Changes of serum levels of TGF-β1 and IL-6 in patients with diabetic retinopathy and its clinical significance

The relationship between type 1 diabetes mellitus (T1DM) and periodontal disease may exhibit by the alteration of bone metabolism. However, evidence for this relationship is scarce and inconclusive. Thus, the aims of the present study were to investigate salivary receptor activator of nuclear factor kappa-β (RANK), receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG) gene expression and the RANKL:OPG ratio in T1DM and non-T1DM. Secondary objective was to determine the relationships of RANK, RANKL and OPG gene expression to clinical parameters of T1DM and periodontal disease. Twenty patients with T1DM and twenty age-matched non-T1DM were recruited. Clinical periodontal parameters were measured. Total RNA was isolated from non-stimulated saliva, and the relative gene expressions of RANK, RANKL, OPG and RANKL:OPG ratio were determined by quantitative real-time polymerase chain reaction. The T1DM group had significantly higher mean periodontal parameters than the non-T1DM group, while the mean plaque scores of both groups were not significantly different. There was a trend of higher relative gene expression of RANK, RANKL, and the RANKL:OPG ratio and lower expression of OPG in T1DM group but no statistic significant different when compared to non-T1DM. In the T1DM group, RANKL:OPG correlated with the percentage of bleeding sites, whereas RANK, RANKL, and HbA1c levels correlated with pocket depth. Bone metabolisms demonstrating by decreased OPG gene expression and upregulated of RANK, RANKL, RANKL:OPG with higher pocket depth and bleeding in T1DM may play an important role in periodontal destruction in T1DM.

Objective To investigate the expression and clinical significance of miR-126 and vascular endothelial growth factor (VEGF) in proliferative diabetic retinopathy (PDR). Methods 226 cases of diabetic retinopathy (DR) patients admitted in our hospital were studied, including 110 cases of PDR (group PDR), 116 non proliferative diabetic retinopathy (NPDR) (group NPDR). 80 patients with diabetes mellitus without retinopathy (NDR) were enrolled in DR group at the same period, another 80 healthy subjects (control group) were selected as control group. The plasma miR-126 level of all subjects was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The enzyme linked im-munosorbent assay (ELISA) method was used to detect plasma VEGF level. The clinical diagnostic value of miR-126 and VEGF in PDR patients was further analyzed. Results Plasma levels of miR-126 in PDR group, NPDR group and NDR group were lower than those in control group (P<0.05), PDR group was lower than NPDR group and NDR group (P<0.05); plasma levels of VEGF in PDR group, NPDR group and NDR group were higher than those in control group (P<0.05), PDR group was higher than NPDR group and NDR group (P<0.05). Total cholesterol (TC), triglyceride (TG) and glycated hemoglobin (HbA1c) in PDR group were higher than those in NPDR group and NDR group (P<0.05), low density lipoprotein cholesterol (LDL-C) in PDR group, NPDR group and NDR group were higher than those in control group (P<0.05), and LDL-C in PDR group was higher than that in NPDR group and NDR group (P<0.05). High density lipoprotein cholesterol (HDL-C) in PDR group and NDR group was lower than that in control group (P<0.05), C-reactive protein (CRP) in PDR group, NPDR group and NDR group was higher than that in control group (P<0.05); plasma miR-126 levels in PDR group were negatively correlated with TC, LDL-C, CRP and HbA1c (P<0.05), but positively correlated with HDL-C (P<0.05), and no correlation with TG; the plasma levels of VEGF in PDR patients were positively correlated with TC, TG, LDL-C, CRP and HbA1c (P<0.05), but negatively correlated with the expressions of miR-126 (r=-0.573, P=0.000); the AUC of miR-126 was 0.861, and when the cut-off value was <0.64, the diagnostic sensitivity and specificity were 82.50% , 83.64%; the area under curve (AUC) of VEGF was 0.889, and when the cut-off value was <7.000, the sensitivity and specificity of diagnosis were 82.73%, 86.25%; 0.847 for the AUC of HbA1c, and the sensitivity and specificity 81.82%, 87.50% respectively. Conclusions Plasma miR-126 is low-expressed and VEGF is high-expressed in PDR patients, there is a negative correlation between the two indexes. They may be involved in the course of PDR through abnormal lipid metabolism and inflammatory reaction and may be a potential biomarker for early diagnosis of PDR. Key words: Diabetic retinopathy/BL; MicroRNAs/BL; Vascular endothelial growth factors/BL

