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Insulin is a peptide hormone with a molecular weight of approximately 6000 daltons. Serum insulin determinations may be performed on patients with symptoms of hypoglycemia^4,5 where insulinoma is a possible etiology. Patterns of secretion by insulinomas may be sporadic or constant. Insulinoma is a rare functional tumor of pancreatic origin that secretes insulin inappropriately, causing hypoglycemia. Whipple originally described the tumor and classic diagnostic criteria called “Whipple’s Triad”. The criteria included:

1) neurologic symptoms of hypoglycemia

2) low glucose (<50 mg/dL) which are corrected immediately by giving glucose or carbohydrate.

Today, as described above, we would add inappropriately elevated insulin levels during an episode of hypoglycemia. Usually hypoglycemia is induced with a fast or exercise, and the diagnostic criteria may include a 48 to 72 hour fast with insulin levels greater than 5 μU/mL during a hypoglycemic episode.⁴

Hypoglycemia can, however, also be facilitated intentionally or unintentionally (factitious hypoglycemia),^4,5 C-peptide levels along with insulin levels may be helpful in ruling out factitious insulin use, however note the limited reactivity of various insulin analogs. Accordingly, one use of the insulin test is to screen patients with low glucose for insulinoma if other factors such as glucose-lowering drugs or reactive hypoglycemia are excluded.

Insulin levels can be also useful in predicting susceptibility to the development of type II diabetes.⁴ However, the American Diabetes Association recommendations for the diagnosis of diabetes do not include the measurement of insulin levels.⁶

Insulin levels may also be measured to estimate the patient’s capacity for insulin secretion (eg, glucagon test) or in the evaluation of insulin sensitivity (eg, oral glucose tolerance test). Although the adequacy of pancreatic insulin synthesis is frequently assessed via the determination of C-peptide, fasting insulin is also measured to assess insulin resistance.

In treated patients therapeutic administration of insulin can lead to the formation of insulin binding antibodies. Insulin binding antibodies invariably interfere with insulin measurement methods and results are unreliable. For patients with known autoantibodies to insulin should measure free and total insulin to assess biologically active fraction of insulin (free insulin) and total insulin. Measurements of free and total insulin, C-peptide, insulin antibodies and hemoglobin A1C are often tested in conjunction to clarify the contribution of endogenous and exogenous insulin to overall diabetic management.