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EClinicalMedicine Mar 2024Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and is associated with high mortality rates. The influence of routine clinical parameters on...
BACKGROUND
Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and is associated with high mortality rates. The influence of routine clinical parameters on DKD onset in patients with type 2 diabetes mellitus (T2DM) remains uncertain.
METHODS
In this systematic review and meta-analysis, we searched multiple databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane Library, for studies published from each database inception until January 11, 2024. We included cohort studies examining the association between DKD onset and various clinical parameters, including body mass index (BMI), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and serum uric acid (UA). Random-effect dose-response meta-analyses utilizing one-stage and/or cubic spline models, were used to estimate correlation strength. This study is registered in PROSPERO (CRD42022326148).
FINDINGS
This analysis of 46 studies involving 317,502 patients found that in patients with T2DM, the risk of DKD onset increased by 3% per 1 kg/m increase in BMI (relative risk (RR) = 1.03, confidence interval (CI) [1.01-1.04], I = 70.07%; GRADE, moderate); a 12% increased risk of DKD onset for every 1% increase in HbA1c (RR = 1.12, CI [1.07-1.17], I = 94.94%; GRADE, moderate); a 6% increased risk of DKD onset for every 5 mmHg increase in SBP (RR = 1.06. CI [1.03-1.09], I = 85.41%; GRADE, moderate); a 2% increased risk of DKD onset per 10 mg/dL increase in TG (RR = 1.02, CI [1.01-1.03], I = 78.45%; GRADE, low); an 6% decreased risk of DKD onset per 10 mg/dL increase in HDL (RR = 0.94, CI [0.92-0.96], I = 0.33%; GRADE, high), and a 11% increased risk for each 1 mg/dL increase in UA (RR = 1.11, CI [1.05-1.17], I = 79.46%; GRADE, moderate). Subgroup analysis revealed a likely higher risk association of clinical parameters (BMI, HbA1c, LDL, and UA) in patients with T2DM for less than 10 years.
INTERPRETATION
BMI, HbA1c, SBP, TG, HDL and UA are potential predictors of DKD onset in patients with T2DM. Given high heterogeneity between included studies, our findings should be interpreted with caution, but they suggest monitoring of these clinical parameters to identify individuals who may be at risk of developing DKD.
FUNDING
Shenzhen Science and Innovation Fund, the Hong Kong Research Grants Council, and the HKU Seed Funds, and Scientific and technological innovation project of China Academy of Chinese Medical Sciences.
PubMed: 38374967
DOI: 10.1016/j.eclinm.2024.102482 -
Endocrine Regulations Jan 2023Hyperglycemia in diabetes mediates the release of angiogenic factors, oxidative stress, hypoxia, and inflammation, which in turn stimulate angiogenesis. Excessive...
Hyperglycemia in diabetes mediates the release of angiogenic factors, oxidative stress, hypoxia, and inflammation, which in turn stimulate angiogenesis. Excessive angiogenesis can cause diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. All of these complications are debilitating, which may lead to an increased susceptibility to lower-limb amputations due to ulcerations and infections. In addition, microvascular alterations, segmental demyelination, and endoneurial microangiopathy may cause progressive deterioration ultimately leading to kidney failure and permanent blindness. Some medicinal plants have potent anti-angiogenic, antioxidant or anti-inflammatory properties that can ameliorate angiogenesis in diabetes. The purpose of this systematic review is to demonstrate the potential of medicinal plants in ameliorating the neovascularization activities in diabetes. Manuscripts were searched from PubMed, Science Direct, and Scopus databases, and Google Scholar was used for searching additional papers. From 1862 manuscripts searched, 1854 were excluded based on inclusion and exclusion criteria and 8 were included into this systematic review, whereas the required information was extracted and summarized. All identified medicinal plants decreased the high blood glucose levels in diabetes, except the aqueous extract of Lonicerae japonicae flos (FJL) and Vasant Kusumakar Ras. They also increased the reduced body weight in diabetes, except the aqueous extract of FL and total lignans from Fructus arctii. However, methanolic extract of Tinospora cordifolia and Vasant Kusumakar Ras were not tested for their ability to affect the body weight. Besides, all medicinal plants identified in this systematic review decreased the vascular endothelial growth factor (VEGF) protein expression and vasculature activity demonstrated by histopathological examination indicating promising anti-angiogenic properties. All medicinal plants identified in this systematic review have a potential to ameliorate neovascularization activities in diabetes by targeting the mechanistic pathways related to oxidative stress, inflammation, and angiogenesis.
