From the Guidelines
Proinsulin and C-peptide measurements are essential in diagnosing pancreatic conditions, particularly in distinguishing between type 1 and type 2 diabetes, as they provide insight into beta cell function and insulin production. According to the most recent guidelines, C-peptide measurements may help distinguish type 1 from type 2 diabetes in ambiguous cases, such as individuals who have a type 2 phenotype but present in ketoacidosis 1. Proinsulin is the precursor to insulin, which is cleaved to form insulin and C-peptide in equal amounts. Elevated proinsulin levels with normal or low insulin can indicate beta cell dysfunction, as seen in early type 2 diabetes. C-peptide serves as a reliable marker of endogenous insulin production since it has a longer half-life than insulin and isn't affected by insulin antibodies or exogenous insulin.
Some key points to consider when using proinsulin and C-peptide measurements in diagnosis include:
- Low C-peptide levels in a hyperglycemic patient suggest type 1 diabetes or advanced type 2 diabetes with beta cell failure, while normal or high levels point to insulin resistance.
- The fasting reference range for C-peptide is typically 0.8-3.1 ng/mL, with values below this range suggesting insufficient insulin production.
- C-peptide measurements can aid in instances where it is difficult to differentiate between the diagnosis of type 1 and type 2 diabetes, particularly in individuals with a type 2 phenotype who present in ketoacidosis 1.
- Proinsulin and C-peptide measurements are also useful in identifying factitious hypoglycemia, where C-peptide would be low with high insulin, and in monitoring beta cell function after pancreatitis or pancreatic surgery.
The most recent study from 2024 provides a flowchart for the investigation of suspected type 1 diabetes in newly diagnosed adults, which includes C-peptide testing as a key component in determining the type of diabetes 1. In summary, proinsulin and C-peptide measurements are valuable tools in the diagnosis of pancreatic conditions, and their use should be guided by the most recent clinical guidelines and evidence-based recommendations.
From the Research
Proinsulin and C-Peptide in Diagnosing Pancreatic Conditions
- Proinsulin and C-peptide are used to diagnose pancreatic conditions, particularly in cases of hypoglycemia and diabetes 2.
- During fasting trials, insulinoma diagnosis relies on high insulin and C-peptide serum levels concomitant with hypoglycemia, and proinsulin assay can be useful in cases of discrepancy between these parameters 2.
- In diabetes, proinsulin/insulin ratio increases with the degree of insulin resistance, and proinsulin/C-peptide ratio could predict the onset of diabetes in relatives 2.
Proinsulin Levels in Pancreatic Diabetes
- Hyperproinsulinaemia has been reported in patients with type 2 diabetes, and it is associated with defects in insulin secretion rather than a reduction in β-cell area 3.
- Proinsulin levels are not associated with impaired β-cell area, but there is a strong inverse relationship between homeostasis model assessment index of β-cell function and proinsulin/insulin ratio 3.
Insulin Assays and Reference Values
- Insulin is produced by beta cells in pancreatic islets of Langherans via a complex process of proteolytic conversion, and proinsulin is a precursor molecule that is converted to insulin and C-peptide 4.
- Insulin immunoassays can be used to measure proinsulin levels, and reference values must be determined for normoglycaemic subjects with a normal body weight 4.
Latent Autoimmune Diabetes in Adults (LADA)
- LADA is a type of diabetes characterized by slow autoimmune damage of pancreatic β cells, and it is distinct from classical type 1 diabetes and type 2 diabetes 5, 6.
- Proinsulin and C-peptide levels may be useful in diagnosing LADA, particularly in cases where there is a discrepancy between insulin and C-peptide levels 2.