The Correlation Between Serum Ism-1 And Pancreatic β-cell Function,insulin Resistance,and Diabetic Retinopathy In Patients With Type 2 Diabetes

Background and purposeIsthmin-1(Ism-1),a novel adipokine modulating energy metabolism,appears to have beneficial effects on glucose and lipid metabolism.The relationship between serum Ism-1 levels and β-cell function,insulin resistance,and DR in patients with type 2 diabetes has never been studied.Therefore,this study aims to explore the relationship between serum Ism-1 levels and β-cell function,insulin resistance and DR in patients with T2DM,so as to provide effective laboratory indicators for early screening,early prevention and early treatment of diabetes and diabetes complications.MethodWe recruited patients with T2DM who were hospitalized in Qilu Hospital of Shandong University from October 2020 to October 2021.And all patients met the inclusion and exclusion criteria.Clinical parameters,Laboratory testing and Fundus examination were collected through the electronic medical record of Qilu Hospital.Serum Ism-1 levels were quantified using ELISA kits.The first study aims to demonstrate the associations of serum Ism-1 levels with β-cell function and insulin resistance,assessed by the circulating levels of Ism-1.The second part was divided into non-diabetic retinopathy group and diabetic retinopathy group according to the results of fundus examination,to explored the relationship between serum Ism-1 levels and DR in T2DM patients.All analyses were performed with SPSS V.25.0 software.Independent samples t-test or analysis of variance(ANOVA)was used to compare continuous variables with a normal distribution.For continuous variables with non-normal distribution,Mann-Whitney U test or Kruskal-Wallis H test was used.Categorical variables were analyzed using the chi-squared test.The association between serum Ism-1 levels and clinical parameters was assessed using Spearman’s correlation analysis.Univariate and multivariable logistic regression analyses were used to assess the association of serum Ism-1 levels with DR in different models.Smoothed curve fitting and generalized additive model(GAM)in this study were used to verify the existence of non-linear relationships between serum Ism-1 levels and DR.Finally,we also performed a subgroup analysis based on diabetes duration,hypertension,and HbAlc to determine the association between the serum Ism-1 levels and DR across various subgroups,and p for interaction was calculated.A p-value of less than 0.05 was considered statistically significant.Result1.The associations of serum Ism-1 levels with β-cell function and insulin resistance in patients with T2DM① A total of 154 patients with T2DM were included in this study,including 95 male patients and 59 female patients.The average age was 61.40±9.36 years and The average course of disease was 144.00(72.00-240.00)months.And we grouped the subjects to four quartiles according to the circulating levels of Ism-1.We found AUC-Ins/Glu,AUC-CP/Glu,HOMA2-%β,HOMA2-%S and HOMA2-IR were not significantly different among these four groups.② As shown in bivariate correlation analyses,Ism-1 levels did not correlate with β-cell function-related variables(AUC-Ins/Glu,AUC-CP/Glu,and HOMA2-%β)or insulin resistance-related variables(HOMA2-%S and HOMA2-IR)in T2DM subjects.After controlling multiple covariates,no significant correlation was observed between the Ism-1 levels and β-cell function-related variables or insulin resistance-related variables.2.The relationship between serum Ism-1 levels and DR in T2DM patients①In total,134 patients with T2DM were enrolled in the present study.The average age was 60.39±9.50 years and the average course of disease was 144.00(84.00-240.00)months.There were 75 DR cases including 50 males and 25 females.There were 59 NDR cases including 37 males and 22 females.Notably,the DR group presented a significantly higher Ism-1 levels compared to the control group(0.89±0.33 ng/mL vs.1.05±0.42 ng/mL).②As shown in bivariate correlation analyses,FPG,TC,HDL-C and eGFR negatively correlated with Ism-1 levels(r=-0.177,-0.199,-0.236,-0.277,p<0.05).While UA positively correlated with Ism-1 levels(r=0.275,p<0.05).③Univariate logistic analysis demonstrated that fasting C-peptide was a protective factor of DR and diabetes duration,SBP,Ism-1 were risk factors of DR.Multivariate logistic regression analysis showed that Ism-1 remained significant after adjusting for confounders.④For further assessment of the relationship between serum Ism-1 levels and the risk of DR,smooth curve fitting(penalized spline method)and generalized additive model(GAM)regression were conducted.Results of our study demonstrated a positively linear relationship between serum Ism-1 levels and DR prevalence after adjusting for confounders.⑤We performed a subgroup analysis based on diabetes duration,hypertension,and HbAlc to determine the association between the serum Ism-1 levels and DR across various subgroups.elevated Ism-1 levels was found to be associated with a higher prevalence of DR in the longer diabetes duration,hypertension,and poor control of blood glucose subgroup.However,all p-values for interaction were not statistically significant,which means that it can still be applied to all types of people.ConclusionSerum Ism-1 levels were not correlated with β-cell function or insulin resistance but positively correlated with DR prevalence in patients with T2DM.And increased serum Ism-1 levels were an independent risk factor for DR in T2DM patients.