Systems biology perspective on diabetic nephropathy may reveal molecular mechanism of diabetic retinopathy

Microvascular complications of Type 2 Diabetes Mellitus (T2DM), (retinopathy and nephropathy) have a similar etiopathogenetic mechanism besides genetic predisposition. Even though these two complications frequently co-exist, their frequency varies. The association of these two signicant complications and their coexistence needs a relook. To study prevalence of retinopathy and nephropathy in Type 2 diabetes mel Aim: litus. Comparison of diabetic retinopathy and nephropathy in Type 2 diabetes mellitus and its correlation of diabetic retinopathy and nephropathy with duration of illness and various risk factors that affects development, progression and severity of diabetic retinopathy and nephropathy. 100 diabetic patients were taken up for study for a period of one year meeti Methodology: ng the criteria for the present study. Detailed history was taken from patient and meticulous examination was done of all patients with special emphasis on renal and ophthalmic symptoms. Clinical data and investigation prole was tabulated. Statistical analysis was done. Among 100 patients, 22 had diabetic retinopathy. Among patients with diab Results & Conclusion: etic retinopathy, 68.18% patients had positive family history. Among 100 patients, 32 had diabetic nephropathy, mean FBS was 207 mg%, PPBS was 317.8 mg% and mean HbA was 9.2%. Among patients with diabetic retinopathy, mean FBS was 211 mg%, PPBS was 324.9 1c mg%, HbA was 9.5%. From this study it is found that diabetic nephropathy starts earlier than retinopathy. In this study 1c hypertension was found to accelerate progression into nephropathy and retinopathy.

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Silencing of long noncoding RNA XIST protects against renal interstitial fibrosis in diabetic nephropathy via microRNA-93-5p-mediated inhibition of CDKN1A

AJP Renal Physiology ◽

10.1152/ajprenal.00254.2019 ◽

2019 ◽

Vol 317 (5) ◽

pp. F1350-F1358 ◽

Cited By ~ 6

Author(s):

Jindou Yang ◽

Yan Shen ◽

Xia Yang ◽

Yanjun Long ◽

Shuang Chen ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Molecular Mechanism ◽

High Glucose ◽

Noncoding Rna ◽

Transforming Growth Factor ◽

Interstitial Fibrosis ◽

Kidney Tissue ◽

Luciferase Reporter ◽

Renal Interstitial Fibrosis ◽

Endogenous Expression

Long noncoding RNAs (lncRNAs) have been reported to play an important role in diabetic nephropathy (DN). However, the molecular mechanism involved in this process remains poorly understood. Thus, the present study aimed to explore the function and molecular mechanism of dysregulated lncRNA X-inactive specific transcript (XIST) in DN. DN mouse models were established by streptozotocin treatment, and human renal tubular epithelial HK-2 cells were exposed to high glucose to produce an in vitro model. XIST was highly expressed in renal tissues of patients with DN, mice with DN, and high glucose-exposed HK-2 cells. To identify the interaction among XIST, miR-93-5p, and cyclin-dependent kinase inhibitor 1A (CDKN1A) and to analyze the functional significance of their interaction in renal interstitial fibrosis, we altered endogenous expression of XIST and miR-93-5p and CDKN1A. Dual-luciferase reporter assay results suggested that XIST was highly expressed in the kidney tissue of DN mice and high glucose-exposed HK-2 cells. XIST was identified to be a lncRNA that could bind to miR-93-5p, and CDKN1A was a target of miR-93-5p. Downregulated expression of XIST led to an increase in miR-93-5p expression, thereby decreasing CDKN1A and suppressing renal interstitial fibrosis in DN. Consistently, XIST knockdown reduced the expression of fibrosis markers (fibronectin, collagen type IV, and transforming growth factor-β1). Restoration of CDKN1A or decreasing miR-93-5p yielded a reversed effect on renal interstitial fibrosis. In conclusion, our study demonstrated that silenced XIST inducing miR-93-5p-dependent CDKN1A inhibition was beneficial for preventing renal interstitial fibrosis in DN, which may provide a future strategy to prevent the progression of DN.

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Treatment of diabetic retinopathy in the patient with diabetic nephropathy

Management of Diabetic Nephropathy ◽

10.3109/9780203502976-21 ◽

2003 ◽

pp. 217-222

Author(s):

Ruth Axer-Siegel ◽

Gad Dotan

Keyword(s):

Diabetic Retinopathy ◽

Diabetic Nephropathy

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Effects of TNF-α-308G/A Polymorphism on the Risk of Diabetic Nephropathy and Diabetic Retinopathy: An Updated Meta-Analysis

Hormone and Metabolic Research ◽

10.1055/a-1161-0088 ◽

2020 ◽

Vol 52 (10) ◽

pp. 724-731

Author(s):

Mengwei Liu ◽

Mengke Shang ◽

Yue Wang ◽

Qian Li ◽

Xiuping Liu ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Diabetic Nephropathy ◽

