With an aging and increasingly overweight population, the number of diabetic patients is expected to rise by 1.5 million new cases per year. While this may be a sobering statistic, the good news is that testing for, monitoring, and controlling diabetes continues to become more robust, cost-effective, and nuanced.
By Chris Wolski
The numbers don’t lie, approximately 10% of the adult U.S. population or 34.2 million people have diabetes and 88 million are in the pre-diabetic range1.
And with an aging and increasingly overweight population, these numbers are expected to rise by 1.5 million new cases per year1. And while these may be sobering statistics, the good news is that testing for, monitoring, and controlling diabetes continues to become more robust, cost-effective, and nuanced.
But is there more that can be done and what does the future of diabetes testing in the U.S. look like? CLP put these questions to several industry experts, and they provided insights into these and other issues affecting diabetes testing and monitoring. The upshot: Laboratory testing will continue to be needed and will continue to evolve to better meet patient needs.
Testing Today
Regular glucose testing is typically done either with finger sticks or continuous monitoring — often with the help of smartphone apps — giving patients a regular snapshot of how well they are controlling their glucose, preventing hypoglycemia, or other complications of the disease.
Testing patients’ glycated hemoglobin or HbA1C continues to be the gold standard in clinical settings to determine if they are diabetic or have well-controlled disease. For those who are either at normal or low risk for disease, monitoring A1C twice a year is typically sufficient, and those who need more stringent monitoring or have uncontrolled disease should be monitored up to four times per year, according to Dennis Begos, MD, FACS, FACRS, associate medical director for Medical and Scientific Affairs at Nova Biomedical.
“These tests all paint a picture of where the disease is at,” notes Heidi Cassaletto, senior vice president Portfolio Strategy and Global Marketing for Ortho Clinical Diagnostics.
And with more home testing products coming to market and most primary care physicians using A1C as their go-to testing control, it wouldn’t be a stretch to think that diabetes testing has reached a sort of end point; what we have now is enough.
However, while the experts agree that A1C and glucose testing are well established and can be effective, there’s other testing avenues that may offer better results.
“There’s always a desire to find other controls,” notes Gavin Jones, global product manager for Diabetes Care at EKF Diagnostics. “Glucose monitoring doesn’t always work best.”
A New Gold Standard?
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Thomas Lohmann, MD, director of Medical and Scientific affairs at Sebia, couldn’t agree more.
“We need to focus on other things than A1C,” he says. “There’s some instances in which A1C is not always accurate.”
That isn’t to say that A1C should be thrown out as a testing methodology. Lohmann’s point is more nuanced than making an either/or argument for or against A1C.
“It’s important to run A1C, but a method needs to be chosen that will take ‘silent’ issues into account,” he says. “Unfortunately, many labs choose from equipment available on a menu, pick one, and run it. It does make a difference the method you choose.”
Lohmann recommends laboratorians work closely with clinicians to choose the testing method best suited to the patient.
From Cassaletto’s perspective, while there’s some changes occurring in testing, the right balance has yet to be achieved. Certainly, early screening and monitoring has its benefits, but there is the balance between screening everyone and certain populations based on lifestyle, age, and weight.
“We definitely need to use better algorithms and risk factors,” she says.
For Lohmann, there needs to be more than a single datapoint — A1C — to make a determination whether a patient has diabetes.
Shane O’Neill, global director of Scientific Affairs at EKF, says that, for those patients who are tougher to monitor, glycated albumin (GA) could be the answer.
“It can be harder to monitor some diabetics with A1C who have issues or treatments that affect their red blood cells (RBC),” he says. “GA levels are not affected by the life span of RBC, it is a useful substitute for A1C when the interpretation of A1C is problematic, e.g., in the presence of hemoglobinopathies, iron deficiency, and anemias.”
That being said, he notes that A1C has a specific benefit
“The beauty of A1C is that it is standardized across manufacturers, and has been available for decades and has been the gold standard,” he says. However, one of the limitations of A1C is that it measures a two- to three-month period of a person’s life; in other words, it isn’t as immediate. Particularly for those diabetics with chronic kidney disease (CKD), it’s also not as accurate according to research published by the NCBI2.
This research points to glycated albumin as a more effective way to measure blood glucose control in patients with CKD. And with the number of people worldwide suffering from CKD, this could have significant advantages in monitoring and, more importantly, controlling disease progression.
