Presentation (CTI)

OBJECTIVES: Clinical remission in type 1 diabetes (T1D) is a transient phase marked by reduced insulin needs, improved glycemic control, and preserved endogenous insulin secretion. Partial remission occurs in 23-37% of patients and complete remission in ~4%. Preserved C-peptide may reflect residual beta-cell function and contribute to metabolic and vascular benefits. However, the biological mechanisms linking remission, C-peptide preservation, and clinical outcomes remain incompletely understood. We developed an evidence-based conceptual model describing remission and the underlying immunometabolic state.
METHODS: A systematic literature review (SLR) of MEDLINE, Embase, and the Cochrane Database of Systematic Reviews (inception to January 28, 2026) identified studies on remission predictors and clinical outcomes in T1D. A targeted literature review (TLR) examined remission mechanisms, including glucotoxicity reduction, beta-cell rest, immune modulation, and C-peptide-mediated effects. Findings were synthesized into a conceptual model integrating baseline patient and disease characteristics; metabolic and immunologic mechanisms associated with remission; C-peptide preservation pathways; and downstream clinical outcomes.
RESULTS: Across 82 SLR studies, remission was associated with older age at onset, male sex, higher baseline C-peptide, absence of diabetic ketoacidosis, lower HbA1c, lower insulin dose, and a favorable metabolic profile. The conceptual model suggested that rapid correction of hyperglycemia may reduce glucotoxicity and beta-cell stress, enabling temporary preservation of beta-cell function and recovery of endogenous insulin secretion. This is associated with better glycemic stability, fewer acute glycemic events, reduced oxidative stress and improved lipid metabolism. Together, studies of remission and clinical complications support a pathway in which remission is associated with fewer hypoglycemic events, favorable lipid profiles, and lower early microvascular burden.
CONCLUSIONS: Clinical remission in T1D represents a biologically meaningful state of immunometabolic recovery characterized by preserved beta-cell function and C-peptide-mediated protection. This conceptual model supports remission as a potentially modifiable therapeutic target and highlights opportunities to prolong remission and reduce early complications in T1D.