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

2021 ◽  
Vol 8 ◽  
Author(s):  
Xinyuan Zhang ◽  
Bingjie Qiu ◽  
Qiyun Wang ◽  
Sobha Sivaprasad ◽  
Yanhong Wang ◽  
...  

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.

Author(s):  
Irina S. Sobolevskaya ◽  
◽  
Oleg D. Myadelets ◽  
Natalʼya N. Yarotskaya

The purpose of this study was to substantiate the possibility of correcting lipid metabolism changes at dark deprivation using linseed oil, melatonin, and their combination. Materials and methods. The experiment involved 130 white outbred male rats with a body weight of 170–220 g. The animals were divided into 5 groups: rats under standard fixed lighting conditions (12 hours light/12 hours dark); rats under modelled dark deprivation with round-the-clock lighting (24 hours light); rats under modelled dark deprivation with round-the-clock lighting (24 hours light) receiving intragastric injections of linseed oil, melatonin or their combination from day 1 of the experiment. Serum concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total phospholipids (TPL) and atherogenic index (AI) were determined. Results. Long-term dark deprivation led to dyslipoproteinemia, which consists in an increase in serum concentrations of TC by a factor of 1.33 (p = 0.0009), TG by a factor of 1.62 (p = 0.013), LDL-C by a factor of 1.2 (p = 0.026) and TPL by a factor of 1.15 (p = 0.0082). The severity of changes in TC, TG, LDL-C, HDL-C and TPL concentrations varied depending on the duration of the experiment. During the use of linseed oil, melatonin or their combination under dark deprivation, the severity of disorders caused by desynchronosis decreased and lipid metabolism in rat serum normalized, especially at the initial stages of the research. Conclusion. Changes in lipid metabolism due to desynchronosis in rats injected with the substances under study were significantly smaller compared with animals that did not receive them. The most pronounced effects of administering these substances were observed in the group of rats treated with linseed oil and melatonin at the same time.


2019 ◽  
Vol 8 (11) ◽  
pp. 1960
Author(s):  
Andrea Russo ◽  
Antonio Longo ◽  
Teresio Avitabile ◽  
Vincenza Bonfiglio ◽  
Matteo Fallico ◽  
...  

The study’s purpose was to determine the incidence, risk factors, and outcomes of tractional macular detachment after anti-vascular endothelial growth factor (VEGF) pretreatment before vitrectomy for complicated proliferative diabetic retinopathy. Patients who underwent primary vitrectomy for complicated proliferative diabetic retinopathy, from January 2012 to 31 December 2018, were enrolled. Ophthalmic and pre-operative data were extracted from electronic record systems. All eyes with a valuable Optical Coherence Tomography (OCT)performed within 5 days before injection of anti-VEGF and on the day of vitrectomy were included. Multivariable logistic regression showed that significant risk factors for developing tractional macular detachment included days between anti-VEGF and vitrectomy (OR, 0.71 [95% CI 0.65–0.76]; p < 0.001), vitreous hemorrhage (OR, 0.23 [95% CI 0.11–0.49]; p < 0.001), and age (OR, 1.05 [95% CI 1.02–1.08]; p < 0.001). Decision-tree analysis showed that the stronger predictors of tractional macular detachment were the time between anti-VEGF injection and vitrectomy (p < 0.001). Secondary predictors were the presence of vitreous hemorrhage (p = 0.012) in eyes that underwent vitrectomy between 6 and 10 days after anti-VEGF injection and younger age (p = 0.031) in eyes that underwent vitrectomy 10 days after anti-VEGF injection. Tractional macular detachment occurs in 10% of eyes after anti-VEGF injection, the main risk factors being days between anti-VEGF injection and vitrectomy, vitreous hemorrhage, and age.


