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Diabetic nephropathy (DN) is a major healthcare challenge for individuals with diabetes and associated with increased cardiovascular morbidity and mortality. The existing rodent models do not fully represent the complex course of the human disease. Hence, developing a translational model of diabetes that reproduces both the early and the advanced characteristics of DN and faithfully recapitulates the overall human pathology is an unmet need. Here, we introduce the Nile grass rat (NGR) as a novel model of DN and characterize key pathologies underlying DN. NGRs spontaneously developed insulin resistance, reactive hyperinsulinemia, and hyperglycemia. Diabetic NGRs evolved DN and the key histopathological aspects of the human advanced DN, including glomerular hypertrophy, infiltration of mononuclear cells, tubular dilatation, and atrophy. Enlargement of the glomerular tufts and the Bowman's capsule areas accompanied the expansion of the Bowman's space. Glomerular sclerosis, renal arteriolar hyalinosis, Kimmelsteil-Wilson nodular lesions, and protein cast formations in the kidneys of diabetic NGR occurred with DN. Diabetic kidneys displayed interstitial and glomerular fibrosis, key characteristics of late human pathology as well as thickening of the glomerular basement membrane and podocyte effacement. Signs of injury included glomerular lipid accumulation, significantly more apoptotic cells, and expression of KIM-1. Diabetic NGRs became hypertensive, a known risk factor for kidney dysfunction, and showed decreased glomerular filtration rate. Diabetic NGRs recapitulate the breadth of human DN pathology and reproduce the consequences of chronic kidney disease, including injury and loss of function of the kidney. Hence, NGR represents a robust model for studying DN-related complications and provides a new foundation for more detailed mechanistic studies of the genesis of nephropathy, and the development of new therapeutic approaches.
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Nefropatias Diabéticas , Modelos Animais de Doenças , Animais , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/metabolismo , Ratos , Masculino , Humanos , Resistência à Insulina , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Rim/patologia , Rim/metabolismo , Glomérulos Renais/patologia , Glomérulos Renais/metabolismoRESUMO
Diabetes, a chronic disease characterized by hyperglycemia, is associated with significantly accelerated complications, including diabetic kidney disease (DKD), which increases morbidity and mortality. Hyperglycemia and other diabetes-related environmental factors such as overnutrition, sedentary lifestyles, and hyperlipidemia can induce epigenetic changes. Working alone or with genetic factors, these epigenetic changes that occur without alterations in the underlying DNA sequence, can alter the expression of pathophysiological genes and impair functions of associated target cells/organs, leading to diabetic complications like DKD. Notably, some hyperglycemia-induced epigenetic changes persist in target cells/tissues even after glucose normalization, leading to sustained complications despite glycemic control, so-called metabolic memory. Emerging evidence from in vitro and in vivo animal models and clinical trials with subjects with diabetes identified clear associations between metabolic memory and epigenetic changes including DNA methylation, histone modifications, chromatin structure, and noncoding RNAs at key loci. Targeting such persistent epigenetic changes and/or molecules regulated by them can serve as valuable opportunities to attenuate, or erase metabolic memory, which is crucial to prevent complication progression. Here, we review these cell/tissue-specific epigenetic changes identified to-date as related to diabetic complications, especially DKD, and the current status on targeting epigenetics to tackle metabolic memory. We also discuss limitations in current studies, including the need for more (epi)genome-wide studies, integrative analysis using multiple epigenetic marks and Omics datasets, and mechanistic evaluation of metabolic memory. Considering the tremendous technological advances in epigenomics, genetics, sequencing, and availability of genomic datasets from clinical cohorts, this field is likely to see considerable progress in the upcoming years.