Objective To investigate the correlation of urinary albumin excretion rate (UAER) with diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). Methods Two hundred and twenty-one patients with type 2 diabetes mellitus were selected and divided into non DR group (NDR), non proliferative DR (NPDR) group and proliferative DR group (PDR) according to fundus examination results. The clinical biochemical indexes and risk factors of DR lesions were observed and analyzed. Results The prevalence rate of DR group was 39.36%, and was 35.29%, 4.07% of NPDR group and PDR group, respectively. The indexes of diabetes, glycosylated hemoglobin (HbAlc) and other indicators of NPDR and PDR group were higher than those of NDR group (P<0.05). In PDR group, the systolic blood pressure (SBP), total cholesterol and other indicators were higher than those in NDR group; the levels of serum creatinine (Cr), urine albumin was also higher than those in NDR and NPDR group (P<0.05); The glomerular filtration rate of NDR and NPDR group was higher than that of PDR group (P<0.05). There was positive correlation of the incidence of UAER with DR (P<0.05). Regression results showed that the duration of diabetes, HbA1c, UAER were the independent risk factors of DR. Conclusions There is close relationship between UAER and DR, which can be detected as early as possible by screening DR. Key words: Type 2 diabetes mellitus; Urinary albumin excretion rate; Retinopathy; Correlation

Objective To observe the amount of endothelial progenitor cells(EPCs)at different stages of diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(DM).Methods Sixty patients with type 2 DM were divided into no DR(NDR)group,non-proliferative DR(NPDR)group and proliferative DR(PDR)group according to the examination of fundus and fundus fluorescein angiography,20patients in each group.Twenty healthy people were collected as the control group.6 ml blood samples were taken from all the subjects,and then the EPCs contents in peripheral blood were detected by flow cytometry.Results The EPCs contents in peripheral blood of the control,NDR,NPDR and PDR group were(0.0179±0.0047)% ,(0.0151±0.0086)% ,(0.0123±0.1137)% ,(0.0316±0.0294)% .The EPCs contents in peripheral blood of the PDR group was significantly higher than those in others(χ2=43.780,P＜0.05);the EPCs contents in peripheral blood of the NDR and NPDR group were slightly lower than that in the control group(χ2=5.244,P=0.73);the EPCs contents in peripheral blood of the NPDR group was lower than that in the NDR group(χ2=6.0 1 6,P=0.12).Conclusion The EPCs contents in peripheral blood decreases in NDR,NPDR patients,while significantly increases in PDR patients. Key words: Diabetic retinopathy/pathophysiology; Endothelium,vascular; Myeloid progenitor cells; Diabetes mellitus,type 2/complications

Objective To evaluate the variations of serum OPG, TGF-β and IL-6 levels with bone loss in postmenopausal women with or without type 2 diabetes mellitus (T2DM), to elucidate the role of serum OPG, TGF-β and IL-6 levels in prediction for 10-year probability of fracture risk, and to explore the impact of serum OPG, TGF-β and IL-6 levels on the progression of type 2 diabetic fracture. Methods This study included 128 postmenopausal women who were diagnosed as osteopenia (areal bone mineral density at spine and hip of all subjects were measured by DXA, patients with T score more than -2.5 and less than -1.0 were diagnosed as osteopenea). They were divided into two groups, T2DM group and non-T2DM group. Besides of BMD, all subjects were measured the serum levels of OPG, TGF-β and IL-6. Furthermore, we predicted the 10-year probability of fracture risk in all cohorts by FRAX® and analyzed the correlations of the risk with serum levels of OPG, TGF-β and IL-6 in all subjects. Results There were no significant differences of BMD between the two groups (Z=0.841, P>0.05). However, the serum levels of OPG (Z=2.264, P=0.024), TGF-β (Z=2.836, P=0.005) and IL-6 (Z=2.431, P=0.015) in T2DM group were higher than that in non-T2DM group. Furthermore, the serum levels of OPG, TGF-β and IL-6 were correlated with the 10-year probability of fracture risk in T2DM group. Conclusion The serum levels of OPG, TGF-β and IL-6 increased in osteopenia patients with T2DM, suggesting that the increased inflammatory factors could be used as predictors for the 10-year probability of fracture risk in osteopenia patients with T2DM. Key words: Diabetes mellitus, Type 2; Osteoporosis; Serum response factor; Fracture risk

