NEW YORK (360Dx) – A new mass spectrometry blood test from Quest Diagnostics aims to provide physicians with an easy tool for assessing insulin resistance as an early predictor of future diabetes.
The test, called the Cardio IQ Insulin Resistance Panel with Score, has been offered for about two months through Quest and is performed at Quest's Nichols Institute in San Juan Capistrano, California.
Measuring insulin resistance could enable physicians to identify a patient's progression toward diabetes before the emergence of other factors more commonly associated with pre-diabetes, according to Michael McPhaul, medical director for endocrinology and metabolism at Quest's Nichols Institute.
"There are quite a number of people who are significantly insulin resistant where all or part of those clinical or laboratory signals are missing, so this test actually allows one to identify those resistant patients before glycemia or hemoglobin A1c becomes abnormal," McPhaul said. "You can think of it as being able to diagnose insulin resistance before the period of time where pre-diabetes has emerged."
The development of the test grew out of an effort at Quest's Nichols Institute to codify and regiment assays to measure insulin and C-peptide. Tests for both of the hormones have had wide variations in results, according to McPhaul.
"Studies have demonstrated in some cases as much as ten- or twentyfold variation in levels using one commercial platform versus another when standardized pools have been distributed across the laboratory testing group," he said.
Quest's Nichols Institute, which has invested heavily in mass spectrometry and assembled a large internal team with mass spectrometry expertise, developed multiplexed measurements of C-peptide and insulin using a multiplex assay that measures both intact insulin and intact C-peptide by tandem mass spectrometry. The first description of the assay was published in Clinica Chimica Acta in April 2016 and in the Journal of Clinical Chemistry in July 2016.
The test established a method to standardize the measurement of insulin and C-peptide using tandem mass spectrometry so that results would not vary going forward, McPhaul said. Quest assigned values to results using the assay in accordance with American Diabetes Association insulin and C-peptide rules.
"It permitted something that had been impossible before this kind of standardization took place," McPhaul said. "When you look over time at epidemiologic studies, most times people do not talk about cut points in terms of concentrations, they talk about quartiles and quintiles simply because there has been so much variation among the results."
In September of this year, results of a 535-patient study conducted by Quest in conjunction with the Stanford University School of Medicine were published in the Journal of the Endocrine Society establishing the test as a clinically practical probability score for assessing insulin resistance in apparently healthy individuals.
Researchers at Stanford had measured insulin resistance in 1,072 patients between 1999 and 2011 using insulin suppression tests, a "gold-standard" method of measuring insulin resistance that is significantly complex, McPhaul noted.
The insulin suppression test process involves placing multiple intravenous lines and giving patients infusions of octreotide, insulin, and glucose. The insulin and glucose infusions are administered over a period of two and a half hours, and the test produces a result known as steady state plasma glucose, McPhaul said.
Quest performed its mass spectrometry insulin and C-peptide test on samples of the baseline fasting bloodwork taken immediately prior to the insulin suppression tests from patients in the Stanford study. Results of the Quest test were compared to results of the insulin suppression tests conducted by Stanford researchers. Quest excluded patients who were pregnant, already had diabetes, or had a history of insulin treatment or cardiovascular disease, or were older than 80 years of age or younger than 18, bringing its study size down to 535.
The study found that insulin and C-peptide were the most significant signals in predicting whether a patient was insulin resistant, and that both insulin and C-peptide were necessary in order to accurately score insulin resistance in patients.
"Where you see a depiction of the odds ratios for insulin, for C-peptide, and for insulin and C-peptide together, you see it is a great improvement in terms of ability to discriminate the insulin-resistant individuals when both are included," McPhaul said.
As a blood test, the Quest Cardio IQ Insulin Resistance Panel with Score is much simpler to administer to patients than the insulin suppression test performed in the Stanford study or other tests for insulin resistance that are considered accurate.
"That was part of the point of developing this. Basically we can provide a very good ability to assess insulin resistance with a single blood test, and give that information in the context of how it compared to a validated cohort in which [steady state plasma glucose] measurements were used to formally test insulin resistance," McPhaul said.
But the historic difficulty of performing insulin resistance testing may be a challenge in encouraging adoption of the new test as well. A spokeswoman for the National Institute Health's National Institute of Diabetes and Digestive and Kidney Disease noted that literature on the NIDDK website states that insulin resistance testing is rarely performed in clinical practice due to its complexity.
"Doctors use blood tests to find out if someone has prediabetes, but they don't usually test for insulin resistance. The most accurate test for insulin resistance is complicated and used mostly for research," the insulin resistance literature on the site states.
But McPhaul believes that there are some groups that do forms of insulin resistance testing in clinical practice, and that a barrier to using this testing has been lack of accessible tools.
"There are no tools that have been based on these types of gold-standard measures," he said.
Researchers involved in the Stanford study predicted several uses for the test.
"Because [insulin resistance] has been demonstrated to be an early predictor of future diabetes and other clinical syndromes, we believe that clinicians would find it useful to assess [insulin resistance] for three reasons," wrote Fahim Abbasi, senior research scientist and clinical assistant professor at Stanford University School of Medicine, who was first author on the Stanford study article.
The Quest test could help assess diabetes risk for patients who are not prediabetic, but have reasons to be concerned about diabetes risk, he suggested. In addition, it could identify patients with a high probability of insulin resistance who could benefit from preventative programs, and it could be used by physicians to monitor the success of patients on preventative programs by assessing how their insulin resistance level changes, he wrote.
McPhaul noted that there has been increased interest in recent years in efforts diagnose and treat diabetes earlier in its progression. He cited as an example the National Diabetes Prevention Program, developed by public and private health organizations in conjunction with the Centers for Disease Control and Prevention, which targets preventing or delaying progression to type 2 diabetes.
"The CDC has identified the fact that if you use medication and you use lifestyle interventions, you can significantly reduce the number of individuals who develop diabetes at four years following that intervention," he said.
The Quest Cardio IQ Insulin Resistance Panel with Score could potentially support those types of programs, McPhaul speculated.
"I do think it's interesting to consider that if you are able to identify those individuals who are responding to those interventions, where their insulin resistance scores are going down appropriately as they lose weight, as they exercise more, as they go through the program, and discriminated from those whose scores are not changing, it might be possible to actually improve the outcome of these type of programs," he said.