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Biomedicine & Pharmacotherapy =... Feb 2022Diabetes mellitus (DM) is considered as a main challenge in both developing and developed countries, as lifestyle has changed and its management seems to be vital. Type... (Review)
Review
Diabetes mellitus (DM) is considered as a main challenge in both developing and developed countries, as lifestyle has changed and its management seems to be vital. Type I and type II diabetes are the main kinds and they result in hyperglycemia in patients and related complications. The gene expression alteration can lead to development of DM and related complications. The AMP-activated protein kinase (AMPK) is an energy sensor with aberrant expression in various diseases including cancer, cardiovascular diseases and DM. The present review focuses on understanding AMPK role in DM. Inducing AMPK signaling promotes glucose in DM that is of importance for ameliorating hyperglycemia. Further investigation reveals the role of AMPK signaling in enhancing insulin sensitivity for treatment of diabetic patients. Furthermore, AMPK upregulation inhibits stress and cell death in β cells that is of importance for preventing type I diabetes development. The clinical studies on diabetic patients have shown the role of AMPK signaling in improving diabetic complications such as brain disorders. Furthermore, AMPK can improve neuropathy, nephropathy, liver diseases and reproductive alterations occurring during DM. For exerting such protective impacts, AMPK signaling interacts with other molecular pathways such as PGC-1α, PI3K/Akt, NOX4 and NF-κB among others. Therefore, providing therapeutics based on AMPK targeting can be beneficial for amelioration of DM.
Topics: AMP-Activated Protein Kinases; Animals; Diabetes Complications; Diabetes Mellitus; Humans; Insulin Resistance; Mice; Rats; Signal Transduction
PubMed: 35062059
DOI: 10.1016/j.biopha.2021.112563 -
Diabetologia Apr 2021Hypoxia-inducible factors (HIFs) are the key regulators of oxygen homeostasis in response to hypoxia. In diabetes, multiple tissues are hypoxic but adaptive responses to... (Review)
Review
Hypoxia-inducible factors (HIFs) are the key regulators of oxygen homeostasis in response to hypoxia. In diabetes, multiple tissues are hypoxic but adaptive responses to hypoxia are impaired due to insufficient activation of HIF signalling, which results from inhibition of HIF-1α stability and function due to hyperglycaemia and elevated fatty acid levels. In this review, we will summarise and discuss current findings about the regulation of HIF signalling in diabetes and the pathogenic roles of hypoxia and dysregulated HIF signalling in the development of diabetes and its complications. The therapeutic potential of targeting HIF signalling for the prevention and treatment of diabetes and related complications is also discussed.
Topics: Animals; Apoptosis Regulatory Proteins; Basic Helix-Loop-Helix Transcription Factors; Blood Glucose; Cell Hypoxia; Cellular Microenvironment; Diabetes Complications; Diabetes Mellitus; Humans; Hypoglycemic Agents; Hypoxia-Inducible Factor 1, alpha Subunit; Molecular Targeted Therapy; Oxygen; Prolyl-Hydroxylase Inhibitors; Repressor Proteins; Signal Transduction
PubMed: 33496820
DOI: 10.1007/s00125-021-05380-z -
Frontiers in Endocrinology 2022Diabetes mellitus (DM) is an endocrine disorder characterized by a relative or absolute lack of insulin due to the dysfunction or destruction of β-cells. DM is one of... (Review)
Review
Diabetes mellitus (DM) is an endocrine disorder characterized by a relative or absolute lack of insulin due to the dysfunction or destruction of β-cells. DM is one of the fastest growing challenges to global health in the 21 century and places a tremendous burden on affected individuals and their families and countries. Although insulin and antidiabetic drugs have been used to treat DM, a radical cure for the disease is unavailable. The pathogenesis of DM remains unclear. Emerging roles of circular RNAs (circRNAs) in DM have become a subject of global research. CircRNAs have been verified to participate in the onset and progression of DM, implying their potential roles as novel biomarkers and treatment tools. In the present review, we briefly introduce the characteristics of circRNAs. Next, we focus on specific roles of circRNAs in type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus and diabetes-associated complications.
Topics: Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; RNA, Circular
PubMed: 35979435
DOI: 10.3389/fendo.2022.885650 -
Arteriosclerosis, Thrombosis, and... Aug 2020Peripheral artery disease (PAD) stems from atherosclerosis of lower extremity arteries with resultant arterial narrowing or occlusion. The most severe form of PAD is...
