analysis of insulinBefore I address the issue raised in the title of this post, I want to highlight the indispensability of the use of insulin for treatment of type 1 and type 2 diabetes for the last nine decades.

Insulin, extracted from pancreatic beta cells, was first used successfully to treat a dying diabetes patient, 14-year-old Leonard Thompson, in 1922 at the Toronto General Hospital in Canada. Today, one million people in the United Kingdom alone are kept alive with daily insulin injections. Perhaps more than any other drug, insulin has allowed people to control a disease and live normal, full-term lives, where previously early death was a certainty.

Nonetheless, every 7 seconds someone dies of diabetes, and globally 1 in 12 suffer from diabetes, with North America having the highest prevalence among the populous countries. In the U.S., 1 in 9 have the disease. And, alarmingly, several Pacific island nations and countries in the Middle East now have diabetes prevalence higher than 25%! With so many patients, it’s probably no surprise that the global insulin market now exceeds $25 Billion.

Check out this fascinating 1.29-min animation on diabetes.

 

 

What About Too Much Insulin?

Insulin saves lives, but unfortunately excessive insulin administration can also cause death through spontaneous hypoglycaemia, often resulting in neurological injury, coma or death. Thankfully, surreptitious or malicious exogenous insulin administration is rare, but should be considered in patients with unexplained hypoglycaemia and access to diabetes drugs. Furthermore, it is critical that tests to identify these incidents are effective.

Knowing the exact quantity of endogenous insulin (produced in the body) and exogenous insulin analogs (injected into the body) in a patient’s system is critical in making correct diagnoses. Insulin analogs have been developed using cells from other species, or have been engineered genetically or modified chemically to change the pharmacokinetic properties of the drug, for example, long-lasting insulin analogs may have additional chemical chains bonded to the insulin to reduce drug metabolism.

There are a huge range of insulins and insulin analogs on the market, derived from various species’ cells, with different speeds of effect and dose requirements. Basal and bolus insulin dosing uses various short and long-lasting insulin analogs at different times of day. When testing for insulin, it is important to be able to test for all types of administered insulin analog products in the system too. After all, a drug lethal in moderately high doses and undetectable in conventional lab tests would be a perfect poison.

 

“The dose makes the poison.” Paracelsus

 

There are a range of established clinical tests for insulin and analogs in serum in the UK. Most are based on immunometric methods. Immunoassays are highly specific tests based on antibody binding. Consequently, immunoassay tests developed to recognize endogenous human insulin, may not necessarily recognize commercial insulin analogs administered for treatment of diabetes.

The current tests in use may not be cross-reactive (able to detect a range of insulin analogs). Consequently, the insulin tests used in many clinical laboratories could effectively be blind to commercial diabetes medicines and unable to accurately quantify the total insulin analog dose.

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Do Conventional Clinical Tests Work for Insulin Analogs?

Recent work from Parfitt et al. analyzed 15 insulins and insulin analogs with 9 commercial immunometric clinical assays available in the UK, to evaluate the degree of cross-reactivity of the commercial drugs available with the insulin assays used in hospital laboratories.

Additionally, Parfitt et al. used a new and alternative method to analyze the insulin products: our Mass Spectrometric Immunoassay Thermo Scientific MSIA (pronounced mee-sah, in case you were wondering) which is a hybrid bio-analytical workflow based on micro-affinity capture combined with mass spectrometric detection. By utilizing high resolution accurate mass spectrometry for detection within MSIA, a solution is created in which insulin analogs can be selectively identified and quantified together with endogenous insulin in the donor’s samples.

Watch this 3-min video for more details on the MSIA technology.

 

 

Parfitt found that:

  • None of the nine clinical immunoassay insulin tests were effective for all of the commercial insulin and insulin-related products.
  • Some insulin products could not be effectively quantified by any of the common clinical immunoassay tests evaluated.
  • Only MSIA was able to detect and identify all of the commercial insulin analogs tested along with endogenous insulin.

The MSIA technology shows promise as a new and comprehensive test for insulin analogs and Parfitt goes on to advise:

“Clinical laboratories need to be aware of the limitations of the local assay and where possible, samples should be referred to specialist centres for insulin level confirmation if surreptitious insulin administration is suspected, which ideally should be carried out using a validated and fully-quantitative mass spectrometry-based method.”

 

Additional Resources

To find out more about how MSIA technology can be used to accurately quantify proteins in complex matrices visit our Biologics Quantitation website.

Also, do check out our Pharma & Biopharma Community which is a wonderful resource, totally dedicated to the development and production of tomorrow’s medicines. It features the latest on-demand webinars, videos, application notes, and more.

 

Are you looking for applications on the analysis of proteins biomarkers, therapeutic antibodies, antibody drug conjugate (ADC), and/or drug antibody ratio (DAR)? Tell us in the comments section; we look forward to hearing from you!