Topics: Plants, Medicinal; Vascular Endothelial Growth Factor A; Diabetic Nephropathies; Hyperglycemia; Inflammation; Body Weight; Diabetes Mellitus
PubMed: 38345496
DOI: 10.2478/enr-2024-0004 -
PloS One 2024Diabetic nephropathy (DN) is a long-term kidney disease among diabetic patients. It is the leading cause of end-stage renal failure. In Ethiopia, DN affects the majority... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Diabetic nephropathy (DN) is a long-term kidney disease among diabetic patients. It is the leading cause of end-stage renal failure. In Ethiopia, DN affects the majority of diabetic populations, but there were inconsistent findings about the determinant factors across the studies.
METHODS
We have accessed studies using PubMed, Embase, EBSCO, Web of Science, OVID, and search engines including Google and Google Scholar published up to June 2023. The study populations were diabetic patients with nephropathy. The quality of each included article was assessed using the Newcastle-Ottawa quality assessment scale. The odds ratios of risk factors were pooled using a random-effect meta-analysis model. Heterogeneity was assessed using the Cochrane Q statistics and I-Square (I2). The publication bias was detected using the funnel plot and/or Egger's test (p< 0.05). Trim and fill analysis was carried out to treat the publication bias. The protocol has been registered with the reference number CRD42023434547.
RESULTS
A total of sixteen articles were used for this reviewed study. Of which, eleven articles were used for advanced age, ten articles for duration of diabetic illness, ten articles for poor glycemic control, and eleven articles for having co-morbid hypertension. Diabetic patients with advanced age (AOR = 1.11, 95% CI: 1.03-120, I2 = 0.0%, p = 0.488), longer duration of diabetic illness (AOR = 1.23, 95% CI = 1.05-1.45, I2 = 0.0%, p = 0.567), poor glycemic control (AOR = 2.57, 95% CI: 1.07-6.14; I2 = 0.0%, p = 0.996), and having co-morbid hypertension (AOR = 4.03, 95% CI: 2.00-8.12, I2 = 0.0%, p = 0.964) were found to be factors associated with DN.
CONCLUSIONS
The findings of the study revealed that diabetic patients with advanced age, longer duration of diabetic illness, poor glycemic control status, and co-morbid hypertension were the determinant factors of DN. Therefore, treatment of co-morbid hypertension and high blood glucose and regular screening of renal function should be implemented to detect, treat, and reduce the progression of DN. Furthermore, healthcare workers should give due attention to diabetes with advanced age and a longer duration of diabetes illness to prevent the occurrence of DN.
Topics: Humans; Diabetic Nephropathies; Ethiopia; Risk Factors; Hyperglycemia; Hypertension; Prevalence; Diabetes Mellitus
PubMed: 38306369
DOI: 10.1371/journal.pone.0297082 -
Mini Reviews in Medicinal Chemistry 2024Diabetes is one of the important and growing diseases in the world. Among the most common diabetic complications are renal adverse effects. The use of apigenin may...
PURPOSE
Diabetes is one of the important and growing diseases in the world. Among the most common diabetic complications are renal adverse effects. The use of apigenin may prevent the development and progression of diabetes-related injuries. The current study aims to review the effects of apigenin in the treatment of diabetic nephropathy.
METHODS
In this review, a systematic search was performed based on PRISMA guidelines for obtaining all relevant studies on "the effects of apigenin against diabetic nephropathy" in various electronic databases up to September 2022. Ninety-one articles were obtained and screened in accordance with the predefined inclusion and exclusion criteria. Seven eligible articles were finally included in this review.
