From the Guidelines
You should not always check for C-peptide and GAD antibodies in every patient to rule out type 1 diabetes, but rather order these tests selectively based on clinical suspicion or unclear diagnosis, as recommended by the 2025 standards of care in diabetes 1. When evaluating a patient for type 1 diabetes, it is essential to consider their clinical presentation, age, and other factors to determine the need for testing.
- The 2025 standards of care in diabetes suggest that testing for islet autoantibodies, such as GAD, should be considered in patients with suspected type 1 diabetes, especially those under 35 years old or with atypical presentations 1.
- C-peptide testing is only indicated in people receiving insulin treatment, and a random sample with concurrent glucose can replace a formal C-peptide stimulation test in the context of classification 1.
- The presence of GAD antibodies indicates autoimmune destruction of beta cells, while low C-peptide levels suggest insulin deficiency characteristic of type 1 diabetes.
- However, routine testing in patients with typical type 2 features, such as older age, obesity, gradual onset, and family history, is unnecessary and not cost-effective.
- Clinical judgment should guide selective testing to ensure appropriate diabetes classification and management, as misdiagnosing type 1 as type 2 could delay appropriate insulin therapy 1.
- The staging of type 1 diabetes, as outlined in the 2025 standards of care, can help guide the diagnosis and management of the disease, with stage 1 characterized by the presence of autoantibodies and normoglycemia, and stage 2 characterized by autoantibodies and dysglycemia 1.
From the Research
C-Peptide and GAD Antibodies in Diabetes Diagnosis
- C-peptide is a measure of pancreatic beta cell function and can be used to guide diabetes diagnosis and management 2
- A c-peptide level of less than 0.2 nmol/l is associated with a diagnosis of type 1 diabetes mellitus (T1DM) 2
- GAD antibodies can be useful for clinical classification of diabetes mellitus in clinically unclear cases 3
- The presence of elevated GAD antibodies identifies patients suitable for early insulin therapy 3
Relation to Age, BMI, and C-Peptide
- GADA positivity may persist in T1D and LADA patients many years after the appearance of diabetes 3
- LADA patients who were GADA negative were more obese than GADA positive LADA diabetics 3
- Postprandial C-peptide was higher in LADA patients who were GADA negative 3
Clinical Applications
- C-peptide measurement can be used to identify patients with T1DM and LADA 2, 4
- A random C-peptide level can be an effective screening test for LADA, with low or normal levels indicating the need for further testing for anti-GAD antibodies 4
- C-peptide replacement combined with regular insulin therapy may exert beneficial effects on kidney and nerve dysfunction in T1DM patients 5