2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Byung Ju Jung ◽  
Mee Yon Lee ◽  
Sohee Jeon

This study is for identifying systemic factors correlating with intraocular levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in diabetic retinopathy. Forty-two consecutive patients undergoing pars plana vitrectomy (PPV) for PDR were included in this cross-sectional study. The aqueous humor was sampled just prior to PPV for assay of IL-6 and VEGF. One day before PPV, patient characteristics were recorded and a number of systemic markers were amassed, including fasting and postprandial glucose, homeostasis model assessment- (HOMA-) IR, HOMA-beta, C-peptide, insulin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein- (Apo-) A, Apo-B, and lipoprotein A (Lp-A). Relationships between systemic determinants and intraocular cytokine levels were analyzed by regression analysis. Mean levels of IL-6 and VEGF were 15.3 pg/mL (range, 2.4–10124.5 pg/mL) and 21.1 pg/mL (range, 3.2–766.1 pg/mL), respectively. After adjustment for age, gender, duration of diabetes, and BMI, multivariate analysis showed significant association of smoking (p=0.002) and HOMA-IR (p=0.003) with intraocular IL-6 levels, while intraocular VEGF and systemic Lp-A levels correlated significantly (p=0.032). Insulin resistance and smoking status impacted intraocular levels of IL-6, while intraocular VEGF levels were influenced by Lp-A. An appreciation for the relationship between systemic factors and intraocular cytokines may help elucidate the complex pathophysiology of diabetic retinopathy.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Zhen Li ◽  
Qi Huang ◽  
Li Sun ◽  
Tengfei Bao ◽  
Zhe Dai

Objective. This study was designed to investigate risk factors related to atherogenic index of plasma (AIP), as well as the relationship between AIP and chronic microvascular complications in patients with type 2 diabetes (T2DM). Methods. This study included 2523 patients with T2DM who had not been treated with lipid-lowering drugs and were admitted to the Department of Endocrinology at Zhongnan Hospital, Wuhan University, during the period from January 2015 to February 2018. Anthropometric indicators were measured after overnight fasting. Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) were detected by enzymatic analysis. Standard 75 g oral glucose tolerance testing was performed to measure 0 and 2 hr plasma levels of glucose and insulin. Insulin sensitivity was assessed with HOMA-IR. Results. Increase in AIP was associated with an increased risk for hypertension (P<0.05), HbA1c (P<0.05), HOMA-IR (P<0.05), UA (P<0.05), and decreased eGFR levels (P<0.05). Furthermore, AIP values directly correlated with BMI (r=0.182, P<0.001), waist circumference (r=0.129, P<0.001), blood glucose index (FBG (r=0.153, P<0.001), PPBG (r=0.117, P<0.001), and HbA1c (r=0.074, P<0.001)), insulin resistance (HOMA-IR; r=0.112, P<0.001), and uric acid (UA, r=0.177, P<0.001). Multiple logistic regression analysis showed that waist circumference, HOMA-IR, FBG, systolic blood pressure, and UA were independent risk factors for AIP (all P<0.05). The prevalence of diabetic neuropathy and metabolic syndrome was significantly higher among patients with higher AIP. Conclusion. AIP represents a clinically convenient indicator for the detection of T2DM with high risk of complications and associated diseases and thus is a good predictor and indicator for follow-up monitoring in the treatment of patients with high-risk type 2 diabetes.


2018 ◽  
Vol 2 (4) ◽  
pp. 200-207
Author(s):  
Pablo Yang ◽  
José D. Luna ◽  
Emilio Alcoba ◽  
Aylén Sein ◽  
Ana L. Gramajo ◽  
...  

Purpose: Diabetic retinopathy (DR) is one of the chronic retinal disorders linked to diabetes and remains the leading cause of blindness in working-age people. Many studies have demonstrated the existence of associations between type 2 diabetes mellitus (T2DM) and variants in the cyclin-dependent kinase 5 regulatory subunit–associated protein 1-like 1 ( CDKAL1) gene. Here, we performed a case-control study in the CDKAL1 gene (rs4712527 polymorphism) to investigate the potential association between this single-nucleotide polymorphism (SNP) and DR risk. Methods: Two hundred thirty-one patients with T2DM (126 patients with proliferative diabetic retinopathy [PDR] and 105 patients without diabetic retinopathy [WDR]), who assisted at the Centro Privado de Ojos Romagosa, Fundación VER, were studied. An independent cohort of 98 patients (56 with PDR and 42 with WDR) from the Hospital Nacional de Clínicas was taken for replication. A complete ophthalmological examination included an external examination of the eye and adnexa, pupil responsiveness, and slit-lamp biomicroscopic examination. Genotyping of rs4712527 was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratio (OR) and 95% CI were calculated by unconditional logistic regression adjusted for diabetes duration, body mass index, insulin therapy, HbA1c, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and systolic and diastolic blood pressure. Results: Analysis from the rs4712527 SNP in the Centro Privado de Ojos Romagosa, Fundación VER, cohort was found to be associated with decreased risk of PDR both before and after adjustment, under the codominant (adjusted OR = 0.16 [95% CI, 0.06-0.44]; P = 4e-04), dominant (adjusted OR = 0.17 [95% CI, 0.07-0.43]; P = 1e-04), overdominant (adjusted OR = 0.20 [95% CI, 0.08-0.52]; P = 5e-04), and log-additive (adjusted OR = 0.28 [95% CI, 0.13-0.59]; P = 4e-04) models. In the combined analysis including both cohorts, the rs4712527 was nominally involved as a protective factor in the development of DR. Conclusions: Our findings suggest that the rs4712527 in the CDKAL1 gene might be involved in the protection to develop PDR in T2DM.


