A group of diabetes professionals is proposing a change from the term prediabetes to the use of a three-stage classification of type 2 diabetes (T2D), with the aim of promoting earlier treatment and risk reduction.

“When is it too early to start to intervene in the process of diabetes?” said Moshe Phillip, MD, director of the Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children’s Medical Center, Petah Tikva, Israel, co-author of a comment paper on the topic published earlier this year in the Lancet Diabetes & Endocrinology.

One of the mistakes that “we as a community have done in the past” is to label people as having prediabetes “because ‘prediabetes’ means that you are healthy,” he told Medscape Medical News.

Actually, many of those that are defined as having prediabetes have a higher risk for all complications, mainly cardiovascular, he explained.

Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are both labeled as prediabetes and have long been linked to increased risks for cardiovascular diseases, chronic kidney disease, early-onset dementia, and certain cancers, Phillip and his colleagues noted.

Yet there is no drug approval process for prediabetes, despite the evidence that agents such as metformin, pioglitazone, and GLP-1 drugs can prevent progression to T2D and reduce cardiovascular risk.

Proposed Three-Stage Classification

The proposed staging, outlined briefly in the comment paper, would be the following: 

Stage 1: A gradual increase in fasting plasma glucose but within currently defined normal range (ie, < 100 mg/dL or < 5.6 mmol/L).

Stage 2: Glucose concentrations above normal but lower than currently defined T2D (ie, IFG, impaired 1- or 2-hour oral glucose tolerance test, or A1c 5.7%-6.4% [39-46 mmol/mol]). Stages 2a and 2b further define “slow” vs “fast” progressors.

Stage 3: Overt T2D, where stage 3a can be managed initially with noninsulin therapies.

The effort is led by members of the Time in Range Coalition, a project of the diaTribe Foundation with industry support. An official international consensus statement is in the works, and the hope is that multiple professional societies will sign on, co-author Tadej Battelino, MD, head of the Department of Endocrinology at UCH-UMC Ljubljana, and chair and professor of pediatrics at the University of Ljubljana, Ljubljana, Slovenia, told Medscape medical News.

“What we really want to do is to make stage 1 and stage 2 [T2D] a disease, which means you can treat it,” said Battelino.

It would become a diagnosis and have indications with the FDA, and treatment could be reimbursable even in stage 1, “which could make a huge impact on the outcomes,” he added.

The effort would be akin to the staging that has already been established for preclinical and clinical type 1 diabetes (T1D), as well as the establishment of hypertension stages 1-4 and removal of the “mild hypertension” and “prehypertension” terms by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC) in 2017, the authors wrote in the comment.

The consensus statement could be out by the end of the year, Battelino said.

History of Prediabetes

M. Sue Kirkman, MD, who served as senior vice president of medical affairs and community information for the American Diabetes Association (ADA) in 2007-2012, told Medscape Medical News that the term “pre-diabetes” (with a hyphen) dates back to 1979, from the National Diabetes Data Group, to describe IGT, and became more common in the early 2000’s as a term describing both IGT and IFG.

In 2009, the ADA and the European Association for the Study of Diabetes convened an expert panel to suggest A1c cut-points for the diagnosis of diabetes. While some suggested dropping the intermediate terms, a subsequent American panel led by ADA decided to keep them.

“Part of the push to keep the term prediabetes was that people thought the concept of continuous graded risk, although scientifically valid, was difficult to convey and might not spur clinicians or people at risk for type 2 diabetes,” said Kirkman, who was also professor of medicine at The University of North Carolina at Chapel Hill, and is now retired.

Confusing for Clinicians?

Regarding the new proposed T2D staging, Kirkman said that the idea is “interesting,” but that she has some concerns.

For instance, while the JNC changes were meant to spur change in hypertension treatment “I’m not aware that the frequent changes made by the JNC have changed levels of blood pressure control significantly. In fact, I think it’s been very confusing for clinicians.”

Kirkman questioned whether telling people they have stage 2 T2D and that they need to prevent progression to stage 3 will have a greater impact than telling them they have prediabetes and need to do things to delay or prevent T2D. “People seem to understand prediabetes, but will they understand stages of diabetes?”

She also noted that in contrast to the stages of T1D, “people with stage 1 T1D are virtually certain to develop clinical T1D, whereas in the proposed schema most people with stage 1 T2D will actually be at very low risk of progressing to clinical T2D, as will many with stage 2, or with prediabetes.”

Phillip reported serving as advisory board member of AstraZeneca, Eli Lilly, MannKind, Medtronic Diabetes, Pfizer, Sanofi, DOMPE, LifeScan, Novo Nordisk, Insulet, Provention Bio, Merck, Ascensia, Bayer, Embecta, and Tandem. He reported receiving consulting fee from: QuLab Medical, Provention Bio. The institute he heads received research grants from: Eli Lilly, Medtronic Diabetes, Novo Nordisk, Pfizer, Sanofi, DreaMed Diabetes, NG Solutions, DOMPE, Lumos, GWAVE, OPKO, Provention Bio, AstraZeneca. He reported being the stock owner for DreaMed Diabetes and NG Solutions. Battelino reported receiving research grants (paid to his institution) from Abbott, Medtronic, Novo Nordisk, Sanofi, Novartis, Sandoz, and Zealand Pharma. Kirkman reported having no disclosures.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X @MiriamETucker and BlueSky @miriametucker.bsky.social.