Purpose To measure the concentrations of various cytokines in the aqueous humor from patients with different stages of diabetic retinopathy. Methods All selected cataract patients were categorized into 4 groups: the control group (patients without diabetes), nonretinopathy (NDR) group (diabetic patients without retinopathy), nonproliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. The aqueous concentrations of interleukin- (IL-) 1β, IL-2, IL-4, IL-5, IL-6, IL-10, interferon-γ, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) from patients were measured using the cytometric bead array technique. Results In this study, 10, 22, 15, and 14 patients were included in the control, NDR, NPDR, and PDR groups, respectively. No difference was observed in the aqueous concentrations of all cytokines between the control group and the NDR group. By contrast, comparison of these groups revealed that the aqueous concentrations of most inflammatory cytokines were significantly higher in the PDR and NPDR groups. In addition, the concentrations of IL-2, IL-5, and VEGF were higher in the PDR group than those in the NPDR group. Conclusions Aqueous concentrations of various cytokines increased with the severity of patients' diabetic retinopathy. This finding implies that these cytokines might play a role in the progression of diabetic retinopathy.

Background Some aboard studies showed that polyatomic pathway play an important role in the microsvasculopathy of type 2 diabetes,and sorbitol dehydrogenase (SDH) gene is involved in the pathogenesis of diabetic retinopathy(DR).There is no relevant research at home up to now.Objective This study was to investigate the correlation of sorbitol dehydrogenase (SDH) G-888C gene polymorphism with diabetic retinopathy (DR) in type 2 diabetes mellitus.Methods The SDH genotypes were determined by polymerase chain reactionreaction fragment length polymorphism (PCR-RFLP) in 187 patients with diabetes and 123 normal contrels.Patients were divided into two groups depending on the presence or absence of DR(DR:n=118;NDR:n=69).The frequencies of SDH genotype and allele were assayed and compared among these groups.This study was approved by Ethic Committee of Guangdong General Hospital.Written informed consent was obtained from each individual prior to any relevant medical procedure.Results The disease course in the DR group was significantly longer than that in NDR group(t=2.070,P=0.042),and other clinical features in both groups were non-significant (all P>0.05).The genotype frequencies in the DR group,NDR group and normal control group were 24.6%,8.7% and 8.1%,respectively,and frequencies of the G allele were 42.4%,25.4% and 29.7%,showing statistically significant differences among these three groups.The GG genotype and G allele frequencies were significantly higher in the DR group than those in the NDR group and normal control group (GG:P=0.007,P=0.001;G:P=0.001,P=0.004).There were no significant differences in the frequencies of the GG genotype and G allele between the NDB group and normal control group ( P>0. 05) as well as the proliferative DR group and non-proliferative DR group (P>0.05).Conclusion SDH G-888C gene polymorphism is associated with the development of diabetic retinopathy in southern Chinese. Key words: Sorbitol dehydrogenase gene; Gene polymorphism; Type 2 diabetes mellitus; Retinopathy

Objective To evaluate the value of color Doppler ultrasound in the assessment of post-ocular hemodynamic changes in diabetic patients. Methods Sixty patients with type 2 diabetes mellitus (120 eyes) treated at our hospital from January, 2016 to May, 2017 were selected as an observation group and divided into a non-proliferative diabetic retinopathy (NPDR) group, a diabetic no-retinopathy (DNR) group, and a proliferative diabetic retinopathy (PDR) group according to the patients' conditions, 20 cases (40 eyes) for each group. And 60 normal subjects (120 eyes) were set as a control group. All were examined with color Doppler ultrasound. The blood flow parameters of the posterior ciliary artery (PCA), the central retinal artery (CRA), and the ocular artery (OA) of each group were compared. Results The EDV, PSV, and RI of CRA were (5.69 ± 1.23) cm/s, (12.57 ± 2.20) cm/s, and (0.56 ± 0.07) in the control group, were (4.72±1.06)cm/s, (10.33±2.10)cm/s, and (0.63±0.06) in the DNR group, were (3.56±1.04)cm/s, (9.69±1.42)cm/s, and (0.73±0.07) in the NPDR group, and were (2.56±0.89) cm/s, (7.26±1.34)cm/s, and (0.79±0.08) in the PDR group, with statistical differences (P <0.05) The end-diastolic velocity (EDV) and peak systolic velocity (PSV) were the highest in the control group, those in the DNR group came next, and those in the NPDR group, and those in the PDR group; the resistance index (RI) was the lowest in the control group, and second lowest in the DNR group, third in the NPDR group, and fourth in the PDR group; there were statistical differeces (P <0.05). Conclusions Color Doppler ultrasound can dynamically monitor the retinal blood flow status and determine the degree of diabetic retinopathy according to the changes of blood flow and can provide some references for clinical treatment. Key words: Diabetic eye disease; Color Doppler ultrasound; Hemodynamics