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Metilação de DNA , Nefropatias Diabéticas , Epigênese Genética , Humanos , Animais , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Complicações do Diabetes/metabolismo , Complicações do Diabetes/genéticaRESUMO
Type 2 diabetes (T2D) prevalence in adults at a younger age has increased but the disease status may go unnoticed. This study aimed to determine whether the onset age and subsequent diabetic complications can be attributed to the polygenic architecture of T2D in the Taiwan Han population. A total of 9,627 cases with T2D and 85,606 controls from the Taiwan Biobank were enrolled. Three diabetic polygenic risk scores (PRSs), PRS_EAS and PRS_EUR, and a trans-ancestry PRS (PRS_META), calculated using summary statistic from East Asian and European populations. The onset age was identified by linking to the National Taiwan Insurance Research Database, and the incidence of different diabetic complications during follow-up was recorded. PRS_META (7.4%) explained a higher variation for T2D status. And the higher percentile of PRS is also correlated with higher percentage of T2D family history and prediabetes status. More, the PRS was negatively associated with onset age (ß = -0.91 yr), and this was more evident among males (ß = -1.11 vs. -0.76 for males and females, respectively). The hazard ratio of diabetic retinopathy (DR) and diabetic foot were significantly associated with PRS_EAS and PRS_META, respectively. However, the PRS was not associated with other diabetic complications, including diabetic nephropathy, cardiovascular disease, and hypertension. Our findings indicated that diabetic PRS which combined susceptibility variants from cross-population could be used as a tool for early screening of T2D, especially for high-risk populations, such as individuals with high genetic risk, and may be associated with the risk of complications in subjects with T2D. NEW & NOTEWORTHY Our findings indicated that diabetic polygenic risk score (PRS) which combined susceptibility variants from Asian and European population affect the onset age of type 2 diabetes (T2D) and could be used as a tool for early screening of T2D, especially for individuals with high genetic risk, and may be associated with the risk of diabetic complications among people in Taiwan.
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Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Masculino , Adulto , Feminino , Humanos , Diabetes Mellitus Tipo 2/genética , Estratificação de Risco Genético , Taiwan , Predisposição Genética para Doença , Idade de Início , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla , Fatores de RiscoRESUMO
Aims: This study aims to explore the potential role of vascular endothelial growth factor-B (VEGF-B) in the pathogenesis of diabetic peripheral neuropathy (DPN). The expression of VEGFRs were reanalysed by using gene arrays of peripheral nerve samples from mouse models of DPN retrieved from the GEO database. 213 T2D patients as well as 31 healthy individuals were recruited. The serum VEGF-B was detected and its relationship with DPN was analysed. The elevated VEGFR1 was the only change of VEGFR gene expression in the peripheral nerve from mouse models of DPN. The level of serum VEGF-B in T2D patients with DPN was higher than that in T2D patients without DPN and healthy people. Analysis of correlation and binary logistic regression confirmed that the increased serum VEGF-B level was an independent risk factor of DPN in T2D patients. VEGF-B-VEGFR1 signaling pathway may be involved in the development of DPN.
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Over the past few decades, diabetes gradually has become one of the top non-communicable disorders, affecting 476.0 million in 2017 and is predicted to reach 570.9 million people in 2025. It is estimated that 70 to 100% of all diabetic patients will develop some if not all, diabetic complications over the course of the disease. Despite different symptoms, mechanisms underlying the development of diabetic complications are similar, likely stemming from deficits in both neuronal and vascular components supplying hyperglycaemia-susceptible tissues and organs. Diaph1, protein diaphanous homolog 1, although mainly known for its regulatory role in structural modification of actin and related cytoskeleton proteins, in recent years attracted research attention as a cytoplasmic partner of the receptor of advanced glycation end-products (RAGE) a signal transduction receptor, whose activation triggers an increase in proinflammatory molecules, oxidative stressors and cytokines in diabetes and its related complications. Both Diaph1 and RAGE are also a part of the RhoA signalling cascade, playing a significant role in the development of neurovascular disturbances underlying diabetes-related complications. In this review, based on the existing knowledge as well as compelling findings from our past and present studies, we address the role of Diaph1 signalling in metabolic stress and neurovascular degeneration in diabetic complications. In light of the most recent developments in biochemical, genomic and transcriptomic research, we describe current theories on the aetiology of diabetes complications, highlighting the function of the Diaph1 signalling system and its role in diabetes pathophysiology.
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Forminas , Transdução de Sinais , Humanos , Animais , Forminas/metabolismo , Transdução de Sinais/fisiologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Complicações do Diabetes/metabolismo , Neuropatias Diabéticas/metabolismoRESUMO
Diabetes mellitus, a chronic metabolic disease, often leads to numerous chronic complications, significantly contributing to global morbidity and mortality rates. High glucose levels trigger epigenetic modifications linked to pathophysiological processes like inflammation, immunity, oxidative stress, mitochondrial dysfunction, senescence and various kinds of cell death. Despite glycemic control, transient hyperglycemia can persistently harm organs, tissues, and cells, a latent effect termed "metabolic memory" that contributes to chronic diabetic complications. Understanding metabolic memory's mechanisms could offer a new approach to mitigating these complications. However, key molecules and networks underlying metabolic memory remain incompletely understood. This review traces the history of metabolic memory research, highlights its key features, discusses recent molecules involved in its mechanisms, and summarizes confirmed and potential therapeutic compounds. Additionally, we outline in vitro and in vivo models of metabolic memory. We hope this work will inform future research on metabolic memory's regulatory mechanisms and facilitate the development of effective therapeutic compounds to prevent diabetic complications.
