The link between diabetic retinal and renal microvasculopathy is associated with dyslipidemia and upregulated circulating level of cytokines.

To investigate the mechanisms underlying the correlations between diabetic retinopathy (DR) and diabetic nephropathy (DKD) and examine whether circulating cytokines and dyslipidemia contribute to both DR and DKD in patients with 2 diabetes mellitus (T2DM). A total of 122 patients with T2DM were enrolled and categorized into the DM group (without no DR and DKD), DR group [non-proliferative DR (NPDR), and proliferative DR (PDR)] with no DKD), DR complicated with DKD groups (DR+DKD group). The biochemical profile, including fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and lipid profile were estimated, and plasma inflammatory and angiogenic cytokines [monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF)-A, C, D, and placental growth factor (PlGF)] were analyzed by protein microarrays. The atherogenic plasma index (API) was defined as low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein-cholesterol (HDL-C); atherogenic index (AI) was calculated as [(total cholesterol (TC) -HDL-C)/HDL-C], and atherogenic index of plasma (AIP) was defined as log (TG/HDL-C). By multivariable disordered regression analysis, after controlling for duration of DM and hypertension, LDL-C (p = 0.019) and VEGF-D (p = 0.029) resulted as independent risk factors for DR. Albumin-to-creatinine ratio (uACR) (p = 0.003) was an independent risk factor for DR with DKD. In DR, NPDR, and PDR groups, grades of A1, A2, and A3 of albuminuria increased with the severity of DR. In A1, A2, and A3 grade groups, the severity of DR (DM, NPDR, and PDR) increased with higher albuminuria grades. Kendall's tau-b correlation coefficient analysis revealed that FBG (p = 0.019), circulating level of PlGF (p = 0.002), and VEGF-D (p = 0.008) were significantly positively correlated with the grades of uACR (p < 0.001), and uACR grades were significantly correlated with DR severity (p < 0.001). The occurrence and severity of DR are closely correlated with kidney dysfunction. Among the three kidney functional parameters, uACR resulted as the better indicator of DR severity and progression than glomerular filtration (eGFR) and serum creatinine (Scr). Impaired FBG was associated with microalbuminuria, emphasizing that well-controlled FBG is important for both DR and DKD. The link between diabetic retinal and renal microvasculopathy was associated with dyslipidemia and upregulated circulating level of angiogenic cytokines.

Chen X ，Zhang X ，Gong Z ，Yang Y ，Zhang X ，Wang Q ，Wang Y ，Xie R ... -  《Frontiers in Public Health》

Dysregulated Serum Lipid Metabolism Promotes the Occurrence and Development of Diabetic Retinopathy Associated With Upregulated Circulating Levels of VEGF-A, VEGF-D, and PlGF.

Purpose: This study aims to explore the correlations of arteriosclerosis-associated plasma indices with various severity levels of diabetic retinopathy (DR) and to test the hypothesis that elevated circulating level of known angiogenic cytokines induced by hyperglycemia is associated with dyslipidemia on DR. Methods: This cross-sectional study consists of 131 patients with type 2 diabetes. The patients were categorized based on their DR status into those with no DR (diabetes mellitus, DM), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) groups. The biochemical profile including fasting glucose, glycated hemoglobin (HbA1c), lipid profile were estimated, plasma angiogenic cytokines (vascular endothelial growth factor, VEGF-A, -C, -D) and placental growth factor (PlGF) were analyzed by protein microarrays. The atherogenic plasma index (API) was defined as low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C); atherogenic index (AI) was calculated as (TC-(HDL-C))/HDL-C and atherogenic index of plasma (AIP) was defined as log (TG/HDL-C). Results: No significant differences were detected in the duration of hypertension, age, and gender between the three groups. Serum TC and LDL-C, AI, and API in the NPDR group and PDR group were significantly higher than those in the DM group. The circulating level of PlGF, VEGF-A, and VEGF-C were significantly correlated with the severity of DR. VEGF-D is a risk factor independent of API (Z = -2.61, P = 0.009) and AI (Z = -2.40, P = 0.016). Multivariate logistic regression showed that AI and API are strong risk factors for the occurrence and severity of DR. Associated with AI and API, VEGF-D and PlGF contribute to DR: VEGF-D [AI: P = 0.038, odd ratio (OR) = 1.38; VEGF-D: P = 0.002, OR = 1.00. API: P = 0.027, OR = 1.56, VEGF-D:P = 0.002, OR = 1.00] and PlGF [AI: P = 0.021, OR = 1.43; VEGF-D: P = 0.004, OR = 1.50. API: P = 0.011, OR = 1.66; VEGF-D: P = 0.005, OR = 1.49]. Conclusions: Total cholesterol (TC) and LDL-C are risk factors for presence of any DR. Atherogenic index and API are novel and better predictive indicators for the occurrence and severity of DR in comparion with the traditional lipid profiles. Abnormal lipid metabolism are associated with the upregulation of circulating cytokines that are linked to the severity of DR.