Subclinical left ventricular (LV) dysfunction is prevalent in type 2 diabetes (T2DM). As obesity has been proposed as one causal factor in the disease process, this could bias the reported prevalences. We wanted to characterize echocardiographic LV dysfunction in obese T2DM subjects as compared to non-diabetic obese controls. One hundred patients with T2DM without clinical signs of heart failure (29% females, mean ± SD age 58.4 ± 10.5 years, body mass index (BMI) 30.1 ± 5.5 kg/m(2), blood pressure (BP) 141 ± 18/83 ± 9 mmHg) and 100 non-diabetic controls (29% females) matched for age (58.6 ± 10.5 years), BMI (29.8 ± 4.0 kg/m(2) and systolic BP (140 ± 14 mmHg) underwent echocardiography and color tissue Doppler imaging (TDI). Diastolic function was evaluated with conventional Doppler recordings and early (e') and late (a') myocardial velocities. The ratio between early transmitral filling (E) and the corresponding myocardial tissue velocity (e') served as an index of LV filling pressure. T2DM patients had more concentric hypertrophy with a relative wall thickness of 0.42 ± 0.07 vs controls 0.38 ± 0.07, P < 0.001. The T2DM group had signs of diastolic dysfunction with lower E/A ratio (0.91 ± 0.27 vs. 1.12 ± 0.38, P < 0.001), deceleration time (195 ± 49 vs 242 ± 72 ms, P < 0.001), e' (5.7 ± 2.0 vs. 6.6 ± 1.8 cm/s, P = 0.001), and a' (6.5 ± 2.0 vs. 7.6 ± 1.5 cm/s, P < 0.001) compared to the controls, and higher E/e' (13.3 ± 4.7 vs. 11.1 ± 3.5, P < 0.001). Thus, there were indications of pseudo normalization and increased filling pressure in the T2DM group, whereas the controls had evidence for relaxation abnormalities without elevated filling pressure. Compared to a non-diabetic obese group, more advanced subclinical impairment of diastolic function was seen in T2DM.

Background Inflammation is one of the most popular aspects in the studies of diabetic retinopathy (DR) mechanisms.Researches showed that S100A8/A9 participate in the inflammatory procedure of many diseases, however, the relationship between S100A8/A9 complex and retinal inflammation of DR needs to be researched. Objective This study was to detect the serum S100A8/A9 level of diabetes mellitus (DM) and DR patients, and explore its role in DM an DR development. Methods A cases-controlled study was carried out.The DR patients, type 2 DM patients without retinal change and heathy controls were enrolled in Shanghai Xuhui Central Hospital from January to June 2014, and 30 patients for each group.The DR patients were subgrouped to non-proliferative DR (NPDR) group and proliferative DR (PDR) group.The periphery blood was collected to isolate the serum, and serum S100A8/A9 complex level was detected by ELISA.Serum high-sensitivity C-reactive protein (hsCRP) and glycosylated hemoglobin A1C (HbAlc) level was assayed by immunity turbidimetry and immune agglutination respectively. Results Serum S100A8/A9 complex levels in the DR group, DM group and normal control group were (9.74±0.59), (11.41±0.64) and (6.46±0.62)μg/L, respectively, and the serum S100A8/A9 complex level in the DM group and DR group was significantly higher than that in the normal control group, and the serum S100A8/A9 complex level in the DM group raised in compared with the DR group (all at P<0.01). Serum hsCRP levels in the DR group, DM group and normal control group were (1.40±0.34), (1.27±0.13) and (1.11±0.12)mg/L, respectively, with the highest value in the DR group and the lowest value in the normal control group ( all at P=0.00). The serum HbAlc levels were higher in the DR group and DM group than those in the normal control group (both at P=0.00), while no significant difference was found in the serum HbAlc level between DR group and DM group (P=0.12). There was no significant differece in the serum S100A8/A9, hsCRP and HbAlc levels between NPDR group and PDR group (t=-0.10, P=0.92; t=-0.17, P=0.87; t=0.66, P=0.51). A weak positive correlation was seen between serum S100A8/A9 level and serum hsCRP level (r=0.36, P=0.00). Conclusions As an inflammatory marker, S100A8/A9 complex might play an important role in the pathogenesis and development of DR.Intensive control of glycemia can alleviate retinal inflammation in DM patients. Key words: Diabetes mellitus/complications; Diabetic retinopathy; Inflammation; S100A8/A9 complex

