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Acta Diabetologica Jul 2023To examine the association of homocysteine (Hcy) with diabetic nephropathy (DN) and diabetic retinopathy (DR) in a representative United States population.
AIMS
To examine the association of homocysteine (Hcy) with diabetic nephropathy (DN) and diabetic retinopathy (DR) in a representative United States population.
METHODS
This was a cross-sectional study using data from participants in the National Health and Nutrition Examination Survey 2005-2006. Metrics including Hcy level, urinary albumin to creatinine ratio, estimated glomerular filtration rate, and retinopathy grading were collected. Multiple logistic regression models were employed to assess the association of Hcy with DN and DR.
RESULTS
630 participants were included in this study. The Hcy level was significantly higher in those with DN and DR than those without DN and DR. Hcy was associated with an increased risk of DN (OR = 1.31, 95% CI 1.18-1.46; P < 0.001). In the fully adjusted model of DN (model II), compared to participants in quartiles 1 of Hcy, the adjusted ORs for participants in quartiles 2-4 were 1.49 (95% CI 0.52-4.26; P = 0.426), 3.81 (95% CI 1.35-10.73; P = 0.015), and 14.08 (95% CI 3.84-51.66; P = 0.001), respectively. Hcy was also associated with an increased risk of DR (OR = 2.260, 95% CI 1.212-4.216; P = 0.014), but this association was non-significant in the fully adjusted model of DR (model II).
CONCLUSIONS
In diabetic patients, Hcy was associated with increased risk of DN in a non-linear manner. In addition, Hcy was associated with the risk of DR, but the association was attenuated after adjusting for confounders. In the future, Hcy can potentially be used as an early screening indicator for diabetic microvascular complications.
Topics: Humans; Diabetic Nephropathies; Diabetic Retinopathy; Nutrition Surveys; Cross-Sectional Studies; Kidney Function Tests; Diabetes Mellitus, Type 2; Risk Factors; Homocysteine
PubMed: 36997800
DOI: 10.1007/s00592-023-02075-2 -
European Journal of Pharmacology Dec 2023Diabetes and its complications are increasing worldwide in the working population as well as in elders. Prolonged hyperglycemia results in damage to blood vessels of... (Review)
Review
Diabetes and its complications are increasing worldwide in the working population as well as in elders. Prolonged hyperglycemia results in damage to blood vessels of various tissues followed by organ damage. Hyperglycemia-induced damage in small blood vessels as in nephrons, retina, and neurons results in diabetic microvascular complications which involve nephropathy, retinopathy, and diabetic neuropathy. Additionally, damage in large blood vessels is considered as a macrovascular complication including diabetic cardiomyopathy. These long-term complications can result in organ failure and thus becomes the leading cause of diabetic-related mortality in patients. Members of the Forkhead Box O family (FOXO) are involved in various body functions including cell proliferation, metabolic processes, differentiation, autophagy, and apoptosis. Moreover, increasing shreds of evidence suggest the involvement of FOXO family members FOXO1, FOXO3, FOXO4, and FOXO6 in several chronic diseases including diabetes and diabetic complications. Hence, this review focuses on the role of FOXO transcription factors in the regulation of diabetic complications.
Topics: Humans; Aged; Forkhead Transcription Factors; Diabetes Complications; Diabetic Cardiomyopathies; Cell Differentiation; Hyperglycemia; Diabetes Mellitus
PubMed: 37838103
DOI: 10.1016/j.ejphar.2023.176089 -
Diabetes/metabolism Research and Reviews Mar 2024This publication represents a scheduled update of the 2019 guidelines of the International Working Group of the Diabetic Foot (IWGDF) addressing the use of systems to...
BACKGROUND
This publication represents a scheduled update of the 2019 guidelines of the International Working Group of the Diabetic Foot (IWGDF) addressing the use of systems to classify foot ulcers in people with diabetes in routine clinical practice. The guidelines are based on a systematic review of the available literature that identified 28 classifications addressed in 149 articles and, subsequently, expert opinion using the GRADE methodology.
METHODS
First, we have developed a list of classification systems considered as being potentially adequate for use in a clinical setting, through the summary of judgements for diagnostic tests, focussing on the usability, accuracy and reliability of each system to predict ulcer-related complications as well as use of resources. Second, we have determined, following group debate and consensus, which of them should be used in specific clinical scenarios. Following this process, in a person with diabetes and a foot ulcer we recommend: (a) for communication among healthcare professionals: to use the SINBAD (Site, Ischaemia, Bacterial infection, Area and Depth) system (first option) or consider using WIfI (Wound, Ischaemia, foot Infection) system (alternative option, when the required equipment and level of expertise is available and it is considered feasible) and in each case the individual variables that compose the systems should be described rather than a total score; (b) for predicting the outcome of an ulcer in a specific individual: no existing system could be recommended; (c) for characterising a person with an infected ulcer: the use of the IDSA/IWGDF classification (first option) or consider using the WIfI system (alternative option, when the required equipment and level of expertise is available and it is considered as feasible); (d) for characterising a person with peripheral artery disease: consider using the WIfI system as a means to stratify healing likelihood and amputation risk; (e) for the audit of outcome(s) of populations: the use of the SINBAD score.