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Complicações do Diabetes , Humanos , Animais , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/etiologia , Epigênese Genética , Estresse Oxidativo , Hiperglicemia/metabolismoRESUMO
AIMS: To investigate if diabetic complications increase the risk of depression and/or anxiety among adults with type 2 diabetes. METHODS: This register-based, prospective study included 265,799 adult individuals diagnosed with type 2 diabetes between 1997 and 2017 without a recent history of depression or anxiety. Diabetic complications included cardiovascular disease, amputation of lower extremities, neuropathy, nephropathy and retinopathy. Both diabetic complications and depression and anxiety were defined by hospital contacts and prescription-based medication. All individuals were followed from the date of type 2 diabetes diagnosis until the date of incident depression or anxiety, emigration, death or 31 December 2018, whichever occurred first. RESULTS: The total risk time was 1,915,390 person-years. The incidence rate of depression and/or anxiety was 3368 per 100,000 person-years among individuals with diabetic complications and 1929 per 100,000 person-years among those without. Having or developing any diabetic complication was associated with an increased risk of depression and/or anxiety (HR 1.77, 95% CI 1.73-1.80). The risk for depression and/or anxiety was increased for all types of diabetic complications. The strongest association was found for amputation of lower extremities (HR 2.16, 95% CI 2.01-2.31) and the weakest for retinopathy (HR 1.13, 95% CI 1.09-1.17). CONCLUSION: Individuals with type 2 diabetes and diabetic complications are at increased risk of depression and anxiety. This points towards the importance of an increased clinical focus on mental well-being among individuals with type 2 diabetes and complications.
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Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Doenças Retinianas , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Depressão/epidemiologia , Depressão/etiologia , Estudos Prospectivos , Ansiedade/epidemiologia , Ansiedade/etiologia , Complicações do Diabetes/epidemiologiaRESUMO
AIMS: England's Diabetic Eye Disease Screening Programme offers screening to every resident over age 12 with diabetes, starting as soon as possible after diagnosis and repeated annually. People first diagnosed with diabetes at older ages have shorter life expectancy and therefore may be less likely to benefit from screening and treatment. To inform decisions about whether diabetic eye screening policy should be stratified by age, we investigated the probability of receiving treatment according to age at first screening episode. METHODS: This was a cohort study of participants in the Norfolk Diabetic Retinopathy Screening Programme from 2006 to 2017, with individuals' programme data linked to hospital treatment and death data recorded up to 2021. We estimated and compared the probability, annual incidence and screening costs of receiving retinal laser photocoagulation or intravitreal injection and of death, in age groups defined by age at first screening episode. RESULTS: The probability of death increased with increasing age at diagnosis, while the probability of receiving either treatment decreased with increasing age. The estimated cost of screening per person who received either or both treatments was £18,608 among all participants, increasing with age up to £21,721 in those aged 70-79 and £26,214 in those aged 80-89. CONCLUSIONS: Diabetic retinopathy screening is less effective and less cost-effective with increasing age at diagnosis of diabetes, because of the increasing probability of death before participants develop sight-threatening diabetic retinopathy and can benefit from treatment. Upper age limits on entry into screening programmes or risk stratification in older age groups may, therefore, be justifiable.
