ADULTS diagnosed with Type 1 diabetes may reach clinical diagnosis at different stages of declining insulin production, according to a prospective cohort study identifying three clinical and metabolic subtypes.
The findings suggest that differences at diagnosis may partly reflect the interaction between autoimmunity and insulin sensitivity. This could help researchers identify opportunities to investigate more individualised approaches, although the study did not test whether subtype-guided treatment improves outcomes.
Researchers analysed 600 adults in the German Diabetes Study, with an average follow-up of 6.1 years. They used machine learning to group participants according to antibody status and metabolic measurements.
Three subtypes emerged: two positive for glutamic acid decarboxylase antibodies and one antibody-negative group. A similar structure was observed in a separate registry cohort of 483 adults.
One antibody-positive group, described as classic Type 1 diabetes, had lower BMI, greater insulin sensitivity and more severe impairment of beta-cell function. The other, described as mixed Type 1 diabetes, had higher BMI, lower insulin sensitivity and better-preserved beta-cell function.
Despite their metabolic differences, the two antibody-positive groups did not differ in measured autoimmunity or genetic risk scores for Type 1 diabetes.
Longitudinal modelling placed the mixed group approximately 6.1 years earlier along the beta-cell decline trajectory than the classic group. The findings suggest that lower insulin sensitivity may bring clinical diabetes forward, while more endogenous insulin production remains.
This estimate requires careful interpretation. It describes a modelled difference between groups and does not mean that treatment delayed diabetes by six years.
Complication patterns also differed. The mixed group had a higher adjusted hazard of retinopathy than the classic group, although the confidence interval was wide. Risks of hypoglycaemia and cardiovascular autonomic neuropathy also varied across the subtypes.
The results suggest that preserved insulin production at diagnosis should not automatically be interpreted as a uniformly favourable risk profile.
For researchers, the subtype framework offers a way to examine whether disease stage and metabolic characteristics influence responses to future interventions. However, identifying groups with different trajectories does not establish that assigning patients to those groups improves care.
Further prospective studies will need to test the practical value of the classification, including whether it adds useful information beyond existing clinical assessment. The findings provide a rationale for more targeted research while stopping short of establishing a new treatment pathway.
Reference
Prystupa K et al. Clinical and metabolic subtypes of recent-onset adult type 1 diabetes: a prospective cohort study. Lancet Diabetes Endocrinol. Published online 30 October 2026. doi:10.1016/S2213-8587(26)00233-0.
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