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The article offers information on the continuing medical education for ophthalmologists on advance caring of patients with neurotrophic keratitis.

Inflammation is part of the body's innate immune response and is an essential process that not only defends against harmful bacteria and pathogens but also plays a key role in the maintenance and repair of tissues. Under pathological conditions, there is bilateral crosstalk between immune regulation and aberrant metabolism resulting in persistent inflammation in the absence of infection. This phenomenon is ref erred to as sterile metabolic inflammation (metainflammation) and occurs if the initi ating stimulus is not removed or if the resolution process is disrupted. Disruption of this tightly regulated immune response and its failure to resolve as is evident in metabolic disorders is not only associated with disease progression but also leads to immune senescence and should not be neglected in the clinical management of patients. This review gives an overview of the mechanisms underlying chronic metabolic inflamma tion, the aberrant metabolic activation of innate immune cells (neutrophils, macro phages, mast cells, dendritic cells), and its role in disease progression using obe sity-diabetes as a prime example. Addressing the underlying subclinical metabolic inflammation in addition to achieving glucose control may contribute significantly towards t herapeutic interventions aimed at preventing the onset of co-morbidities in diabetic patients. [ABSTRACT FROM AUTHOR]

Introduction: Primary studies have estimated the prevalence of depression and its determinants among diabetes patients. However, studies synthesizing this primary evidence are limited. Hence, this systematic review aimed to determine the prevalence of depression and identify determinants of depression among diabetes in Ethiopia. Methods: This systematic review and meta-analysis included a search of PubMed, Google Scholar, Scopus, Science Direct, PsycINFO, and Cochrane library. Data were extracted using Microsoft Excel and analyzed using STATA statistical software (v. 14). Data were pooled using a random-effects model. Forest plots, and Egger's regression test were all used to check for publication bias. Heterogeneity (I)2 was computed. Subgroup analysis was done by region, publication year, and depression screening instrument. In addition, the pooled odds ratio for determinants was calculated. Results: Sixteen studies, including 5808 participants were analyzed. The prevalence of depression in diabetes was estimated to be 34.61% (95% CI: 27.31–41.91). According to subgroup analysis by study region, publication year, and screening instrument, the highest prevalence was observed in Addis Ababa (41.98%), studies published before 2020 (37.91%), and studies that used Hospital Anxiety and Depression Scale (HADS-D) (42.42%,) respectively. Older age > 50 years (AOR = 2.96; 95% CI: 1.71–5.11), being women (AOR = 2.31; 95% CI: 1.57, 3.4), longer duration with diabetes (above 5 years) (AOR = 1.98; 95% CI: 1.03–3.8), and limited social support (AOR = 2.37; 95% CI: 1.68–3.34), were the determinants of depression in diabetic patients. Conclusion: The results of this study suggest that the prevalence of depression in diabetes is substantial. This result underscores the importance of paying particular attention to prevent depression among diabetes. Being older, not attending formal education, longer duration with diabetes, having comorbidity, and low adherence to diabetes management were all associated. These variables may help clinicians identify patients at high risk of depression. Future studies focusing on the causal association between depression and diabetes are highly recommended. [ABSTRACT FROM AUTHOR]

The decline of oocyte quality has profound impacts on fertilization, implantation, embryonic development, and the genetic quality of future generations. One factor that is often ignored but is involved in the decline of oocyte quality is mitochondrial DNA (mtDNA) abnormalities. Abnormalities in mtDNA affect the energy production of mitochondria, the dynamic balance of the mitochondrial network, and the pathogenesis of mtDNA diseases in offspring. In this review, we have detailed the characteristics of mtDNA in oocytes and the maternal inheritance of mtDNA. Next, we summarized the mtDNA abnormalities in oocytes derived from aging, diabetes, obesity, and assisted reproductive technology (ART) in an attempt to further elucidate the possible mechanisms underlying the decline in oocyte health. Because multiple infertility factors are often involved when an individual is infertile, a comprehensive understanding of the individual effects of each infertility-related factor on mtDNA is necessary. Herein, we consider the influence of infertility-related factors on the mtDNA of the oocyte as a collective perspective for the first time, providing a supplementary angle and reference for multi-directional improvement strategies of oocyte quality in the future. In addition, we highlight the importance of studying ART-derived mitochondrial abnormalities during every ART procedure. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease (ASCVD) is the primary cause of death globally, with nine million deaths directly attributable to ischemic heart diseases in 2020. Since the last few decades, great effort has been put toward primary and secondary prevention strategies through identification and treatment of major cardiovascular risk factors, including hypertension, diabetes, dyslipidemia, smoking, and a sedentary lifestyle. Once labelled "the forgotten organ", the gut microbiota has recently been rediscovered and has been found to play key functions in the incidence of ASCVD both directly by contributing to the development of atherosclerosis and indirectly by playing a part in the occurrence of fundamental cardiovascular risk factors. Essential gut metabolites, such as trimethylamine N-oxide (TMAO), secondary bile acids, lipopolysaccharides (LPS), and short-chain fatty acids (SCFAs), have been associated with the extent of ischemic heart diseases. This paper reviews the latest data on the impact of the gut microbiome in the incidence of ASCVD. [ABSTRACT FROM AUTHOR]

Diabetes is a metabolic disease characterized by high blood glucose levels. With economic development and lifestyle changes, the prevalence of diabetes is increasing yearly. Thus, it has become an increasingly serious public health problem in countries around the world. The etiology of diabetes is complex, and its pathogenic mechanisms are not completely clear. The use of diabetic animal models is helpful in the study of the pathogenesis of diabetes and the development of drugs. The emerging vertebrate model of zebrafish has many advantages, such as its small size, large number of eggs, short growth cycle, simple cultivation of adult fish, and effective improvement of experimental efficiency. Thus, this model is highly suitable for research as an animal model of diabetes. This review not only summarizes the advantages of zebrafish as a diabetes model, but also summarizes the construction methods and challenges of zebrafish models of type 1 diabetes, type 2 diabetes, and diabetes complications. This study provides valuable reference information for further study of the pathological mechanisms of diabetes and the research and development of new related therapeutic drugs. [ABSTRACT FROM AUTHOR]

