Monday, August 12, 2019

Is "prediabetes" a useful term?

- Jennifer Middleton, MD, MPH

The ADA's goal in defining prediabetes,"blood glucose levels that are higher than normal but not yet high enough to be diagnosed as diabetes," is to identify those persons who would benefit from interventions to reduce their risk of developing type 2 diabetes. While reducing the incidence of type 2 diabetes is a laudable goal, the term "prediabetes" may be problematic; a 2017 meta-analysis found that "[a]s screening is inaccurate, many people will [receive] an incorrect diagnosis and be referred on for interventions while others will be falsely reassured and not offered the intervention." The imprecise label of "prediabetes" may be hampering efforts to identify effective interventions to delay or prevent the onset of type 2 diabetes.

A pair of editorials in the current issue of AFP explore the controversy surrounding metformin prescribing in persons determined to have prediabetes. Dr. Lin reviews these editorials and their evidence base in a recent tweetorial; in summary, asserting that metformin is beneficial in prediabetes, Dr. Tannaz Moin cites the Diabetes Prevention Program (DPP) which found that, in obese persons with prediabetes, metformin delayed onset of type 2 diabetes over three years (number needed to treat = 14). Dr. Moin advocates, however, for considering more than just a prediabetes test result when considering metformin treatment: "higher A1C (i.e., 6.0% to 6.4%), but also other important risk factors, such as family history of diabetes, higher fasting plasma glucose levels, and higher triglyceride levels, may predict greater risk of progression to diabetes." 

Arguing against the use of metformin is Dr. Steven Brown, who describes his concern with using prediabetes as an impetus to prescribe medication. He cites the above-mentioned 2017 meta-analysis' findings that, "[c]ompared with the reference standard of an oral glucose tolerance test, a single A1C measurement is 49% sensitive and 79% specific for prediabetes." He interprets the DPP findings differently:
 At four years, the average A1C was 5.9% in the metformin or lifestyle groups and 6.1% in the placebo group. Although these surrogate outcome differences are statistically significant, they are not clinically meaningful. Treating borderline glucose values does not improve quality of life, mortality, or any other patient-oriented outcomes.
It's quite possible that the DPP's findings were less significant because of the inherent imprecision in the "prediabetes" label. As Dr. Lin wrote in an earlier post on the Community Blog, "the term prediabetes is misleading: many of these patients will not develop diabetes." A more precise risk elucidation may be found in that same 2017 meta-analysis, where "those most at risk of developing diabetes had both impaired fasting glucose and impaired glucose tolerance." 

A reasonable middle ground may be to consider glucose readings between the ranges of normal and diabetic as just one risk factor among many for developing type 2 diabetes. There's an AFP By Topic on Diabetes: Type 2 if you'd like to read more about diabetes screening and diagnosis, and there's an AFP Department Collection with more Controversies in Family Medicine with more pro/con editorial pairs, too.