Z.L.CHAN1, S.L.T.PEK1, A.Z.B.M.FADZIL2, K.ANG1, M.X.Q.LIN1, C.F.SUM3, S.C.LIM1, S. TAVINTHARAN1
Khoo Teck Puat Hospital1, Republic Polytechnic2, Admiralty Medical Centre3
Diabetic Retinopathy(DR) is a common complication in Type 2 Diabetes (T2D). Excess Matrix metalloprotease(MMPs) leads to lower Fibronection-1(FN1), leading to impaired healing. We validated deregulation of FN1 and upregulation of MMP8 from peripheral white cells in T2D cohorts.
We enrolled 2057 patients with T2D from 2011 to 2014. Out of 2057 patients, 178 were selected for the sub-cohort study. All patients took retinal eye examination and DR was diagnosed by eye specialist. Anthropometric data, demographics, biochemical indices were recorded. After isolation of peripheral white blood cells, total RNA from cases and controls were extracted from baseline blood. Gene expression profiling of MMP8 and FN1 were performed using real-time PCR. Data was analysed by SPSS, version 22.
Of the 178 samples measured, 125 patients did not have DR and 53 patients have DR. Characteristics/Results of No DR vs DR: Age(years): 49.7±12.8vs57.71±9.3, Duration of Diabetes(years) (8.4±7.8vs15.4.±10.2,p<0.001), Systolic Blood Pressure (135.5±19.6vs144.1±18.9,p=0.008), urine albumin-to-creatinine ratio (ACR) (19.0[5.0-63.3]vs106.0[15.0-816.5],p<0.001), neuropathy(%) (13.6vs52.8,p<0.0001) chronic kidney disease(%) (10.4vs34,p<0.0001), Angiotensin-converting enzyme inhibitor(%) (17.6vs32.7,p=0.024), Statin(%) (72vs84.9,p=0.047), Insulin(%) (28vs47.2,p=0.011) FN1(Relative Quantification) (0.998[0.558-1.623] vs 0.888[0.491-1.081],p=0.016). There were no significant differences in gender, ethnicity, and MMP8. FN1 Correlations: MMP8 (r=0.375,p<0.001), Duration of Diabetes (r=0.151,p=0.044). MMP8 Correlations: Heart Rate (r=0.245,p=0.001), Lower FN1[OR(95%CI):0.278(0.117-0.659),p=0.004], Longer duration of Diabetes[OR(95%CI):1.062 (1.014-1.113),p=0.012], higher urine albumin-creatinine ratio [OR(95%CI):2.164 (1.271-3.684),p=0.004] remained significant predictors of DR, after adjustment for age, gender, ethnicity, BMI, and fasting glucose.
T2D patients with DR has lower expression of FN1 compared with T2D patients without DR. Validation will be required in a larger cohort.