Peripheral artery disease (PAD) stems from atherosclerosis of lower extremity arteries with resultant arterial narrowing or occlusion. The most severe form of PAD is termed chronic limb-threatening ischemia and carries a significant risk of limb loss and cardiovascular mortality. Diabetes mellitus is known to increase the incidence of PAD, accelerate disease progression, and increase disease severity. Patients with concomitant diabetes mellitus and PAD are at high risk for major complications, such as amputation. Despite a decrease in the overall number of amputations performed annually in the United States, amputation rates among those with both diabetes mellitus and PAD have remained stable or even increased in high-risk subgroups. Within this cohort, there is significant regional, racial/ethnic, and socioeconomic variation in amputation risk. Specifically, residents of rural areas, African-American and Native American patients, and those of low socioeconomic status carry the highest risk of amputation. The burden of amputation is severe, with 5-year mortality rates exceeding those of many malignancies. Furthermore, caring for patients with PAD and diabetes mellitus imposes a significant cost to the healthcare system-estimated to range from $84 billion to $380 billion annually. Efforts to improve the quality of care for those with PAD and diabetes mellitus must focus on the subgroups at high risk for amputation and the disparities they face in the receipt of both preventive and interventional cardiovascular care. Better understanding of these social, economic, and structural barriers will prove to be crucial for cardiovascular physicians striving to better care for patients facing this challenging combination of chronic diseases.
Topics: Amputation, Surgical; Diabetes Complications; Health Care Costs; Humans; Peripheral Arterial Disease; Risk; Risk Factors
PubMed: 32580632
DOI: 10.1161/ATVBAHA.120.314595 -
Current Diabetes Reports Jan 2021Racial and ethnic minority populations have a higher burden of diabetes-related complications. There have been many epidemiologic studies to better define these... (Review)
Review
PURPOSE OF REVIEW
Racial and ethnic minority populations have a higher burden of diabetes-related complications. There have been many epidemiologic studies to better define these racial/ethnic disparities in diabetes outcomes with additional studies offering interventions to mitigate them. This narrative review highlights the epidemiologic trends in diabetes complications specific to racial and ethnic minorities and underscores differences in microvascular and macrovascular complications of diabetes, health care utilization, and diabetes prevention efforts and also reviews interventions aimed to reduce racial/ethnic disparities and their limitations.
RECENT FINDINGS
While we have seen in general an overall improvement in complication rates for all people with diabetes, the disparities between Black and Hispanic compared to non-Hispanic White people with diabetes seem to persist. There is a continued need to better understand the underlying causes of and strategies to mitigate race/ethnicity disparities in diabetes complications in the USA.
Topics: Diabetes Complications; Diabetes Mellitus; Ethnicity; Healthcare Disparities; Hispanic or Latino; Humans; Minority Groups; United States; White People
PubMed: 33420878
DOI: 10.1007/s11892-020-01369-x -
The Korean Journal of Internal Medicine Nov 2022Musculoskeletal conditions are common in patients with diabetes. Several musculoskeletal disorders are viewed as chronic complications of diabetes because... (Review)
Review
Musculoskeletal conditions are common in patients with diabetes. Several musculoskeletal disorders are viewed as chronic complications of diabetes because epidemiological studies have revealed high correlations between such complications and diabetes, but the pathophysiological links with diabetes remains unclear. Genetic predispositions, shared risk factors, microvascular impairments, progressive accumulation of advanced glycation end-products, and diabetic neuropathy may underlie the development of musculoskeletal disorders. Musculoskeletal complications of diabetics have received less attention than life-threatening microvascular or macrovascular complications. Here, we review several diabetic musculoskeletal complications with a focus on the clinical importance of early recognition and management, which would improve quality of life and physical function.