Meta Analysis ◽

Asian Population ◽

Recessive Model ◽

China National Knowledge Infrastructure ◽

Knowledge Infrastructure ◽

Tnf Α ◽

Patients With Diabetes ◽

Major Factors

AbstractDiabetic nephropathy (DN) and diabetic retinopathy (DR) are the major factors of morbidity and mortality in the patients with diabetes mellitus (DM). Growing studies have investigated the relationship between the TNF-α-308G/A polymorphism and the susceptibility to DN and DR, without achieving consensus. Thus, we conducted this meta-analysis to reach more comprehensive conclusions for these issues. Eligible studies were retrieved through electronic databases such as PubMed, Embase, Web of Science and China National Knowledge Infrastructure. Summary of odds ratios (OR) and 95% confidence intervals (CIs) were generated to evaluate the intensity of the associations. Statistical analyses were performed by STATA 11.0 and RevMan 5.2. There are fourteen eligible publications involving nineteen studies in this meta-analysis. TNF-α-308G/A polymorphism was significantly related to increasing risk of DN under recessive model (OR=1.37, 95% CI=1.03–1.83) and homozygous model (OR=1.54, 95% CI=1.15–2.06). Moreover, the similar results were also obtained in Asian groups for DN (recessive: OR=1.69, 95% CI=1.18–2.42; homozygous: OR=1.99, 95% CI=1.38–2.86; respectively), and significant association was also detected between TNF-α-308G/A and DN susceptibility in type 2 DM in recessive model (OR=1.39, 95% CI=1.02–1.89). No significant association was observed between TNF-α-308G/A and DR susceptibility in total analyses and subgroup analyses by ethnicity and type of DM. TNF-α-308G/A polymorphism may enhance the susceptibility to diabetic nephropathy, especially in Asian population and in T2DM patients, but not diabetic retinopathy.

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Computational systems biology approach to identify novel pharmacological targets for diabetic retinopathy

Biochemical Pharmacology ◽

10.1016/j.bcp.2018.09.016 ◽

2018 ◽

Vol 158 ◽

pp. 13-26 ◽

Cited By ~ 15

Author(s):

Chiara Bianca Maria Platania ◽

Gian Marco Leggio ◽

Filippo Drago ◽

Salvatore Salomone ◽

Claudio Bucolo

Keyword(s):

Diabetic Retinopathy ◽

Systems Biology ◽

Computational Systems Biology ◽

Pharmacological Targets ◽

Computational Systems

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Early Diabetic Nephropathy and Retinopathy in Patients with Type 1 Diabetes Mellitus Attending Sudan Childhood Diabetes Centre

Journal of Diabetes Research ◽

10.1155/2020/7181383 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Hana Ahmed ◽

Tayseer Elshaikh ◽

Mohamed Abdullah

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Type 1 Diabetes ◽

Diabetic Retinopathy ◽

Risk Factor ◽

Diabetic Nephropathy ◽

Type 1 Diabetes Mellitus ◽

Ethnic Group ◽

Childhood Diabetes

Objective. Data on microvascular complications in children and adolescents with type 1 diabetes mellitus (T1DM) in Sudan are scarce. This study was aimed at determining the prevalence of diabetic nephropathy (DN) and retinopathy (DR) and their relationship to certain risk factors in children with T1DM attending the Sudan Childhood Diabetes Centre. Design and Methods. A clinic-based cross-sectional study of 100 patients with T1DM aged 10-18 years. Patients with disease duration exceeding 5 years if the onset of diabetes was prepubertal and 2 years if it was postpubertal were included. Relevant sociodemographic, clinical, and biochemical information was obtained. Blood pressure was measured. The patients were screened for DN and DR using urinary microalbumin estimation and fundus photography, respectively. Results. The frequency of microalbuminuria and diabetic retinopathy was 36% and 33%, respectively. Eleven percent had both retinopathy and microalbuminuria. Seven percent of the patients were found to be hypertensive. Patients with diabetic retinopathy had significantly higher HbA1c levels ( p = 0.009 ) and longer diabetes duration ( p = 0.02 ) than patients without retinopathy. Logistic regression showed that high HbA1c (odds ratio (OR) 0.83, confidence interval (CI) 0.68-1.00, p = 0.04 ), but not age, duration, ethnic group, BMI, blood pressure, and presence of nephropathy, was an independent risk factor for retinopathy. Likewise, high blood pressure (OR 6.89, CI 1.17-40.52, p = 0.03 ), but not age, duration, ethnic group, BMI, HbA1c, and presence of retinopathy, was a predictor for nephropathy. Conclusion. High prevalence of incipient DN and early stages of DR were observed in this study. Longer diabetes duration and higher HbA1c were associated with the presence of diabetic retinopathy. High blood pressure was a risk factor for DN. So regular screening for these complications and optimization of glycemic control are needed.

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