1669-P: Proinsulin: C-Peptide Ratios in Relatives of Persons with Type 1 Diabetes

Abstract

Biomarkers are needed to characterize heterogeneity within populations at risk for type 1 diabetes (T1D). The ratio of proinsulin to C-peptide (PI:C ratio), a biomarker of beta cell dysfunction, has been associated with progression to T1D, but relationships between PI:C ratios and autoantibody (Ab) type and number have not been explored. We sought to characterize PI:C ratios in multiple islet Ab positive, single Ab positive and Ab negative relatives of individuals with T1D. We measured PI:C ratios and Abs with both electrochemiluminescence (ECL) assays (ECL-IAA, ECL-GADA and ECL-IA2)and radio-binding (RBA) assays (mIAA, GADA, IA2A and ZnT8A) in 98 relatives of persons with T1D followed in the Pathway to Prevention Study at the Barbara Davis Center. Of these subjects, 31 were multiple Ab positive, 37 were single Ab positive and 22 were Ab negative at the most recent visit. Eight subjects progressed to T1D over a mean follow-up of 5.5±3.6 years. In cross-sectional analyses, there were no significant differences in PI:C ratios between T1D and/or multiple Ab positive subjects (4.16±4.06) compared to single Ab positive subjects (4.08±4.34) and negative Ab subjects (3.72±3.78) (p=0.92) overall or after adjusting for age, sex and BMI. Higher PI:C ratios were associated with ECL-IA2A (p=0.03) and ECL-IAA (p=0.03) levels, but not with mIAA, GADA, ECL-GADA, IA2A nor ZnT8A levels. In mixed-effects longitudinal models, the trajectories of PI:C ratio over time were not significantly different between the 4 groups, overall or after adjusting for sex, age, and BMI. In conclusion, higher PI:C ratios were associated with ECL-IAA and ECL-IA2A levels, which have previously been associated with progression to T1D. Disclosure T.M. Triolo: None. L. Pyle: None. S. Seligova: None. L. Yu: None. K. Simmons: None. P. Gottlieb: Consultant; Self; Bristol-Myers Squibb Company, Eli Lilly and Company, Kamada, Tolerion, Inc. Research Support; Self; Intrexon, Janssen Pharmaceuticals, Inc., Mercia/NovaImmune, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc. Stock/Shareholder; Self; IM Therapeutics. Other Relationship; Self; Viacyte, Inc. C. Evans-Molina: None. A. Steck: None. Funding American Diabetes Association (1-14-CD-17 to A.S.)