Sustained tissue hypoxia is associated with many pathophysiological conditions, including chronic inflammation, chronic wounds, slow-healing fractures, microvascular complications of diabetes, and metastatic spread of tumors. This extended deficiency of oxygen (O2) in the tissue sets creates a microenvironment that supports inflammation and initiates cell survival paradigms. Elevating tissue carbon dioxide levels (CO2) pushes the tissue environment toward "thrive mode," bringing increased blood flow, added O2, reduced inflammation, and enhanced angiogenesis. This review presents the science supporting the clinical benefits observed with the administration of therapeutic CO2. It also presents the current knowledge regarding the cellular and molecular mechanisms responsible for the biological effects of CO2 therapy. The most notable findings of the review include (a) CO2 activates angiogenesis not mediated by hypoxia-inducible factor 1a, (b) CO2 is strongly anti-inflammatory, (c) CO2 inhibits tumor growth and metastasis, and (d) CO2 can stimulate the same pathways as exercise and thereby, acts as a critical mediator in the biological response of skeletal muscle to tissue hypoxia. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a heterogeneous chronic metabolic disorder characterized by the presence of hyperglycemia, commonly preceded by a prediabetic state. The excess of blood glucose can damage multiple organs, including the brain. In fact, cognitive decline and dementia are increasingly being recognized as important comorbidities of diabetes. Despite the largely consistent link between diabetes and dementia, the underlying causes of neurodegeneration in diabetic patients remain to be elucidated. A common factor for almost all neurological disorders is neuroinflammation, a complex inflammatory process in the central nervous system for the most part orchestrated by microglial cells, the main representatives of the immune system in the brain. In this context, our research question aimed to understand how diabetes affects brain and/or retinal microglia physiology. We conducted a systematic search in PubMed and Web of Science to identify research items addressing the effects of diabetes on microglial phenotypic modulation, including critical neuroinflammatory mediators and their pathways. The literature search yielded 1327 records, including 18 patents. Based on the title and abstracts, 830 papers were screened from which 250 primary research papers met the eligibility criteria (original research articles with patients or with a strict diabetes model without comorbidities, that included direct data about microglia in the brain or retina), and 17 additional research papers were included through forward and backward citations, resulting in a total of 267 primary research articles included in the scoping systematic review. We reviewed all primary publications investigating the effects of diabetes and/or its main pathophysiological traits on microglia, including in vitro studies, preclinical models of diabetes and clinical studies on diabetic patients. Although a strict classification of microglia remains elusive given their capacity to adapt to the environment and their morphological, ultrastructural and molecular dynamism, diabetes modulates microglial phenotypic states, triggering specific responses that include upregulation of activity markers (such as Iba1, CD11b, CD68, MHC-II and F4/80), morphological shift to amoeboid shape, secretion of a wide variety of cytokines and chemokines, metabolic reprogramming and generalized increase of oxidative stress. Pathways commonly activated by diabetes-related conditions include NF-κB, NLRP3 inflammasome, fractalkine/CX3CR1, MAPKs, AGEs/RAGE and Akt/mTOR. Altogether, the detailed portrait of complex interactions between diabetes and microglia physiology presented here can be regarded as an important starting point for future research focused on the microglia–metabolism interface. [ABSTRACT FROM AUTHOR]

The human body is inhabited by numerous bacteria, fungi, and viruses, and each part has a unique microbial community structure. The gastrointestinal tract harbors approximately 100 trillion strains comprising more than 1000 bacterial species that maintain symbiotic relationships with the host. The gut microbiota consists mainly of the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Of these, Firmicutes and Bacteroidetes constitute 70-90% of the total abundance. Gut microbiota utilize nutrients ingested by the host, interact with other bacterial species, and help maintain healthy homeostasis in the host. In recent years, it has become increasingly clear that a breakdown of the microbial structure and its functions, known as dysbiosis, is associated with the development of allergies, autoimmune diseases, cancers, and arteriosclerosis, among others. Metabolic diseases, such as obesity and diabetes, also have a causal relationship with dysbiosis. The present review provides a brief overview of the general roles of the gut microbiota and their relationship with metabolic disorders. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a major public health problem in all countries due to its high human and economic burden. Major metabolic alterations are associated with the chronic hyperglycemia that characterizes diabetes and causes devastating complications, including retinopathy, kidney failure, coronary disease and increased cardiovascular mortality. The most common form is type 2 diabetes (T2D) accounting for 90 to 95% of the cases. These chronic metabolic disorders are heterogeneous to which genetic factors contribute, but so do prenatal and postnatal life environmental factors including a sedentary lifestyle, overweight, and obesity. However, these classical risk factors alone cannot explain the rapid evolution of the prevalence of T2D and the high prevalence of type 1 diabetes in particular areas. Among environmental factors, we are in fact exposed to a growing amount of chemical molecules produced by our industries or by our way of life. In this narrative review, we aim to give a critical overview of the role of these pollutants that can interfere with our endocrine system, the so-called endocrine-disrupting chemicals (EDCs), in the pathophysiology of diabetes and metabolic disorders. [ABSTRACT FROM AUTHOR]

Coronary artery calcification (CAC) is one of the critical cardiovascular complications that lead to elevated morbidity and mortality among patients with type 2 diabetes (T2M). The association between osteoprotegerin (OPG) and CAC could potentially provide a reasonable chance for preventive therapy in type 2 diabetic patients and benefit the rate of mortality. Since measurement of CAC score is relatively expensive and requires radiation exposure, the current systematic review aims to provide clinical evidence for evaluating the prognostic role of OPG in determining CAC risk among subjects with T2M. Web of Science, PubMed, Embase, and Scopus, were investigated until July 2022. We assessed human studies investigating the association of OPG with CAC in type 2 diabetic patients. Quality assessment was performed by Newcastle–Ottawa quality assessment scales (NOS). Out of 459 records, 7 studies remained eligible to be included. Observational studies that provided odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between OPG and the risk of CAC were analyzed by random-effects model. In order to provide a visual summary of our findings, the estimation of pooled OR from cross-sectional studies was reported as 2.86 [95% CI 1.49–5.49], which is consistent with the findings of the cohort study. Results revealed that the association between OPG and CAC was significant among diabetic patients. OPG is hypothesized to be a potential marker in predicting the presence of high coronary calcium score among subjects with T2M that could be recognized as a novel target for further pharmacological investigations. [ABSTRACT FROM AUTHOR]

