代谢指标在预测糖尿病性黄斑水肿患者雷珠单抗疗效中的作用

The role of metabolic indicators in predicting ranibizumab efficacy in diabetic macular edema

摘要

目的 探讨循环代谢特征作为预测糖尿病性黄斑水肿 (diabetic macular edema, DME) 患者雷珠单抗治疗反应的预后因素。方法 本研究为观察性临床研究, 纳入 46 例确诊为累及中央凹的 DME 患者 [基线中央视网膜厚度 (central retinal thickness, CRT)] ≥320μm, 均接受 3 个月雷珠单抗玻璃体内注射治疗。治疗前及治疗后 3 个月后分别评估 CRT 和最佳矫正视力 (best corrected visual acuity, BCVA)。并检测治疗前 (基线) 血液中糖代谢、胱氨酸代谢和肌酸代谢等代谢指标, 经单因素分析筛选后, 采用多因素 Logistic 回归分析 (调整年龄、性别等混杂因素) 探究代谢指标与 CRT 和 BCVA 治疗反应的关联。结果 治疗 3 个月后, CRT 从 (568.20±103.30) μm 显著降低至 (453.60±03.30) μm (P=0.0004), BCVA 从 (0.90±0.56) 改善至 (0.69±0.54) (P<0.0001)。对全身因素和临床结果的分析显示, 糖代谢相关指标 (丙酮酸 P=0.0200、乳酸 P=0.0103、葡萄糖 P=0.0051、糖化血红蛋白 P=0.0053) 及肌酸代谢相关的肌酐 (P=0.0318) 水平与 CRT 的改善存在显著负相关。此外, 对全身因素和视力预后的分析结果显示, 乳酸 (P=0.0300)、葡萄糖 (P=0.0283)、糖化血红蛋白 (P=0.0139) 和胱氨酸代谢相关的胱抑素 (P=0.0197) 水平与 BCVA 的改善也呈显著负相关。多因素 logistic 回归分析进一步证实: 糖代谢指标 [葡萄糖比值比 (Odds Ratio, OR)=1.66, 糖化血红蛋白 OR=1.71, 乳酸 OR=2.19] 及肌酐 (OR=1.02) 独立预测 CRT 改善 (均 P<0.05); 胱抑素 (OR=8.55) 联合糖代谢指标 (葡萄糖 OR=1.42, 糖化血红蛋白 OR=1.64, 乳酸 OR=1.91) 独立预测 BCVA 改善 (均 P<0.05)。结论 DME 患者循环代谢特征, 特别是糖代谢、肌酸代谢和胱氨酸代谢相关指标, 能够有效预测雷珠单抗治疗反应, 为临床提供潜在的生物标志物。

Abstract

Objective To investigate the prognostic value of circulatory metabolic characteristics as predictors of treatment response to ranibizumab in patients with diabetic macular edema (DME). Methods This study was an observational clinical trial involving 46 patients diagnosed with DME involving the central fovea [baseline central retinal thickness (CRT) ≥320μm]. All participants received intravitreal injections of ranibizumab for 3 months. CRT and best-corrected visual acuity (BCVA) were assessed at baseline and 3 months post-treatment. Baseline blood levels of metabolic markers related to glucose metabolism, cysteine metabolism, and creatine metabolism were measured. Univariate analyses were first performed to screen candidate variables, and then multivariate logistic regression analyses (adjusted for confounding factors such as age and sex) were conducted to investigate the associations between baseline metabolic markers and anatomical (CRT) and functional (BCVA) treatment responses. Results After 3 months of treatment, CRT significantly decreased from (568.20±103.30) μm to (453.6±103.30)μm (P=0.0004), and BCVA improved from 0.90±0.56 to 0.69±0.54 (P<0.0001). Analysis of systemic factors and clinical outcomes revealed significant negative correlations between glucose metabolism-related indicators (pyruvate, P=0.0200; lactate, P=0.0103; glucose, P=0.0051; glycated hemoglobin, P=0.0053) and CRT improvement. Additionally, creatinine levels related to creatine metabolism (P=0.0318) were significantly negatively correlated with CRT improvement. Further analysis of systemic factors and visual prognosis showed significant negative correlations between lactate (P=0.0300), glucose (P=0.0283), glycated hemoglobin (P=0.0139), and cysteine metabolism-related cystatin (P=0.0197) with BCVA improvement. Multivariate logistic regression analysis further confirmed that glucose metabolism markers [glucose odds ratio (OR)=1.66, HbA1c OR=1.71, lactate OR=2.19] and creatinine (OR=1.02) independently predicted CRT improvement (all P<0.05), cystatin C (OR=8.55) combined with glucose metabolism indicators (glucose OR=1.42, HbA1c OR=1.64, lactate OR=1.91) independently predicted improvements in BCVA (all P<0.05). Conclusion Circulating metabolic characteristics in DME patients, particularly indicators related to glucose metabolism, creatine metabolism, and cysteine metabolism, can effectively predict the response to ranibizumab treatment, providing potential biomarkers for clinical practice.

关键词

糖尿病性黄斑水肿 / 糖尿病视网膜病变 / 雷珠单抗 / 代谢特征 / 临床疗效 / 生物标志物

Key words

Diabetic macular edema / Diabetic retinopathy / Ranibizumab / Metabolic characteristics / Clinical efficacy / Biomarkers

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