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Plasma matrix metalloproteinases and tissue inhibitors of metalloproteinases explored in relation to the severity and progression of diabetic retinopathy in patients with type 1 diabetes : Baseline and prospective analyses

Hector, Sven LU ; Thulesius, Hans Olav LU ; Thunander, Maria LU ; Hillman, Magnus LU ; Landin-Olsson, Mona LU and Melin, Eva Olga LU (2024) In BMJ Open Ophthalmology 9(1).
Abstract

Aims 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... (More)

Aims 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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Inflammation, Retina
in
BMJ Open Ophthalmology
volume
9
issue
1
article number
e001583
publisher
BMJ Publishing Group
external identifiers
  • scopus:85198604598
  • pmid:38991835
ISSN
2397-3269
DOI
10.1136/bmjophth-2023-001583
language
English
LU publication?
yes
id
c33d9f54-0b70-4601-9b6a-b3c4b4af2c57
date added to LUP
2024-09-23 12:58:15
date last changed
2024-09-24 03:00:12
@article{c33d9f54-0b70-4601-9b6a-b3c4b4af2c57,
  abstract     = {{<p>Aims 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&lt;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.</p>}},
  author       = {{Hector, Sven and Thulesius, Hans Olav and Thunander, Maria and Hillman, Magnus and Landin-Olsson, Mona and Melin, Eva Olga}},
  issn         = {{2397-3269}},
  keywords     = {{Inflammation; Retina}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{BMJ Open Ophthalmology}},
  title        = {{Plasma matrix metalloproteinases and tissue inhibitors of metalloproteinases explored in relation to the severity and progression of diabetic retinopathy in patients with type 1 diabetes : Baseline and prospective analyses}},
  url          = {{http://dx.doi.org/10.1136/bmjophth-2023-001583}},
  doi          = {{10.1136/bmjophth-2023-001583}},
  volume       = {{9}},
  year         = {{2024}},
}