Author(s):  
Qian Zhang ◽  
Da-long Zhang ◽  
Xiao-li Zhou ◽  
Qian Li ◽  
Ning He ◽  
...  

Background: The incidence and mortality of hyperlipidemia are increasing year by year, showing a younger trend. At present, the treatment of hyperlipidemia is mainly dependent on western medicine, but its side effects on liver and kidney function are common in clinics. Therefore, it is necessary to study the treatment of hyperlipidemia by augmenting effective dietary nutrition supplements. Vitamin B6 (VitB6), as an essential cofactor for enzymes, participates in lipid metabolism. The effects of VitB6 on hyperlipidemia, however, have not been reported until now. Aim: The present study was to investigate the influence of VitB6 on hepatic lipid metabolism in hyperlipidaemia rats induced by a high-fat diet (HFD). Methods: Male Sprague-Dawley rats were kept on HFD for two weeks to establish the hyperlipidemia model. The rats in low-dosage and high-dosage groups were received 2.00 and 3.00 mg/kg/day of VitB6 for eight weeks, respectively. Results: The results showed that both doses of VitB6 reduced HFD-induced hepatic low-density lipoprotein cholesterol (LDL-C); decreased blood cholesterol (TC), triglycerides, LDL-C, atherogenic index (AI), atherogenic index of plasma (AIP), apolipoprotein B (ApoB) and ApoB/apolipoprotein A-1(ApoA1) ratio; increased liver high-density lipoprotein cholesterol (HDL-C) and serum ApoA1; reduced hepatic steatosis and triglyceride accumulation, lowered fat storage, and recovered heart/body and brain/body ratio to a normal level. In addition, VitB6 supplementation markedly decreased HMGR level, increased the mRNA abundance of LDLR and CYP7A1, and protein expression of SIRT1, following the downregulation of SREBP-1 and PPARγ protein expression in the liver of hyperlipidemia rats. Conclusion: In summary, oral VitB6 supplementation can ameliorate HFD-induced hepatic lipid accumulation and dyslipidemia in SD rats by inhibiting fatty acid and cholesterol synthesis, promoting fatty acid decomposition and cholesterol transport.


Author(s):  
Md. Golam Kabir ◽  
Deaniel Hossain ◽  
Suman Mohajan ◽  
Monsor Rahman

Background: Diabetic retinopathy (DR) is a micro-vascular complication which is the main cause of blindness among people with Diabetes Mellitus. Identification and mitigation of the risk factors associated with DR will help to reduce the visual disability in diabetic subjects. Aims and objective: The study has been undertaken to explore the association of lipids profile and electrolytes with the diabetic retinopathy in Bangladeshi type 2 diabetic subjects. Material and methods: In the present study, 63 people diabetic with retinopathy (DR) and 80 people diabetic without retinopathy (DWR) were studied along with 92 healthy controls without family history diabetes and prediabetes. Anthropometric parameters, glucose, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, glycosylated haemoglobin (HbA1c) and electrolytes Na+, K+, Cl-, HCO3- were measured by standard methods.   Results: HbA1c of DWR group and DR group were 8.60±1.17 and 11.80±1.63 respectively. Total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) were significantly higher (p<0.001) in both DWR and DR group compared to the healthy control. Triglyceride was significantly (p<0.001) higher in the DR group but no difference was found in DWR compared to the control group. K+ was significantly increased in the DR group. Na+, Cl-, HCO3- were significantly decreased in the DR group compared to control group. Conclusion: These results indicate that diabetic retinopathy patients exhibit dyslipidemia and electrolyte imbalance. Hypertriglyceridemia along with electrolyte imbalance is one the major risk factors toward the progression of diabetic retinopathy.