Objective To observe the serum vascular endothelial growth factor (VEGF), apelin and heme oxygenase-1 (HO-1) levels in patients with type 2 diabetes mellitus (T2DM) and to explore their their relationship with diabetic retinopathy (DR). Methods A total of 208 patients with T2DM and 50 healthy subjects (control group) from the Central Hospital of Western Hainan during January 2014 and December 2017 were selected in this study. Vision, slit lamp microscope, indirect ophthalmoscope and FFA examinations were performed on all the subjects. According to the results of the examinations combined with the DR clinical staging criteria, the patients were divided into non-DR (NDR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group, with 72, 76 and 60 patients in each, respectively. The clinical data of each group were recorded, and the levels of fasting blood glucose (FPG), HbA1c, total cholesterol (TC), three acylglycerol (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), VEGF, apelin and HO-1 were detected in each group. The receiver operating characteristic curve (ROC) were used to analyze the value of VEGF, apelin and HO-1 in predicting the occurrence of PDR. Correlation analysis of serum VEGF, Apelin and HO-1 with clinical parameters in PDR patients by Pearson correlation analysis. Results The level of VEGF (56.82±10.16 vs 91.74±22.83, 140.15±36.40, 195.28±42.26 pg/ml) and apelin (2.95±0.53 vs 4.68±0.74, 7.25±1.13, 10.16±1.35 ng/ml) in PDR group were significantly higher than those in NPDR, NDR and control groups (F=17.306, 21.814; P<0.05). The level of HO-1 (50.37±10.14 vs 43.58±8.16, 30.25±6.28, 22.60±4.72 mmol/L) in PDR group was significantly lower than those in NPDR, NDR and control groups (F=15.827, P<0.05). The ROC curve analysis showed that the best cut-off values of serum VEGF, apelin and HO-1 were 162.50 pg/ml, 8.30 ng/ml, 27.13 mmol/L, and the three combined to predict PDR of AUC (95%CI) was 0.906 (0.849−0.962), and their sensitivity (90.3%) and specificity (83%) were better. The correlation analysis showed that the VEGF, apelin and HO-1 of PDR patients were correlated with the course of diabetes (r=0.382, 0.416, −0.36; P<0.05), FPG (r=0.438, 0.460, −0.397; P<0.05) and HbAlc (r=0.375, 0.478, −0.405; P<0.05), and the serum VEGF were correlated with apelin and HO-1 (r=0.793, −0.594; P<0.01). Conclusion Elevated serum VEGF and apelin levels and reduced HO-1 levels are associated with the progression of DR, and the three combination helps predict the occurrence of PDR. Key words: Diabetic retinopathy/etiology; Diabetes mellitus, type 2; Vascular endothelial growth factors; Receptors, angiotensin; Heme oxygenase-1

To investigate the association between angiotensin converting enzyme (ACE) gene locus rs1799752 insertion/deletion (I/D) polymorphism and diabetic retinopathy (DR) in type 2 diabetes mellitus. Case-control study. Type 2 diabetes patients were recruited and assigned into DR group, which included proliferative diabetic retinopathy (PDR) group or diabetes without retinopathy (DWR) group. Volunteers without diabetes from the same community were recruited as the control group. PCR and agarose gel electrophoresis methods were adopted to determine the rs1799752 I/D polymorphism genotypes of the ACE gene. The frequency of genotypes and alleles was compared among the various groups. Four hundred and twelve diabetes patients: (207 subjects of DR, including 53 subjects of PDR and 205 subjects of DWR) and 97 non-diabetic control subjects were included in the study. The frequencies of the I and D alleles of ACE rs1799752 polymorphism were 54.1% and 45.9%, respectively, in the DR group, 52.8% and 47.2% in the PDR group, and 48.0% and 52.0% in the DWR group. There were no statistical differences between DR and DWR groups (χ(2) = 3.02, P > 0.05) or between PDR and DWR groups (χ(2) = 0.77, P > 0.05). Moreover, there were no statistical differences in the distribution of the ACE genotypes between DR group (II 25.1%, ID 58.0%, DD 16.9%) and DWR group (II 22.0%, ID 52.2%, DD 25.9%) (χ(2) = 4.92, P > 0.05) or between PDR group (II 20.7%, ID 64.2%, DD 15.1%) and DWR group (χ(2) = 3.19, P > 0.05). No statistical differences were found in the frequencies of the I and D alleles, and the distributions of I/D genotypes between diabetic group and the control group (χ(2) = 0.25, 4.98; P > 0.05). In the multiple regressions model including clinical factors such as the age of onset of diabetes, urinary albumin, insulin usage, creatinine, glycated hemoglobin, fast glucose, and the use of ACE inhibitor, no association was found between ACE gene polymorphism and DR (OR = 0.80, 95%CI: 0.59 - 1.09) or PDR (OR = 1.23, 95%CI: 0.78 - 1.93). There is no association between ACE rs1799752 gene insertion/deletion (I/D) polymorphism and DR in patients with type 2 diabetes mellitus.