O’Neill notes that one of the other advantages of measuring glycated albumin is that it fills the gap between at-home and in-lab glucose monitoring and yearly or twice yearly A1C measurements, giving a diagnostic window of the patient’s condition over two to three weeks. He predicts that, as with A1C, glycated albumin tests will eventually become standardized across manufacturers and widely used.
At-home glucose monitoring has been around for years, and has been a reliable method for patients to monitor and control their diabetes disease. However, Begos sees this longtime at-home gold standard needing some fundamental improvements.
“All self-monitoring glucose devices must go through the FDA approval process, verifying precision and accuracy with a reference laboratory method. However, over the years, strip-based devices — for home testing at least — have become a commodity and are being made with cheaper components with questionable durability and reliability,” he says. “There are well-known factors which interfere with glucose measurement by these devices, and, although these mainly play a role in measuring glucose in hospitalized patients, they could be a factor in home measurement. Meters that are used in the hospital can even have problems with these interferences.”
Will continuous glucose monitors (CGMs) solve some of these inference problems? For Begos, the jury’s still out.
“In terms of self-monitoring of patients with existing diabetes, CGM is becoming more affordable and there are more devices becoming available every year. This will likely make CGM an option for more and more people living with diabetes, but whether this will improve overall outcomes remains to be seen,” he says.
Achieving Quantity and Quality
While there may be changes and shifts and questions related to diabetes testing itself, at the fundamental level, laboratories may need to look at their operations to make sure that whatever tests they’re running related to diabetes are as accurate as possible.
The question that labs need to ask, according to John Yundt-Pacheco, MSCS, senior principal scientist at Bio-Rad, is how to keep potential harm from erroneous results to a low or acceptable level.
“If you can’t make sure you’re running a good test, you’re better off not testing,” he says.
What this will mean is that laboratories will need to shift their focus from the instrument to the patient. What he means by this is that quality has to be related to when the patient was tested, not whether the machine was accurate at a given time. In fact, Yundt-Pacheco says that the instrument focus only works if the quality control and the patient are tested at the same time.
“You really need to look at the frequency of the test and how many patients are being tested,” he says. “For example, if you run a quality control test every eight hours, but patients are tested in a three-hour cluster, you will have a much higher risk of publishing erroneous results before detecting them if there is a problem.”
While he’s advocating for a patient-centered testing approach, Yundt-Pacheco understands the continued instrument-focused quality control.
“Labs have gotten complacent, because the instruments and the tests are so much better than they used to be,” he says.
Yundt-Pacheco recommends that the way laboratory instruments should be controlled is with a fixed target. This way, drift can be better monitored and corrected. He also notes that labs should at the very least follow the CLIA-recommended two QC specimens per day protocol, but that may need to be increased based on volume.
“Knowing that the instrument was working at the time of the QC isn’t enough,” he says.
The focus of every lab should be managing the risk of patient harm from erroneous results, according to Yundt-Pacheco.
“When you start looking at severity of harm, the greater the severity of harm the less tolerance you have for it,” he says. “While no one wants to inconvenience patients, our tolerance for inconvenience is far greater than causing impairment. Our QC practices should reflect that.”
COVID-19 and Diabetes
Without a doubt, COVID-19 impacted medical services across the board, and diabetes diagnosis and monitoring is no exception.
However, the precise impact of the pandemic on diabetes testing and care is still up for debate.
“Since patient visits to their healthcare providers were dramatically cut back, or in many cases eliminated, screening for diabetes likely suffered greatly, although there is no hard data on this yet,” says Begos. “In addition, individuals were discouraged from going into hospitals or other healthcare settings, making laboratory testing for screening purposes, or for monitoring compliance greatly reduced. It seems likely, although it remains to be seen, that diabetes diagnoses will increase over the next few years because of the delay in screening, and it is also possible that complications from poorly controlled diabetes may rise as well.”
Echoing Begos, Casselletto says that stay-at-home orders may have contributed to patients being less active and having poorer diets, thus increasing both the onset of diabetes and poorer control. On the plus side, some patients were able to take advantage of telehealth services and provide tests to secondary labs.