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Diabetes Mellitus , Retinopatia Diabética , Idoso , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Incidência , Programas de Rastreamento , Probabilidade , Idade de InícioRESUMO
AIMS: We evaluated the involvement of lncRNAs in the development of pathologies associated with chronic hyperglycaemia in rat models in a model of type 1, type 2 and gestational diabetes. METHODS: Reports were searched in Dialnet, Scielo, HINARI, Springer, ClinicalKey, OTseeker, PubMed and different grey literature databases with any restrictions. Bibliography databases will be searched from their inception to December 2022. RESULTS: Thirty-seven studies met our criteria, and they had the following characteristics: original experimental studies on diabetes, the lncRNAs were extracted or measured from tissues of specific areas and the results were expressed in terms of standard measures by RT-PCR. In most studies, both primary and secondary outcomes were mentioned. On the other hand, we found a total of nine diabetic complications, being retinopathy, nephropathy and neuropathy the most representatives. Additionally, it was found that MALAT1, H19, NEAT1 and TUG1 are the most studied lncRNAs about these complications in rats. On the other hand, the lncRNAs with the highest rate of change were MSTRG.1662 (17.85; 13.78, 21.93), ENSRNOT00000093120_Aox3 (7.13; 5.95, 8.31) and NONRATG013497.2 (-5.55; -7.18, -3.93). CONCLUSIONS: This review found a significant involvement of lncRNAs in the progression of pathologies associated with chronic hyperglycaemia in rat models, and further studies are needed to establish their potential as biomarkers and therapeutic targets for diabetes.
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Diabetes Mellitus , Hiperglicemia , RNA Longo não Codificante , Animais , Ratos , RNA Longo não Codificante/genética , Hiperglicemia/genética , BiomarcadoresRESUMO
Disturbances in copper (Cu) homeostasis have been observed in diabetes and associated complications. Cu is an essential micronutrient that plays important roles in various fundamental biological processes. For example, diabetic cardiomyopathy is associated with elevated levels of Cu in the serum and tissues. Therefore, targeting Cu may be a novel treatment strategy for diabetic complications. This review provides an overview of physiological Cu metabolism and homeostasis, followed by a discussion of Cu metabolism disorders observed during the occurrence and progression of diabetic complications. Finally, we discuss the recent therapeutic advances in the use of Cu coordination complexes as treatments for diabetic complications and their potential mechanisms of action. This review contributes to a complete understanding of the role of Cu in diabetic complications and demonstrates the broad application prospects of Cu-coordinated compounds as potential therapeutic agents.
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Cobre , Complicações do Diabetes , Humanos , Cobre/metabolismo , Animais , Complicações do Diabetes/metabolismo , Complicações do Diabetes/tratamento farmacológico , HomeostaseRESUMO
BACKGROUND: Peyronie's disease (PD) is a connective tissue disorder that affects the penis and is characterized by abnormal collagen structure in the penile tunica albuginea, resulting in plaque formation and penile deformity. PD's overall prevalence is estimated at 3.2% to 8.9%, with rates as high as 20.3% among men with type 2 diabetes mellitus (DM). However, the characteristics of DM associated with PD complications remain unclear. AIM: To explore clinical associations between DM characteristics and PD complications. METHODS: We conducted a retrospective analysis of patients with DM and PD who presented at our institution between 2007 and 2022. We examined patients' clinical histories, DM- and PD-related clinical parameters, and complications. Penile deformities were assessed through physical examination, photographs, and penile Doppler ultrasound. Patients were categorized into subgroups based on age of DM onset: early (<45 years), average (45-65 years), and late (>65 years). OUTCOMES: Outcomes included effects of DM characteristics on PD development, progression, and severity. RESULTS: In total, 197 patients were included in the evaluation. Early-onset diabetes and elevated hemoglobin A1c (HbA1c) levels exhibited significant correlations with the early development of PD (ρ = 0.66, P < .001, and ρ = -0.24, P < .001, respectively). Furthermore, having DM at an early age was associated with the occurrence of penile plaque (ρ = -0.18, P = .03), and there were no significant differences in plaque dimensions (ρ = -0.29, P = .053). A rise in HbA1c levels after the initial PD diagnosis displayed positive correlations with the formation of penile plaque (ρ = 0.22, P < .006). CLINICAL IMPLICATIONS: These findings emphasize the need for comprehensive assessments and personalized treatment strategies for individuals with DM and PD. Enhanced management approaches can improve outcomes for those facing both challenges. STRENGTHS AND LIMITATIONS: Limitations include the single-site retrospective design with potential selection bias, inaccuracies in medical record data, and challenges in controlling confounding variables. CONCLUSIONS: This study highlights that early-onset diabetes and poor diabetes control, as indicated by a subsequent rise in HbA1c levels following PD diagnosis, are significantly correlated with the onset and severity of PD. Revealing the mechanisms behind these findings will help us develop better management strategies for individuals with DM and PD.
