Study findings suggest that death or shift to normoglycemia from prediabetes appears to be more frequent than progression to full disease among older adults with prediabetes.

C linicians may want to consider skipping a prediabetes diagnosis in older, communitydwelling adults, as regression to normoglycemia or death was more frequent than progression to diabetes, according to the authors of a study published in JAMA Internal Medicine.

In a prospective cohort analysis of 3,412 older adults (mean age: 75.6) without diabetes, the prevalence of prediabetes was high, but during the 6.5-year follow-up period, less than 12% of older adults progressed from prediabetes to diabetes, regardless of the definition of prediabetes, according to Mary R. Rooney, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and co-authors. Specifically, 13% of study participants with A1C levels of 5.7% to 6.4% at baseline regressed to normoglycemia during follow-up, compared with 44% of those with baseline impaired fasting glucose (IFG) levels of 100-125 mg/dL.

Reserve Prediabetes Concept for Healthier, Middle-Aged Adults

“These findings suggest that prediabetes in older age may not be a robust diagnostic entity for predicting diabetes progression,” the study authors concluded. In an invited commentary accompanying the study, Kenneth Lam, MD, and Sei J. Lee, MD, MAS, both of the University of California San Francisco and the San Francisco Veterans Affairs Health Care System, agreed that “the concept of prediabetes may be of limited importance for older adults.” As a result, guidelines, such as those from the American Diabetes Association—which call for all patients with prediabetes to undergo annual monitoring and be referred to diabetes prevention programs—may need reconsideration when it comes to older adults, they noted.

Dr. Rooney’s group noted that guidelines from The Endocrine Society support older adults with A1C or IFG-defined prediabetes receiving more screening to avoid underdiagnosis of diabetes, but a separate study cast doubt on that recommendation, and for good reasons, according to Drs. Lam and Lee. “First, in older adults with frailty and limited life expectancy, prediabetes is irrelevant and can safely be ignored,” they stated. “Because the benefits of prediabetes management are most likely accrued 10 or more years in the future, older adults with frailty and limited life expectancy are unlikely to benefit from prediabetes management. Guidelines should clarify that prediabetes is a concept that should be reserved for healthier, middle-aged adults rather than older adults with frailty.” They also noted that “the modern definition of diabetes is conceptually closer to being a risk factor itself than an illness… Prediabetes, then, is a risk factor twice removed… In healthy adults older than 75 years… we should recognize that prediabetes, as a risk factor twice removed, should be lower priority than symptomatic conditions… or traditional risk factors.” Prediabetes diagnostic thresholds were developed for middle-aged adults, so whether they apply to older adults needs to be reassessed, Drs. Lam and Lee advised, adding that “for many older adults, new-onset diabetes will often be mild and asymptomatic and only one of many potentially life-threatening conditions.”

Dr. Rooney and co-authors concurred that “most prior studies on progression from prediabetes to diabetes were conducted in middle-aged populations,” and that “consensus is lacking regarding optimal prediabetes definitions, with five definitions in current clinical use.”

Participant & Outcome Details

Participants for the current study came from the cardiovascular ARIC trial and attended the fifth follow-up visit (2011-2013, baseline). Of those, 60% were female and 17% were Black. The researchers noted that the prevalence of A1Cdefined prediabetes was higher among Black participants versus White participants (60% vs 41%), higher among Black older adults versus White older adults (11% vs 8%,), and similar across sex (8% of men vs 9% of women).

Of the total study population at baseline, 2,497 attended the follow-up visit or died. During the follow-up period, there were 156 incident total diabetes cases (with 118 diagnosed) and 434 deaths. Among participants, 44% had A1C levels of 5.7% to 6.4%, 59% had IFG, 73% met the A1C or IFG criteria, and 29% met both. Among participants with A1C levels of 5.7% to 6.4% at baseline, only 9% progressed to diabetes, while 13% regressed to normoglycemia (A1C <5.7%) and 19% died. Of those with IFG at baseline, 8% progressed to diabetes, 44% regressed to normoglycemia (FG <100 mg/dL), and 16% died.

Among patients with baseline A1C levels lower than 5.7%, 17% progressed to A1C levels of 5.7% to 6.4% and 3% developed diabetes. In those with baseline FG levels less than 100 mg/dL, 8% progressed to IFG of 100-125 mg/dL and 3% developed diabetes.

Various Prediabetes Definitions & Other Limitations

The study team noted that “there are several definitions for prediabetes used in current clinical practice and no consensus on which definition is optimal”—at least based on the 2018 Cochrane meta-analysis—such as IFG5.6, IFG6.1, impaired glucose tolerance (IGT), oral GT test, combined IFG and IGT, and elevated A1C. Other viable definitions come from the International Expert Committee (A1C levels of 6.0% to 6.4%) and the World Health Organization (23% based on FG levels of 110-126 mg/dL). “Depending on the definition, the prevalence of prediabetes in our study ranged from 29% to 73%,” noted Dr. Rooney and colleagues. “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 different definitions of prediabetes also have differing performance for assessing future diabetes.”

Study limitations included the fact that 27% of ARIC participants who turned up for the baseline visit did not return for the follow-up visit. Also, a 2-hour glucose test was not done in ARIC, and all prediabetes results were reported to ARIC participants whose healthcare providers may have guided them toward lifestyle modifications at higher rates than other populations.

The authors note that The Diabetes Prevention Program trial “demonstrated that an intensive lifestyle intervention…reduced the risk of diabetes progression in high-risk adults 25 years or older at baseline…The findings of the current study support a focus on lifestyle improvement when feasible and safe, especially given the broader benefits of lifestyle modification beyond diabetes prevention.”