Disertasi

Pengaruh Pemberian Kolagen terhadap Perubahan Penanda Inflamasi, Gula Darah Puasa, Glycated Albumin, dan Albumin Serum pada Perbaikan Ulkus Kaki Diabetik = The Effects of Collagen Supplementation on Inflammatory Biomarkers, Fasting Blood Glucose, Glycated Albumin, and Serum Albumin in Diabetic Foot Ulcer Healing.

Latar Belakang: Ulkus kaki diabetik (UKD) merupakan salah satu komplikasi diabetes melitus yang ditandai oleh inflamasi persisten, gangguan kontrol glikemik, hipoalbuminemia, dan hambatan penyembuhan luka. Kolagen berpotensi menjadi terapi nutrisi suportif melalui efek antiinflamasi serta penyediaan asam amino yang berperan dalam regenerasi jaringan. Namun, bukti klinis mengenai efek pemberian kolagen oral pada pasien UKD masih terbatas. Penelitian ini bertujuan menganalisis pengaruh pemberian kolagen terhadap penanda inflamasi, gula darah puasa, glycated albumin, albumin serum, dan perbaikan ulkus kaki diabetik. Metode: Penelitian ini merupakan uji klinis acak tersamar ganda yang melibatkan pasien diabetes melitus tipe 2 dengan UKD derajat Wagner 2–3. Subjek dibagi secara acak ke dalam kelompok intervensi yang menerima kolagen 10 g/hari selama 21 hari (n=36) dan kelompok kontrol yang menerima plasebo (n=33). Parameter yang dievaluasi meliputi kadar interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP), gula darah puasa, glycated albumin, albumin serum, dan skor penyembuhan luka menggunakan skala DMIST. Hasil: Perubahan kadar IL-6 lebih besar pada kelompok kolagen dibandingkan kontrol (−3,38 vs 0,87 pg/mL; p=0,009), demikian pula hsCRP (−4,0 vs 0,5 mg/L; p=0,012). Peningkatan kadar albumin serum lebih tinggi pada kelompok kolagen dibandingkan kontrol (0,21±0,36 vs −0,07±0,35 g/dL; p=0,002) dan tetap bermakna setelah penyesuaian faktor perancu (p=0,031). Tidak terdapat perbedaan bermakna perubahan gula darah puasa (p=0,351) antar kelompok. Glycated albumin menurun secara bermakna setelah intervensi, namun perubahan antar kelompok tidak berbeda signifikan (p=0,264). Perbaikan UKD berdasarkan skor DMIST secara signifikan lebih besar pada kelompok kolagen dibandingkan kontrol (−4,22±2,81 vs −1,00 [−2–0]; p < 0,001), dan tetap bermakna setelah analisis multivariat dengan effect size besar (η²=0,199). Kesimpulan: Pemberian kolagen 10 g/hari selama 21 hari meningkatkan kadar albumin serum dan mempercepat perbaikan luka secara bermakna. Kolagen juga memperbaiki respons inflamasi melalui penurunan IL-6 dan hsCRP, meskipun tidak memberikan pengaruh bermakna terhadap gula darah puasa. Hasil penelitian ini memberikan dasar ilmiah bagi pemanfaatan kolagen sebagai terapi nutrisi pendukung dalam penatalaksanaan ulkus kaki diabetik.
Kata kunci: kolagen, ulkus kaki diabetik, IL-6, hsCRP, albumin serum, glycated albumin, DMIST


Background: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus characterized by persistent inflammation, impaired glycemic control, hypoalbuminemia, and delayed wound healing. Collagen has emerged as a potential supportive nutritional therapy due to its anti-inflammatory properties and its provision of amino acids essential for tissue regeneration. However, clinical evidence regarding the effects of collagen supplementation in patients with DFU remains limited. This study aimed to evaluate the effects of collagen supplementation on inflammatory biomarkers, fasting blood glucose, glycated albumin, serum albumin, and diabetic foot ulcer healing. Methods: This double-blind randomized controlled trial enrolled patients with type 2 diabetes mellitus and Wagner grade 2–3 diabetic foot ulcers. Participants were randomly assigned to either an intervention group receiving 10 g/day of collagen for 21 days (n = 36) or a control group receiving a placebo (n = 33). The evaluated outcomes included serum interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fasting blood glucose, glycated albumin, serum albumin, and wound healing assessed using the DMIST score. Results: Reductions in IL-6 were greater in the collagen group than in the control group (−3.38 vs. 0.87 pg/mL; p = 0.009), as were reductions in hsCRP (−4.0 vs. 0.5 mg/L; p = 0.012). The increase in serum albumin was significantly greater in the collagen group than in the control group (0.21 ± 0.36 vs. −0.07 ± 0.35 g/dL; p = 0.002) and remained significant after adjustment for potential confounding factors (p = 0.031). No significant between-group difference was observed in changes in fasting blood glucose (p = 0.351). Although glycated albumin decreased significantly following the intervention, the between-group difference was not statistically significant (p = 0.264). Improvement in DFU healing, as measured by the DMIST score, was significantly greater in the collagen group than in the control group (−4.22 ± 2.81 vs. −1.00 [−2 to 0]; p < 0.001), and this difference remained significant after multivariable analysis, with a large effect size (η² = 0.199). Conclusions: Oral collagen supplementation at a dose of 10 g/day for 21 days significantly increased serum albumin levels and accelerated diabetic foot ulcer healing. Collagen also improved the inflammatory response by reducing IL-6 and hsCRP concentrations, although it did not significantly affect fasting blood glucose. These findings provide scientific evidence highlighting the role of collagen as a supportive nutritional therapy in the comprehensive management of diabetic foot ulcers.
Keywords: collagen; diabetic foot ulcer; IL-6; hsCRP; serum albumin; glycated albumin; DMIST