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Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Induração Peniana , Humanos , Induração Peniana/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/complicações , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Idoso , Idade de Início , Adulto , Progressão da Doença , Pênis/diagnóstico por imagem , Fatores de RiscoRESUMO
BACKGROUND: The formation of advanced glycation end products (AGEs) is the central process contributing to diabetic complications in diabetic individuals with sustained and inconsistent hyperglycemia. Methylglyoxal, a reactive carbonyl species, is found to be a major precursor of AGEs, and its levels are elevated in diabetic conditions. Dysfunction of pancreatic beta cells and impairment in insulin secretion are the hallmarks of diabetic progression. Exposure to methylglyoxal-induced AGEs alters the function and maintenance of pancreatic beta cells. Hence, trapping methylglyoxal could be an ideal approach to alleviate AGE formation and its influence on beta cell proliferation and insulin secretion, thereby curbing the progression of diabetes to its complications. METHODS AND RESULTS: In the present study, we have explored the mechanism of action of (+)-Catechin against methylglyoxal-induced disruption in pancreatic beta cells via molecular biology techniques, mainly western blot. Methylglyoxal treatment decreased insulin synthesis (41.5%) via downregulating the glucose-stimulated insulin secretion pathway (GSIS). This was restored upon co-treatment with (+)-Catechin (29.9%) in methylglyoxal-induced Beta-TC-6 cells. Also, methylglyoxal treatment affected the autocrine function of insulin by disrupting the IRS1/PI3k/Akt pathway. Methylglyoxal treatment suppresses Pdx-1 and Maf A levels, which are responsible for beta cell maintenance and cell proliferation. (+)-Catechin could significantly augment the levels of these transcription factors. CONCLUSION: This is the first study to examine the impact of a natural compound on methylglyoxal with the insulin-mediated autocrine and paracrine activities of pancreatic beta cells. The results indicate that (+)-Catechin exerts a protective effect against methylglyoxal exposure in pancreatic beta cells and can be considered a potential anti-glycation agent in further investigations on ameliorating diabetic complications.
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Catequina , Complicações do Diabetes , Diabetes Mellitus , Células Secretoras de Insulina , Humanos , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Aldeído Pirúvico/farmacologia , Aldeído Pirúvico/metabolismo , Catequina/farmacologia , Catequina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Insulina/metabolismo , Diabetes Mellitus/metabolismo , Complicações do Diabetes/metabolismo , Produtos Finais de Glicação Avançada/metabolismoRESUMO
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.
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Diabetes Mellitus , MicroRNAs , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , AnimaisRESUMO
Type 2 diabetes mellitus (T2DM), a metabolic disease with persistent hyperglycemia primarily caused by insulin resistance (IR), has become one of the most serious health challenges of the 21st century, with considerable economic and societal implications worldwide. Considering the inevitable side effects of conventional antidiabetic drugs, natural ingredients exhibit promising therapeutic efficacy and can serve as safer and more cost-effective alternatives for the management of T2DM. Saponins are a structurally diverse class of amphiphilic compounds widely distributed in many popular herbal medicinal plants, some animals, and marine organisms. There are many saponin monomers, such as ginsenoside compound K, ginsenoside Rb1, ginsenoside Rg1, astragaloside IV, glycyrrhizin, and diosgenin, showing great efficacy in the treatment of T2DM and its complications in vivo and in vitro. However, although the mechanisms of action of saponin monomers at the animal and cell levels have been gradually elucidated, there is a lack of clinical data, which hinders the development of saponin-based antidiabetic drugs. Herein, the main factors/pathways associated with T2DM and the comprehensive underlying mechanisms and potential applications of these saponin monomers in the management of T2DM and its complications are reviewed and discussed, aiming to provide fundamental data for future high-quality clinical studies and trials.
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Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Saponinas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Saponinas/farmacologia , Saponinas/química , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Animais , Plantas Medicinais/química , Resistência à InsulinaRESUMO
Diabetic complications pose a significant threat to life and have a negative impact on quality of life in individuals with diabetes. Among the various factors contributing to the development of these complications, endothelial dysfunction plays a key role. The main mechanism underlying endothelial dysfunction in diabetes is oxidative stress, which adversely affects the production and availability of nitric oxide (NO). Flavonoids, a group of phenolic compounds found in vegetables, fruits, and fungi, exhibit strong antioxidant and anti-inflammatory properties. Several studies have provided evidence to suggest that flavonoids have a protective effect on diabetic complications. This review focuses on the imbalance between reactive oxygen species and the antioxidant system, as well as the changes in endothelial factors in diabetes. Furthermore, we summarize the protective mechanisms of flavonoids and their derivatives on endothelial dysfunction in diabetes by alleviating oxidative stress and modulating other signaling pathways. Although several studies underline the positive influence of flavonoids and their derivatives on endothelial dysfunction induced by oxidative stress in diabetes, numerous aspects still require clarification, such as optimal consumption levels, bioavailability, and side effects. Consequently, further investigations are necessary to enhance our understanding of the therapeutic potential of flavonoids and their derivatives in the treatment of diabetic complications.
