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Hubungan antara kadar Transforming Growth Factor Beta1 dengan kejadian retinopati diabetik pada penderita diabetes mellitus tipe 2

SUYANTO, Prof.dr. Paulus Wiyono, PhD.,SpPD-KEMD

2006 | Tesis | PPDS I Ilmu Penyakit Dalam

Latar belakang: Retinopati dan nefropati merupakan morbiditas utama pada pen-derita diabetes mellitus. Patogenesis keduanya dikenal mirip. Transforming growth factor (TGF)-β1 dianggap sebagai molekul efektor utama pada nefropati diabetik. Namun, penelitian TGF-β1 pada retinopati jarang dilakukan. Kondisi diabetik me-ningkatkan aktivitas TGF-β1. Peran TGF-β1 adalah meningkatkan matriks ekstra-seluler dan migrasi perisit dan sel endotel kapiler retina. Hasil akhir aktivitas terse-but adalah neovaskularisasi yang merupakan gambaran retinopati proliferatif. Tujuan: untuk mengetahui perbedaan kadar TGF-β1 serum pada penderita diabetes mellitus tipe 2 dengan retinopati dan penderita tanpa retinopati. Subjek dan metoda: Penelitian dilakukan dengan cara studi potong lintang, dengan pengambilan sampel consecutive dan perbandingan jumlah sampel 1:2. Subjek penelitian adalah penderita DM tipe 2 yang berobat di poliklinik RS Dr Sardjito Yogyakarta dari bulan Mei sampai Agustus 2005. Didapatkan 48 subjek sesuai dengan kriteria inklusi, 4 di antaranya tereksklusi. Sebanyak 14 orang retinopati dan 30 orang tanpa retinopati dibandingkan dalam kadar TGF-β1 dan beberapa variabel lain seperti umur, lama menderita DM, rasio albumin-kreatinin urin, kadar gula da-rah dan klirens kreatinin. Perbedaan rerata dianalisis menggunakan student t test atau U Mann-Whitney. Regresi logistik berganda digunakan untuk melihat peran variabel terhadap retinopati. Hasil: Rerata umur subjek penelitian adalah 57,5 ±9,4 tahun; rerata lama menderita DM 8,59 ±5,39 tahun; median rasio albumin-kreatinin urin 102,5 (20-544) μg/mg; median klirens kreatinin 57,80 (34,55-146,48) mL/menit/1,73m2; median kadar TGF-β1 8,80 (7,0-12,4) ng/mL. Terdapat perbedaan antara penderita retinopati dan tidak retinopati dalam umur (62,21 ±7,18 vs 55,60 ±9,67 tahun, p=0,028), lama menderita DM (10,0 [5,0-18,0] vs 7,0 [0,4-20,0] tahun, p=0,015) dan kadar TGF-β1 (10,73 ±1,39 vs 8,45 ±0,94 ng/mL, p<0,001). Dari variabel tersebut, efek terbesar terhadap retinopati terdapat pada umur (efek regresi standar, ERS 0,012; p=0,045) dan kadar TGF-β1 (ERS 0,779; p=0,001). Antara umur dan kadar TGF-β1 tidak terdapat interaksi maupun korelasi. Kesimpulan: Terdapat hubungan antara kadar TGF-β1 dengan retinopati diabetik pada penderita DM tipe 2. Umur penderita dan kadar TGF-β1 berperan terhadap ter-jadinya retinopati diabetik.

Background: Retinopathy and nephropathy become the major morbidity in patients of diabetes mellitus. Pathogenesis of them was known similarly. Transforming growth factor (TGF)-β1 considered as major effector molecule in diabetic nephro-pathy. But, study about TGF-β1 on retinopathy was infrequently done. Diabetic state increased TGF-β1 activity. Role of TGF-β1 in retinopathy is increase extra-cellular matrix deposit and retinal capillary pericyte and endothelial cell migration. Outcome of this activity is neovascularisation, one of the proliferative retinopathy characteristics. The aim: The study was aimed to investigate the association between serum TGF-β1 level and diabetic retinopathy among type 2 diabetic patients. Subjects and methods: Research was conducted in cross-sectional design with consecutive sampling and sample number ratio 1:2. Subjects were type 2 diabetes patients who attended clinics of Dr. Sardjito Hospital from May to August 2005. There were 48 subjects fulfilled the inclusion criteria, 4 of them were excluded. Fourteen retinopathy patients and 30 no retinopathy patients were compared in serum TGF-β1 level and some variables like age, diabetes duration, urinary albumin-creatinine ratio, blood glucose and creatinine clearance. Student t test or U Mann-Whitney test used to analyze mean difference. Multiple logistic regressions used to investigate role of variables on retinopathy. Results: Mean of subjects’ age was 57,5 ±9,4 years; mean of diabetes duration was 8,59 ±5,39 years; median of urinary albumin-creatinine ratio was 102,5 (20-544) μg/mg; median of cretinine clearance was 57,80 (34,55-146,48) mL/second/1,73m2; median of serum TGF-β1 level was 8,80 (7,0-12,4) ng/mL. There were differences between retinopathy patients and no retinopathy patients in age (62,21 ±7,18 vs 55,60 ±9,67 years, p=0,028), diabetes duration (10,0 [5,0-18,0] vs 7,0 [0,4-20,0] years, p=0,015) and serum TGF-β1 level (10,73 ±1,39 vs 8,45 ±0,94 ng/mL, p<0,001). Among these variables, the most close effect to retinopathy were found in age (standardized regression effects, SRE 0,012; p=0,045) and TGF-β1 level (SRE 0,779; p=0,001). Between age and TGF-β1 level had neither interaction nor corre-lation. Conclutions: There was association between serum TGF-β1 and diabetic retino-pathy in type 2 DM patients. Patients’ age and serum TGF-β1 level had role in diabetic retinopathy.

Kata Kunci : DM Tipe II,Retinopati,Kadar TGF Beta1, Type 2 DM – retinopathy – TGF-β1 level


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