Objective To observe the macular capillary morphology in diabetic patients. Methods A total of 61 patients (104 eyes) with diabetes mellitus (DM group) and 31 healthy controls (41 eyes) were enrolled in the study. According to the degree of diabetic retinopathy (DR), the DM group was divided into non-DR (NDR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group. There were 13 patients (23 eyes), 21 patients (34 eyes) and 27 patients (47 eyes) in each group, respectively. According to whether there was diabetic macular edema (DME), the DM patients were divided into DME group and non-DME group, each had 20 patients (28 eyes) and 41 patients (76 eyes), respectively. The age (F=2.045) and sex (χ2=2.589) between the control group, the NDR group, the NPDR group and PDR group were not statistically significant (P=0.908, 0.374). The 3 mm × 3 mm region in macula was scanned by optical coherence tomography angiography (OCTA), and the retinal capillary morphological changes of superficial capillary layer (SCL) and deep capillary layer (DCL) were observed. Chi-square test and t test were used to compare data among different groups. Results There was no abnormal change of retinal capillary morphology in control group. Microaneurysms and foveal avascular zone (FAZ) integrity erosion can be found in NDR group. There were microaneurysms, FAZ integrity erosion, vascular tortuosity bending, capillary non-perfusion and venous beading in NPDR and PDR groups. The microaneurysms of DCL were significantly more than that of the SCL (t=4.759, P<0.001). The eyes with microaneurysms in NDR group, NPDR group, and PDR group showed significant differences (χ2=44.071, P<0.001), and the eyes with FAZ integrity erosion among these three groups also showed significant differences (χ2=30.759, P<0.001). Compared with NPDR group and PDR group, there were significant differences in vascular tortuosity bending and capillary non-perfusion (vascular tortuosity bending: OR=0.213, 95%CI 0.070−0.648, P=0.004; capillary non-perfusion: OR=0.073, 95%CI 0.022−0.251, P<0.001), and there was no significant difference in venous beading (OR=0.415, 95%CI 0.143−1.208, P=0.102). SCL blood flow density in the 4 groups (control, NDR, NPDR and PDR group) was 49.233±1.694, 48.453±2.581, 45.020±4.685 and 40.667±4.516, respectively. While the difference between the control and NDR group was not significant, the differences between other pairs (control vs NPDR/PDR, NDR vs NPDR/PDR, NPDR vs PDR) were significant. The ratio of FAZ integrity erosion and non-perfusion of DME group was significantly higher than those of non-DME group (vascular tortuosity bending: OR=7.719, 95%CI 1.645−36.228, P=0.004; capillary non-perfusion: OR=14.560, 95%CI 3.134−67.646, P<0.001). Conclusions OCTA can distinctively detect the abnormal retinal capillary changes of SCL and DCL in diabetic patients. Even in DM patients without diabetic retinopathy, OCTA can detect abnormal blood vessels. Key words: Diabetic retinopathy; Regional blood flow; Tomography, optical coherence; Foveal avascular zone