The pancreas represents an important organ that has not been comprehensively studied in many fields. To fill this gap, many models have been generated, and traditional models have shown good performance in addressing pancreatic-related diseases, but are increasingly struggling to keep up with the need for further research due to ethical issues, genetic heterogeneity and difficult clinical translation. The new era calls for new and more reliable research models. Therefore, organoids have been proposed as a novel model for the evaluation of pancreatic-related diseases such as pancreatic malignancy, diabetes, and pancreatic cystic fibrosis. Compared with common traditional models, including 2D cell culture and gene editing mice, organoids derived from living humans or mice cause minimal harm to the donor, raise fewer ethical concerns, and reasonably address the claims of heterogeneity, which allows for the further development of pathogenesis studies and clinical trial analysis. In this review, we analyse studies on the use of pancreatic organoids in research on pancreatic-related diseases, discuss the advantages and disadvantages, and hypothesize future trends. [ABSTRACT FROM AUTHOR]

Diabetic foot infection (DFI) management requires complex multidisciplinary care pathways with off-loading, debridement and targeted antibiotic treatment central to positive clinical outcomes. Local administration of topical treatments and advanced wound dressings are often used for more superficial infections, and in combination with systemic antibiotics for more advanced infections. In practice, the choice of such topical approaches, whether alone or as adjuncts, is rarely evidence-based, and there does not appear to be a single market leader. There are several reasons for this, including a lack of clear evidence-based guidelines on their efficacy and a paucity of robust clinical trials. Nonetheless, with a growing number of people living with diabetes, preventing the progression of chronic foot infections to amputation is critical. Topical agents may increasingly play a role, especially as they have potential to limit the use of systemic antibiotics in an environment of increasing antibiotic resistance. While a number of advanced dressings are currently marketed for DFI, here we review the literature describing promising future-focused approaches for topical treatment of DFI that may overcome some of the current hurdles. Specifically, we focus on antibiotic-impregnated biomaterials, novel antimicrobial peptides and photodynamic therapy. [ABSTRACT FROM AUTHOR]

In recent years, due to the aging of the population and the development of diagnostic medicine, the number of identified diseases associated with the accumulation of amyloid proteins has increased. Some of these proteins are known to cause a number of degenerative diseases in humans, such as amyloid-beta (Aβ) in Alzheimer's disease (AD), α-synuclein in Parkinson's disease (PD), and insulin and its analogues in insulin-derived amyloidosis. In this regard, it is important to develop strategies for the search and development of effective inhibitors of amyloid formation. Many studies have been carried out aimed at elucidating the mechanisms of amyloid aggregation of proteins and peptides. This review focuses on three amyloidogenic peptides and proteins—Aβ, α-synuclein, and insulin—for which we will consider amyloid fibril formation mechanisms and analyze existing and prospective strategies for the development of effective and non-toxic inhibitors of amyloid formation. The development of non-toxic inhibitors of amyloid will allow them to be used more effectively for the treatment of diseases associated with amyloid. [ABSTRACT FROM AUTHOR]

Diabetic neuropathy (DN) is one of the main microvascular complications of both type 1 and type 2 diabetes mellitus. Sometimes, this could already be present at the time of diagnosis for type 2 diabetes mellitus (T2DM), while it appears in subjects with type 1 diabetes mellitus (T1DM) almost 10 years after the onset of the disease. The impairment can involve both somatic fibers of the peripheral nervous system, with sensory-motor manifestations, as well as the autonomic system, with neurovegetative multiorgan manifestations through an impairment of sympathetic/parasympathetic conduction. It seems that, both indirectly and directly, the hyperglycemic state and oxygen delivery reduction through the vasa nervorum can determine inflammatory damage, which in turn is responsible for the alteration of the activity of the nerves. The symptoms and signs are therefore various, although symmetrical painful somatic neuropathy at the level of the lower limbs seems the most frequent manifestation. The pathophysiological aspects underlying the onset and progression of DN are not entirely clear. The purpose of this review is to shed light on the most recent discoveries in the pathophysiological and diagnostic fields concerning this complex and frequent complication of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Metabolic diseases have become a serious threat to human health worldwide. It is crucial to look for effective drugs from natural products to treat metabolic diseases. Curcumin, a natural polyphenolic compound, is mainly obtained from the rhizomes of the genus Curcuma. In recent years, clinical trials using curcumin for the treatment of metabolic diseases have been increasing. In this review, we provide a timely and comprehensive summary of the clinical progress of curcumin in the treatment of three metabolic diseases, namely type 2 diabetes mellitus (T2DM), obesity and non-alcoholic fatty liver disease (NAFLD). The therapeutic effects and underlying mechanisms of curcumin on these three diseases are presented categorically. Accumulating clinical evidence demonstrates that curcumin has good therapeutic potential and a low number of side effects for the three metabolic diseases. It can lower blood glucose and lipid levels, improve insulin resistance and reduce inflammation and oxidative stress. Overall, curcumin may be an effective drug for the treatment of T2DM, obesity and NAFLD. However, more high-quality clinical trials are still required in the future to verify its efficacy and determine its molecular mechanisms and targets. [ABSTRACT FROM AUTHOR]

A decrease in the activity of the insulin signaling system of the brain, due to both central insulin resistance and insulin deficiency, leads to neurodegeneration and impaired regulation of appetite, metabolism, endocrine functions. This is due to the neuroprotective properties of brain insulin and its leading role in maintaining glucose homeostasis in the brain, as well as in the regulation of the brain signaling network responsible for the functioning of the nervous, endocrine, and other systems. One of the approaches to restore the activity of the insulin system of the brain is the use of intranasally administered insulin (INI). Currently, INI is being considered as a promising drug to treat Alzheimer's disease and mild cognitive impairment. The clinical application of INI is being developed for the treatment of other neurodegenerative diseases and improve cognitive abilities in stress, overwork, and depression. At the same time, much attention has recently been paid to the prospects of using INI for the treatment of cerebral ischemia, traumatic brain injuries, and postoperative delirium (after anesthesia), as well as diabetes mellitus and its complications, including dysfunctions in the gonadal and thyroid axes. This review is devoted to the prospects and current trends in the use of INI for the treatment of these diseases, which, although differing in etiology and pathogenesis, are characterized by impaired insulin signaling in the brain. [ABSTRACT FROM AUTHOR]

