PDF(Pubmed)
Abstract：
OBJECTIVE: 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).
METHODS: 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\'.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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\'.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：探讨循环基质金属蛋白酶-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与1型糖尿病（T1D）患者糖尿病视网膜病变（DR）的严重程度和进展有关。
方法：在10.5人年的时间内进行了基线和前瞻性分析。2009年，招聘和生化分析(MMPs，TIMP,糖化血红蛋白（HbA1c），血清肌酐,进行大量白蛋白尿）。眼底摄影,根据区域筛查计划在基线和随访时进行，根据国际临床糖尿病视网膜病变疾病严重程度量表进行分类后进行比较。计算了“至少一个级别的DR进展”。高MMP-2定义为≥178ng/mL（≥第75百分位数），高TIMP-2定义为≥205ng/mL（≥第75百分位数）。将DR分为“至少中度DR”或“无/轻度DR”。
结果：该研究包括267名参与者，其中57%是男性。在基线,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（校正OR（AOR）2.4，p=0.008）和大量白蛋白尿（AOR3.6，p=0.025）与高MMP-2独立相关。至少中度DR（AOR2.3，p=0.009）和大量白蛋白尿（3.4，p=0.031）与高TIMP-2独立相关。101例（46%）患者发生DR进展（p<0.001）。HbA1c≥53mmol/mol与DR进展相关（粗OR3.8，p=0.001）。没有其他MMP或TIMPs与DR的严重程度或进展相关。
结论：高水平的MMP-2和TIMP-2表明更严重的DR或糖尿病肾病。只有HbA1c与267例T1D患者的DR进展相关。
方法：在10.5人年的时间内进行了基线和前瞻性分析。2009年，招聘和生化分析(MMPs，TIMP,糖化血红蛋白（HbA1c），血清肌酐,进行大量白蛋白尿）。眼底摄影,根据区域筛查计划在基线和随访时进行，根据国际临床糖尿病视网膜病变疾病严重程度量表进行分类后进行比较。计算了“至少一个级别的DR进展”。高MMP-2定义为≥178ng/mL（≥第75百分位数），高TIMP-2定义为≥205ng/mL（≥第75百分位数）。将DR分为“至少中度DR”或“无/轻度DR”。
结果：该研究包括267名参与者，其中57%是男性。在基线,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（校正OR（AOR）2.4，p=0.008）和大量白蛋白尿（AOR3.6，p=0.025）与高MMP-2独立相关。至少中度DR（AOR2.3，p=0.009）和大量白蛋白尿（3.4，p=0.031）与高TIMP-2独立相关。101例（46%）患者发生DR进展（p<0.001）。HbA1c≥53mmol/mol与DR进展相关（粗OR3.8，p=0.001）。没有其他MMP或TIMPs与DR的严重程度或进展相关。
结论：高水平的MMP-2和TIMP-2表明更严重的DR或糖尿病肾病。只有HbA1c与267例T1D患者的DR进展相关。
