Quantitatively Evaluating The Relationships Between Insulin Resistance And Retinal Neurodegeneration In Early Type 2 Diabetes Mellitus

Purpose:To quantitatively assess retinal neurodegenerative changes with optical coherence tomography(Cirrus HD-OCT)in type 2 diabetes mellitus(T2DM)patients without diabetic retinopathy(DR),and evaluate their relationships with insulin resistance(IR)and associated systemic indicators.Methods:This observational cross-sectional study included 102 T2 DM patients without DR and 48 healthy controls from the ophthalmology clinic of the Affiliated Hospital of Medical College,Qingdao University from April 2021 to July 2022.The OCT parameters of macular retinal thickness(MRT)and ganglion cell-inner plexiform layer(GCIPL)thicknesses were measured between diabetic and normal eyes to quantitatively evaluate retinal neurodegenerative changes.The receiver operating characteristics(ROC)curve was generated to evaluate the discrimination power of early diabetes.Correlation and multiple regression analysis were performed to determine the relationships between ophthalmological parameters and systemic indicators,including demographic and anthropometric variables,and serum biomarkers and homeostasis model assessment of insulin resistance(HOMA-IR)scores.Results:1.No significant differences were obtained in terms of age(P = 0.10),sex(P = 0.25),visual acuity(VA,P = 0.74),intraocular pressure(IOP,P = 0.21),and spherical equivalent(P = 0.78)between two groups.MRT(P = 0.008)and GCIPL thicknesses showed significant thinning in T2 DM patients,especially in the inferotemporal area(GCIPL: average,P = 0.001;minimum,P = 0.001;superior,P = 0.004;superotemporal,P = 0.002;inferotemporal,P ＜ 0.001;inferior,P = 0.001,inferonasal,P = 0.003;superonasal,P = 0.03).Regarding the discriminating ability for early diabetes,the highest area under the ROC curve(AUC)value was 0.675 for the inferotemporal GCIPL thickness.2.In the group of T2 DM patients without DR,age,body mass index(BMI),waist-to-hip circumference ratio(WHR),and HOMA-IR scores were negatively correlated with some OCT parameters.High-density lipoprotein(HDL)and fasting C-peptide(CP0)were associated with GCIPL thickness but only in inferotemporal region(HDL,r = 0.20,P = 0.04;CP0,r =-0.20,P = 0.05).No correlation coefficients with statistical significance were found between OCT parameters and diabetes duration,systolic blood pressure(SBP),glycosylated hemoglobin(Hb A1c),and triglycerides(TG).3.In the multiple regression analysis,increased HOMA-IR scores independently predicted both average(β =-0.30,P = 0.05)and inferotemporal(β =-0.34,P = 0.03)GCIPL thinning,and age was an independent influence factor for average GCIPL thickness(β =-0.22,P = 0.04).4.The results of correlation analysis between important glaucoma marker IOP and systemic indicators showed that IOP was positively associated with BMI(r = 0.20,P = 0.05)and SBP(r=0.22,P=0.03).A positive correlation tendency was also obtained between IOP and HOMA-IR scores(r = 0.19,P = 0.07).Conclusion:1.Retinal neurodegeneration was present even in early T2 DM patients without clinical detected DR,suggesting that it may precede microvasculopathy.2.Aberrant fat distribution and metabolism,and IR were risk factors for retinal neurodegeneration in early diabetes.3.IR as an independent risk factor for retinal neurodegeneration may increase the risk of developing glaucoma in early T2 DM.