Ubiquitination and deubiquitination are reversible processes that modify the characteristics of target proteins, including stability, intracellular localization, and enzymatic activity. Ubiquitin-specific proteases (USPs) constitute the largest deubiquitinating enzyme family. To date, accumulating evidence indicates that several USPs positively and negatively affect metabolic diseases. USP22 in pancreatic β-cells, USP2 in adipose tissue macrophages, USP9X, 20, and 33 in myocytes, USP4, 7, 10, and 18 in hepatocytes, and USP2 in hypothalamus improve hyperglycemia, whereas USP19 in adipocytes, USP21 in myocytes, and USP2, 14, and 20 in hepatocytes promote hyperglycemia. In contrast, USP1, 5, 9X, 14, 15, 22, 36, and 48 modulate the progression of diabetic nephropathy, neuropathy, and/or retinopathy. USP4, 10, and 18 in hepatocytes ameliorates non-alcoholic fatty liver disease (NAFLD), while hepatic USP2, 11, 14, 19, and 20 exacerbate it. The roles of USP7 and 22 in hepatic disorders are controversial. USP9X, 14, 17, and 20 in vascular cells are postulated to be determinants of atherosclerosis. Moreover, mutations in the Usp8 and Usp48 loci in pituitary tumors cause Cushing syndrome. This review summarizes the current knowledge about the modulatory roles of USPs in energy metabolic disorders. [ABSTRACT FROM AUTHOR]

Machine learning (ML) has succeeded in improving our daily routines by enabling automation and improved decision making in a variety of industries such as healthcare, finance, and transportation, resulting in increased efficiency and production. However, the development and widespread use of this technology has been significantly hampered by concerns about data privacy, confidentiality, and sensitivity, particularly in healthcare and finance. The "data hunger" of ML describes how additional data can increase performance and accuracy, which is why this question arises. Federated learning (FL) has emerged as a technology that helps solve the privacy problem by eliminating the need to send data to a primary server and collect it where it is processed and the model is trained. To maintain privacy and improve model performance, FL shares parameters rather than data during training, in contrast to the typical ML practice of sending user data during model development. Although FL is still in its infancy, there are already applications in various industries such as healthcare, finance, transportation, and others. In addition, 32% of companies have implemented or plan to implement federated learning in the next 12–24 months, according to the latest figures from KPMG, which forecasts an increase in investment in this area from USD 107 million in 2020 to USD 538 million in 2025. In this context, this article reviews federated learning, describes it technically, differentiates it from other technologies, and discusses current FL aggregation algorithms. It also discusses the use of FL in the diagnosis of cardiovascular disease, diabetes, and cancer. Finally, the problems hindering progress in this area and future strategies to overcome these limitations are discussed in detail. [ABSTRACT FROM AUTHOR]

People affected by diabetes are at higher risk for complications from certain vaccine-preventable diseases. Suboptimal vaccination coverages are reported in this population sub-group. The purpose of this study is to estimate the proportion of diabetic patients who express hesitation to the COVID-19 vaccine worldwide. Seven studies were included in the meta-analysis and systematic review, selected from scientific articles available in the MEDLINE/PubMed, Google Scholar and Scopus databases from 2020 to 2022. The following terms were used for the search strategy: (adherence OR hesitancy OR compliance OR attitude) AND (covid* OR SARS*) AND (vaccin* OR immun*) AND (diabet*). The vaccine hesitation rate among persons with diabetes was 27.8 % (95 %CI = 15.6–41.9 %). In the comparison of vaccine hesitancy between sexes and educational status, the RRs were 0.90 (95 %CI = 0.71–1.15) and 0.88 (95 %CI = 0.76–1.02), respectively. The main reasons of unwillingness were lack of information, opinion that the vaccine was unsafe or not efficient, and fear of adverse events. In order to achieve a high vaccination coverage, multifactorial approach is needed, which requires major social, scientific and health efforts. The success of the vaccination campaign in this population depends on the capillarity and consistency of the interventions implemented. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy is prevalent in a myriad of pathological conditions, such as diabetes, denervation, long-term immobility, malnutrition, sarcopenia, obesity, Alzheimer's disease, and cachexia. This is a critically important topic that has significance in the health of the current society, particularly older adults. The most damaging effect of muscle atrophy is the decreased quality of life from functional disability, increased risk of fractures, decreased basal metabolic rate, and reduced bone mineral density. Most skeletal muscle in humans contains slow oxidative, fast oxidative, and fast glycolytic muscle fiber types. Depending on the pathological condition, either oxidative or glycolytic muscle type may be affected to a greater extent. This review article discusses the prevalence of skeletal muscle atrophy and several mechanisms, with an emphasis on high-fat, high-sugar diet patterns, obesity, and diabetes, but including other conditions such as sarcopenia, Alzheimer's disease, cancer cachexia, and heart failure. [ABSTRACT FROM AUTHOR]

O-linked b-N-acetyl-glucosaminylation (O-GlcNAcylation) is one of the most common post-translational modifications of proteins, and is established by modifying the serine or threonine residues of nuclear, cytoplasmic, and mitochondrial proteins. O-GlcNAc signaling is considered a critical nutrient sensor, and affects numerous proteins involved in cellular metabolic processes. O-GlcNAcylation modulates protein functions in different patterns, including protein stabilization, enzymatic activity, transcriptional activity, and protein interactions. Disrupted O-GlcNAcylation is associated with an abnormal metabolic state, and may result in metabolic disorders. As the liver is the center of nutrient metabolism, this review provides a brief description of the features of the O-GlcNAc signaling pathway, and summarizes the regulatory functions and underlying molecular mechanisms of O-GlcNAcylation in liver metabolism. Finally, this review highlights the role of O-GlcNAcylation in liver-associated diseases, such as diabetes and nonalcoholic fatty liver disease (NAFLD). We hope this review not only benefits the understanding of O-GlcNAc biology, but also provides new insights for treatments against liver-associated metabolic disorders. [ABSTRACT FROM AUTHOR]

