'Prediabetes' Unlikely to Progress to Diabetes in Older Adults

Miriam E. Tucker

February 09, 2021

Older adults with "prediabetes" are more likely to revert to normoglycemia or die than to progress to diabetes, new data suggest.

Findings from more than 3000 participants in the Atherosclerosis Risk in Communities (ARIC) study were published online February 8 in JAMA Internal Medicine by Mary R. Rooney, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, and colleagues.

Among participants aged 71-90 years with "prediabetes" — defined as A1c 5.7%-6.4% or fasting glucose 100-125 mg/dL (impaired fasting glucose, IFG)— less than 10% progressed to diabetes over 6.5 years of follow-up. In contrast, death, reversion to normal blood glucose levels, and remaining unchanged were all more common.

"Our results suggest that for older adults with blood sugar levels in the prediabetes range, few will actually develop diabetes," says the study's senior author Elizabeth Selvin, PhD, also at the Bloomberg School of Public Health, in a press release from her institution.

"Given the low risk of diabetes progression in this study (especially relative to mortality risk), it is unlikely that pharmacologic intervention or other aggressive approaches to diabetes prevention in older age will provide large benefits and could have unintended harmful effects, [such as] overdiagnosis, anxiety, and implications for insurance coverage," the authors say in their article.

Selvin adds: "The category of prediabetes doesn't seem to be helping us identify high-risk people. Doctors instead should focus on healthy lifestyle changes and important disease risk factors such as smoking, high blood pressure, and high cholesterol."

Screening for Diabetes in Older Adults Is Futile

Moreover, Rooney and colleagues note that the findings call into question guidelines by the American Diabetes Association for annual diabetes screening in adults who meet "prediabetes" criteria and recommendations from the Endocrine Society for oral glucose tolerance testing in older adults with prediabetes because it wouldn't change treatment.

"The current study further highlights the potential futility of aggressive diabetes screening in older adults given the very low rates of diabetes progression among those with prediabetes," the authors write.

Asked to comment, Rozalina G. McCoy, MD, an endocrinologist and primary care physician at the Mayo Clinic, Rochester, Minnesota, told Medscape Medical News that the conclusions of Rooney and coauthors make "a lot of sense. Mild hyperglycemia is a disease of aging. We're recognizing that hormone levels change with age. Human bodies change with age."

"I think it would go a long way toward preventing over-treatment if we don't obsess about mild elevations in blood glucose levels that don't cause any long-term harm to people," she added.

"Prediabetes A Risk Factor Twice Removed"

In an accompanying editorial, geriatricians Kenneth Lam, MD and Sei J. Lee, MD, of the University of California, San Francisco, and the San Francisco Veterans Affairs Health Care System, say that the clinical messages from these data differ depending on whether the individuals in question have frailty and limited life expectancy or are older than 75 but otherwise healthy.

For the former group, Lam and Lee say that "prediabetes is irrelevant and can safely be ignored. 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."

And even for the majority of the healthier elder group, Lam and Lee say prediabetes isn't a priority.

They describe it as a "risk factor twice removed," given that modern-day treated [type 2] diabetes can be viewed as an asymptomatic risk factor for end-organ vascular complications, rather than an illness unto itself that patients experience.

Therefore, they say, prediabetes "should be lower priority than symptomatic conditions...or traditional risk factors...Diagnosing prediabetes and then expending time and effort discussing management strategies should not come at the expense of attending to other issues of immediate importance to the patient."

Normoglycemia, Death Both More Common Than Diabetes

The study involved 3412 individuals without diabetes at baseline for this analysis of the ARIC data during 2011-2013, at which point participants were aged 71-90 years. Prediabetes was present in 44% when defined by an A1c of 5.7%-6.4%, and in 59% by IFG. Nearly a third (29%) met both criteria.

Participants were evaluated again during 2016-2017. Among those who had prediabetes by A1c at baseline, 59% had no change in status, 19% had died, and 13% regressed to normoglycemia, whereas just 9% had progressed to diabetes. There were no differences in progression by age or sex, but older Blacks were more likely than Whites to progress to diabetes (11% vs 8%; P = .04).

Among those with prediabetes defined by IFG, 44% regressed to normoglycemia, 32% had no change in status, 16% died, and 8% progressed to diabetes. Again, Black adults were more likely to progress than Whites (11% vs 7%; P = .004), but there were no differences by age or sex.

As expected, progression to diabetes during follow-up was even lower among those with normoglycemia (A1c < 5.7% or fasting glucose < 100 mg/dL) at baseline. When assessed by A1c levels, 17% progressed to prediabetes, 16% died, and just 3% developed diabetes. By fasting glucose, 8% progressed to IFG, 19% died, and 3% developed diabetes.

Should Diabetes Diagnostic Thresholds in Elderly Be Re-examined?

In their editorial, Lam and Lee make the further point that if diagnostic thresholds for prediabetes developed in middle-aged adults are less applicable to older adults, then perhaps the cut-offs for diabetes should also be re-evaluated for appropriateness in older adults, given that a large proportion with only mild diabetes might revert to prediabetes or even normoglycemia.

"Additional studies are needed to determine whether newly diagnosed mild diabetes in older adults leads to adverse outcomes if left untreated. If it does not, shifting the cut-offs for diagnosing diabetes in older adults would help us focus treatment on those older adults for whom diabetes is likely to result in symptomatic end-organ damage, while avoiding identifying many older adults for whom diabetes is unlikely to cause harm," the editorialists say.

Ultimately, they advise, "To ensure high-value care for older adults, we should focus our care and research on what matters most to older adults and deprioritize twice-removed risk factors, such as prediabetes."

The ARIC study is funded by the National Heart, Lung, and Blood Institute. Lee has reported receiving grants from the US Department of Veterans Affairs Health Services and the National Institute on Aging. McCoy has reported receiving funding from the National Institute of Diabetes, Digestive, and Kidney Diseases.

JAMA Intern Med. Published online February 8, 2021. Abstract, Editorial

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