850-P: Modeling Pathways between Psychological Distress, Emergent Symptoms and Side Effects, and Endpoint A1C during Treatment

Achieving glycemic targets is often hampered by emerging symptoms and side effects (SSE). We previously showed that higher baseline psychological distress was associated with worsening treatment-related SSE; however, causal pathways among demographic, psychological and endpoint A1C (E-A1C) measures remain unclear. To explore these pathways, we used latent variable, structural equation models (SEM) and pooled data from 17 randomized clinical trials (N = 5209 patients, 712 centers) employing 32 different regimens of insulin and oral agents alone or in combination during 24 -52 weeks of treatment. Questionnaires of psychological distress (PD) and well-being (PWB) (24 items), and SSE distress (54 items) were completed longitudinally. At baseline, 707 patients (13.6%) were T1D (54.2% male, age 32.7 ± 14.4 years, A1C 8.0 ± 1.0%, BMI 25.1 ± 3.9 kg/m²) and 4,502 (86.4%) were T2D (58.5% male, age 57.3 ± 10.3 years, A1C 8.7 ± 1.3%, BMI 30.8 ± 5.2 kg/m²). The PD latent variable consisted of depression, anxiety, and loss of behavioral control scales. Controlling for baseline age, sex, A1C, BMI and SSE, the SEM model indicated that for T2D a 1 standard deviation (sd) better baseline PD in the PD -->SSE path resulted in an 11% sd improvement in SSE, while a 1 sd improvement in the SSE --> E-A1C path resulted in a 15% sd decrease in A1C (both p < 0.001). Neither coefficient was significant for T1D. Adding a PWB latent variable to the combined T1D and T2D SEM added no explanatory value, while adding an additional feedback path (E-A1C-->SSE) showed that influences could be bidirectional (p < 0.001). Results indicate that pre-existing mental health conditions, as well as worsening treatment-emergent symptoms and side effects, can interfere with A1C lowering. These findings support therapeutic regimens that include a plan for the proactive treatment of psychological and symptom distress to improve diabetes medication acceptance and adherence in order to better achieve diabetes treatment goals.