From the Guidelines
Proinsulin can be tested through a blood test that specifically measures proinsulin levels in the serum, typically after an overnight fast of 8-12 hours, using immunoassay techniques such as enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), or more advanced methods like liquid chromatography-mass spectrometry (LC-MS) 1.
Testing for Proinsulin
To test for proinsulin, a healthcare provider will collect a blood sample, which is then analyzed to determine proinsulin levels.
- Normal proinsulin levels are typically less than 20 pmol/L, though reference ranges may vary between laboratories.
- Elevated proinsulin levels can indicate insulin resistance, beta cell dysfunction, or insulinomas (insulin-producing tumors) 1.
Importance of Proinsulin Testing
The test is particularly useful in diagnosing conditions where there is abnormal insulin processing, as proinsulin is the precursor molecule that gets cleaved to form insulin and C-peptide in healthy pancreatic beta cells.
- For accurate results, patients should follow their healthcare provider's instructions regarding medication use and dietary restrictions prior to the test.
- The test is not routinely ordered but may be included as part of a comprehensive evaluation of glucose metabolism disorders 1.
Clinical Recommendations
According to recent guidelines, routine testing for insulin or proinsulin is not recommended for most people with diabetes or at risk for diabetes or cardiovascular disease, as these assays are useful primarily for research purposes 1.
- However, C-peptide measurements may help distinguish type 1 from type 2 diabetes in ambiguous cases, and insulin and C-peptide assays should be standardized to facilitate measures of insulin secretion and sensitivity that will be comparable across research studies 1.
From the Research
Testing for Proinsulin
To test for proinsulin, several methods and criteria can be considered based on the available evidence:
- Fasting Proinsulin Levels: Studies have shown that fasting proinsulin levels can be an indicator of β-cell dysfunction and are elevated in patients with hyperglycemia 2. A proinsulin concentration of ≥ 5 pmol/L has been suggested as a cutoff for the diagnosis of insulinoma, but this value may not be specific enough to distinguish cases from controls 3.
- Proinsulin Assays: Different assays are available for measuring proinsulin, including radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) 4, 5. The choice of assay may affect the results and interpretation of proinsulin levels.
- Reference Ranges: Reference ranges for proinsulin levels have been established in non-diabetic individuals, with a range of 1.8-11.0 pmol/L reported in one study 5.
- Sample Stability: The stability of proinsulin in different sample types has been investigated, with intact proinsulin found to be stable in EDTA whole blood samples for up to two days at room temperature 5.
- Glucose-Stimulated Proinsulin: Proinsulin levels after a glucose load have also been studied, with results suggesting that both fasting and glucose-stimulated proinsulin levels can predict hyperglycemia and incident type 2 diabetes 2.
Diagnostic Criteria
The following diagnostic criteria have been proposed based on proinsulin levels:
- Proinsulin Cutoff: A proinsulin concentration of ≥ 22 pmol/L has been suggested as a cutoff to distinguish cases from controls 3.
- Insulin and Proinsulin Ratios: The ratio of proinsulin to insulin has also been investigated as a potential diagnostic marker, with elevated ratios reported in subjects with impaired glucose tolerance and diabetes 6.