While the effects of COVID on diabetes testing and monitoring have been a mixed bag, Casselletto has a more fundamental question: “In the longer term, the question is really when are people going to be able to get back to normal?”
What’s Next?
COVID pandemic has affected diabetes testing and monitoring, but ultimately it will likely be a short-term phenomenon. As COVID becomes an endemic disease with ongoing testing, better treatments, and longer-lasting vaccines, focus will be able to return to chronic diseases like diabetes and CKD.
Casselletto notes that the future does look bright for diabetic testing.
“There are several improvements on the horizon, including better testing sensitivity, faster turnaround times, and new biomarkers,” she says, adding that one of the biggest benefits will be getting diagnoses at an earlier stage in the patient’s disease.
This will be critical considering that obesity levels are not improving, and more young people are being diagnosed with diabetes. Caselletto also sees that some of the coming tests will be less invasive, and that screening protocols will improve.
Precision medicine has become a recurring theme for many diseases. Diabetes could be a prime candidate for more individualized testing. This will include a combination of looking at the individual’s genetic makeup and lifestyle.
“Precision medicine is a perfect way to treat and manage diabetes, because it is geared to the individual,” says Caselletto. “We’ll have a better understanding of the diabetes subtypes and better treatments and outcomes, instead of the trial-and-error approach we see today.”
Lohmann hopes that precision medicine will be able to impact diabetes diagnosis, noting that 8% of A1C tests are inaccurate.
The biggest weakness of testing today he says is that it’s designed to “chase a number” instead of focusing on the patient.
“We need to improve patients’ health instead of following an algorithm,” he says.
And even more to the point he notes that this fixation on A1C alone can be in some cases detrimental to patient health.
“In some cases, no result is better than a bad result, and relying on a test without questioning it,” he says.
For Begos, precision medicine could have a number of benefits for diabetic patients.
“Now that the human genome is decoded, there is a tremendous amount of research being done to use this for screening, diagnosing, and treating individuals for just about every imaginable disease. Diabetes is no exception, he says. “Identifying genetic abnormalities that predispose someone to develop diabetes or that cause diabetes are being identified and this will greatly improve screening. Additionally, it will likely become possible to insert an insulin-producing gene into a person with diabetes and cure them. A less glamorous way to deliver precision medicine to diabetics is with a combination of an insulin pump and CGM. Using artificial intelligence, the CGM can ‘talk’ to the insulin pump and the pump can deliver the appropriate dose of insulin without requiring involvement of the patient. This scenario is much closer to reality than gene therapy at this point and should be available in the coming years.”
Beyond testing methodologies, gold standards, and advanced diagnostic and treatment technologies, Begos brings up a larger societal issue related to diabetes testing that needs to be addressed: access.
“Screening can be a particular problem in low- and middle-income countries (LMIC), and in remote areas with poor access to laboratory testing, and point-of-care (POC) devices can be useful in these settings,” he says.
For him, one of the most exciting trends related to access is the availability of POC out-of-hospital tests that can allow untrained staff to run A1C and glucose tests, helping to give access to these tests and motivating those even with access to take and even seek out testing.
“People want convenience and instant gratification, and this gives them both,” Begos says. “These devices are small and affordable enough to also be placed in clinics and provider’s offices, making both screening and follow-up of diabetes easier and faster. With real-time data on HbA1C compliance can be monitored and appropriate guidance can be given. Additionally, devices such as these will be able to test for not only glucose and HbA1C, but cholesterol, creatinine, electrolytes, and other analytes. This will allow for screening of diabetic-related diseases and adjustment in medication dosages as appropriate.”
Taken together, there is no question that we haven’t seen the end of improvements of diabetes testing and monitoring. Only time will tell what the next chapter will be.
About the Author
Chris Wolski is chief editor of CLP.
REFERENCES
1. “Statistics About Diabetes.” American Diabetes Association.[ www.diabetes.org/resources/statistics/statistics-about-diabetes](http://www.diabetes.org/resources/statistics/statistics-about-diabetes). Accessed August 13, 2021.
2. “Glycated Albumin Versus HbA1c in the Evaluation of Glycemic Control in Patients With Diabetes and CKD.” Ting Gan, Xin Liu, and Gaosi Xu. National Center for Biotechnology Information (NCBI). Nov. 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976809. Accessed August 13, 2021.