Sodium glucose cotransporter 2 inhibitor (SGLT2i) is a class of drugs that were originally intended for decreasing blood glucose in diabetes. However, recent trials have shown that there are other beneficial effects. Major clinical trials involving SGLT2i medications from 2015 to 2022 were reviewed using PUBMED search. Recent major SGLT2i landmark trials have demonstrated benefits for cardiovascular disease (reduce major adverse cardiovascular events (heart attack, stroke, cardiovascular death), hospitalization for heart failure, all-cause death), and renal disease (delay the onset of dialysis) regardless of diabetic status. The consistent cardiorenal benefits observed in major landmark trials have resulted in the rapid adoption of SGLT2i therapy not only in diabetes guidelines but also cardiovascular and renal guidelines. [ABSTRACT FROM AUTHOR]

Thyroid function and glucose status are linked; experimental, clinical, and epidemiological studies have shown this. Iodine is a vital trace element that is inextricably linked to thyroid hormone synthesis. The latter is also associated with glucose metabolism and diabetes. Recently, some—but not all—studies have shown that iodine is linked to glucose metabolism, glucose intolerance, impaired fasting glucose, prediabetes, diabetes mellitus, or gestational diabetes. In this concise review, we review these studies, focusing on iodine and glucose metabolism and prediabetic conditions or type 2 diabetes mellitus. The potential beneficial effect of iodine on glucose metabolism may be attributed to its antioxidant properties. [ABSTRACT FROM AUTHOR]

Introduction: The duodenal-jejunal bypass liner (DJBL) is a less-invasive treatment of obesity and type 2 diabetes mellitus (T2DM). Methods: This is a systematic review and meta-analysis including randomized clinical trials (RCTs) comparing DJBL versus sham or pharmacotherapies aiming to evaluate the effectiveness and safety of DJBL. Results: Ten RCTs (681 patients) were included. The DJBL group showed superior excess weight loss (+ 11.4% [+ 7.75 to + 15.03%], p < 0.00001) and higher decrease in HbA1c compared to the control group (− 2.73 ± 0.5 vs. − 1.73 ± 0.4, p = 0.0001). Severe adverse events (SAEs) occurred in 19.7%. Conclusion: The DJBL did not reach the ASGE/ASMBS thresholds for the treatment of obesity. However, it is important to state that many SAEs were not really severe. Therefore, we believe this therapy plays an important role in the management obesity and T2DM. [ABSTRACT FROM AUTHOR]

Background: Fractional Flow Reserve (FFR) is a widely applied invasive physiological assessment, endorsed by major guidelines to aid in the decision to perform or defer revascularisation. While a threshold of > 0.8 has been applied universally, clinical outcomes may be affected by numerous factors, including the presence of diabetes. This meta-analysis aims to investigate the outcomes of diabetic versus non-diabetic patients in whom revascularisation was deferred based on negative FFR. Methods: We performed a meta-analysis investigating the outcomes of diabetic and non-diabetic patients in whom revascularisation was deferred based on negative FFR. A search was performed on MEDLINE, PubMed and EMBASE, and peer-reviewed studies that reported MACE for diabetic and non-diabetic patients with deferred revascularisation based on FFR > 0.8 were included. The primary end point was MACE. Results: The meta-analysis included 7 studies in which 4275 patients had revascularisation deferred based on FFR > 0.8 (1250 diabetic). Follow up occurred over a mean of 3.2 years. Diabetes was associated with a higher odds of MACE (OR = 1.66, 95% CI 1.35–2.04, p = < 0.001), unplanned revascularisation (OR = 1.48, 95% CI 1.06–2.06, p = 0.02), all-cause mortality (OR = 1.74, 95% CI 1.20–2.52, p = 0.004) and cardiovascular mortality (OR = 2.08, 95% CI 1.07–4.05, p = 0.03). Conclusions: For patients with stable coronary syndromes and deferred revascularisation based on FFR > 0.8, the presence of diabetes portends an increased long-term risk of MACE compared to non-diabetic patients. Trail registration URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42022367312. [ABSTRACT FROM AUTHOR]

Background: There is increasing intervention activities provided during pharmacist-led diabetes management. Nevertheless, there is an unclear definition of the activities involved during the intervention. Thus, this study aimed to describe the type of intervention strategies and service model provided during pharmacist-led type 2 diabetes management and service outcomes. Methods: This study utilized the scoping review methodology of the Joanna Briggs Institute Reviewers' Manual 2015. Articles on pharmacist-led diabetes management focusing on the service content, delivery methods, settings, frequency of appointments, collaborative work with other healthcare providers, and reported outcomes were searched and identified from four electronic databases: Ovid Medline, PubMed, Scopus, and Web of Science from 1990 to October 2020. Relevant medical subject headings and keywords, such as "diabetes," "medication adherence," "blood glucose," "HbA1c," and "pharmacist," were used to identify published articles. Results: The systematic search retrieved 4,370 articles, of which 61 articles met the inclusion criteria. The types of intervention strategies and delivery methods were identified from the studies based on the description of activities reported in the articles and were tabulated in a summary table. Conclusion: There were variations in the descriptions of intervention strategies, which could be classified into diabetes education, medication review, drug consultation/counseling, clinical intervention, lifestyle adjustment, self-care, peer support, and behavioral intervention. In addition, most studies used a combination of two or more intervention strategy categories when providing services, with no specific pattern between the service model and patient outcomes. [ABSTRACT FROM AUTHOR]

