Normalization of BMI was associated with a lower risk for progression to clinical type 1 diabetes (T1D) among people with overweight or obesity and T1D-associated autoantibodies, new research found.

Data from the TrialNet Pathway to Prevention Study showed a 48% lower adjusted risk of clinical, or stage 3, T1D among participants, primarily youth, whose BMI normalized.

“What we can say is that people who lost weight had a lower risk of developing stage 3 type 1 diabetes and of progressing from stage 2 [multiple autoantibody positivity with dysglycemia but asymptomatic] to stage 3,” study author Maria J. Redondo, MD, PhD, a pediatric endocrinologist and professor of pediatrics at Baylor College of Medicine in Houston told Medscape Medical News.

“At this point, we have to be very cautious because this is an observational study, not a clinical trial. The only way we can prove causality is a prospective study where we try an intervention and see what happens,” she noted.

The study, published in Diabetes Care, was the first to examine the association between BMI reduction and progression to T1D among autoantibody-positive participants with overweight/obesity. However, extensive prior evidence had linked elevated BMI not only to progression to clinical T1D but also to the development of earlier disease stages and the onset of autoantibody positivity. Redondo’s team summarized that research in a separate review published in Diabetes Care earlier in 2026.

The current study addressed a different question, Redondo said: “It’s not whether BMI contributes to type 1 diabetes, but actually the opposite: When BMI normalizes, what happens?”

Does BMI Normalization Protect Against T1D?

TrialNet was established in 2000 with funding from the National Institutes of Health to identify people at risk for T1D and prevent disease progression. Pathway to Prevention, the prospective observational arm of TrialNet, followed individuals — mostly first-degree relatives of people with T1D — who screened positive for islet autoantibodies.

The current study included 833 Pathway to Prevention autoantibody-positive participants who had preclinical T1D and overweight or obesity at baseline.

During a median follow-up of 4.1 years, BMI declined to the normal range in 26.8% of participants. At baseline, participants whose BMI later normalized were significantly younger than those whose BMI remained elevated (17.1 vs 25.5 years; P < .001) and had lower BMI z scores (0.956 vs 1.585; P < .001).

The distribution of T1D stages also differed significantly between the groups (P = .038). Among participants whose BMI normalized vs remained elevated, 35.2% vs 33.9% had stage 0 disease (positive for a single autoantibody but normoglycemic), 49.5% vs 42.4% had stage 1 disease (positive for multiple autoantibodies but normoglycemic), and 15.3% vs 23.8% had stage 2 disease. The number of positive autoantibodies did not differ between the groups.

The cumulative incidence of stage 3 T1D was significantly lower among participants whose BMI normalized (hazard ratio [HR], 0.652; P = .022). The association persisted after adjustment for baseline age, BMI z score, and T1D stage at baseline (HR, 0.516; P < .001).

Because weight loss related to hyperglycemia often preceded a clinical T1D diagnosis, Redondo and colleagues also analyzed progression to stage 2 disease. BMI normalization remained associated with a lower risk for progression after adjustment (HR, 0.641; P = .003).

Associations Differed by Age and Sex

Analyses stratified by baseline age, BMI z score, and T1D stage showed that BMI normalization was significantly associated with a lower risk for progression to stage 3 disease among participants younger than 18 years (HR, 0.50; P = .004) but not among adults (P = .130).

Among children younger than 12 years, BMI normalization was significantly associated with a lower risk for T1D in boys (HR, 0.272; P < .001) but not girls (P = .870). Among adolescents, however, the association was significant in girls (HR, 0.232; P = .043) but not boys (P = .246).

Among adults, BMI normalization was not significantly associated with stage 3 T1D risk in either men (P = .908) or women (P = .994).

In exploratory models, adjustment for insulin sensitivity or insulin resistance weakened the association between BMI normalization and T1D progression, whereas adjustment for insulin secretion and C-peptide strengthened it.

What Comes Next?

A clinical trial testing an intervention to achieve a BMI normalization — rather than weight loss itself in children — is a future goal, Redondo said. In the meantime, she and her colleagues are conducting Breakthrough T1D-funded research into the biological mechanisms that might explain the association.

“We are looking at insulin resistance, which is an obvious potential mechanism, as well as obesity-induced inflammation by measuring cytokines and adipokines,” she told Medscape Medical News. “We are also studying beta cell stress because that’s another way obesity could be causing beta cells to fail sooner.”

“Our ultimate goal is to find the mechanism so that we can tailor a preventive strategy,” she added.

The study was funded by Breakthrough T1D and the National Institutes of Health. Redondo reported receiving honoraria and reimbursement for travel and meals from Eli Lilly, Sanofi, and MedLearn, as well as research funding from Breakthrough T1D and the National Institutes of Health. 

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.