1118-OR: Risk Factors for 30-Year Incidence of Distal Symmetric Polyneuropathy (DSP) by Glycemic Exposure Trajectories in Type 1 Diabetes (T1D)

Introduction and Objective: DSP is a common T1D complication but data are limited on factors related to long-term risk and how they may differ by glycemic exposure. Thus, we aimed to identify independent risk factors associated with 30-year DSP incidence by latent HbA1c trajectory in the Epidemiology of Diabetes Complications (EDC) study of childhood-onset (<17 years) T1D. Methods: DSP was defined as ≥2 of: neuropathy symptoms on exam, abnormal sensory exam, or reduced tendon reflexes. In DSP-free participants with ≥ 2 HbA1c measures over 30 years (n=359, mean baseline age 24 yrs, T1D duration 16 yrs, median 6 study visits), latent HbA1c trajectories and their association with time-to-DSP were simultaneously assessed using joint latent class mixed models. Within each HbA1c trajectory group, age-adjusted multivariable Cox models identified baseline and time-varying (most recent [MR] and updated mean [UM]) risk factors. Results: We identified two HbA1c trajectories with respect to differential DSP hazard: “higher” mean HbA1c always >9% (n=181; 147 (81.2%) incident DSP cases) and “lower” mean HbA1c always <9% (n=178; 51 (28.7%) incident DSP cases). In higher HbA1c, significant risk factors were MR pulse rate (HR per 5 bpm 1.13, p=0.003), MR antidepressant use (HR 3.23, p<0.001), baseline HbA1c (HR per % 1.26, p<0.001), and height (HR per cm 1.02, p=0.028); baseline insulin dose was protective (U/kg/day, HR per SD 0.77, p=0.021). In lower HbA1c, risk factors included UM pulse rate (HR per 5 bpm 1.26, p=0.047), MR Beck Depression Inventory score (HR per unit 1.05, p=0.005), and baseline BMI (HR per kg/m2 1.11, p=0.028). Conclusion: Our results suggest pulse rate and markers of depression may be important intervention targets for DSP regardless of long-term glycemic exposure. The protective association of higher insulin dose in the high HbA1c group suggests intensive insulin therapy may be neuroprotective even when glycemic targets are not met, warranting further study. Disclosure J. Zhou: Employee; Ended; Iovance Biotherapeutics.