Persistence of β-Cell Responsiveness for Over Two Years in Autoantibody-Positive Children With Marked Metabolic Impairment at Screening.
OBJECTIVE: We studied longitudinal differences between progressors and nonprogressors to type 1 diabetes with similar and substantial baseline risk.
RESEARCH DESIGN AND METHODS: Changes in 2-h oral glucose tolerance test indices were used to examine variability in diabetes progression in the Diabetes Prevention Trial-Type 1 (DPT-1) study (n = 246) and Type 1 Diabetes TrialNet Pathway to Prevention study (TNPTP) (n = 503) among autoantibody (Ab)+ children (aged
RESULTS: Longitudinal analyses revealed annualized area under the curve (AUC) of C-peptide increases in nonprogressors versus decreases in progressors (P ≤ 0.026 for DPT-1 and TNPTP). Vector indices for AUC glucose and AUC C-peptide changes (on a two-dimensional grid) also differed significantly (P < 0.001). Despite marked baseline metabolic impairment of nonprogressors, changes in AUC C-peptide, AUC glucose, AUC C-peptide-to-AUC glucose ratio (AUC ratio), and Index60 did not differ from Ab- relatives during follow-up. Divergence between nonprogressors and progressors occurred by 6 months from baseline in both cohorts (AUC glucose, P ≤ 0.007; AUC ratio, P ≤ 0.034; Index60, P < 0.001; vector indices of change, P < 0.001). Differences in 6-month change were positively associated with greater diabetes risk (respectively, P < 0.001, P ≤ 0.019, P < 0.001, and P < 0.001) in DPT-1 and TNPTP, except AUC ratio, which was inversely associated with risk (P < 0.001).
CONCLUSIONS: Novel findings show that even with similarly abnormal baseline risk, progressors had appreciably more metabolic impairment than nonprogressors within 6 months and that the measures showing impairment were predictive of type 1 diabetes. Longitudinal metabolic patterns did not differ between nonprogressors and Ab- relatives, suggesting persistent β-cell responsiveness in nonprogressors.
Child; Humans; C-Peptide; Diabetes Mellitus, Type 1; Blood Glucose; Glucose Tolerance Test; Autoantibodies; Glucose; Disease Progression
C-Peptide; Diabetes Mellitus, Type 1; Blood Glucose; Glucose Tolerance Test; Autoantibodies; Glucose; Disease Progression
Sims EK, Cuthbertson D, Felton JL, et al. Persistence of β-Cell Responsiveness for Over Two Years in Autoantibody-Positive Children With Marked Metabolic Impairment at Screening. Diabetes Care. 2022;45(12):2982-2990. doi:10.2337/dc22-1362