CONCLUSIONS
For all recommendations made using GRADE, the certainty of evidence was judged, at best, as being low. Nevertheless, based on the rational application of current data this approach allowed the proposal of recommendations, which are likely to have clinical utility.
Topics: Humans; Diabetic Foot; Ulcer; Reproducibility of Results; Foot Ulcer; Ischemia; Diabetes Mellitus
PubMed: 37179483
DOI: 10.1002/dmrr.3648 -
Expert Review of Endocrinology &... 2024This review highlights the pathogenesis of both microvascular and macrovascular complications of diabetes and how these mechanisms influence both the management and... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
This review highlights the pathogenesis of both microvascular and macrovascular complications of diabetes and how these mechanisms influence both the management and preventative strategies of these complications. The cumulative data shown in this review suggest hyperglycemic and blood pressure control remain central to this intricate process.
AREAS COVERED
We reviewed the literature including retrospective, prospective trials as well as meta-analysis, and post hoc analysis of randomized trials on microvascular andmacrovascular complications.
EXPERT OPINION
Further research is needed to explore the ideal intervention targets and preventative strategies needed to prevent macrovascular complications. Furthermore, as the data for trials looking at microvascular complications lengthen more long-term data will further elucidate the role that the duration of diabetes has on these complications. Additionally, trials looking to maximize hyperglycemic control with multiple agents in diabetes, such as metformin, SGL2isand GLP-1 receptor agonists are currently in process, which will have implications for rates of microvascular as well as macrovascular complications.
Topics: Humans; Diabetic Angiopathies; Prospective Studies; Retrospective Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies
PubMed: 37947481
DOI: 10.1080/17446651.2023.2279533 -
Human Genetics Jan 2024Diabetes mellitus (DM) has become a significant health concern with an increasing rate of morbidity and mortality worldwide. India ranks second in the number of diabetes... (Review)
Review
Diabetes mellitus (DM) has become a significant health concern with an increasing rate of morbidity and mortality worldwide. India ranks second in the number of diabetes cases in the world. The increasing burden of DM can be explained by genetic predisposition of Indians to type 2 diabetes mellitus (T2DM) coupled with rapid urbanization and socio-economic development in the last 3 decades leading to drastic changes in lifestyle. Environment and lifestyle changes contribute to T2DM development by altering epigenetic processes such as DNA methylation, histone post-translational modifications, and long non-coding RNAs, all of which regulate chromatin structure and gene expression. Although the genetic predisposition of Indians to T2DM is well established, how environmental and genetic factors interact and lead to T2DM is not well understood. In this review, we discuss the prevalence of diabetes and its complications across different states in India and how various risk factors contribute to its pathogenesis. The review also highlights the role of genetic predisposition among the Indian population and epigenetic factors involved in the etiology of diabetes. Lastly, we review current treatments and emphasize the knowledge gap with respect to genetic and epigenetic factors in the Indian context. Further understanding of the genetic and epigenetic determinants will help in risk prediction and prevention as well as therapeutic interventions, which will improve the clinical management of diabetes and associated macro- and micro-vascular complications.
Topics: Humans; Diabetes Mellitus, Type 2; Epigenesis, Genetic; DNA Methylation; Histones; Genetic Predisposition to Disease; India; Diabetes Complications
PubMed: 37999799
DOI: 10.1007/s00439-023-02616-3 -
Current Obesity Reports Sep 2023Chronic kidney disease (CKD) is a common condition and a major cause of morbidity and mortality in adults, but children and adolescents are also at risk for early kidney... (Review)
Review
PURPOSE OF REVIEW
Chronic kidney disease (CKD) is a common condition and a major cause of morbidity and mortality in adults, but children and adolescents are also at risk for early kidney injury and development of CKD. Obesity contributes both directly and indirectly to the development of CKD. The purpose of this review is to describe obesity-related kidney disease (ORKD) and diabetic kidney disease (DKD) and their impact in the pediatric population.
RECENT FINDINGS
Although obesity-related CKD in childhood and adolescence is uncommon, nascent kidney damage may magnify the lifetime risk of CKD. Glomerular hyperfiltration is an early phenotype of both ORKD and DKD and typically manifests prior to albuminuria and progressive decline in GFR. Novel treatments for obesity and type 2 diabetes exerting protective effects on the kidneys are being investigated for use in the pediatric population. It is important to understand the impact of obesity on the kidneys more fully in the pediatric population to help detect injury earlier and intervene prior to the onset of irreversible progression of disease and to guide future research in this area.
