Despite recent advances, neuropathy screening is not consistently performed in clinical practice. We aimed to determine if neuropathy risk could be predicted using the trajectories of routinely-performed eye and kidney screening tests in T1D. We used 28-year data from the DCCT/EDIC study, available via the NIH public repository. We used the Early Treatment Diabetic Retinopathy Study Research (ETDRS) Group 23-point scale, albumin excretion rate (AER), and eGFR treated as longitudinal outcomes. Simultaneously, we represented neuropathy as a 3-state progressive multistate outcome using nerve conduction studies and the Michigan Neuropathy Screening Instrument (MNSI) for early-stage neuropathy and the occurrence of serious foot ulcer or amputation for late-stage neuropathy. To model these interrelated disease processes, we used and developed joint models with multistate submodels. Our “joint multistate model” accounted for interval censoring: due to the visit schedule, the exact time of transition to early-stage neuropathy was known only to occur in between consecutive visits. A Bayesian estimation procedure was used. We found that the risk of transition from no to early-stage neuropathy was affected by the current value of ETDRS, the current slope of ETDRS, and the current value of AER. For example, controlling for all covariates including eGFR, the there was a 23% higher rate of occurrence of this early-stage for a 3-step higher ETDRS scale. In the same model controlling for all covariates, progression from early-stage to late-stage neuropathy was affected mainly by AER (11% higher rate for a doubling of AER). Routinely-performed clinical eye and kidney test results can be leveraged to help identify the risk of neuropathy. Future work will develop dynamic predictions integrated into an electronic medical record.


L.Lovblom: None. L.Briollais: None. G.Tomlinson: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO).

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