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Antioxidantes , Diabetes Mellitus , Endotélio Vascular , Flavonoides , Estresse Oxidativo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Flavonoides/química , Humanos , Estresse Oxidativo/efeitos dos fármacos , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Animais , Espécies Reativas de Oxigênio/metabolismo , Óxido Nítrico/metabolismo , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
"Limb salvage" efforts, such as performing minor amputations before infections spread proximally from the foot to decrease major lower extremity amputation, are an important part of healthcare today. It is unclear whether these efforts are preventing the number of major amputations and improving patients' quality of life and the cost-effectiveness of the U.S. healthcare system. Rates of non-traumatic lower extremity amputation (NLEA) among patients with diabetes decreased in the early 2000s but rebounded in the 2010s. We analyzed the proportion of major amputations and differences in amputation rates between age groups in Texas. Patient data was extracted from the Texas Hospital Discharge Data Public Use Data File. Population estimates were obtained from the Texas Population Estimates Program from 2011 to 2015 and from intercensal estimates provided by the U.S. Census Bureau from 2006 to 2010. Raw numbers of minor, major, and all NLEA surgeries and the ratio of major amputations to total amputations per year were reported for each age group. Poisson regression and Joinpoint analyses were performed to capture these changes in trends. Rates of amputations increased, with significant decreasing relative prevalence of major amputations. Patients aged 45 to 64 with diabetes are likely driving these increases. Rates of lower extremity amputation in patients with diabetes increased from 2009 to 2015. This holds for all and minor amputations. In contrast, the ratio of major to all amputations decreased from 2010. Utilization of major and minor amputation differs between age groups, remaining stable in the youngest subjects, with minor amputation rates increasing in those aged 45 to 64.
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Amputação Cirúrgica , Pé Diabético , Salvamento de Membro , Humanos , Amputação Cirúrgica/estatística & dados numéricos , Pessoa de Meia-Idade , Pé Diabético/cirurgia , Salvamento de Membro/estatística & dados numéricos , Idoso , Adulto , Masculino , Texas , Feminino , Fatores Etários , Adulto JovemRESUMO
OBJECTIVE: Acute Charcot neuro-osteoarthropathy (CN) is highly destructive, causing bone and joint damage that can result in devastating structural changes to the foot. The objective of this study was to determine the characteristics of assessment, diagnosis and management of people with acute CN attending a large regional Australian health service. DESIGN: Three-year retrospective medical record audit. SETTING: Large regional health service with catchment area of >250 000 people in regional Australia. PARTICIPANTS: People with acute CN who attended emergency, orthopaedic clinics or High Risk Foot Clinic (HRFC). MAIN OUTCOME MEASURES: Participant characteristics and acute CN assessment, diagnosis and management characteristics. Trends in characteristics were investigated according to rurality as measured by the Modified Monash Model (MMM) scale. RESULTS: Seventeen participants (20 presentations) of acute CN were identified. Mean age was 57.1 ± 10.8 years, with 11 female participants. Median duration to seek help was 31 (IQR 14-47) days. Total Contact Casting was undertaken for 85% of cases, with those who resided in MMM1-2 regions experienced significantly shorter time to TCC therapy compared to those residing in MMM3-7 regions (U = 3.0, p < 0.01). Resolution of acute CN with or without deformity occurred in 70% of cases. CONCLUSIONS: Those who lived in smaller regional and rural communities were more likely to experience delayed access to gold standard treatment for acute CN. Regional models of care for acute CN should include activities to improve the knowledge of people at risk of acute CN about the condition and upskill regional health professionals for timely and local TCC therapy.