Topics: Humans; Quality of Life; Diabetes Mellitus; Diabetes Complications; Musculoskeletal Diseases; Risk Factors
PubMed: 36300322
DOI: 10.3904/kjim.2022.168 -
Journal of Diabetes Research 2021Ferroptosis is a novel form of nonapoptotic regulated cell death (RCD). It features iron-dependent lipid peroxide accumulation accompanied by inadequate redox enzymes,... (Review)
Review
Ferroptosis is a novel form of nonapoptotic regulated cell death (RCD). It features iron-dependent lipid peroxide accumulation accompanied by inadequate redox enzymes, especially glutathione peroxidase 4 (GPX4). RAS-selective lethal 3 (RSL3), erastin, and ferroptosis inducing 56 (FIN56) induce ferroptosis via different manners targeting GPX4 function. Acyl-CoA synthetase long-chain family 4 (ACSL4), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and lipoxygenases (LOXs) participate in the production of lipid peroxides. Heat shock protein family B member 1 (HSPB1) and nuclear receptor coactivator 4 (NCOA4) regulate iron homeostasis preventing ferroptosis caused by the high concentration of intracellular iron. Ferroptosis is ubiquitous in our body as it exists in both physiologic and pathogenic processes. It is involved in glucose-stimulated insulin secretion (GSIS) impairment and arsenic-induced pancreatic damage in the pathogenesis of diabetes. Moreover, iron and the iron-sulfur (Fe-S) cluster influence each other, causing mitochondrial iron accumulation, more reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, failure in biosynthesis of insulin, and ferroptosis in -cells. In addition, ferroptosis also engages in the pathogenesis of diabetic complications such as myocardial ischemia and diabetic cardiomyopathy (DCM). In this review, we summarize the mechanism of ferroptosis and especially its association with type 2 diabetes mellitus (T2DM).
Topics: Apoptosis Regulatory Proteins; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Ferroptosis; Humans; Iron; Lipid Peroxidation; Metabolic Networks and Pathways; Mevalonic Acid; Mitochondrial Proteins; Myocardial Ischemia; Phospholipid Hydroperoxide Glutathione Peroxidase; Reactive Oxygen Species
PubMed: 34258295
DOI: 10.1155/2021/9999612 -
Diabetes/metabolism Research and Reviews Feb 2021The outbreak of the coronavirus disease 2019 (Covid-19) has become an evolving worldwide health crisis. With the rising prevalence of obesity and diabetes has come an... (Review)
Review
The outbreak of the coronavirus disease 2019 (Covid-19) has become an evolving worldwide health crisis. With the rising prevalence of obesity and diabetes has come an increasing awareness of their impacts on infectious diseases, including increased risk for various infections, post-infection complications and mortality from critical infections. Although epidemiological and clinical characteristics of Covid-19 have been constantly reported, no article has systematically illustrated the role of obesity and diabetes in Covid-19, or how Covid-19 affects obesity and diabetes, or special treatment in these at-risk populations. Here, we present a synthesis of the recent advances in our understanding of the relationships between obesity, diabetes and Covid-19 along with the underlying mechanisms, and provide special treatment guidance for these at-risk populations.
Topics: COVID-19; Comorbidity; Critical Illness; Diabetes Complications; Diabetes Mellitus; Humans; Obesity; Pandemics; Prevalence; Prognosis; Risk Factors; SARS-CoV-2; Severity of Illness Index
PubMed: 32588943
DOI: 10.1002/dmrr.3377 -
Frontiers in Endocrinology 2021Diabetes mellitus (DM) is a metabolic disease, now prevalent worldwide, which is characterized by a relative or absolute lack of insulin secretion leading to chronically... (Review)
Review
Diabetes mellitus (DM) is a metabolic disease, now prevalent worldwide, which is characterized by a relative or absolute lack of insulin secretion leading to chronically increased blood glucose levels. Diabetic patients are often accompanied by multiple macrovascular complications, such as coronary heart disease, hypertension, macrovascular arteriosclerosis, and microvascular complications. Microvascular complications include diabetic kidney injury, diabetic encephalopathy, and diabetic foot, which reduce the quality of life and survival status of patients. Mesenchymal stem cell exosomes (MSC-Exos) possess repair functions similar to MSCs, low immunogenicity, and ease of storage and transport. MSC-Exos have been proven to possess excellent repair effects in repairing various organ damages. This study reviews the application of MSC-Exos in the treatment of DM and its common complications. MSC-Exos may be used as an effective treatment for DM and its complications.
Topics: Animals; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diabetic Nephropathies; Erectile Dysfunction; Exosomes; Female; Humans; Hyperglycemia; Inflammation; Male; Mesenchymal Stem Cells; Microcirculation; Neoplasms; Quality of Life; RNA, Untranslated; Risk; Ulcer
PubMed: 33995278
DOI: 10.3389/fendo.2021.646233 -
Diabetologia Feb 2021Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality,... (Meta-Analysis)
Meta-Analysis
AIMS/HYPOTHESIS
Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes.
METHODS
Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593).
RESULTS
Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001).
CONCLUSIONS/INTERPRETATION
Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality. Graphical abstract.
Topics: Age of Onset; Cerebrovascular Disorders; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Humans; Mortality; Odds Ratio; Peripheral Vascular Diseases
PubMed: 33313987
DOI: 10.1007/s00125-020-05319-w