Background: Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We aimed to investigate whether plasma ELABELA, recently identified as a latent biomarker for DKD, is related to the severity of NAFLD. Methods: A total of 362 patients with T2DM were enrolled in this study. Noninvasive clinical markers of hepatic fibrosis including fibrosis-4 (FIB-4) index, NAFLD fibrosis score (NFS) and aspartate aminotransferase-to-platelet ratio index (APRI) were determined. The levels of plasma ELABELA, UACR, creatinine and glucometabolic parameters were measured. The relationships between plasma ELABELA and the clinical markers were statistically evaluated. Results: Based on the median value of the plasma ELABELA, subjects were divided into low and high ELABELA groups. The low ELABELA group showed a significantly longer duration of diabetes, worsened nephropathic indices, and a more enhanced hepatic fibrosis index. A lower ELABELA was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (OR, 0.98; 95% CI, 0.966 to 0.994). Multiple regression analysis including confounding factors showed that ELABELA independently contributed to decreases in FIB-4 index (P=0.044), NFS (P=0.012). In addition, logistic regression analysis for the prevalence of advanced hepatic fibrosis defined by the cutoff points of the clinical scores showed that ELABELA was the sole and common negative factor for prevalence of advanced hepatic fibrosis (FIB-4 index: P=0.016, NFS: P=0.005). Conclusion: The decline of plasma ELABELA was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of plasma ELABELA as an effective biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future. Disclosure M. Shi: None. H. Cao: None. Y. Liu: None. W. Gu: None. H. Zhang: None. Funding Jiangsu Province Science and Technology Plan Special Funds (BE2023745); Jiangsu Health Commission Medical Scientific Research Project (H2023137)

Background: The growing evidence has been verified that C1q/TNF-related protein 6 (CTRP6) and CTRP9, secreted by adipose tissue, can regulate glucose and lipid metabolism. However, the effect of CTRP6 and CTRP9 in gestational diabetes mellitus (GDM) is scarcely known. This study aimed to evaluate the potential clinical value of CTRP6 and CTRP9 in GDM. Methods: A total of 35 GDM subjects and 37 healthy controls, between 24 and 28 weeks of gestation, were included in the study. Diagnosis of GDM was made according to American Diabetes Association criteria. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of CTRP6 and CTRP9. Fasting insulin (FINS), IL-6, and TNF-α were detected by Luminex-xMAP technology. The main clinical characteristics, such as Anthropological data and metabolic parameters, were also obtained. Results: Circulating CTRP6, CTRP9, IL-6 and TNF-α were significantly elevated in GDM subjects compared with controls. Pearson correlation analysis showed that CTRP6 and CTRP9 were positively correlated with FPG (r = 0.280, P = 0.017 and r = 0.559, P < 0.001, respectively) and HOMA-IR (r = 0.250, P = 0.035 and r = 0.382, P = 0.001, respectively). Moreover, CTRP9 was also positively correlated with FINS (r = 0.253, P = 0.032), IL-6 (r = 0.283, P = 0.016) and TNF-α (r = 0.266, P = 0.024). The area under the receiver operating characteristic curve (AUC-ROC) indicated that the combination of CTRP6 and CTRP9 was more effective in predicting GDM than single indicators. Conclusion: Elevated CTRP6 and CTRP9 in GDM patients may be related to insulin resistance. And inflammatory factors may mediate the role of CTRP9 in insulin resistance. In addition, CTRP6 and CTRP9 may serve as candidate predictors in patients with early GDM. Disclosure Y.Liu: None. Y.Chen: None. W.Gu: None. L.Yin: None. H.Cao: None. M.Shi: None. Funding National Natural Science Foundation of China (81700723)

