Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2009, vol. 18, nr 4, July-August, p. 353–360

Publication type: original article

Language: English

Connection Between Ischemia−Modified Albumin Levels and Markers of Diabetic Nephropathy and Oxidative Protein Damage in Type 2 Diabetic Patients

Związek albuminy modyfikowanej niedokrwieniem z markerami nefropatii cukrzycowej i oksydacyjnego uszkodzenia białek u chorych na cukrzycę typu 2

Agnieszka Piwowar1,, Maria Knapik−Kordecka2,, Maria Warwas1,

1 Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Poland

2 Department and Clinic of Angiology, Hypertension and Diabetology, Wroclaw Medical University, Poland

Abstract

Background. Ischaemia and hypoxia are observed in diabetic patients in addition to chronic hyperglycemia and intensified oxidative stress. It is reflected by increased markers levels of oxidative protein damage, especially in patients with vascular complications, as well as ischemia−modified albumin (IMA).
Objectives. To assess the plasma levels of IMA in T2DM patients with different degrees of diabetic nephropathy and their relationship with routine markers of kidney disease severity (urinary albumin/creatinine, plasma creatinine concentration) and parameters of oxidative processes, i.e. advanced oxidation protein products (AOPPs) and sufhydryl (SH) and carbonyl (CO) groups.
Material and Methods. Plasma IMA levels were manually determined in 78 patients and 22 healthy people by spectrophotometric Co(II)−albumin binding assay. Diabetic nephropathy stage was determined on the basis of the urinary albumin/creatinine ratio. Plasma AOPP levels as well as SH and CO groups (as DNPH reactive derivatives) were determined by spectrophotometric methods.
Results. The IMA levels in the diabetic patients were significantly higher than in the healthy controls and increased progressively with the degree of DN. The normoalbuminuria group had the lowest IMA level, which was significantly different from those in the micro(p < 0.05) and macroalbuminuria (p < 0.01) groups. There were significant relationships between IMA and markers of DN (r = 0.47 for urinary albumin/creatinine and r = 0.36 for plasma creatinine) and oxidative stress (r = 0.38 for AOPPs and r = –0.44 for SH groups).
Conclusion. This study indicates that the observed increased IMA in T2DM is connected with diabetic nephropathy and oxidative protein damage. Measuring IMA plasma levels provided no additional information about nephropathy development, but it may be helpful in assessing the severity of oxidative stress, which causes kidney dysfunction.

Streszczenie

Wprowadzenie. U chorych na cukrzycę oprócz przewlekłej hiperglikemii i nasilonego stresu oksydacyjnego występują stany niedokrwienia i niedotlenienia, czego odzwierciedleniem jest zwiększone stężenie markerów oksydacyjnego uszkodzenia białek, szczególnie u osób z powikłaniami naczyniowymi, oraz albuminy modyfikowanej niedokrwieniem.
Cel pracy. Pomiar stężenia albuminy modyfikowanej niedotlenieniem (IMA) w osoczu pacjentów chorych na cukrzycę typu 2 (T2DM) i z różnym stopniem nefropatii cukrzycowej (DN) oraz ocena związku między IMA, a rutynowymi markerami odzwierciedlającymi stopień niewydolności nerek (indeks albumina/kreatynia w moczu, stężenie kreatryniny w osoczu) oraz wskaźnikami oksydacyjnego uszkodzenia białek (zaawansowane produkty utleniania białek (AOPP), grupy sufhydrylowe (SH) i karbonylowe (CO)).
Materiał i metody. W osoczu 78 osób chorych oraz 22 zdrowych oznaczono stężenie IMA spektrofotometryczną metodą manualną opartą na pomiarze zdolności wiązania jonów kobaltu (Co(II)) przez zmodyfikowaną albuminę. Stopień nefropatii cukrzycowej określono na podstawie wartości indeksu albumina/kreatynina. Stężenie AOPP oraz grup SH i CO (w postaci pochodnych DNPH) w osoczu oznaczono metodami spektrofotometrycznymi.
Wyniki. Stężenie IMA u chorych na cukrzycę było istotnie wyższe niż w grupie kontrolnej i wzrastało progresywnie wraz z rozwojem stopnia DN. Najniższe stężenie IMA w grupie z normoalbuminurią było znacząco różne od wartości u pacjentów z mikroalbuminurią (p < 0,05) i makroalbuminurią (p < 0,01). Stwierdzono istotny związek między IMA a markerami DN (r = 0,47 z indeksem albumina/kreatynina oraz r = 0,36 ze stężeniem kreatyniny w osoczu), jak również z parametrami stresu oksydacyjnego (r = 0,38 z AOPP i r = –0,44 z grupami SH).
Wnioski. Wyniki badań własnych wskazują, że obserwowany w T2DM wzrost IMA jest związany ze stopniem nefropatii cukrzycowej oraz oksydacyjnym uszkodzeniem białek. Pomiar stężenia IMA w osoczu tych chorych nie dostarcza dodatkowych informacji na temat rozwoju nefropatii, ale może być pomocny w oszacowaniu intensywności stresu oksydacyjnego, który powoduje uszkodzenie i zaburzenie czynności nerek.

Key words

type 2 diabetes mellitus, IMA, diabetic nephropathy, oxidative protein damage

Słowa kluczowe

cukrzyca typu 2, IMA, nefropatia cukrzycowa, oksydacyjne uszkodzenie białek

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