Supplementary Material for: Evaluation of a Stepped Care Approach to Manage Depression and Diabetes Distress in Patients with Type 1 Diabetes and Type 2 Diabetes: Results of a Randomized Controlled Trial (ECCE HOMO Study)

<b><i>Introduction:</i></b> Depression is a common and serious complication of diabetes. Treatment approaches addressing the specific demands of affected patients are scarce. <b><i>Objective:</i></b> The aim of this work was to test whether a stepped care approach for patients with diabetes and depression and/or diabetes distress yields greater depression reduction than treatment-as-usual. <b><i>Methods:</i></b> Two-hundred and sixty patients with diabetes and elevated depressive symptoms (CES-D ≥16) and/or elevated diabetes distress (PAID ≥40) were randomized to stepped care for depression or diabetes treatment-as-usual. The primary outcome was the rate of meaningful depression reduction at the 12-month follow-up according to the HAMD (score &lt;9 or reduction by ≥50%). Secondary outcomes were changes in depression scores (HAMD/CES-D), diabetes distress (PAID), diabetes acceptance (AADQ), well-being (WHO-5), quality of life (EQ-5D/SF-36), self-care behavior (SDSCA/DSMQ), HbA_1c, and biomarkers of inflammation. <b><i>Results:</i></b> One-hundred and thirty-one individuals were assigned to stepped care and 129 to treatment-as-usual. Overall, 15.4% were lost to follow-up. Meaningful depression reduction was observed in 80.2 versus 51.2% in stepped care versus treatment-as-usual (<i>p</i> &lt; 0.001, intention-to-treat analysis). Of the secondary measures, the HAMD (∆ –3.2, <i>p</i> &lt; 0.001), WHO-5 (∆ 1.5, <i>p</i> = 0.007), and AADQ (∆ –1.0, <i>p</i> = 0.008) displayed significant treatment effects, while effects on CES-D (∆ –2.3, <i>p</i> = 0.065), PAID (∆ –3.5, <i>p</i> = 0.109), and SDSCA (∆ 0.20, <i>p</i> = 0.081) were not significantly different. Both groups showed comparable changes in EQ-5D/SF-36, DSMQ, HbA_1c, and biomarkers of inflammation (all <i>p</i> ≥ 0.19). <b><i>Conclusions:</i></b> The stepped care approach improved depression, well-being, and acceptance. The results support that increasing treatment intensity on demand is effective and can help provide more optimal treatment. The inclusion of diabetes-specific interventions may be beneficial for patients with diabetes and elevated depression.

**引言**：抑郁是糖尿病常见且严重的并发症，目前针对糖尿病合并抑郁患者的个体化诊疗方案仍较为匮乏。
**研究目的**：本研究旨在验证，针对糖尿病合并抑郁及/或糖尿病痛苦的患者，采用阶梯治疗方案是否比常规治疗能更有效地改善抑郁症状。
**研究方法**：本研究纳入260名糖尿病合并抑郁症状评分升高（流调中心用抑郁量表（CES-D）≥16分）及/或糖尿病痛苦评分升高（糖尿病痛苦量表（PAID）≥40分）的患者，按随机原则将其分为抑郁阶梯治疗组与常规糖尿病治疗组。本研究的主要结局指标为：随访12个月时，根据汉密尔顿抑郁量表（HAMD）评分判定的显著抑郁改善率（评分<9分，或较基线评分降低≥50%）。次要结局指标包括：抑郁评分（HAMD/CES-D）、糖尿病痛苦（PAID）、糖尿病接受度（糖尿病接受问卷（AADQ））、幸福感（世界卫生组织5项幸福感量表（WHO-5））、生活质量（欧洲五维健康量表（EQ-5D）/简明健康调查问卷（SF-36））、自我护理行为（自我护理行为量表（SDSCA）/糖尿病自我管理量表（DSMQ））、糖化血红蛋白（HbA₁c）以及炎症生物标志物的变化情况。
**研究结果**：阶梯治疗组共纳入131名患者，常规治疗组共129名患者。整体随访失访率为15.4%。意向治疗分析显示，阶梯治疗组与常规治疗组的显著抑郁改善率分别为80.2%与51.2%（p < 0.001）。在次要结局指标中，汉密尔顿抑郁量表（HAMD）评分变化值（Δ–3.2，p < 0.001）、世界卫生组织5项幸福感量表（WHO-5）评分变化值（Δ1.5，p = 0.007）以及糖尿病接受问卷（AADQ）评分变化值（Δ–1.0，p = 0.008）均显示出显著的组间治疗效应；而流调中心用抑郁量表（CES-D）评分变化值（Δ–2.3，p = 0.065）、糖尿病痛苦量表（PAID）评分变化值（Δ–3.5，p = 0.109）以及自我护理行为量表（SDSCA）评分变化值（Δ0.20，p = 0.081）的组间差异无统计学意义。两组在欧洲五维健康量表（EQ-5D）/简明健康调查问卷（SF-36）、糖尿病自我管理量表（DSMQ）、糖化血红蛋白（HbA₁c）以及炎症生物标志物的变化方面均无显著组间差异（所有p值均≥0.19）。
**结论**：阶梯治疗方案可有效改善患者的抑郁症状、幸福感与糖尿病接受度。研究结果支持，根据患者需求调整治疗强度的诊疗模式具有临床有效性，可为糖尿病合并抑郁症状升高的患者提供更优化的治疗方案。纳入糖尿病特异性干预措施或可使此类患者获益。