Introduction & Objective: Endogenous insulin production in T1D, as measured by detectable C-peptide, is associated with lower HbA1c and insulin dose, as well as lower hypoglycemia and retinopathy risk. We aimed to determine if detectable C-peptide is also associated with decreased risk of DKA.
Methods: We accessed data from the Diabetes Control and Complications Trial (DCCT) from the NIDDK central repository to investigate the effects of detectable stimulated C-peptide measured annually (≥0.2 pmol/ml, exposure) on DKA incidence (outcome) over mean 6.5-year trial follow-up. Analysis was conducted using the Andersen-Gill model for recurrent DKA events with time-varying covariates; crude unadjusted models and models adjusted for age, sex, diabetes duration, and trial assignment (intensive vs. conventional) were fit. Sensitivity analysis also adjusted for HbA1c.
Results: Of the 1441 participants with a median age of 27 years and median duration of diabetes of 49 months, 53% were male, 21% had detectable C-peptide levels (>0.2 pmol/ml) at baseline, and the median HbA1c level was 8.8%. During the trial, 129 participants (9%) had 180 DKA events. Only 1 of these 129 DKA events occurred in an individual with detectable C-peptide, while 128 events occurred in individuals after C-peptide became undetectable. In crude analysis, detectable C-peptide level had a 93% reduction in the hazard for recurrent DKA [hazard ratio (HR) 0.07, 95% CI 0.01 to 0.48, p=0.007]. Results were similar in the first adjusted model (HR 0.06, 95% CI 0.01 to 0.44, p=0.006) and in the final adjusted model (HR 0.08, 95% CI 0.01 to 0.60, p=0.012).
Conclusion: In addition to previously identified clinical benefits, this analysis demonstrates that endogenous insulin production dramatically lowers the risk of DKA in T1D. This implies that therapies that may preserve insulin production - such as immune, cell-based, or other therapies - are likely to reduce the burden of DKA.
M.I. Abuabat: None. D.R. Budhram: None. P. Bapat: None. A.M.K. Bakhsh: None. N. Verhoeff: None. D. Mumford: None. A. Orszag: None. M. Fralick: Consultant; singal1, proofdx. A. Weisman: None. L. Lovblom: None. B.A. Perkins: Advisory Panel; Abbott. Other Relationship; Novo Nordisk. Advisory Panel; Insulet Corporation, Nephris. Other Relationship; Medtronic. Advisory Panel; Sanofi, Vertex Pharmaceuticals Incorporated, Dexcom, Inc.
Diabetes Canada (Operating Grant OG-3-21-5572-BP)