Zhang X ，Qiu B ，Wang Q ，Sivaprasad S ，Wang Y ，Zhao L ，Xie R ，Li L ，Kang W ... -  《Frontiers in Medicine》

Circulating level of homocysteine contributes to diabetic retinopathy associated with dysregulated lipid profile and impaired kidney function in patients with type 2 diabetes mellitus.

To test the hypothesis that elevated plasma levels of homocysteine (Hcy) and lipoprotein (a) (LPA) contribute to diabetic retinopathy (DR) associated with dysregulated lipid profile, dyslipidaemia, and kidney function. A total of 83 patients with type 2 diabetes mellitus (T2DM) were enrolled in this prospective case-control study. Patients were categorized into those with no DR (DM), non-proliferative DR (NPDR), and proliferative DR (PDR). Age and sex-matched individuals with no diabetes were included in the control group. Biochemical tests, including fasting blood glucose (FBG), glycated hemoglobin (HbA1c), Hcy, LPA, lipid profile, and urine microalbumin (UMA), were evaluated. Hcy was negatively correlated with high-density lipoprotein-cholesterol (HDL-C) (p < 0.05), but positively correlated with [total cholesterol (TC)-HDL-C)/HDL-C] (p < 0.05), low-density lipoprotein cholesterol (LDL-C)/HDL-C (p < 0.05), and UMA (p < 0.05). Traditional risk factors, Hcy, arteriosclerosis-associated plasma indices, and UMA, resulted as the independent risk factors for the occurrence of DM and DR. After controlling for age, sex, duration of DM, and FBG, a multiple ordinal logistic regression model showed that LPA [OR = 2.90, 95% confidence interval (95% CI) 1.16-7.23, p = 0.023)], LDL-C (OR = 4.28, 95% CI 1.24-14.79, p = 0.021), and (TC-HDL-C)/HDL-C (OR = 1.92, 95% CI 1.05-3.53, p = 0.035) were risk factors for DM and DR. Hcy and LPA contributed to DM and DR. Hcy was positively correlated with kidney dysfunction and the ratios of lipid profiles, and negatively with HDL-C, LPA, LDL-C, and (TC-HDL-C)/HDL-C resulted as predictors of the occurrence of DM and severity of DR.

Chen X ，Zhang X ，Nie Y ，Gong Z ，Sivaprasad S ，Fung AT ，Wang Q ，Qiu B ，Xie R ，Wang Y ... -  《-》

Plasma Apolipoproteins Predicting the Occurrence and Severity of Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus.

Apolipoproteins are amphipathic molecules and the major components of plasma lipoproteins. This study aims to investigate the effects of dysregulated apolipoprotein (apo) profiles and their ratios on type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) further to test the hypothesis that altered serum level of apolipoproteins is strong biomarkers for DR. This case-control study consists of 157 patients with T2DM including DM without DR, non-proliferative DR (NPDR), and proliferative DR (PDR). Fifty-eight age- and sex-matched healthy subjects were enrolled as normal controls. Blood biochemistry profile including serum levels of glucose, glycated hemoglobin (HbA1c), lipid profile [total cholesterol (TC), Triglycerides (TG), high and low-density lipoprotein (HDL-C and LDL-C)] was estimated. Apolipoproteins (apos, A-I, A-II, B, C-II, C-III, and E) was evaluated by protein chips (Luminex technology). Apolipoprotein ratios and arteriosclerosis-associated plasma indices were calculated. The Kruskal-Wallis test, independent sample t-test or Mann-Whitney U test, and multivariate regression analysis were performed to investigate the association of serum lipid biomarkers and the DR severity. Serum level of apoA-I was negatively correlated with TC-(HDL-C)/HDL-C (p < 0.001), fasting glucose (p < 0.001), HbA1c (p < 0.001), and (p<0.001), while apoE, apoC-II/apoC-III, apoA-II/apoA-I were positively correlated with above traditional biomarkers (p < 0.001). Single variable logistic analysis results showed that body mass index (BMI) (p = 0.023), DM duration (p < 0.001), apoE (p < 0.001), apoC-II/apo C-III (p < 0.001), apoE/apoC-II (p < 0.001), atherogenic index (p = 0.013), fasting glucose (p < 0.001), HbA1c (p < 0.001), LPA (p = 0.001), and LDL-C/HDL-C (p = 0.031) were risk factors for the occurrence and severity of DR. Multivariate logistic regression mode showed that apoC-II/apoC-III and apoB/non-HDL-C (p < 0.001) as well as apoE/apoC-II (p = 0.001) were the independent risk factors for the occurrence and severity of DR-apopA-I and apoA-II are protective factors for DR-after controlling for the duration of DM, HbA1c, fasting glucose, and LPA. apoE, apoC-II/apoC-III, apoE/apoC-II, and apoB/non-HDL-C could be used as novel biomarkers for occurrence and severity of DR, whereas apoA-I and apoA-II resulted as protective factors for DR.

Zhang X ，Nie Y ，Gong Z ，Zhu M ，Qiu B ，Wang Q ... -  《Frontiers in Endocrinology》

Plasma level of miR-93 is associated with higher risk to develop type 2 diabetic retinopathy.

Zou HL ，Wang Y ，Gang Q ，Zhang Y ，Sun Y ... -  《-》