After 4 years of work, the Association for Diagnostics & Laboratory Medicine (ADLM, formerly AACC), in collaboration with the American Diabetes Association, released an update to their evidence-based guidelines and recommendations to diagnose and manage patients with diabetes using the most recent laboratory analysis tools (Clin Chem 2023;69:777-84).
The guidelines replace previous versions published in 2002 and 2011. To prepare this update, an expert committee comprising five clinicians, three clinical laboratorians, and one chemist painstakingly pored over the medical literature to rate the quality of the evidence (high, moderate, low, or very low) and grade the strength of the studies’ recommendations, from an A grade (strongly recommend for or against adoption of a particular practice or technique) to a C grade (insufficient information to make a recommendation). The guidance also includes a number of good practice points—recommendations mostly driven by expert consensus or widely accepted standards of best practice—as well as information about emerging considerations and knowledge gaps or research needs in the areas covered.
As the document authors write, the guidance addresses numerous “practical aspects of care to assist decisions related to the use or interpretation of laboratory tests while screening, diagnosing, or monitoring for diabetes,” including use of glucose and glucose meters, and diagnosis and management of gestational diabetes. The document aslo addresses the potential roles of noninvasive glucose monitoring, genetic testing and measurement of ketones, autoantibodies, urine albumin, insulin, proinsulin, and C-peptide.
KEEPING UP WITH A RAPIDLY EVOLVING FIELD
Overall, the number of recommendations has increased over the previous guidance released in 2011 because there is substantially more evidence now, said lead author David Sacks, MBChB, FRCPath, senior investigator and chief of clinical chemistry at the National Institutes of Health Clinical Center. In fact, the guidance contains more than 80 recommendations.
There are a few areas that have changed significantly, Sacks said. The most progress noted in the document has been in the area of continuous glucose monitors (CGM), devices that measure interstitial glucose, which correlates highly with blood glucose, every 5−15 minutes. CGMs—which consist of a glucose sensor placed under the skin, a transmitter worn on the skin, and a receiver for the data such as a smart watch—also inform users of trends in blood glucose over several hours and alert them to current or impending high or low glucose.
“The number of recommendations in this field has doubled because there’s so much more evidence to support the use of continuous glucose monitors and show that they are very effective in many patients with type 1 diabetes. They are being used much more widely now,” Sacks said.
The guidance strongly recommends that real-time CGM be used in conjunction with insulin to lower HbA1c levels and/or reduce hypoglycemia in teens and adults with type 1 diabetes who are not meeting glycemic targets or have hypoglycemia unawareness and/or episodes of hypoglycemia. An associated good practice point suggests that for individuals using CGMs that require calibration, a blood glucose meter should be used to calibrate the device, and that calibration should be done during a time when glucose is not rising or falling rapidly. Another says that CGM data reports should be available in consistent formats that include standard metrics such as time in range versus in hyperglycemia or hypoglycemia.
In another new point, the authors recommend that to minimize glycolysis, healthcare workers use blood-collection tubes that contain a rapidly effective glycolytic inhibitor such as a citrate buffer for collecting blood glucose samples.
Unfortunately, Sacks said, these types of tubes are not available in the United States. “We are trying with this recommendation to encourage manufacturers to make these available in the U.S. because the evidence clearly shows they are much more effective than any other way,” he said.
Historically, sodium fluoride has been used to minimize glycolysis, but the process still can continue for up to 4 hours in test tubes. An alternative method recommended by the guidance to minimize glucose breakdown is to immediately place the sample tubes in an ice-water slurry and subject them to centrifugation within 30 minutes to remove cells. “This approach is very difficult in routine clinical practice,” Sacks acknowledged.
Two important updates have been added to recommendations regarding gestational diabetes, Sacks said. First, all pregnant women with risk factors for diabetes should be tested for undiagnosed prediabetes and diabetes during their first prenatal visit using standard diagnostic criteria. Typically, pregnant women are not screened for gestational diabetes until 24 weeks’ gestation. This recommendation could allow for earlier treatment to prevent deleterious effects to the woman and fetus, Sacks said.
