What is the role of serum proinsulin in diagnosing and managing pancreatic conditions, such as hyperglycemia (elevated blood sugar) and impaired pancreatic function?

From the Guidelines

Serum proinsulin measurement is essential in diagnosing pancreatic conditions, particularly in distinguishing between type 1 and type 2 diabetes, and identifying insulin-producing tumors, as it provides valuable information on beta cell function and insulin production. According to the guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus 1, serum proinsulin levels can help diagnose and monitor pancreatic conditions. Key points to consider when using serum proinsulin measurement include:

• Elevated serum proinsulin levels can indicate insulin-producing tumors (insulinomas), beta cell dysfunction in type 2 diabetes, or early pancreatic beta cell failure
• In insulinomas, proinsulin levels are disproportionately high compared to insulin, creating a useful diagnostic marker
• Rising proinsulin-to-insulin ratios can signal progressive beta cell dysfunction before clinical symptoms appear
• Proinsulin testing is particularly valuable when hypoglycemia occurs with normal or elevated insulin levels, as it can distinguish between insulinoma, factitious hypoglycemia, and other causes The measurement of serum proinsulin, along with other markers such as C-peptide and glucose, can aid in the diagnosis and management of pancreatic conditions, as stated in the guidelines 1. It is worth noting that routine testing for insulin or proinsulin is not recommended for most people with diabetes or risk for diabetes or cardiovascular disease, except in specific cases where it can provide valuable diagnostic information 1. In clinical practice, the use of serum proinsulin measurement should be guided by the individual patient's clinical presentation and medical history, and should be interpreted in conjunction with other diagnostic tests and markers, as recommended by the guidelines 1.

From the Research

Role of Serum Proinsulin in Pancreatic Conditions

• Serum proinsulin plays a significant role in assessing pancreatic beta-cell function and insulin resistance in various pancreatic conditions, including diabetes 2, 3, 4, 5.
• Proinsulin is a precursor to insulin, and its levels can indicate the status of beta-cell secretion and insulin resistance 2, 4.
• In type 2 diabetes, the proinsulin/insulin ratio increases with the degree of insulin resistance, making it a potential marker for monitoring beta-cell dysfunction 2, 5.
• In type 1 diabetes, the proinsulin/C-peptide ratio may predict the onset of diabetes in relatives, and aberrant proinsulin processing has been observed in individuals with recent-onset type 1 diabetes 6.

Diagnostic and Prognostic Value

• Serum proinsulin levels can be used to diagnose and monitor pancreatic conditions, including insulinoma and diabetes 2, 3.
• The proinsulin/insulin ratio can help identify individuals with impaired beta-cell function and insulin resistance 3, 5.
• Proinsulin levels have been correlated with various biochemical markers of insulin resistance and beta-cell function, including fasting C-peptide, postprandial blood glucose, and triglyceride levels 5.

Measurement and Assays

• Serum proinsulin can be measured using various assays, including ELISA and chemiluminescence tests 4.
• The stability of intact proinsulin in EDTA whole blood samples has been demonstrated, making it a practical marker for routine assessment of beta-cell dysfunction and insulin resistance 4.
• The proinsulin/insulin ratio can be used as a complementary marker to C-peptide and insulin assays in relation to glycemia to label hypoglycemia 2.