Variables predicting decline of β-cell function in LADA

Background: Prediction of C-peptide loss over time could inform therapeutic decision in latent autoimmune diabetes in adults (LADA). The LADASAXADAPA study showed that 12-months therapy with saxagliptin/dapagliflozin was non-inferior to insulin glargine in terms of b-cell function in LADA. Nevertheless, a c-peptide reduction was observed in both study arms during the study. Objective. To investigate for predictors of c-peptide loss in LADA among variables routinely collected in clinical practice. Methods. People with LADA and fasting c-peptide ≥0.6ng/ml were enrolled. Mixed meal tolerance tests were performed at baseline and after 12 months in 27 participants. Two-hour stimulated c-peptide areas under the curve (AUC_Cpep) were calculated. Multivariate regression models were used to evaluate baseline features (gender, age, age at diagnosis, disease duration, body mass index, HbA1c, lipid profile, glomerular filtration rate, fasting c-peptide) as possible predictors of AUC_Cpep change over 1 year (Δ^AUC_Cpep). Results: At baseline, median [25^th; 75^th percentile] age was 49 [46;57] years, disease duration 3 [1; 7] years, fasting c-peptide 1.17 [0.75; 1.68] ng/mL, HbA1c 7.4 [6.6; 7.7]%, and BMI 23.2 [21.0; 25.6] kg/m². A significant decrease of AUC_Cpep was observed during the study (Δ^AUC_Cpep: -17.8 [-91.9; -4.3]; p-value 0.023). Disease duration was the only variable associated withΔ^AUC_Cpepp: based on tertiles of Δ^AUC_Cpep, subjects experiencing the highest c-peptide loss (Δ^AUC_Cpep: -98.8 [-124.9; -91.9] ng*min/ml) had a disease duration of 2 [1; 4] years, while subjects with less or no c-peptide loss (Δ^AUC_Cpep: +18.9 [-4.3; +79.3] ng*min/ml) had a disease duration of 7 [3; 13] years (p-value for the association of disease duration with tertiles of Δ^AUC_Cpep: 0.0037). Conclusions: Among people with LADA and fasting C-peptide levels ≥0.6ng/ml, a further deterioration of β-cell function can be expected in those with a short (<5 years) disease duration, while it will less likely occur among patients with a longer disease duration.