Objective To investigate the relationship between the level of serum undercarboxylated osteocalcin (ucOC) with the development and progression of diabetic retinopathy (DR) in male patients with type 2 diabetes mellitus (T2DM). Methods A total of 125 male patients with T2DM cared at Tangshan Gongren Hospital from October 2015 to November 2016 were recruited as subjects, they were divided into three groups as: T2DM without DR group (NDR, n=45), T2DM none-proliferative DR group (NPDR, n=42) and T2DM with proliferative DR group (PDR, n=38). 50 male subjects without T2DM from the medical examination center were selected as normal control group (NC). Data including age, diabetes duration, body mass index, systolic blood pressure, diastolic blood pressure were recorded, and clinical biochemical indicators including fasting plasma glucose, glycated hemoglobin A1c, triglyceride, total cholesterol, low-density lipoprotein-cholestrol, high-density lipoprotein-cholestrol (HDL-C), 24 h urinary albumin excretion rate (UAER) and fasting insulin were collected, homeostasis model assessment of insulin resistance (HOMA-IR) was calculated, ucOC was measured by enzyme linked immunosorbent assay. Multiple-group comparisons were analyzed by one-way ANOVA or Kruskal-Wallis H test. Two-group comparisons were analyzed by LSD test or LSD test by rank conversion. Multivariate correlation analysis was used Pearson or Spearman correlation analysis. Risk factor screening was used multiple stepwise regression analysis. Results (1) The serum ucOC level of T2DM groups were lower than NC group. The order of serum ucOC level from low to high were PDR, NPDR, NDR and NC [(1.4±0.6), (2.1±0.9), (2.7±0.9), (3.3±0.9) μg/L, F=63.149, all P<0.05]. (2) Serum ucOC was negatively associated with HbA1c, HOMA-IR, 24hUAER (r=-0.379,-0.237,-0.429, all P<0.05), and was positively associated with HDL-C (r=0.223, P<0.05). (3) Logistic regression analysis showed that duration of diabetes, HOMA-IR, 24hUAER and ucOC were independent risk factors of DR in male T2DM patients (OR=0.396-2.523, all P<0.05). Conclusion The reduction of serum ucOC in male T2DM patients may be related to the development and progression of DR. Key words: Diabetes mellitus, type 2; Male; Diabetic retinopathy; Undercarboxylated osteocalcin

Objective To analyze the expression levels of miR-15 and miR-29a in serum of patients with diabetic retinopathy (DR) and their diagnostic values for DR. Methods 155 patients (155 eyes) with type 2 diabetes mellitus (DM) were treated in our hospital from June 2016 to August 2018, according to the occurrence of retinopathy and the degree of retinopathy, the patients were divided into five groups: 50 cases of non-retinopathy group (NDR group), 56 cases of simple retinopathy group (SDR group), 49 cases of proliferative retinopathy group (PDR group) and another 50 healthy persons in the same period were selected as the control group. Triglyceride (TG), total cholesterol (TC), and fasting blood glucose (FPG) were measured. Levels of serum miR-15 and miR-29a were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Pearson correlation method was used to analyze the relationships between levels of serum miR-15 and miR-29a with clinical indicators in DR patients. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic values of miR-15 and miR-29a in DR. Results The relative expression of miR-15 in serum of NDR group, SDR group, and PDR group were lower than that of control group (P<0.05), and the relative expression of miR-15 in NDR group, SDR group, and PDR group decreased gradually (P<0.05); the relative expression of miR-29a in serum of NDR group, SDR group, and PDR group were higher than that of control group (P<0.05), and the mRNA relative expression of miR-29a in NDR group, SDR group, and PDR group increased gradually (P<0.05); the expression of serum miR-15 in DR patients was negatively correlated with urinary albumin/creatinine (UACR), glycosylated hemoglobin (HbA1c) and the course of DM (r=-0.732, -0.492, -0.589, P<0.05); the expression level of miR-29a was positively correlated with UACR, HbA1c and the course of DM (r=0.744, 0.508, 0.556, P<0.05); the areas under the ROC curve (AUC) of miR-15 and miR-29a for DR diagnosis were 0.796 (95% CI: 0.724-0.857) and 0.677 (95% CI: 0.597-0.749), with diagnostic thresholds 0.63 and 1.11, sensitivities 84.9% and 53.8%, specificities 65.3% and 79.6%, repectively; miR-29a was a risk factor for DR, while miR-15 was a protective factor for DR. Conclusions The expression of mir-15 and miR-29a in the serum of DR patients is decreased, which is related to the degree of retinopathy and can be used as biomarkers for early diagnosis of DR. Key words: Diabetic retinopathy; miR-15; miR-29a; Early diagnosis