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Advanced glycation end products (AGEs) are formed within the body as a part of normal metabolism and are also the by-products of cooking food. The elevated levels of AGEs in the body are considered pathogenic. The modern diets contain high levels of AGEs which are getting incorporated into the body AGEs pool and contribute to post-diabetic and age-related complications. The objective of the present study is to estimate the cross-linked AGEs (AGE-fluorescence) and the more stable carboxymethyl-lysine (CML) by spectrofluorimetry and ELISA in 58 kinds of foods in India. It was evident from the results that the foods cooked at higher temperatures showed high levels of AGEs. Among the studied foods, the highest fluorescence was observed in Biscuits 2 (362 AU), and the highest level of carboxymethyl lysine (CML) was found in Soya milk (659.3 ng/g). However, there was less correlation between the AGE-fluorescence and the CML content of the food samples. Processed food such as tomato sauce, chilli sauce, and cheese, along with western foods like chicken nuggets, pizza, and biscuits like Biscuits 2, are known to contain high levels of AGEs. In the present study a preliminary database of AGE-fluorescence and CML content of 58 foods was developed, which is the first attempt among Indian foods. Furthermore, elaborated database can be developed including maximum consumed foods in India which will help in suggesting a better diet for the diabetic population.
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Bebidas , Ensaio de Imunoadsorção Enzimática , Análise de Alimentos , Produtos Finais de Glicação Avançada , Lisina , Espectrometria de Fluorescência , Produtos Finais de Glicação Avançada/análise , Lisina/análogos & derivados , Lisina/análise , Espectrometria de Fluorescência/métodos , Bebidas/análise , Ensaio de Imunoadsorção Enzimática/métodos , Análise de Alimentos/métodos , Índia , Culinária/métodosRESUMO
OBJECTIVE: To identify the structural and intermediate determinants associated with avoidable hospitalizations (AH) of patients with type2 diabetes mellitus (T2DM). DESIGN: Literature review based on narrative synthesis. DATA SOURCES: Databases: PubMed, Science Direct, and Latin American and Caribbean Literature in Health Sciences (LILACS). STUDY SELECTION: Documents were selected and analyzed under a critical literature review, considering inclusion and exclusion criteria. DATA EXTRACTION: Information extracted from each selected article was synthesized based on the countries' income levels and the social determinants of health framework. RESULTS: A total of 4,166 articles were relevant, 36 were selected for review. From this selection, 21 were publications conducted in high-income countries, 14 in upper-middle-income countries, and one in lower-middle-income countries. The review identified that the coverage of health services -mainly primary health care- and health insurance contribute to reducing the risk of AH for T2DM, while social inequalities tend to increase the risk. CONCLUSIONS: The AH due to T2DM are susceptible to reduction through policies that contribute to increasing effective access to health services (availability, insurance), since they express social inequality, occurring to a greater extent in socioeconomically vulnerable populations. This review also provides evidence of the need to expand research on this topic in middle and low-income countries.
RESUMO
Diabetes mellitus(DM) is a chronic endocrine disease characterized by hyperglycemia caused by carbohydrate or lipid metabolism disorders or insulin dysfunction. Hyperglycemia and long-term metabolic disorders in DM can damage tissues and organs throughout the body, leading to serious complications. Mitochondrial autophagy(mitophagy) is an important mitochondrial quality control process in cells and a special autophagy phenomenon, in which damaged or redundant mitochondria can be selectively removed by autophagic lysosome, which is crucial to maintain cell stability and survival under stress. Studies have confirmed that changes in autophagy play a role in the development and control of DM and its complications. Mitophagy has become a research hotspot in recent years and it is closely associated with the pathogenesis of a variety of diseases. Substantial evidence suggests that mitophagy plays a crucial role in regulating the metabolic homeostasis in the case of DM and its complications. Because the destructive great vessel complications and microvascular complications cause increased mortality, blindness, renal failure, and declined quality of life of DM patients, it is urgent to develop targeted therapies to intervene in DM and its complications. Traditional Chinese medicine(TCM), with a multi-component, multi-target, and multi-level action manner, can prevent the development of drug resistance and have significant therapeutic effects in the prevention and treatment of DM and its complications. Therefore, exploring the mechanisms of TCM in regulating mito-phagy may become a new method for treating DM and its complications. With focus on the roles and mechanisms of mitophagy in DM and its complications, this paper summarizes and prospects the research on the treatment of DM and its complications with TCM via re-gulating mitophagy, aiming to provide new ideas for the clinical practice.