Women who have gestational diabetes are at higher risk of developing type 2 diabetes years later, he said. As such, the guidance recommends that after delivery, women who had gestational diabetes receive lifelong screening for diabetes, at least every 3 years.
NONINVASIVE GLUCOSE MEASUREMENTS NOT READY FOR PRIMETIME
Some recommendations advise against testing and indicate areas in which there is a lack of evidence for use of tests. One is handheld glucose meters for patients with diabetes who do not use insulin. The recommendation is that they should not do any self-monitoring of glucose with fingersticks because the evidence doesn’t support it.
Another area the guidance does not recommend at this time is noninvasive glucose measurements. The guidance states these systems cannot be recommended as replacements either for blood glucose meters or CGM technologies. Noninvasive systems are designed to measure blood glucose concentration in a painless manner that avoids puncturing the skin and they have gotten a lot of hype. To date, however, none have been approved by the Food and Drug Administration for clinical use in the United States, said guideline coauthor Mark Arnold, PhD, the Edwin B. Green chair professor in laser chemistry and director of the Center for Biocatalysis and Bioprocessing at the University of Iowa, who worked on this section.
“A lot of people think that the technology is right there, like it’s going to come out next year when in fact, it’s not,” Arnold said. “I think that’s important for the clinicians, who are going to give this information to patients, to put in perspective.”
There are two approaches to noninasive measurements, he said: noninvasive fluid sampling and spectroscopy. Considerable attention has been given to noninvasive glucose measurements in tear fluid, in particular from a type of contact lens researched by Google that contained an electrochemical sensor to measure glucose. Ultimately it was determined that the concentration of glucose could be measured in tear fluid but didn’t correlate well to glucose in the blood, so the project was dropped. Some scientists have now been looking at the potential of glucose measurements from saliva, although Arnold said he expects the results to be similar.
“It’s really easy in this day and age to lock in on something that you want to be true, but it doesn’t necessarily mean that it’s going to be true,” he said. With that said, Arnold added that there have been some advances in the use of Raman and near infrared spectroscopy for noninvasive glucose measurements since this portion of the guidance was written. “The promise is there; we just don’t want to hype it.”
OTHER RECOMMENDATIONS ON TESTING FOR DIABETES
In other areas of note, the guidance:
- Supports measuring fasting glucose in venous plasma to establish the diagnosis of diabetes, with a value of >7.0 mmol/L (>126 mg/dL) diagnostic of diabetes.
- States that frequent self-monitoring of blood glucose is recommended for all insulin-treated patients with diabetes who use intensive insulin regimens (with multiple daily injections or insulin pump therapy) and who are not using CGMs.
- Gives a very high recommendation that annual testing for albuminuria should begin in pubertal or postpubertal individuals 5 years after the diagnosis of type 1 diabetes and at the time of diagnosis of type 2 diabetes, regardless of treatment.
- States urine albumin should be measured annually in adults with diabetes using morning spot urine albumin to creatinine ratio.
- Notes that there is no published evidence to support the use of insulin antibody testing for routine care of patients with diabetes.
The guidance already has generated a lot of interest, Sacks said. During a meeting of the Clinical Chemistry editorial board at the 2023 AACC Annual Scientific Meeting, the editor shared metrics demonstrating that within just a few days of the guidance’s release, it already had been mentioned by more than 75 news outlets and was generating a lot of interest on social media. Sacks later heard from a laboratory professional who had shared the guidance with a clinician who said he was going to use it in teaching trainees.
“Clearly, people are aware of it and seem very receptive,” he said. “Four years of hard work, I think, is paying dividends.”
Karen Blum is a freelance medical/science writer in Owings Mills, Maryland. +EMAIL: [email protected]