At the recently held 27th Annual Conference of the Chinese Diabetes Society (CDS 2025), Professor Zhou Zhiguang from the National Clinical Research Center for Metabolic Diseases, the Second Xiangya Hospital of Central South University, shared insights on stratified interventions for type 1 diabetes (T1D) based on different disease stages.
In recent years, research on the prevention of T1D has advanced significantly, with explorations into stratified interventions tailored to the disease’s progression from Stage 0 to Stage 3. As the number of autoantibodies increases and dysglycemia gradually develops, pancreatic β‑cell function progressively declines, ultimately leading to the clinical onset of overt diabetes. Based on this natural history, T1D prevention strategies are categorized into primary prevention (intervention in high‑risk populations), secondary prevention (intervention in the subclinical stage), and tertiary prevention (intervention in the clinical stage).
- Primary Prevention of T1D
Current primary prevention of T1D focuses on minimizing exposure to potential environmental risk factors, although definitive causative agents remain incompletely identified. Factors such as infections, vaccinations, weight gain, gut microbiota, infant feeding practices, gluten exposure, antibiotic use, probiotics, vitamin D, and fatty acids have been implicated in T1D development, but evidence strength varies, and most intervention trials have yielded limited results.
Studies suggest that neonatal vitamin D supplementation may be associated with a reduced risk of T1D, indicating a potential protective effect. However, consistent conclusions regarding the protective effect of maternal vitamin D supplementation during pregnancy are lacking, requiring further validation through high‑quality prospective research. Therefore, the most feasible strategy at this stage is to reduce exposure to potentially harmful environmental factors and promote healthy lifestyles to lower T1D risk. - Secondary Prevention of T1D
Secondary prevention of T1D has primarily employed insulin as an antigen‑specific immunotherapy via oral, subcutaneous, and nasal routes, yet none have successfully delayed or prevented clinical onset. Research indicates that oral insulin can slow progression to Stage 3 T1D in individuals with Stage 1/2 T1D who carry the HLA DR4‑DQ8 haplotype and/or have high titers of IA‑2A, demonstrating clear population‑specific efficacy.
The POInT study showed that high‑dose oral insulin immunotherapy reduces the risk of developing Stage 2 or 3 T1D in individuals with susceptible genotypes (a secondary prevention effect), but is associated with an increased incidence of islet autoantibodies in those without susceptible genotypes (suggesting limited primary prevention efficacy). Consequently, current research on oral insulin for T1D prevention has shifted from “whether it works” to “for whom it works, when to intervene, and how to combine therapies,” emphasizing personalized strategies based on antibody profiles and genetic risk.
Notably, Teplizumab has been approved by the FDA and China for delaying progression to Stage 3 T1D in individuals aged ≥8 years with Stage 2 disease. - Tertiary Prevention of T1D
In the realm of tertiary prevention, the early non‑insulin‑dependent clinical phase (Stage 3A T1D) is recognized as a critical intervention window. Remaining in this stage can delay the need for insulin therapy by months or even years.
GLP‑1 receptor agonists significantly reduce insulin requirements in newly diagnosed T1D patients, improve time in range (TIR), and do not increase the risk of severe hypoglycemia or ketosis. Additionally, C‑peptide preservation resulting from immunotherapy correlates linearly with improved HbA1c in T1D patients; greater C‑peptide retention is associated with more pronounced metabolic benefits, making it a key biomarker for evaluating treatment efficacy. - Clinical Practice of Screening for High‑Risk T1D Populations
In December 2022, the Department of Metabolism and Endocrinology at Xiangya Hospital established the Type 1 Diabetes Prevention Clinic, marking a new era in T1D prediction and prevention as China’s first dedicated T1D prevention clinic. Organized by the Department of Metabolism and Endocrinology at the Second Xiangya Hospital of Central South University, the clinic conducts systematic assessments of glycemic metabolism and islet function. By integrating HLA class II genotyping and islet autoantibody testing, it comprehensively evaluates an individual’s future risk of developing T1D.