Amyloidoses include a large variety of local and systemic diseases that share the common feature of protein unfolding or refolding into amyloid fibrils. The most studied amyloids are those directly involved in neurodegenerative diseases, while others, such as those formed by insulin, are surprisingly far less studied. Insulin is a very important polypeptide that plays a variety of biological roles and, first and foremost, is at the basis of the therapy of diabetic patients. It is well-known that it can form fibrils at the site of injection, leading to inflammation and immune response, in addition to other side effects. In this concise review, we analyze the current knowledge on insulin fibrillation, with a focus on the development of peptide-based inhibitors, which are promising candidates for their biocompatibility but still pose challenges to their effective use in therapy. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) as a microangiopathy is the most common complication in patients with diabetes mellitus (DM) and remains the leading cause of blindness among adult population. DM in its complicated pathomechanism relates to chronic hyperglycemia, hypoinsulinemia, dyslipidemia and hypertension—all these components in molecular pathways maintain oxidative stress, formation of advanced glycation end-products, microvascular changes, inflammation, and retinal neurodegeneration as one of the key players in diabetes-associated retinal perturbations. In this current review, we discuss the natural history of DR with special emphasis on ongoing inflammation and the key role of vascular endothelial growth factor (VEGF). Additionally, we provide an overview of the principles of diabetic retinopathy treatments, i.e., in laser therapy, anti-VEGF and steroid options. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetSyn) is a precursor for several cardiometabolic diseases such as obesity, type-2 diabetes mellitus (T2DM), and cardiovascular diseases. Emerging evidence suggests that vitamin D deficiency links to cardiometabolic diseases through microbiota. A combination of poor vitamin D status and dysbiosis may contribute to the progression of cardiometabolic diseases. Therefore, in this review, we present the relationship among vitamin D, microbiota, and cardiometabolic diseases with a focus on MetSyn. We searched major databases for reports on vitamin D, microbiota, and MetSyn until June 2022. We reviewed 13 reports on the relation between vitamin D and MetSyn (6 randomized controlled and 7 cross-sectional studies) and 6 reports on the effect of vitamin D on the gut microbiome. Adequate vitamin D status has a beneficial effect on gut microbiota, therefore preventing the progression of MetSyn. Further, well-controlled studies are needed for a better understanding of the mechanisms of action involving vitamin D and microbiota in the pathogenesis of cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Diabetes is a metabolic disorder characterized by lower responsiveness of tissues to insulin and consequent large variations in circulating levels of glucose. This fluctuation has harmful effects as both hyperglycemia and hypoglycemia can be very injurious. The causes of diabetes are varied but the consequences are rather uniform. Dietary factors are important especially in adult onset type 2 diabetes (T2D) while type 1 diabetes (T1D) is characterized by having a stronger heritable component and involving autoimmune attach on pancreatic beta cells. This review is focused on the relation of the bacterial components found within the intestine, to the establishment and maintenance of diabetes. The precise composition of the gut microbiome is increasingly recognized as a factor in organismic health and its interaction with a variety of disease states has been described. This is especially marked in the case of diabetes since the nature of the diet is an important factor in establishing both the microbiome and the incidence of diabetes. The bidirectional nature of this relationship is discussed. The effects of disease that lead to altered microbiomal composition together with aberrant metabolic changes are also included. Emphasis is given to the important role of short chain fatty acids (SCFAs) as mediators of the microbiome-diabetes relation. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) is a cytosolic organelle that plays an essential role in the folding and processing of new secretory proteins, including insulin. The pathogenesis of diabetes, a group of metabolic disorders caused by dysfunctional insulin secretion (Type 1 diabetes, T1DM) or insulin sensitivity (Type 2 diabetes, T2DM), is known to involve the excess accumulation of "poorly folded proteins", namely, the induction of pathogenic ER stress in pancreatic β-cells. ER stress is known to contribute to the dysfunction of the insulin-producing pancreatic β-cells. T1DM and T2DM are multifactorial diseases, especially T2DM; both environmental and genetic factors are involved in their pathogenesis, making it difficult to create experimental disease models. In recent years, however, the development of induced pluripotent stem cells (iPSCs) and other regenerative technologies has greatly expanded research capabilities, leading to the development of new candidate therapies. In this review, we will discuss the mechanism by which dysregulated ER stress responses contribute to T2DM pathogenesis. Moreover, we describe new treatment methods targeting protein folding and ER stress pathways with a particular focus on pivotal studies of Wolfram syndrome, a monogenic form of syndromic diabetes caused by pathogenic variants in the WFS1 gene, which also leads to ER dysfunction. [ABSTRACT FROM AUTHOR]

The prevalence of both Alzheimer's disease (AD) and diabetes mellitus is increasing with the societies' aging and has become an essential social concern worldwide. Accumulation of amyloid plaques and neurofibrillary tangles (NFTs) of tau proteins in the brain are hallmarks of AD. Diabetes is an underlying risk factor for AD. Insulin resistance has been proposed to be involved in amyloid-beta (Aβ) aggregation in the brain. It seems that diabetic conditions can result in AD pathology by setting off a cascade of processes, including inflammation, mitochondrial dysfunction, and ROS and advanced glycation end products (AGEs) synthesis. Due to the several side effects of chemical drugs and their high cost, using herbal medicine has recently attracted attention for the treatment of diabetes and AD. Saffron and its active ingredients have been used for its anti-inflammatory, anti-oxidant, anti-diabetic, and anti-AD properties. Therefore, in the present review paper, we take account of the clinical, in vivo and in vitro evidence regarding the anti-diabetic and anti-AD effects of saffron and discuss the preventive or postponing properties of saffron or its components on AD development via its anti-diabetic effects. [ABSTRACT FROM AUTHOR]

Obesity is a key target in the treatment and prevention of diabetes and independently to reduce the burden of cardiovascular disease. We reviewed the options now available and anticipated to deal with obesity. We considered the epidemiology, genetics, and causation of obesity and the relationship to diabetes, and the dietary, pharmaceutical, and surgical management of the condition. The literature search covered both popular media via Google Search and the academic literature as indexed on PubMed with search terms including obesity, childhood obesity, adipocytes, insulin resistance, mechanisms of satiety, bariatric surgery, GLP-1 receptor agonists, and SGLT2 inhibitors. Although bariatric surgery has been the primary approach to treating obese individuals, the emergence of agents impacting the brain satiety centers now promises effective, non-invasive treatment of obesity for individuals with and without diabetes. The GLP-1 receptor agonists have assumed the primary role in treating obesity with significant weight loss. Long-term results with semaglutide and tirzepatide are now approaching the success seen with bariatric surgery. Future agents combining the benefits of satiety control and thermogenesis to dissipate caloric excess are under investigation. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is a prevalent, and yet uncurable, autoimmune disease targeting insulin-producing pancreatic β-cells. Despite a known genetic component in T1D onset, genetics alone cannot explain the alarming worldwide rise in T1D incidence, which is attributed to a growing impact of environmental factors, including perturbations of the gut microbiome. Intestinal commensal bacteria plays a crucial role in host physiology in health and disease by regulating endocrine and immune functions. An aberrant gut microbiome structure and metabolic function have been documented prior and during T1D onset. In this review, we summarize and discuss the current studies depicting the taxonomic profile and role of the gut microbial communities in murine models of T1D, diabetic patients and human interventional trials. Compelling evidence have shown that the intestinal microbiota is instrumental in driving differentiation and functions of immune cells. Therefore, any alterations in the intestinal microbiome composition or microbial metabolite production, particularly early in life, may impact disease susceptibility and amplify inflammatory responses and hence accelerate the course of T1D pathogenesis. [ABSTRACT FROM AUTHOR]