RESULTS
The experimental findings revealed that hyperglycemia led to the decreased cell viability of kidney cells and body weight loss and an increased kidney weight of rats; however, apigenin administration had a reverse effect on these evaluated parameters. It was also found that hyperglycemia could induce alterations in the biochemical and renal function-related parameters as well as histopathological injuries in kidney cells or tissue; in contrast, the apigenin administration could ameliorate the hyperglycemia-induced renal adverse effects.
CONCLUSION
The results indicated that the use of apigenin could mitigate diabetes-induced renal adverse effects, mainly through its antioxidant, anti-apoptotic, and anti-inflammatory activities. Since the findings of this study are based on experimental studies, suggesting the use of apigenin (as a nephroprotective agent) against diabetic nephropathy requires further clinical studies.
Topics: Rats; Animals; Diabetic Nephropathies; Apigenin; Oxidative Stress; Kidney; Hyperglycemia; Diabetes Mellitus
PubMed: 38282447
DOI: 10.2174/1389557523666230811092423 -
PloS One 2024Previous research has suggested that the ELMO1 gene may play a role in the development of diabetic kidney disease. Diabetic kidney disease (DKD) is a serious... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous research has suggested that the ELMO1 gene may play a role in the development of diabetic kidney disease. Diabetic kidney disease (DKD) is a serious complication of diabetes and the leading cause of chronic kidney disease and end-stage renal disease (ESRD).
OBJECTIVE AND RATIONALE
This study aim was to systematically review and explore the association between ELMO1 gene polymorphisms and diabetic kidney disease. A comprehensive systematic review provides a clear conclusion and high-level evidence for the association between ELMO1 gene and DKD for future application in personalized medicine.
METHODS
A comprehensive search of electronic databases, per PRISMA instructions, was conducted in Scopus, EMBASE, Web of Science, and PubMed databases from 1980 to January 2023. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using appropriate models. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity and assess the robustness of the findings.
RESULTS
A total of 5794 diabetes patients with DKD, 4886 diabetes patients without DKD, and 2023 healthy controls were included in the 17 studies that made up this systematic review. In the investigation of DM (Diabetes Mellitus) with DKD vs. DM without DKD, the susceptibility for DKD for the EMLO1 rs741301 polymorphism indicated a significant difference under the dominant, homozygote, and recessive genetic models. The susceptibility for DKD for the EMLO1 rs1345365, rs10255208, and rs7782979 polymorphisms demonstrated a significant difference under the allele genetic models in the analysis of DM with DKD vs. DM without DKD groups. There was a considerable increase in DKD risk in the Middle East when the population was stratified by the region.
CONCLUSION
The findings of the meta-analysis show that there are a significant connection between the EMLO1 rs741301 polymorphism and DKD susceptibility in overall analyses; as well as rs1345365, rs10255208, and rs7782979 polymorphisms; especially in the Middle East region.
Topics: Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Polymorphism, Genetic; Renal Insufficiency, Chronic; Adaptor Proteins, Signal Transducing
PubMed: 38277369
DOI: 10.1371/journal.pone.0295607 -
Current Diabetes Reviews Jan 2024Diabetes is one of the chronic and very complex diseases that can lead to microvascular complications. Recent evidence demonstrates that dysbiosis of the microbiota...
BACKGROUND
Diabetes is one of the chronic and very complex diseases that can lead to microvascular complications. Recent evidence demonstrates that dysbiosis of the microbiota composition might result in low-grade, local, and systemic inflammation, which contributes directly to the development of diabetes mellitus and its microvascular consequences.
OBJECTIVE
The aim of this systematic review was to investigate the association between diabetes microvascular complications, including retinopathy, neuropathy, nephropathy, and gut microbiota composition.
METHODS
A systematic search was carried out in PubMed, Scopus, and ISI Web of Science from database inception to March 2023. Screening, data extraction, and quality assessment were performed by two independent authors. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment.
RESULTS
About 19 articles were selected from 590 retrieved articles. Among the included studies, nephropathy has been studied more than other complications of diabetes, showing that the composition of the healthy microbiota is changed, and large quantities of uremic solutes that cause kidney injury are produced by gut microbes. Phyla, including Fusobacteria and Proteobacteria, accounted for the majority of the variation in gut microbiota between Type 2 diabetic patients with and without neuropathy. In cases with retinopathy, an increase in pathogenic and proinflammatory bacteria was observed.