Topics: Child; Humans; Diabetes Mellitus, Type 2; Pediatric Obesity; Kidney; Diabetic Nephropathies; Renal Insufficiency, Chronic
PubMed: 37558892
DOI: 10.1007/s13679-023-00522-3 -
Redox Biology May 2024Diabetes mellitus is a non-communicable metabolic disease hallmarked by chronic hyperglycemia caused by beta-cell failure. Diabetic complications affect the vasculature... (Review)
Review
Diabetes mellitus is a non-communicable metabolic disease hallmarked by chronic hyperglycemia caused by beta-cell failure. Diabetic complications affect the vasculature and result in macro- and microangiopathies, which account for a significantly increased morbidity and mortality. The rising incidence and prevalence of diabetes is a major global health burden. There are no feasible strategies for beta-cell preservation available in daily clinical practice. Therefore, patients rely on antidiabetic drugs or the application of exogenous insulin. Glutaredoxins (Grxs) are ubiquitously expressed and highly conserved members of the thioredoxin family of proteins. They have specific functions in redox-mediated signal transduction, iron homeostasis and biosynthesis of iron-sulfur (FeS) proteins, and the regulation of cell proliferation, survival, and function. The involvement of Grxs in chronic diseases has been a topic of research for several decades, suggesting them as therapeutic targets. Little is known about their role in diabetes and its complications. Therefore, this review summarizes the available literature on the significance of Grxs in diabetes and its complications. In conclusion, Grxs are differentially expressed in the endocrine pancreas and in tissues affected by diabetic complications, such as the heart, the kidneys, the eye, and the vasculature. They are involved in several pathways essential for insulin signaling, metabolic inflammation, glucose and fatty acid uptake and processing, cell survival, and iron and mitochondrial metabolism. Most studies describe significant changes in glutaredoxin expression and/or activity in response to the diabetic metabolism. In general, mitigated levels of Grxs are associated with oxidative distress, cell damage, and even cell death. The induced overexpression is considered a potential part of the cellular stress-response, counteracting oxidative distress and exerting beneficial impact on cell function such as insulin secretion, cytokine expression, and enzyme activity.
Topics: Humans; Glutaredoxins; Diabetes Mellitus; Diabetes Complications; Iron; Insulins
PubMed: 38377787
DOI: 10.1016/j.redox.2024.103043 -
Cell Biochemistry and Function Jun 2024Diabetes mellitus (DM) is a heterogeneous group of disorders characterized by hyperglycemia. Microribonucleic acids (microRNAs) are noncoding RNA molecules synthesized... (Review)
Review
Diabetes mellitus (DM) is a heterogeneous group of disorders characterized by hyperglycemia. Microribonucleic acids (microRNAs) are noncoding RNA molecules synthesized in the nucleus, modified, and exported to the extracellular environment to bind to their complementary target sequences. It regulates protein synthesis in the targeted cells by inhibiting translation or triggering the degradation of the target messenger. MicroRNA-29 is one of noncoding RNA that can be secreted by adipose tissue, hepatocytes, islet cells, and brain cells. The expression level of the microRNA-29 family in several metabolic organs is regulated by body weight, blood concentrations of inflammatory mediators, serum glucose levels, and smoking habits. Several experimental studies have demonstrated the effect of microRNA-29 on the expression of target genes involved in glucose metabolism, insulin synthesis and secretion, islet cell survival, and proliferation. These findings shed new light on the role of microRNA-29 in the pathogenesis of diabetes and its complications, which plays a vital role in developing appropriate therapies. Different molecular pathways have been proposed to explain how microRNA-29 promotes the development of diabetes and its complications. However, to the best of our knowledge, no published review article has summarized the molecular mechanism of microRNA-29-mediated initiation of DM and its complications. Therefore, this narrative review aims to summarize the role of microRNA-29-mediated cross-talk between metabolic organs in the pathogenesis of diabetes and its complications.
Topics: Humans; MicroRNAs; Diabetes Mellitus; Diabetes Complications; Animals
PubMed: 38773932
DOI: 10.1002/cbf.4053 -
MMW Fortschritte Der Medizin Nov 2023
Topics: Humans; Diabetes Mellitus; Diabetes Complications
PubMed: 37919567
DOI: 10.1007/s15006-023-3101-y -
Medicine Oct 2023Diabetes mellitus is a complex chronic metabolic disease characterized by hyperglycemia and various complications. According to the different pathophysiological... (Review)
Review
Diabetes mellitus is a complex chronic metabolic disease characterized by hyperglycemia and various complications. According to the different pathophysiological mechanisms, these complications can be classified as microvascular or macrovascular complications, which have long-term negative effects on vital organs such as the eyes, kidneys, heart, and brain, and lead to increased patient mortality. Diabetes mellitus is a major global health issue, and its incidence and prevalence have increased significantly in recent years. Moreover, the incidence is expected to continue to rise as more people adopt a Western lifestyle and diet. Thus, it is essential to understand the epidemiology, pathogenesis, risk factors, and treatment of vascular complications to aid patients in managing the disease effectively. This paper provides a comprehensive review of the literature to clarify the above content. Furthermore, this paper also delves into the correlation between novel risk factors, such as long noncoding RNAs, gut microbiota, and nonalcoholic fatty liver disease, with diabetic vascular complications.
Topics: Humans; Diabetes Mellitus; Diabetic Angiopathies; Risk Factors; Hyperglycemia; Cardiovascular Diseases
PubMed: 37800828
DOI: 10.1097/MD.0000000000035285