Calcium is involved in bone metabolism, regulation of nerve signaling, and release of neurotransmitters. Phosphorus is a structural component of ATP, participates in metabolic energy regulation, and ensures stability to biological membranes and cells. Vitamin D and vitamin K are important for intestinal absorption and renal excretion of calcium and phosphorus. Vitamin D plays a regulatory role in bone formation, carbohydrate metabolism, immune responses, and cardiovascular regulation. Research has linked vitamin D deficiency to the development of diabetes mellitus, hypertension, cancer, and osteoporosis. Vitamin K has been associated with a reduced risk of osteoporosis, cancer, and cardiovascular diseases (due to improved vascular elasticity). This review highlights the importance of vitamins D and K in the metabolism of calcium and phosphorus and explores various molecular mechanisms that help maintain the system's mineral homeostasis. Moreover, the paper reviews the enzyme nattokinase's role in thrombotic prevention due to its fibrinolytic activity. [ABSTRACT FROM AUTHOR]

Background: In the context of a move to universal health coverage, three separate systematic reviews were conducted to summarise available evidence on the direct costs of interventions for type 2 diabetes mellitus, hypertension, and cardiovascular disease in South Africa. Methods: PubMed® and Web of Science was searched for literature published between 01 and 1995 and 27 October 2022. Additionally, reference and citations lists of retrieved articles and experts were consulted. We also tracked reference lists of previous, related systematic reviews. Eligible publications were cost analyses of clinical interventions targeted at adults age 15 + reporting primary estimates of in- and out-of-hospital costs from a provider perspective. Costs were extracted and converted to 2021 US dollars, and article methodological and reporting quality was appraised using the 2013 CHEERS checklist. Results: Of the 600, 1,172 and 1,466 identified publications for type 2 diabetes mellitus, hypertension, and cardiovascular disease, respectively, 10, 12, and 17 met full inclusion criteria. 60% of articles reported cardiovascular disease costs, 52% were of good reporting quality, and 10%, 50%, and 39% of type 2 diabetes mellitus, hypertension and cardiovascular disease papers reported private-sector costs only. Hypertension drug costs ranged from $2 to $85 per person-month, while type 2 diabetes mellitus drug costs ranged between $57 and $630 per person-year (ppy). Diabetes-related complication treatment costs ranged from $55 for retinopathy treatment to $25,193 ppy for haemodialysis, while cardiovascular disease treatment costs were between $160 and $37,491 ppy. Drugs and treatment of complications were major cost drivers for hypertension and type 2 diabetes mellitus, while hospitalisation drove cardiovascular disease costs. Conclusion: The intervention costs of type 2 diabetes mellitus, hypertension and cardiovascular disease care have received more attention recently, particularly diabetes-related complications and cardiovascular disease. However, 39% of identified cardiovascular disease treatment costs used a private sector perspective, leaving significant research gaps in the public sector and the cheaper to treat hypertension and type 2 diabetes mellitus. This review fills an information gap regarding the intervention costs of these diseases in South Africa. [ABSTRACT FROM AUTHOR]

Diabetes is currently a worldwide health concern. Hyperglycemia, hypertension, obesity, and oxidative stress are the major risk factors that inevitably lead to all the complications from diabetes. These complications severely impact the quality of life of patients, and they can be managed, reduced, or even reverted by several polyphenols, plant extracts and foods rich in these compounds. The goal of this review is to approach diabetes not as a single condition but rather an interconnected combination of risk factors and complications. This work shows that polyphenols have multi target action and effects and they have been systematically proven to be relevant in the reduction of each risk factor and improvement of associated complication. [ABSTRACT FROM AUTHOR]

Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role is not totally clarified but which seems to modulate significantly the metabolism of lipoproteins. ApoC1 is involved in the metabolism of triglyceride-rich lipoproteins by inhibiting the binding of very low density lipoproteins (VLDL) to VLDL-receptor (VLDL-R), to low density lipoprotein receptor (LDL-R) and to LDL receptor related protein (LRP), by reducing the activity of lipoprotein lipase (LPL) and by stimulating VLDL production, all these effects leading to increase plasma triglycerides. ApoC1 takes also part in the metabolism of high density lipoproteins (HDL) by inhibiting Cholesterol Ester Transfer Protein (CETP). The functionality of apoC1 on CETP activity is impaired in diabetes that might account, at least in part, for the increased plasma CETP activity observed in patients with diabetes. Its different effects on lipoprotein metabolism with a possible role in the modulation of inflammation makes the net impact of apoC1 on cardiometabolic risk difficult to figure out and apoC1 might be considered as pro-atherogenic or anti-atherogenic depending on the overall metabolic context. Making the link between total plasma apoC1 levels and the risk of cardio-metabolic diseases is difficult due to the high exchangeability of this small protein whose biological effects might depend essentially on its association with VLDL or HDL. The role of apoC1 in humans is not entirely elucidated and further studies are needed to determine its precise role in lipid metabolism and its possible pleiotropic effects on inflammation and vascular wall biology. In this review, we will present data on apoC1 structure and distribution among lipoproteins, on the effects of apoC1 on VLDL metabolism and HDL metabolism and we will discuss the possible links between apoC1, atherosclerosis and diabetes. [ABSTRACT FROM AUTHOR]

