Insulin: Optimal Testing Recommendations
- Routine measurement of insulin is not recommended to diagnose diabetes or guide treatment of diabetes.
- Measurement of insulin is necessary to establish a diagnosis of insulin-mediated non-diabetes related hypoglycemia.
- Measurement of insulin should be paired with measurement of C-peptide during a hypoglycemia episode, to differentiate exogenous and endogenous hyperinsulinism.
Guidelines for Test Utilization
What does the test tell me?
Measurement of insulin, paired with C-peptide (+/- proinsulin), during an episode of hypoglycemia can establish whether a hypoglycemic episode is insulin-mediated. In healthy individuals or individuals with non-insulin mediated hypoglycemia, insulin and C-peptide will be suppressed during hypoglycemia. Inappropriately non-suppressed concentrations of insulin during a hypoglycemic episode indicate the presence of exogenous or endogenous hyperinsulinism as the cause of hypoglycemia. [back to top]
When should I order this test?
Insulin is ordered in individuals who present with non-diabetes related hypoglycemia, to determine whether the cause of the hypoglycemia is insulin-mediated. If insulin is inappropriately non-suppressed during a hypoglycemic episode, this supports exogenous or endogenous hyperinsulinism. Exogenous hyperinsulinism would occur in patients injecting insulin (either accidental, surreptitious, or malicious administration) and would be accompanied by a suppressed C-peptide concentration, as C-peptide is not present in exogenous insulin formulations. Endogenous hyperinsulinism would present with non-suppressed insulin paired with a non-suppressed C-peptide level during hypoglycemia, and could be secondary to a variety of etiologies, including insulinoma, functional beta-cell disorders (nesidioblastosis), insulin autoimmune hypoglycemia, or administration of an insulin secretagogue medication such as a sulfonylurea. [back to top]
When should I NOT order this test?
Do not order insulin to diagnose diabetes, to monitor patients with diabetes, to distinguish type 1 from type 2 diabetes, or to guide therapy in patients with diabetes. There is no evidence to support the utility of insulin measurements in the clinical care of patients with type 1 or type 2 diabetes, and insulin measurement in patients with type 1 or type 2 diabetes should be limited to research studies only. Additionally, while polycystic ovary syndrome (PCOS) is associated with insulin resistance, clinical assessment of insulin resistance (using a calculation based on fasting insulin and glucose, such as the homeostasis model assessment of insulin resistance [HOMA-IR]) is not recommended and should be reserved for research purposes only. [back to top]
How should I interpret the result?
When glucose concentrations fall below 55 mg/dL, insulin concentrations should normally be suppressed to < 3 U/mL in individuals without insulin mediated hypoglycemia. Insulin levels above this cut-off during a hypoglycemic episode are evidence of exogenous or endogenous hyperinsulinism. It is important to note that while there have been efforts to standardize insulin assays, not all manufacturers have re-calibrated based on a reference method, and therefore insulin concentrations should be interpreted in the context of the specific assay’s calibration. [back to top]
Is the test result diagnostic/confirmatory of the condition?
No. Insulin alone is not diagnostic/confirmatory, but in combination with other laboratory results recommended in the work-up of non-diabetes related hypoglycemia, can assist in diagnosis. For example, non-suppressed insulin in combination with suppressed C-peptide during a hypoglycemic episode is diagnostic for exogenous insulin administration. Non-suppressed insulin and non-suppressed C-peptide during a hypoglycemic episode supports a diagnosis of endogenous hyperinsulinism; additional testing is needed to determine the exact etiology of endogenous hyperinsulinism. To determine the etiology of endogenous hyperinsulinism, additional testing for the presence of insulin autoantibodies or circulating insulin secretagogue medications would confirm diagnoses of insulin autoimmune hypoglycemia or administration of insulin secretagogues, respectively. In the absence of these, radiologic studies can assist with determining whether endogenous hyperinsulinism is secondary to insulinoma (mass present in the pancreas) or nesidioblastosis (diffuse hypertrophy of islet cells). [back to top]
Are there factors that can affect the lab result?
Heterophile antibodies may interfere with insulin assay results. Clinicians should also be aware that insulin assays differ in their ability to detect various injectable insulin analogues, and should contact their clinical laboratory to clarify the detection profile of the assay when exogenous insulin administration is a potential cause of non-diabetes related hypoglycemia. [back to top]
Are there considerations for special populations?
Not applicable. [back to top]
What other test(s) might be indicated?
Measurement of C-peptide is typically paired with insulin to determine whether insulin-mediated hypoglycemia is from endogenous insulin (non-suppressed insulin and C-peptide) or exogenous insulin (non-suppressed insulin, suppressed C-peptide). Both insulin and C-peptide should be measured when the patient has documented hypoglycemia, either due to spontaneous documented hypoglycemia, during a supervised fast to induce hypoglycemia, or with mixed-meal testing in patients with suspected postprandial hypoglycemia. If insulin and C-peptide results are equivocal, measurement of proinsulin may be useful (and should mirror the C-peptide results as it is present only with endogenous hyperinsulinism, but not exogenous hyperinsulinism). [back to top]
References
- Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, Service FJ; Endocrine Society. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009 Mar;94(3):709-28. doi: 10.1210/jc.2008-1410. Epub 2008 Dec 16. PMID: 19088155.
- Sacks DB, Arnold M, Bakris GL, Bruns DE, Horvath AR, Lernmark Å, Metzger BE, Nathan DM, Kirkman MS. Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus. Clin Chem. 2023 Aug 2;69(8):808-868. doi: 10.1093/clinchem/hvad080. PMID: 37473453.
- Katta S, Desimone ME, Weinstock RS. Pancreatic Islet Function Tests. 2021 Mar 16. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. PMID: 25905219.
Last reviewed: April 2024. The content for Optimal Testing: the Association for Diagnostics & Laboratory Medicine’s (ADLM) Guide to Lab Test Utilization has been developed and approved by the Academy of Diagnostics & Laboratory Medicine and ADLM’s Science and Practice Core Committee.
As the fields of laboratory medicine and diagnostic testing continue to grow at an incredible rate, the knowledge and expertise of clinical laboratory professionals is essential to ensure that patients receive the highest quality and most useful laboratory tests. ADLM’s Academy and Science and Practice Core Committee have developed a test utilization resource focusing on commonly misused tests in hospitals and clinics. Improper test utilization can result in poor patient outcomes and waste in the healthcare system. This important resource geared toward medical professionals recommends better tests and diagnostic practices. Always consult your laboratory director to make sure these recommendations are appropriate for your patient population.