CONCLUSION
Our results revealed that increases in Bacteroidetes, proteobacteria and fusobacteria may be associated with the pathogenesis of diabetic nephropathy, neuropathy, and retinopathy. In view of the detrimental role of intestinal dysbiosis in the development of diabetes-related complications, gut microbiota assessment may be used as a biomarker in the future and interventions that modulate the composition of microbiota in individuals with diabetes can be used to prevent and control these complications.
PubMed: 38275035
DOI: 10.2174/0115733998280396231212114345 -
Journal of Diabetes Research 2024Diabetic kidney disease affects approximately 40% of patients with type 2 diabetes mellitus (T2DM) and is associated with an increased risk of end-stage kidney disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic kidney disease affects approximately 40% of patients with type 2 diabetes mellitus (T2DM) and is associated with an increased risk of end-stage kidney disease (ESKD) and cardiovascular (CV) events, as well as increased mortality. Among the indicators of decline in renal function, the eGFR slope is acquiring an increasing clinical interest. The aim of this study was to evaluate, through a systematic review of the literature and meta-analysis of the collected data, the association between the decline of the eGFR slope, chronic complications, and mortality of T2DM patients, in order to understand whether or not the eGFR slope can be defined as a predictive indicator of complications in T2DM.
METHODS
The review and meta-analysis were conducted according to PRISMA guidelines considering published studies on patients with T2DM. A scientific literature search was carried out on PubMed from January 2003 to April 2023 with subsequent selection of scientific papers according to the inclusion criteria.
RESULTS
Fifteen studies were selected for meta-analysis. Risk analysis as hazard ratio (HR) indicated a significant association between all events considered (all-cause mortality, CV events, ESKD, and microvascular events) for patients with steeper eGFR slope decline than subjects with stable eGFR. Calculated HRs (with 95% CI) were as follows: for all-cause mortality, 2.31 (1.70-3.15); for CV events, 1.73 (1.43-2.08); for ESKD, 1.54 (1.45-1.64); and for microvascular events, 2.07 (1.57-2.73). Overall HR was 1.82 (1.72-1.92).
CONCLUSIONS
An association between rapid eGFR decline and chronic diabetes complications was demonstrated, suggesting that eGFR slope variability significantly impacts the course of T2DM and that eGFR slope should be considered as a predictor for chronic complications in patients with T2DM. According to the obtained results, the therapeutic management of the patient with diabetes should not focus exclusively on glycaemic control, and particular attention should be paid to preserve renal function.
Topics: Humans; Diabetes Mellitus, Type 2; Data Collection; Diabetic Nephropathies; Glycemic Control; Kidney Failure, Chronic
PubMed: 38268787
DOI: 10.1155/2024/8859678 -
EXCLI Journal 2023Hesperidin and hesperetin, two flavonoids with potential therapeutic value, have been extensively studied in the context of diabetes management. The main objective of... (Review)
Review
Hesperidin and hesperetin, two flavonoids with potential therapeutic value, have been extensively studied in the context of diabetes management. The main objective of this research is to ascertain their potential as therapeutic options for managing diabetes and its complications. The present study utilized a systematic review methodology and comprehensively explored relevant literature from databases, including PubMed, Scopus, and Web of Science, from inception until July 2023. The review summarized the outcomes related to the molecular, cellular, and metabolic effects of hesperidin and hesperetin in diabetes and its complications. Hesperetin exhibits a potential treatment for preventing diabetes and its associated complications through modulation of inflammatory cytokine release and expression via the pathway of signaling through Toll-like receptor/Myeloid differentiation factor 88/Nuclear factor-kappa B. Hesperidin shows promise as a biomolecule for treating diabetic neuropathy, primarily through activation of nuclear factor erythroid 2-related factor 2 (Nrf-2), as an antioxidant-response element signaling, leading to neuroprotective effects. Both compounds demonstrated the ability to normalize blood glucose levels and reduce serum and liver lipid levels, making them potential candidates for managing hypoglycemia and hypolipidemia in diabetes. Hesperidin also showed potential benefits against diabetic nephropathy by suppressing transforming growth factor-β1-integrin-linked kinase-Akt signaling and enhancing renal function. Furthermore, hesperidin's antioxidant, anti-inflammatory, and anti-depressant effects in diabetic conditions expanded its potential therapeutic applications. This systematic review provides substantial evidence supporting the consideration of hesperidin and hesperetin for diabetes and its complications. It offers exciting possibilities for developing novel, cost-effective treatment options to enhance diabetes management and patient outcomes.
