1094-P: Longitudinal Trajectories of Fasting C-Peptide in Youth-Onset Type 2 Diabetes—The SEARCH for Diabetes in Youth Study

Abstract

In youth-onset type 2 diabetes (YO-T2D; diabetes diagnosed <20 years-old) loss of glycemic control is more rapid than in adults, partly attributed to accelerated beta cell decline. However, no studies have investigated the potential heterogeneity in the longitudinal trajectories of beta cell function and whether genetic factors might contribute to heterogeneity. We derived longitudinal trajectories of fasting C-peptide (FCP) levels, a surrogate measure of beta cell function, via discrete mixture modeling of repeated measures collected over 15 years of follow-up in youth with YO-T2D (antibody negative and insulin resistant; n=266) from the SEARCH for Diabetes in Youth cohort study. We tested the association between the derived trajectories and T2D genetic risk score (GRS) using a multinomial logistic regression model with adjustment for relevant covariates. A four-trajectory model best fit the data, classifying youth with YO-T2D as having either “initial low FCP and stable over time” (32%), “initial high FCP and slow incline” (8%), “initial high FCP and slow decline” (53%), or “initial very high FCP and rapid decline” (7%) (Figure). T2D GRS was not associated with FCP trajectory membership. These data demonstrate substantial heterogeneity in trajectories of FCP in YO-T2D and suggest that genetic predisposition to T2D is not a significant determinant of this heterogeneity. Disclosure A.Shapiro: None. A.Bellatorre: None. J.M.Stafford: None. A.S.Shah: None. C.Pihoker: None. F.Malik: None. A.D.Liese: None. D.J.Pettitt: None. D.Dabelea: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK127208-01, 1UC4DK108173); Centers for Disease Control and Prevention (U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, U18DP006139)