ABSTRACT
Objective:To investigate the correlation between serum levels of heme oxygenase-1 (HO-1) and lipoxin A4 (LXA4) and diabetic nephropathy, and to analyze the value of HO-1 and LXA4 in the diagnosis of diabetic nephropathy.Methods:A prospective cohort study was conducted in 185 patients with type 2 diabetes admitted to the Department of Endocrinology, Yan'an Hospital Affiliated to Kunming Medical University from January 2016 to January 2020. There were 96 cases with diabetic nephropathy (nephropathy group) and 89 cases without diabetic nephropathy (non nephropathy group). According to the stage of chronic kidney disease,the nephrotic group was divided into three subgroups: stage 1-2 group (31 cases), stage 3-4 group (40 cases) and stage 5 group (25 cases). Another 82 healthy volunteers were selected as the control group.Serum HO-1, LXA4, oxidative stress,inflammatory factors, glucose metabolism and renal function were detected. Pearson analysis of HO-1, LXA4 and oxidative stress, inflammatory factors, glucose metabolism and renal function index correlation, binary logistic regression analysis of diabetic nephropathy factors.Results:The serum HO-1 ((0.60 ± 0.20) μg/L) and LXA4 levels ((435.12 ± 22.42) ng/L) in nephrotic group were lower than those in non nephrotic ((0.72 ± 0.23) μg/L, (498.21 ± 29.48) ng/L)( t=29.351, 24.135, all P<0.05). The serum HO-1 and LXA4 levels in the 5 stage group were lower than those in the 3-4 stage and 1-2 stage group (all P<0.05). The serum HO-1 and LXA4 levels in the 3-4 stage group were lower than those in the 1-2 stage group (all P<0.05). Pearson correlation analysis showed that HO-1 was positively correlated with total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and estimated glomerular filtration rate (EGFR) ( r=0.516, 0.602, 0.617; all P<0.05), and was positively correlated with malondialdehyde (MDA) and homeostasis model insulin resistance (homeostasis model insulin resistance) Model assessment insulin resistance (HOMA-IR), urinary albumin creatinine ratio (UACR) LXA4 was negatively correlated with T-AOC, SOD and EGFR ( r=-0.559, 0.597, 0.637; all P<0.05), and positively correlated with MDA, IL-6, TGF-β1, HOMA-IR and UACR There was a negative correlation ( r=-0.498, -0.623, -0.725; all P<0.05). Binary logistic regression analysis showed that malondialdehyde ( OR=1.587, 95% CI 1.402-1.603, P=0.016), TGF-β1 ( OR=1.679, 95% CI 1.642-1.739, P=0.012), HOMA-IR ( OR=1.699、95% CI 1.534-1.739, P=0.009) were risk factors of diabetic nephropathy (all P<0.05). HO-1 ( OR=0.506, 95% CI 0.423-0.653, P<0.001) and LXA4 ( OR=0.492, 95% CI 0.409-0.535, P<0.001) were protective factors for DN ( P<0.001). After adjusting for MDA, TGF-β1 and HOMA-IR, HO-1 ( OR=0.485, 95% CI:0.402-0.564, P<0.001) and LXA4 ( OR=0.416, 95% CI:0.386-0.475, P<0.001) were still associated with DN. ROC analysis showed that the area under curve (AUC) of HO-1 and LXA4 were 0.820 (95% CI:0.760-0.880, P<0.001) and 0.763 (95% CI:0.691-0.836, P<0.001), respectively. The sensitivity and specificity were 71.88%, 80.90%, 75.00% and 84.27%, respectively. Conclusion:The decrease of serum LXA4 and HO-1 levels is closely related to diabetic nephropathy, which can be used as a biological indicator for the diagnosis of diabetic nephropathy.
ABSTRACT
Objective:To explore the predictive value of serum betatrophin and ficolin-3 during early pregnancy for gestational diabetes mellitus (GDM).Methods:Using a prospective research method, from June 2018 to June 2019, 7 to 13 weeks pregnant women were selected in Yan′an Hospital of Kunming City, and their fasting peripheral venous blood samples were reserved. At 24 to 28 weeks of pregnancy, oral glucose tolerance test (OGGT) was performed. Sixty-five cases were diagnosed as GDM (GDM group), and 60 pregnant women with normal OGGT result and matched age and gestational weeks were selected as normal group. In addition, 60 non-pregnant healthy women with matched age were selected as control group. The serum levels of betatrophin and ficolin-3 were measured in GDM group, normal control group (during 7 to 13 weeks of gestation) and control group were measured by enzyme linked immunosorbent assay method. Pearson test was used to analyze the correlation between serum betatrophin, ficolin-3 and glycolipid metabolism indexes during 24 to 28 weeks of gestation. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum betatrophin and ficolin-3 during early pregnancy for GDM.Results:The serum betatrophin and ficolin-3 in GDM group were significantly higher than those in normal group and control group: (35.69 ± 6.15) ng/L vs. (23.90 ± 7.68) and (19.68 ± 6.33) ng/L, (31.75 ± 10.30) μg/L vs. (22.88 ± 12.71) and (18.47 ± 9.54) μg/L, the betatrophin and ficolin-3 in normal group were significantly higher than those in control group, and there were statistical differences ( P<0.05). The correlation analysis result showed that serum betatrophin was positive correlation with total cholesterol (TC), glycosylated hemoglobin (HbA 1c) and homeostatic model assessment insulin resistance index (HOMA-IR) ( r = 0.585, 0.440 and 0.735; P<0.01); the serum ficolin-3 was positively correlated with HbA1c ( r = 0.673, P<0.01), and negatively correlated with high-density lipoprotein cholesterol (HDL-C) ( r = - 0.520, P<0.01). ROC curve analysis result showed that the areas under curve of betatrophin and ficolin-3 for predicting GDM were 0.829 and 0.795, 95% CI 0.753 to 0.905 and 0.718 to 0.872, and the optimum critical values were 27.69 ng/L and 29.72 μg/L, with a sensitivity of 89.36% and 84.58%, a specificity of 72.14% and 79.64% and Yorden index of 0.62 and 0.59. The areas under curve of betatrophin combined with ficolin-3 for predicting GDM was 0.923, 95% CI 0.868 to 0.978, with a sensitivity of 91.25%, a specificity of 87.24% and Yorden index of 0.86. Conclusions:GDM pregnant women have abnormal expression of serum betatrophin and ficolin-3 during early pregnancy, and the indexes are related to glycolipid metabolism. Serum betatrophin and ficolin-3 during early pregnancy have certain predictive value for GDM.