random glucose with symptoms) 1
• If CRP testing is desired as an additional marker, it can be performed without fasting 1
• For ambiguous cases, C-peptide and diabetes-specific autoantibody testing may be more valuable than CRP for differentiating diabetes types 1