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. 2022 Jul;156(1):104-110.
doi: 10.4103/ijmr.IJMR_1293_19.

Selective decrease in alpha1-antitrypsin levels in diabetic retinopathy: Could the levels of it be playing a role in the pathophysiology of diabetic retinopathy?

Mamatha Kunder  1 , V Lakshmaiah  2 , A V Moideen Kutty  1
Affiliations

Selective decrease in alpha1-antitrypsin levels in diabetic retinopathy: Could the levels of it be playing a role in the pathophysiology of diabetic retinopathy?

Mamatha Kunder et al. Indian J Med Res. 2022 Jul.

Abstract

Background & objectives: Type 2 diabetes mellitus (T2DM) is known to induce inflammation and activation of neutrophils causing the release of neutrophil elastase (NE), a pro-inflammatory proteinase. The activity of NE is regulated by endogenous inhibitors alpha1-antitrypsin (α1-AT) and alpha2-macroglobulin (α2-MG). Disrupted proteolytic homeostasis in T2DM patients is one of the causes for vascular complications. This study was carried out for evaluating the levels of plasma NE, α1-AT, α2-MG and NE-α1-AT complex to understand their roles in the pathophysiology of diabetic nephropathy (DN) and diabetic retinopathy (DR).

Methods: A total of 240 participants (Control, n=60; T2DM, n=60; DN, n=60; and DR, n=60) were recruited after recording history, clinical examination and laboratory investigations. Retinopathy was confirmed by fundoscopy and nephropathy by urinary albumin excretion and serum creatinine levels. NE was measured using STANA. α1-AT, α2-MG and NE-α1-AT complex were estimated by ELISA.

Results: Baseline clinical and laboratory findings were confirmatory to the study groups. The mean elastase activity was higher (P<0.0005) in diabetes groups (T2DM=0.73±0.31, DN=0.87±0.35, DR=0.76±0.41) than controls (0.35±0.20). The levels of α1-AT were lower in DR (8.77±2.85) than DN (26.26±6.16) and T2DM (41.13±14.06) when juxtaposed with controls (122.95±25.71). The approximate fold decrease of α1-AT levels was 15 for DR and four for DN compared to controls. The levels of α2-MG were lowered in T2DM (167.29±30.45), DN (144.66±13.72), and DR (104.67±11.47) than controls (208.87±31.16). The NE-α1-AT complex levels were: controls (215.83±13.61), T2DM (98.85±23.85), DN (129.26±20.40) and DR (153.25±17.11).

Interpretation & conclusions: Homeostasis of NE, α1-AT and α2-MG is disrupted in T2DM, DN and DR. Strikingly reduced levels of α1-AT observed in DR are indicative of its possible role in the pathophysiology of retinopathy and emphasizes α1-AT as a plausible therapeutic target.

Keywords: Alpha1-antitrypsin complex; diabetic nephropathy; diabetic retinopathy; inflammation; neutrophil elastase; type 2 diabetes mellitus; α1-antitrypsin; α2-macroglobulin.

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Conflict of interest statement

Conflicts of Interest: None.

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