From the Guidelines
Normal proinsulin levels in fasting adults typically range from 2 to 6 pmol/L (or approximately 0.2 to 0.6 ng/mL), and for C-peptide, normal fasting levels generally fall between 0.5 and 2.0 ng/mL (or 0.17 to 0.67 nmol/L), as indicated by recent studies 1. These values can vary slightly between different laboratories due to differences in testing methods. Both proinsulin and C-peptide are produced during insulin synthesis in the pancreatic beta cells. Proinsulin is the precursor molecule that gets cleaved to form insulin and C-peptide in equal amounts. Measuring these levels can help assess pancreatic beta cell function and insulin production. Elevated proinsulin levels may indicate insulin resistance or early beta cell dysfunction in type 2 diabetes, while low C-peptide levels suggest decreased insulin production as seen in type 1 diabetes. These tests are particularly useful when evaluating hypoglycemia, differentiating between diabetes types, or assessing residual beta cell function in diabetic patients. Some key points to consider include:
- The use of C-peptide measurements to distinguish type 1 from type 2 diabetes in ambiguous cases 1.
- The importance of standardizing insulin and C-peptide assays to facilitate measures of insulin secretion and sensitivity 1.
- The role of genetic testing in identifying monogenic diabetes and its implications for treatment 1.
- The need for careful monitoring and education in individuals with possible type 1 diabetes who are not treated with insulin 1. It is essential to consider the most recent and highest-quality studies when interpreting proinsulin and C-peptide levels, as the evidence is continually evolving 1.
From the Research
Normal Proinsulin and C-Peptide Levels
- Normal proinsulin levels are typically considered to be below 22 pmol/L in non-obese controls and below 5 pmol/L in controls when blood glucose levels are below 2.5 mmol/L 2, 3.
- C-peptide levels above 0.2 nmol/L can be indicative of insulinoma, but not nesidioblastosis 2.
- In patients with insulinoma, proinsulin levels are often elevated, with a median of 100 pmol/L, while controls have a median of 6.8 pmol/L 3.
- A proinsulin concentration of ≥ 22 pmol/L can distinguish cases of insulinoma from controls, while a concentration of ≥ 5 pmol/L may not be specific enough 3.
- Fasting insulin and C-peptide levels can be higher in patients with insulinoma, but may not be significantly different at 3 hours after an oral glucose tolerance test 4.
- Intact proinsulin levels above 10 pmol/L may indicate insulin resistance, while total proinsulin levels above 45 pmol/L may indicate high cardiovascular risk 5.
Diagnostic Thresholds
- An end of fast proinsulin concentration ≥ 5 pmol/L has been suggested as a useful cutoff for the diagnosis of insulinoma, but may not be specific enough 3.
- A proinsulin concentration ≥ 22 pmol/L may be a better discriminator between cases and controls 3.
- An insulin concentration ≥ 3 μIU/mL at the end of a fast may be a useful cutoff for the diagnosis of insulinoma, with a sensitivity of 98% 3, 6.
- A C-peptide level above 0.2 nmol/L may be indicative of insulinoma, but not nesidioblastosis 2.