Author(s):  
A-M. A. Shulhai ◽  
H. A. Pavlyshyn

Vitamin D deficiency and overweight have now become an important global problem in the field of health care as well as public health. A substantial hypovitaminosis D in children with obesity is often accompanied by metabolic disorders. The aim of the study was to determine the relationship between the levels of vitamin D and lipid metabolism markers in adolescents with overweight and obesity. Material and methods. 139 adolescents were examined (63 (45.4 %) girls and 76 (54.7 %) boys). Depending on the body mass index (BMI) 65 children were overweight and 74 were obese children. The mean age of teenagers was (15,4±2,3) years. To establish vitamin D status using the immune-enzyme method, blood serum levels of 25(OH)D were determined. Lipid metabolism markers were determined using the Roche Diagnostics Cholesterol reagent kit using and automatic Cobas c111 analyzer. Results. The study established a direct relationship between the level of vitamin D and high-density lipoprotein cholesterol and indirect with total cholesterol, triglycerides, low-density lipoprotein cholesterol, atherogenic index, body mass index and waist circumference. Using a simple linear regression analysis, it was determined that total cholesterol, low-density lipoprotein cholesterol and atherogenic index have the greatest correlation with vitamin D. Conclusions: Vitamin D deficiency in overweight and obese adolescents is associated with an increase in the body mass index, blood pressure, and atherogenic dyslipidemia.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2003
Author(s):  
Risa Araki ◽  
Akira Yada ◽  
Hirotsugu Ueda ◽  
Kenichi Tominaga ◽  
Hiroko Isoda

The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs were categorized into three types: cyanidin-, delphinidin-, and malvidin-based. Delphinidin-based anthocyanins demonstrated significant effects on triglycerides (mean difference (MD): −0.24, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD: −0.28, p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (MD: 0.11, p < 0.01), whereas no significant effects were observed for cyanidin- and malvidin-based anthocyanins. Although non-significant, favorable effects on total cholesterol (TC) and HDL-C were observed for cyanidin- and malvidin-based anthocyanins, respectively (both p < 0.1). The ascending order of effectiveness on TC and LDL-C was delphinidin-, cyanidin-, and malvidin-based anthocyanins, and the differences among the three groups were significant (both p < 0.05). We could not confirm the significant effects of each main anthocyanin on glucose metabolism; however, insulin resistance index changed positively and negatively with cyanidin- and delphinidin-based anthocyanins, respectively. Therefore, foods containing mainly unmethylated anthocyanins, especially with large numbers of OH groups, may improve glucose and lipid metabolism more effectively than those containing methylated anthocyanins.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Nakhleh E. Abu-Yaghi ◽  
Nafez M. Abu Tarboush ◽  
Ala M. Abojaradeh ◽  
Amal S. Al-Akily ◽  
Esra’a M. Abdo ◽  
...  

Aim. This study aims to measure serum vascular endothelial growth factor (VEGF) levels in a sample of Jordanian patients and to determine their relationship with the different stages of diabetic retinopathy. It also explores the correlation between VEGF concentrations and different biochemical and demographic findings. Materials and Methods. A total of 167 adults participated in the study. Participants were divided into two main categories: patients with diabetes mellitus (DM) type 2 without diabetic retinopathy (DR) (N = 62) and patients with DM type 2 affected by DR (N = 105). DR patients were further subclassified into nonproliferative (N = 41) and proliferative (N = 64). Basic laboratory tests were measured to correlate with VEGF levels. Irisin, a hormone linked to diabetic retinopathy was also measured and correlated with VEGF. Results. Serum VEGF was found to positively correlate with the severity of diabetic retinopathy. The means of VEGF serum concentrations were 60 pg/mL for controls, 133 pg/mL for nonproliferative DR patients, and 229 pg/mL for proliferative DR patients. We found a significant positive correlation with glycosylated hemoglobin (HbA1c), and a significant negative correlation with high-density lipoprotein (HDL) levels, age, and irisin. Conclusion. In this cohort of Jordanian diabetics, serum VEGF concentrations strongly correlated with the presence and stages of diabetic retinopathy, suggesting it as an appropriate indicator for diabetic retinopathy early detection and management in this society. VEGF levels also significantly correlated with HbA1c, HDL, and irisin levels. Further studies are encouraged to explore these relationships in other ethnic groups and with different diabetic complications.


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