Background/Aims: C1q/TNF-related protein 9 (CTRP9) as a member of CTRP super family, participates in the regulation of glycolipid metabolism. However information regarding the role of CTRP9 in gestational diabetes mellitus (GDM) is scarce. The current study aims to ascertain the relationship between serum CTRP9 levels and GDM. Methods: A total of 35 GDM patients and 37 normal pregnant women were enrolled in our study. Serum CTRP9 levels were measured via enzyme-linked immunosorbent assay (ELISA) . Fasting insulin (FINS) , IL-6, Leptin, MCP-1, TNF-α and IL-1β were quantified using Luminex-xMAP technology. Anthropometric data and biochemical parameters were also obtained or measured. Results: The results showed that fasting plasma glucose (FPG) , one hour plasma glucose (1-h PG) , 2 hour plasma glucose (2-h PG) , FINS, IL-6, Leptin, TNF-α and CTRP9 during GDM group were significantly higher than the control group. In addition, serum CTRP9 levels had a significantly positive correlation with FPG (r = 0.559, P < 0.001) , 1h-PG (r = 0.539, P <0.0) , 2h-PG (r = 0.378, P = 0.001) , FINS (r = 0.253, P = 0.032) , HOMA-IR (r = 0.382, P = 0.001) , IL-6 (r = 0.283, P = 0.016) , and TNF-α (r = 0.266, P = 0.024) . Furthermore, binary logistic regression demonstrated that HOMA-IR and CTRP9 were independent risk factors for GDM. The AUC-ROC indicated that the diagnostic efficiency of combined CTRP9 and HOMA-IR was much higher than a single index. Conclusions: The high level of serum CTRP9 is an independent risk factor for GDM. Moreover, the combination of serum CTRP9 and HOMA-IR were more efficient in diagnosing GDM. Key words: Gestational diabetes mellitus, CTRP9, insulin resistance Disclosure H. Zhang: None.

Aim: To analyze the relationship between serum Elabela (ELA) levels and type 2 diabetic retinopathy (DR) . Methods: A total of 81 patients with type 2 diabetes were collected. According to the stages of diabetic retinopathy, the patients were divided into three groups: group 1: no diabetic retinopathy stage, group 2: non-proliferative diabetic retinopathy (NPDR) and group 3: proliferative diabetic retinopathy (PDR) , with 27 patients in each group. Serum ELA levels were detected by ELISA. Relevant clinical datas were recorded and analyzed. Results: There were no statistical significance in age, BMI, FPG, HbA1c, t-chol, TG, LDL-C, HDL-C among 3 groups (all P> 0.05) . The duration of diabetes in group 1 was significantly shorter than that in groups 2 and 3 (all P<0.05) , and there were significant differences in SBP, DBP, eGFR and Cre in groups 3 compared with those in groups 1 and 2 (P<0.05) . From group 1 to group 3, the levels of ELA decreased gradually, with statistical significance among the three groups (P<0.05) . Correlation analysis showed that serum ELA levels were negatively correlated with the course of diabetes, DR, SBP, Cre (P<0.05) , and positively correlated with eGFR (P<0.05) . Stepwise multiple linear regression analysis showed that the most relevant variables for ELA were age, BMI and DR (P=0.005; P = 0.000; P = 0.001) . According to ROC curve analysis, the sensitivity and specificity of ELA in the diagnosis of diabetic retinopathy were 59.3%, 83.3%, and the area under the curve was 0.753 (95%CI: 0.638, 0.869, P=0.000) . Conclusions: With the progressive of diabetic retinopathy, the level of serum ELA decreases gradually. ELA may be a potential clinical predictor and therapeutic target of diabetic retinopathy. Disclosure W.Gu: None. M.Shi: None. Y.Chen: None. Y.Liu: None. J.Song: None. H.Zhang: None. Funding National Natural Science Foundation of China Grant Award (81200595/81400807/81700723) , Six High-peak Talents Project of Jiangsu Province (WSN-101) , Research Project of Jiangsu 333 engineering (BRA2016232) and Research Project of Jiangsu Provincial Commission of Health and Family Planning (F201549/H201667) , and International Science and Technology Cooperation Project of Huaian (HAC201707) .