348-OR: Metabolic Phenotype of Autoantibody Positive (AbPos) Long-Term Nonprogressors (LTNPs) to Type 1 Diabetes (T1D)

Few studies have described the metabolic phenotype of AbPos individuals who remain T1D free for an extended period of time. We aimed to compare C-peptide and glucose (Glu) data from oral glucose tolerance tests (OGTTs) performed longitudinally in 646 AbPos TrialNet Pathway to Prevention (PTP) participants who remained T1D free for ≥5.0 yrs (LTNPs; mean follow-up: 7.8±2.3 yrs) versus 405 Rapid Progressor (RP) PTP participants who progressed to T1D within <2 yrs of study entry (mean follow-up 0.97±0.54 yrs) and 150 Ab negative (AbNeg) controls. At study entry, 48% of LTNPs were single AbPos and 52% were multiple AbPos; 45.8% of single AbPos LTNPs became multiple AbPos during follow-up. LTNPs were older (mean age 18.8 ± 14.1 yrs) compared to RPs (11.8 ± 9.3 yrs) and AbNeg individuals (16 ± 10 yrs) (p<0.001). LTNPS exhibited an intermediate metabolic phenotype, with age and BMIZ-adjusted C-peptide area under the curve (AUC) and 30-0 min C-peptide values that were lower than AbNegs but higher than RPs (p<0.001), and Index60 levels (a composite of glucose and C-peptide values from OGTTs) that were higher than AbNegs but lower than RPs (p<0.001). Longitudinal trends in LTNPs were analyzed using fitted linear mixed models. Multiple AbPos LTNPs had higher Glu AUC (p=0.01) and Index60 values (p=0.032) compared to single AbPos LTNPs. However within both AbPos groups, metabolic patterns were remarkably stable over extended follow-up. When measures were evaluated for non-linear interactions using a regression tree analysis, the combination of Index60<1.06 + Glu AUC<137.7 at baseline was associated with an odds ratio of 8.55 (p<0.001) of being a LTNP. These data suggest that, while β cell function is reduced in LTNPs at the time of AbPos identification, longitudinal Glu and C-peptide patterns are largely stable without evidence of a relapsing or remitting course. Baseline OGTT measures (here, Index 60 and Glu AUC) may be able to predict AbPos individuals with lower risk of progression to T1D.