Prediabetes diagnosis poor predictor of disease progression for older adults
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Older adults with an HbA1c in the prediabetes range were far more likely to revert to normoglycemia or die during 5-year follow-up than to progress to overt type 2 diabetes, according to a community-based study.
The findings suggest that prediabetes may not be a “robust diagnostic entity in older age,” the researchers wrote in a study published in JAMA Internal Medicine.
“Prediabetes is defined by elevated blood glucose levels below the threshold for diabetes diagnosis,” Mary R. Rooney, PhD, MPH, a postdoctoral fellow at Johns Hopkins University Bloomberg School of Public Health, told Healio. “Physicians screen for prediabetes to identify patients at high risk for diabetes. While we knew that a mildly elevated glucose or HbA1c is a common finding in older patients, whether these patients are more likely to progress to diabetes has been an unresolved question.”
Disease incidence low
Rooney and colleagues analyzed data from 3,412 older adults without diabetes at baseline participating in the Atherosclerosis Risk in Communities (ARIC) study (baseline, 2011-2013; mean age, 76 years; 60% women; 17% Black).
Participants were contacted semiannually through December 2017, and attended a follow-up visit between 2016 and 2017; median follow-up was 5 years.
Researchers defined prediabetes as an HbA1c between 5.7% and 6.4%, an impaired fasting glucose level between 100 mg/dL and 125 mg/dL, or both.
Primary outcome was incident total diabetes, defined as a physician diagnosis, glucose-lowering medication use, an HbA1c of at least 6.5% or a fasting glucose of at least 126 mg/dL.
At baseline, 1,490 participants (44%) had HbA1c levels ranging from 5.7% to 6.4%, 1,996 (59%) had IFG, 2,482 (73%) met the HbA1c or IFG criteria for prediabetes, and 1,004 (29%) met both the HbA1c and IFG criteria.
Within the cohort, 2,497 participants attended the follow-up visit or died. During follow-up, researchers observed 156 incident total diabetes cases (118 physician diagnosed) and 434 deaths.
Among participants with baseline HbA1c levels of 5.7% to 6.4%, 97 (9%) progressed to type 2 diabetes, 148 (13%) regressed to normoglycemia and 207 (19%) died. Among those with IFG at baseline, 112 (8%) progressed to type 2 diabetes, 647 (44%) regressed to normoglycemia and 236 (16%) died.
Among participants with a baseline HbA1c level that was less than 5.7%, 239 (17%) progressed to an HbA1c in the prediabetes range and 41 (3%) developed type 2 diabetes. Of those with baseline fasting glucose levels less than 100 mg/dL, 80 (8%) progressed to IFG and 26 (3%) developed type 2 diabetes.
“Indeed, in older adults with prediabetes, regression to normoglycemia or death was more common than progression to diabetes during the study period,” the researchers wrote.
An ‘optimal’ prediabetes definition
Depending on the definition, the prevalence of prediabetes in the study ranged from 29% to 73%, the researchers noted. In secondary analyses, prediabetes prevalence based on international criteria was lower, at 15%, based on the international expert committee criterion of an HbA1c level range of 6% to 6.4%, and 23% based on WHO criteria of fasting glucose levels of 110 mg/dL to 126 mg/dL.
“The various definitions and wide range in prevalence estimates pose challenges for understanding the burden of prediabetes in the population and its clinical and public health relevance,” the researchers wrote. “The different definitions of prediabetes also have differing performance for assessing future diabetes.”
The researchers found that specificity was highest for prediabetes based on a confirmatory definition — both HbA1c levels of 5.7% to 6.4% and IFG — but specificity was lowest when based on either HbA1c levels of 5.7% to 6.4% or IFG.
“Conversely, sensitivity for the association with total or diagnosed diabetes was highest for prediabetes based on HbA1c levels of 5.7% to 6.4% or IFG and lowest for the confirmatory definition,” the researchers wrote. “The more stringent international definitions for prediabetes had higher specificity for the association with both diabetes outcomes, but sensitivity was lower. These differences in diagnostic performance have implications for screening strategies for diabetes.”
Rooney said that a prediabetes diagnosis for an older adult still presents an opportunity for lifestyle changes.
“However, in older adults, as we found, an HbA1c in the prediabetes range may not be a robust predictor of progression to diabetes,” Rooney said. “This common lab finding can still present an opportunity to encourage lifestyle improvements, including exercise and diet, when feasible and safe. This approach has broad benefits for patients.”
For more information:
Mary R. Rooney, PhD, MPH, can be reached at mroone12@jhu.edu.
Perspective
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Kevin M. Pantalone, DO, ECNU, FACE
It is estimated that about 35% of the U.S. population has prediabetes, also commonly referred to as “increased risk for type 2 diabetes.” It is important to note that the prevalence of prediabetes reported in the literature varies depending on the test being used — HbA1c, fasting glucose, oral glucose tolerance test, or a combination of the three — and the diagnostic accuracy of the current tests used to detect prediabetes in screening programs have been reported to be rather low.
Rooney and colleagues conducted a community-based cohort study of older adults with a mean age of 75 years and found that the prevalence of prediabetes was high; however, during follow-up, regression to normoglycemia or death was more frequent than progression to diabetes. The authors conclude that given the low rates of progression to diabetes, prediabetes may not be a robust diagnostic entity in older age.
However, it is important to note that prediabetes, like type 2 diabetes, is a spectrum disorder. The risk for progression is influenced by other factors beyond age. The report did not mention or adjust for a family history of diabetes, BMI, changes in weight, medication use, such as metformin, or comorbidity burden. These are important variables to consider when risk stratifying patients to determine who may progress, who may require subsequent evaluation, and the frequency at which reassessments should occur. Many older patients with complex comorbidities may unintentionally lose weight, and that is often a sign of underlying illness. Such weight loss could be a significant confounder that may be, in part, influencing — or reducing — the risk for progression from prediabetes to overt diabetes in this older population. Further studies are certainly warranted on this topic.
Lastly, it is important to recognize that many patients with prediabetes also have overweight or obesity, which if recognized, formally diagnosed and addressed through lifestyle intervention with or without medication, may reduce their risk for progressing to overt diabetes, as noted in the Diabetes Prevention Program.
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