Clinical Sciences, Ophthalmology, Lund University Faculty of Medicine, Lund, Sweden.
Department of Ophthalmology, Central Hospital, Region Kronoberg Healthcare providers, Växjö, Sweden.
BMJ Open Ophthalmol. 2024 Jul 11;9(1):e001583. doi: 10.1136/bmjophth-2023-001583.
To explore whether circulating matrix metalloproteinase-2 (MMP-2), MMP-9, MMP-9/neutrophil gelatinase-associated lipocalin, MMP-9/tissue inhibitor of metalloproteinase-1 (TIMP-1), MMP-14, TIMP-2 and TIMP-3 were associated with the severity and progression of diabetic retinopathy (DR) in patients with type 1 diabetes (T1D).
Baseline and prospective analyses were conducted over a period of 10.5 person-years. In 2009, recruitment and biochemical analyses (MMPs, TIMPs, glycated haemoglobin (HbA1c), serum creatinine, macroalbuminuria) were performed. Fundus photography, performed at baseline and at follow-up in accordance with the regional screening programme, was compared after being categorised according to the International Clinical Diabetic Retinopathy Disease Severity Scale. 'DR progression at least one leve' was calculated. High MMP-2 was defined as ≥178 ng/mL (≥75th percentile) and high TIMP-2 as ≥205 ng/mL (≥75th percentile). DR was dichotomised as 'at least moderate DR' or 'no/mild DR'.
The study included 267 participants, 57% of whom were men. At baseline, the prevalence of high MMP-2 (p=0.001) and high TIMP-2 (p=0.008) increased with the severity of DR. 'At least moderate DR' (adjusted OR (AOR) 2.4, p=0.008) and macroalbuminuria (AOR 3.6, p=0.025) were independently associated with high MMP-2. 'At least moderate DR' (AOR 2.3, p=0.009) and macroalbuminuria (3.4, p=0.031) were independently associated with high TIMP-2. DR progression occurred in 101 (46%) patients (p<0.001). HbA1c≥53 mmol/mol was associated with the progression of DR (crude OR 3.8, p=0.001). No other MMPs or TIMPs were linked to the severity or the progression of DR.
High levels of MMP-2 and TIMP-2 indicated more severe DR or diabetic nephropathy. Only HbA1c was associated with the progression of DR in 267 patients with T1D.
探讨 1 型糖尿病（T1D）患者循环中基质金属蛋白酶-2（MMP-2）、MMP-9、MMP-9/中性粒细胞明胶酶相关脂质运载蛋白、MMP-9/金属蛋白酶组织抑制剂-1（TIMP-1）、MMP-14、TIMP-2 和 TIMP-3 是否与糖尿病视网膜病变（DR）的严重程度和进展相关。
进行了为期 10.5 年的基线和前瞻性分析。2009 年，进行了招募和生化分析（MMPs、TIMP、糖化血红蛋白（HbA1c）、血清肌酐、大量白蛋白尿）。根据国际临床糖尿病视网膜病变疾病严重程度量表对眼底摄影进行了分类，并在基线和随访时进行了比较。计算“DR 进展至少一个等级”。高 MMP-2 定义为≥178ng/mL（≥75 百分位数），高 TIMP-2 定义为≥205ng/mL（≥75 百分位数）。DR 分为“至少中度 DR”或“无/轻度 DR”。
该研究纳入了 267 名参与者，其中 57%为男性。基线时，高 MMP-2（p=0.001）和高 TIMP-2（p=0.008）的患病率随着 DR 的严重程度而增加。“至少中度 DR”（调整后的 OR（AOR）2.4，p=0.008）和大量白蛋白尿（AOR 3.6，p=0.025）与高 MMP-2 独立相关。“至少中度 DR”（AOR 2.3，p=0.009）和大量白蛋白尿（3.4，p=0.031）与高 TIMP-2 独立相关。101 名（46%）患者发生 DR 进展（p<0.001）。HbA1c≥53mmol/mol 与 DR 进展相关（粗 OR 3.8，p=0.001）。其他 MMP 或 TIMP 与 DR 的严重程度或进展均无关。
高 MMP-2 和 TIMP-2 水平提示更严重的 DR 或糖尿病肾病。在 267 名 T1D 患者中，只有 HbA1c 与 DR 的进展相关。