In addition to hemostasis and thrombosis, blood platelets are involved in various processes such as inflammation, infection, immunobiology, cancer metastasis, wound repair and angiogenesis. Platelets' hemostatic and non‐hemostatic functions are mediated by the expression of various membrane receptors and the release of proteins, ions and other mediators. Therefore, specific activities of platelets responsible for the non‐hemostatic disease are to be inhibited while leaving the platelet's hemostatic function unaffected. Platelets' anti‐aggregatory property has been used as a primary criterion for antiplatelet drugs/bioactives; however, their non‐hemostatic activities are not well known. This review describes the hemostatic and non‐hemostatic function of human blood platelets and the modulatory effects of bioactive food components. Practical applications: In this review, we have discussed the antiplatelet effects of several food components. These bioactive compounds inhibit both hemostatic and non‐hemostatic pathways involving blood platelet. Platelets have emerged as critical biological factors of normal and pathologic vascular healing and other diseases such as cancers and inflammatory and immune disorders. The challenge for therapeutic intervention in these disorders will be to find drugs and bioactive compounds that preferentially block specific sites implicated in emerging roles of platelets' complicated contribution to inflammation, tumour growth, or other disorders while leaving at least some of their hemostatic function intact. [ABSTRACT FROM AUTHOR]

Oregano is the name given to a great variety of herbs belonging mainly to the Lamiaceae and Verbenaceae botanical families. Oregano species are rich sources of phytochemicals such as phenolic compounds like rosmarinic acid, salvianolic acid, and luteolin, among others. A few articles have previously accessed some potential pharmacological bioactivities of oregano plants; however, none has focused on the antidiabetic studies. This review aims to summarize recent studies about the potential effect of phenolic compounds from oregano plant species. The reports were retrieved from electronic databases such as PubMed, Web of Science, National Center for Biotechnology Information (NCBI), and Scopus. In addition, articles related to the mentioned topics and published between 2004–2022 were selected. The results from this study show that the antidiabetic pharmacological reports of oregano phenolic compounds are mainly in vitro reports. Therefore, the diversity of oregano species yields a broad variety of phenolic constituents, where preclinical and clinical studies are strongly recommended. [ABSTRACT FROM AUTHOR]

PPARs stand for 'peroxisome proliferator‐activated receptors' and are ligand‐activated transcription factors of nuclear hormone receptor superfamily. A list of the most commonly used single receptor PPAR agonists, that is α (alpha) PPAR agonists, β/δ(beta/delta) PPAR agonists, γ(gamma) PPAR agonists, along with pan PPAR agents, that are being researched on, are marketed, are in clinical trials or are being studied for further derivative findings, has been listed. Type 2 diabetes constitutes about 90% of total diabetes cases. Pan PPAR ligands could very well pave the foundation for a new class of agents, that can act on all 3 PPAR receptors, and produce better effects in general, than the individual receptor‐acting ligands or dual combination ligands (α/ γ). In this review paper, we have detailed various pan PPAR agonists that can be used to treat type 2 diabetes, which can generate potential derivatives as well. [ABSTRACT FROM AUTHOR]

Diabetes contributes to about 30% morbidity and mortality world-wide and has tidal wave increases in several countries in Asia. Diabetes is a multi-factorial disease compounded by inflammation, dyslipidemia, atherosclerosis, and is sometimes accompanied with gains in body weight. Sphingolipid pathways that interplay in the enhancement of the pathology of this disease may be potential therapeutic targets. Thus, the application of advanced sphingolipidomics may help predict the progression of this disease and therapeutic outcomes in man. Pre-clinical studies using various experimental animal models of diabetes provide valuable information on the role of sphingolipid signaling networks in diabetes and the efficacy of drugs to determine the translatability of innovative discoveries to man. In this review, we discuss three major concepts regarding sphingolipids and diabetes. First, we discuss a possible involvement of a monosialodihexosylceramide (GM3) in insulin–insulin receptor interactions. Second, a potential role for ceramide (Cer) and lactosylceramide (LacCer) in apoptosis and mitochondrial dysfunction is proposed. Third, a larger role of LacCer in antioxidant status and inflammation is discussed. We also discuss how inhibitors of glycosphingolipid synthesis can ameliorate diabetes in experimental animal models. [ABSTRACT FROM AUTHOR]

Intermediate filaments are the most heterogeneous class among cytoskeletal elements. While some of them have been well-characterized, little is known about peripherin. Peripherin is a class III intermediate filament protein with a specific expression in the peripheral nervous system. Epigenetic modifications are involved in this cell-type-specific expression. Peripherin has important roles in neurite outgrowth and stability, axonal transport, and axonal myelination. Moreover, peripherin interacts with proteins involved in vesicular trafficking, signal transduction, DNA/RNA processing, protein folding, and mitochondrial metabolism, suggesting a role in all these processes. This review collects information regarding peripherin gene regulation, post-translational modifications, and functions and its involvement in the onset of a number of diseases. [ABSTRACT FROM AUTHOR]

The global prevalence of diabetes mellitus and Alzheimer's disease is increasing alarmingly with the aging of the population. Numerous epidemiological data suggest that there is a strong association between type 2 diabetes and an increased risk of dementia. These diseases are both degenerative and progressive and share common risk factors. The amyloid cascade plays a key role in the pathophysiology of Alzheimer's disease. The accumulation of amyloid beta peptides gradually leads to the hyperphosphorylation of tau proteins, which then form neurofibrillary tangles, resulting in neurodegeneration and cerebral atrophy. In Alzheimer's disease, apart from these processes, the alteration of glucose metabolism and insulin signaling in the brain seems to induce early neuronal loss and the impairment of synaptic plasticity, years before the clinical manifestation of the disease. The large amount of evidence on the existence of insulin resistance in the brain during Alzheimer's disease has led to the description of this disease as "type 3 diabetes". Available animal models have been valuable in the understanding of the relationships between type 2 diabetes and Alzheimer's disease, but to date, the mechanistical links are poorly understood. In this non-exhaustive review, we describe the main molecular mechanisms that may link these two diseases, with an emphasis on impaired insulin and IGF-1 signaling. We also focus on GSK3β and DYRK1A, markers of Alzheimer's disease, which are also closely associated with pancreatic β-cell dysfunction and type 2 diabetes, and thus may represent common therapeutic targets for both diseases. [ABSTRACT FROM AUTHOR]