Hubungan Kadar Serum Apolipoprotein A1, Apolipoprotein B dengan Tingkat Keparahan, Progresivitas, dan Respon Terapi Diabetic Macular Edema pada Penderita Diabetes Melitus Tipe 2

SOEFIANDI SOEDARMAN, Prof. dr. Madarina Julia, MPH., Ph.D., Sp.A(K); dr. Muhammad Bayu Sasongko, M.Epid., Sp.M(K)., Ph.D.; Prof. dr. Tjahjono D. Gondhowiardjo, Sp.M(K)., Ph.D.

2023 | Disertasi | DOKTOR ILMU KEDOKTERAN DAN KESEHATAN

Tujuan: Mengetahui hubungan antara kadar serum apolipoprotein A1, apolipoprotein B, dan rasio apolipoprotein B/A1 dengan progresivitas DME dan keberhasilan tata laksananya yang dinilai dari pemeriksaan klinis, pemeriksaan ketebalan retina pada daerah makula dengan pemeriksaan optical coherence tomography (OCT), dan luasan area edema dan iskemia dengan pemeriksaan optical coherence tomography angiography (OCT-A). Apolipoprotein diharapkan dapat menjadi penanda progresivitas DME yang lebih baik dan akurat. Metode: Penelitian ini merupakan studi kohort prospektif dari 53 pasien DR dengan mengkaji hubungan antara apolipoprotein A1, apolipoprotein B, dan rasio apolipoprotein B/A1 dengan progresivitas DME, serta hubungannya dengan ketebalan retina sentral, foveal avascular zone, vessel density, dan perfusion density retina. Subjek penelitian berusia > 30 tahun dengan diabetic retinopathy (DR) yang belum pernah mendapatkan terapi DR. Pemeriksaan klinis, pemeriksaan OCT dan OCT-A, serta pengambilan sampel serum (apolipoprotein, profil lipid, dan HbA1c) dilakukan saat bulan 0 dan follow up bulan keenam. Subjek penelitian akan mendapatkan terapi sesuai indikasi. Hasil: Dari 38 subjek yang dianalisis, didapatkan hasil bahwa kadar apolipoprotein tidak berhubungan dengan kondisi terjadinya PDR dan DME pada awal pemeriksaan, namun Apo A1 yang rendah, Apo B yang tinggi, dan rasio Apo B/A1 yang tinggi berhubungan dengan progresivitas dan persistensi DME (p<0,05). Setiap penurunan kadar Apo A1 sebesar 10 mg/dL (p=0,014) dan peningkatan rasio ApoB/A1 sebesar 0,2 (p=0,019) meningkatkan risiko progresivitas/ persistensi DME. Kadar Apo A1>135 mg/dL (p=0,013) dan rasio apolipoprotein B/A1 0,85 (p=0,013) berhubungan signifikan dengan regresi DME. Kadar Apo B >122,5 mg/dL berhubungan dengan peningkatan ketebalan retina (p=0,013), perluasan FAZ (p=0,020), penurunan perfusion density (p=0,039), dan penurunan vessel density (p=0,039). Penurunan apolipoprotein A1 dan peningkatan rasio apolipoprotein B/A1 berhubungan dengan berat badan, indeks massa tubuh, resting metabolic rate, dan persentase lemak viseral yang lebih tinggi. Kesimpulan: Kadar apolipoprotein A1 yang rendah, apolipoprotein B yang tinggi, dan rasio apolipoprotein B/A1 yang tinggi dapat berfungsi sebagai penanda prediktor progresivitas DME yang lebih akurat dibandingkan dengan parameter profil lipid. Peningkatan apolipoprotein B memiliki peran sebagai penanda prediktor perburukan vaskularisasi retina dan iskemia makula pada DME progresif. Peningkatan apolipoprotein A1 dan penurunan rasio apolipoprotein B/A1 bermakna secara klinis sebagai faktor protektif terhadap progresivitas DME pasca terapi 6 bulan.

Objective: This study aims to determine association between serum Apolipoprotein A1 (Apo A1) and Apolipoprotein B (Apo B) levels, as well as the B/A1 ratio with the progression of Diabetic Macular Edema (DME) and DME therapeutic response. This will be achieved through clinical examination, Optical Coherence Tomography (OCT) assessment of retinal thickness in the macular area, and Optical Coherence Tomography Angiography (OCT-A) assessment of edema and ischemic areas. Apolipoprotein is expected to serve as a better and more accurate biomarker of DME progression. Methods: This was a prospective cohort study of 53 Diabetic Retinopathy (DR) patients. The objective was to determine the correlation between Apo A1, Apo B, and the B/A1 ratio with DME progression in relation to Central Retinal Thickness (CRT), Foveal Avascular Zone (FAZ), retinal vessel density, and retinal perfusion density. The participants used were aged 30 years and above, diagnosed with DR with or without DME but never received DR therapy. Clinical, OCT, and OCT-A examinations were conducted along with serum sampling for apolipoprotein, lipid profile, and HbA1c at month 0 (baseline) and follow-up was performed at month six. The participants were provided with every necessary therapy. Results: From 38 subjects analyzed, apolipoprotein parameters were found to have no relationship with PDR and DME occurrence at the beginning of the study, but low Apo A1, high Apo B, and high B/A1 ratio were associated with the progression and persistence of DME (p<0.05). Every 10 mg/dL decrease in apo A1 level (p=0.014) and every 0.2 increase in apo B/A1 ratio (p=0.019) elevated the risk of DME progression/persistence. Apo A1 levels >135 mg/dL (p=0.013) and B/A1 ratio 0.85 (p=0.013) were significantly associated with DME regression. Apo B levels >122.5 mg/dL were associated with an increased retinal thickness (p=0.013), FAZ expansion (p=0.020), decreased perfusion density (p=0.039), and reduced vessel density (p=0.039). Decreased apo A1 and increased B/A1 ratio in DR patients were associated with higher body weight, mass index, resting metabolic rate, and visceral fat percentage. Conclusion: Low levels of Apo A1, high B, and high B/A1 ratio can function as better and more accurate predictors of DME progression than lipid profiles. In particular, increased Apo B has been identified as a predictor of worsening retinal vascular and macular ischemia in progressive DME. Furthermore, increased Apo A1 and decreased B/A1 ratio were found to be clinically significant as protective factors against DME progression six months post-therapy.

Kata Kunci : Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B), rasio Apolipoprotein B/A1, Diabetic Retinopathy (DR), Diabetic Macular Edema (DME), optical coherence tomography (OCT)