Diabetes-related investigations - C-peptide test

Principle

C-peptide (co-secreted with insulin in equimolar amounts from proinsulin cleavage, but not present in exogenous insulin preparations) reflects endogenous insulin production - used to distinguish type 1 (typically low/undetectable, reflecting beta-cell destruction) from type 2 diabetes (typically preserved or elevated, reflecting insulin resistance with compensatory hyperinsulinaemia) when the clinical picture is ambiguous
Because C-peptide (unlike measured insulin, which cannot be distinguished from exogenous injected insulin) is only produced from endogenous proinsulin cleavage, it provides an unconfounded measure of the patient's own beta-cell function even in a patient already established on insulin therapy - this is the key reason C-peptide, not insulin level, is used when endogenous production needs to be assessed in an insulin-treated patient

Particularly useful in atypical presentations - diabetes with an unclear type at diagnosis (e.g. an adult presenting with features overlapping both types, or diabetes diagnosed outside the typical age range for either type) where the distinction has direct treatment implications

Should be interpreted alongside concurrent glucose level (a low C-peptide in the context of hypoglycaemia has different significance than a low C-peptide with hyperglycaemia) and, where relevant, alongside type 1 diabetes-specific autoantibody testing (GAD, islet cell, insulin autoantibodies) for additional diagnostic confirmation
Renal impairment reduces C-peptide clearance and can falsely elevate levels, requiring consideration when interpreting results in patients with reduced kidney function

Low/undetectable C-peptide (with hyperglycaemia) supports type 1 diabetes or significant beta-cell failure -> insulin therapy is essential regardless of other clinical features
Preserved/elevated C-peptide supports type 2 diabetes or a diabetes subtype with retained endogenous insulin production -> broader range of non-insulin treatment options may be appropriate

Atypical diabetes presentation classification (type unclear at diagnosis), MODY (maturity-onset diabetes of the young - another scenario where C-peptide/autoantibody testing helps refine classification), renal impairment falsely elevating results

C-peptide, not measured insulin level, is the correct test for assessing a patient's own endogenous insulin production once they are established on insulin therapy - exogenous injected insulin does not contain C-peptide, so C-peptide testing remains an unconfounded window into residual beta-cell function even in insulin-treated patients, unlike a direct insulin level

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