PubMed: 38234970
DOI: 10.17179/excli2023-6577 -
Journal of Diabetes Science and... Mar 2024Diabetic microvascular complications significantly impact morbidity and mortality. This review focuses on machine learning/artificial intelligence (ML/AI) in predicting... (Review)
Review
IMPORTANCE AND AIMS
Diabetic microvascular complications significantly impact morbidity and mortality. This review focuses on machine learning/artificial intelligence (ML/AI) in predicting diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN).
METHODS
A comprehensive PubMed search from 1990 to 2023 identified studies on ML/AI models for diabetic microvascular complications. The review analyzed study design, cohorts, predictors, ML techniques, prediction horizon, and performance metrics.
RESULTS
Among the 74 identified studies, 256 featured internally validated ML models and 124 had externally validated models, with about half being retrospective. Since 2010, there has been a rise in the use of ML for predicting microvascular complications, mainly driven by DKD research across 27 countries. A more modest increase in ML research on DR and DN was observed, with publications from fewer countries. For all microvascular complications, predictive models achieved a mean (standard deviation) c-statistic of 0.79 (0.09) on internal validation and 0.72 (0.12) on external validation. Diabetic kidney disease models had the highest discrimination, with c-statistics of 0.81 (0.09) on internal validation and 0.74 (0.13) on external validation, respectively. Few studies externally validated prediction of DN. The prediction horizon, outcome definitions, number and type of predictors, and ML technique significantly influenced model performance.
CONCLUSIONS AND RELEVANCE
There is growing global interest in using ML for predicting diabetic microvascular complications. Research on DKD is the most advanced in terms of publication volume and overall prediction performance. Both DR and DN require more research. External validation and adherence to recommended guidelines are crucial.
Topics: Humans; Artificial Intelligence; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Machine Learning; Retrospective Studies
PubMed: 38189280
DOI: 10.1177/19322968231223726 -
Current Diabetes Reviews Jan 2024This article focuses on extracting a standard feature set for predicting the complications of diabetes mellitus by systematically reviewing the literature. It is...
BACKGROUND
This article focuses on extracting a standard feature set for predicting the complications of diabetes mellitus by systematically reviewing the literature. It is conducted and reported by following the guidelines of PRISMA, a well-known systematic review and meta-analysis method. The research articles included in this study are extracted using the search engine "Web of Science" over eight years. The most common complications of diabetes, diabetic neuropathy, retinopathy, nephropathy, and cardiovascular diseases are considered in the study.
METHOD
The features used to predict the complications are identified and categorised by scrutinising the standards of electronic health records.
RESULT
Overall, 102 research articles have been reviewed, resulting in 59 frequent features being identified. Nineteen attributes are recognised as a standard in all four considered complications, which are age, gender, ethnicity, weight, height, BMI, smoking history, HbA1c, SBP, eGFR, DBP, HDL, LDL, total cholesterol, triglyceride, use of insulin, duration of diabetes, family history of CVD, and diabetes. The existence of a well-accepted and updated feature set for health analytics models to predict the complications of diabetes mellitus is a vital and contemporary requirement. A widely accepted feature set is beneficial for benchmarking the risk factors of complications of diabetes.
CONCLUSION
This study is a thorough literature review to provide a clear state of the art for academicians, clinicians, and other stakeholders regarding the risk factors and their importance.
PubMed: 38178670
DOI: 10.2174/0115733998271863231116062601