A Baylor College of Medicine-led team found that moving into a normal weight range was associated with about half the risk of progressing to clinical type 1 diabetes (T1D), particularly in youth. This observational study, published in Diabetes Care , was conducted in individuals with early signs of type 1 diabetes.
"T1D is an autoimmune disease in which the body's immune system attacks the insulin-producing cells of the pancreas, called islets of Langerhans," said first and corresponding author Dr. María Redondo, professor of pediatrics - diabetes and endocrinology at Baylor College of Medicine and Texas Children's Hospital. "Without insulin, cells in the body cannot use sugar circulating in the blood for energy, which can lead to diabetic ketoacidosis, a life-threatening complication, and potentially death if untreated. Over the long term, T1D can also increase the risk of complications affecting the eyes, kidneys, nerves, heart and blood vessels."
Redondo and her colleagues examined whether, among individuals with overweight or obesity who were already at increased risk for T1D, subsequent normalization of the Body Mass Index (BMI, measured as weight relative to height), was associated with a different risk of progression to clinical T1D.
Major advances now allow people at increased risk for T1D to be identified years before symptoms appear and, in some cases, to receive an approved therapy to delay the onset of clinical disease. One way to identify people at risk is by measuring islet autoantibodies in the blood, as they are evidence of the autoimmune process that destroys islet cells. However, despite the advances, outcomes remain suboptimal and additional approaches to delay disease progression are needed.
Previous studies, including some led by Redondo, have linked higher BMI with more rapid progression toward T1D. However, it has been unclear whether subsequent BMI normalization is associated with lower risk of disease progression.
In this study, Redondo and her colleagues studied 833 participants in the TrialNet study, which is focused on preventing T1D. The participants included children and adults who had islet autoantibodies and who were overweight or obese when they entered the study.
"We followed the participants for about 4 years," Redondo said. "In this period, about 27% of participants moved from the overweight or obese range into the normal BMI range. As we had hypothesized, people who achieved a normal BMI had about a 48% lower risk of progressing to clinical T1D compared with those who remained overweight or obese."
The association was most evident in children and adolescents. The strongest associations were seen in boys younger than 12 years and girls 12 to 17 years of age. In adults, however, BMI normalization was not clearly associated with lower risk of progression to T1D. The researchers are investigating factors that may explain this difference.
Since this is an observational study, the findings do not establish that lowering BMI will prevent or delay T1D. "Our study shows an association, not causation," Redondo said. "The findings provide a strong rationale for a prospective intervention trial to determine whether intentionally promoting a healthy BMI trajectory can alter progression of T1D." Importantly, in children, reaching a normal BMI range does not necessarily mean losing weight; it can also happen when weight gain slows or stabilizes as the child grows taller.
Other contributors to this work include Raquel Gupta, Alejandro F. Siller, Sridevi Devaraj and Ashok Balasubramanyam at Baylor College of Medicine. David Cuthbertson and Kendra Vehik are with University of South Florida, and Heba M. Ismail with Indiana University.
The study was supported by a Breakthrough T1D grant (3-SRA-2025-1738-S-B). Genetic data were generated previously with support from the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK121843). Study participants and clinical data were obtained through TrialNet, which is supported by cooperative agreements from the National Institutes of Health and Breakthrough T1D.
