Evaluation of PADI4 (Human Peptidyl Arginine Deiminase Type 4) levels in patients with type 2 diabetes mellitus with/without complications

Year 2025, Volume: 18 Issue: 4, 15 - 15

Başak Ünver Koluman , Semin Melahat Fenkçi , Esin Avcı , Hande Şenol , Tuba Köksoy , Ayten Eraydın

Abstract

Purpose: Human peptidyl arginine deiminase 4 (PADI4) transforms arginine residues on histone tails to citrulline. Recently, researchers have studied PADI4 in inflammation, infection, cancer, and autoimmune disorders. PADI4 also modulates the release of neutrophil extracellular traps (NETs) through a process known as NETosis, which is linked to dysglycemia. PADI4's role in type 2 diabetic mellitus (DM) is not well understood. The goal of this study is to compare PADI4 levels in type 2 DM patients who have not yet experienced diabetic complications, those who have, and a healthy control group.
Materials and methods: This research included three groups of volunteers aged 30-65 years old: a healthy control group, a type 2 diabetic with no diabetic complications, and those with diabetic complications. Serum samples from control and type 2 DM patients were analyzed for complete blood count, biochemistry, and PADI4 (ng/ml).
Results: The control, complicated, and uncomplicated type 2 DM groups did not differ significantly in their serum PADI4 levels (4.94±5.09 ng/ml (med: 2.62, IQR: 2.34-3.87), 5.06±6.58 ng/ml (med: 2.59, IQR: 2.19-2.99), and 4.51±4.76 (med: 2.74, IQR: 2.1- 3.71). Vitamin B12 levels were significantly higher in the complicated type 2 DM group than in the control group (647.83±461.37 vs. 357.32±136.15; p=0.03). The correlation analysis found no significant relationship between nephropathy, retinopathy, or neuropathy and serum PADI4 in the complicated type 2 DM group. There was a statistically significant, negative, and slight correlation with metformin use in the uncomplicated DM group (r=-0.325, p=0.05).
Conclusion: Finally, there was no significant difference in serum PADI4 levels between the type 2 DM groups with complications, those without complications, and the healthy control group. PADI4 is seen as a viable target for illness treatment and surveillance. Prospective studies involving larger patient populations on this subject are needed.

Keywords

PADI4 protein, diabetes mellitus, NETosis, complication

Komplikasyon gelişmemiş ve komplikasyon gelişmiş Tip 2 DM (Diabetes Mellitus) hastalarında PADI4 (İnsan Peptidil Arjinin Deiminaz Tip 4) düzeylerinin incelenmesi

Abstract

Amaç: İnsan peptidil arjinin deiminaz 4 (PADI4), histon kuyruklarındaki arginin kalıntılarını sitrüline dönüştürür. Son yıllarda araştırmacılar, PADI4'ün inflamasyon, enfeksiyon, kanser ve otoimmün bozukluklardaki rolünü araştırmaktadır. PADI4 ayrıca, disglisemi ile bağlantılı olan NETosis olarak bilinen bir süreç aracılığıyla nötrofil ekstraselüler tuzaklarının (NET) salınımını da düzenler. PADI4'ün tip 2 diyabet mellitustaki (DM) rolü tam olarak anlaşılamamıştır. Bu çalışmanın amacı, henüz diyabetik komplikasyonları olan ve olmayan tip 2 DM hastalarındaki ve sağlıklı kontrol bireylerindeki PADI4 seviyelerini karşılaştırmaktır.
Gereç ve yöntem: Bu çalışma 30-65 yaş aralığındaki üç grup gönüllüden oluşmuştur: sağlıklı bir kontrol grubu, diyabetik komplikasyonları olan ve olmayan tip 2 DM hastaları. Kontrol ve tip 2 DM hastalarından alınan serum örneklerinde tam kan sayımı, biyokimya ve PADI4 (ng/ml) tetkikleri çalışılmıştır.
Bulgular: Kontrol, komplike ve komplike olmayan tip 2 DM gruplarında serum PADI4 seviyelerinde anlamlı bir farklılık bulunmamıştır (4,94±5,09 ng/ml (orta: 2,62, IQR: 2,34-3,87), 5,06±6,58 ng/ml (orta: 2,59, IQR: 2,19- 2,99) ve 4,51±4,76 (orta: 2,74, IQR: 2,1-3,71). B12 vitamini seviyeleri komplike tip 2 DM grubunda kontrol grubuna göre anlamlı derecede daha yüksek olarak bulunmuştur (647,83±461,37 vs. 357,32±136,15; p=0,03). Komplike tip 2 DM grubunda nefropati, retinopati veya nöropati ile serum PADI4 arasında anlamlı bir korelasyon bulunamamıştır. Komplike olmayan DM grubunda metformin kullanımıyla istatistiksel olarak anlamlı, negatif ve hafif bir korelasyon saptanmıştır (r=-0,325, p=0,05).
Sonuç: Sonuç olarak, komplikasyon gelişmiş veya gelişmemiş tip 2 DM hastaları ve sağlıklı kontrol grubu arasında serum PADI4 seviyelerinde istatistiksel olarak anlamlı bir fark saptanmamıştır. PADI4 birçok hastalık tedavisi ve gözetimi için uygulanabilir bir hedef olarak görülmektedir. Bu konuda daha fazla hasta popülasyonlarını içeren prospektif çalışmalara ihtiyaç vardır.

Keywords

PADI4 protein, diabetes mellitus, NETosis, komplikasyon

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