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.


M.A. Testa: Stock/Shareholder; Spouse/Partner; GI Windows, Inc. Stock/Shareholder; Self; Phase V Technologies, Inc. M. Su: None. D.C. Simonson: Stock/Shareholder; Self; GI Windows, Inc. Stock/Shareholder; Spouse/Partner; Phase V Technologies, Inc.


Patient-Centered Outcomes Research Institute (CE1304-6756)

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