C-Peptide and islet auto-antibodies

C-Peptide

C-peptide testing gives a measure of endogenous insulin production. C-peptide can be measure in blood or urine, although blood is preferable as less likely to produce artificially low results.

Blood - C-peptide should be measured alongside a blood glucose level and is only valid if blood glucose is >4mmol/l. The sample does not need to be taken on ice. EDTA whole blood samples for C-peptide analysis can be sent at room temperature to be received at the lab within 48 hours of sample collection. Further detail is available from the Exeter laboratory website at C-Peptide Exeter Clinical Laboratory International (exeterlaboratory.com)

Urine - Advice regarding the measurement of urine C-peptide is available on the ‘Diabetes Diagnostics’ App from the University of Exeter and on the Exeter laboratory website (www.diabetesgenes.org). See: https://www.exeterlaboratory.com/test/c-peptide-urine/

It is not recommended to measure c-peptide as a matter of routine if duration of diabetes is <3 years, but it can be measured if a trial of insulin withdrawal is being considered, to aid with the diagnosis of insulin deficiency, or if a monogenic or syndromic form of insulin resistance is suspected.

C-peptide testing is recommended in all individuals with T1D at 3 years, even if a robust diagnosis has been made, as individuals with significant detectable C-peptide have reduced glucose variability, reduced frequency of hypoglycaemia and better long term outcomes.

Does serum C-peptide need repeated after an interval?

Providing serum C-peptide was measured after 3 or more year’s duration of diabetes, there should not be any need for this to be repeated as a matter of routine.

Interpreting C-peptide

The clinical thresholds and interpretation for patients with insulin treated diabetes are shown in the table below:

ANTIBODY RESULTS

How do I interpret pancreatic islet cell antibody results?

Elevated islet cell antibodies are a marker of autoimmunity and thus support a diagnosis of autoimmune diabetes. However, it is important to remember that true false positive antibody results can occur with any immunoassay, while positive islet cell antibodies may occur in the general population and not cause diabetes. On the other hand, approximately 5% of people with true T1D have negative islet cell antibodies, when three antibodies are tested (GAD, IA-2, ZnT8). Broadly speaking, higher antibody titres and/or multiple different positive antibodies are more likely to be ‘real’ results, indicative of a diagnosis of T1D. islet antibody titres >99th centile are considered ‘strongly’ positive, while antibody titres between the 97.5th and 99th centiles are considered ‘weakly’ positive. Specific antibody titre cut-offs are shown in the table below. As with the C-peptide cut-offs, it is important that these cut-offs are not applied rigidly and that clinical judgement is shown. For the purposes of the algorithm, a diagnosis of T1D is considered robust if one or more antibody is ‘strongly’ positive or there is more than one antibody ‘weakly’ positive. Note, in people with long standing diabetes, antibody levels can wane/ reduce with time.

UK Lab Antibody Titres Thresholds

There is useful advice on differentiating between Type 1 and type 2 diabetes at T1T2 Classification // Diabetes Genes