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Bioscience Trends Nov 2023Studies have found that intermittent fasting (IF) can prevent diabetes, cancer, heart disease, and neuropathy, while in humans it has helped to alleviate metabolic...
Studies have found that intermittent fasting (IF) can prevent diabetes, cancer, heart disease, and neuropathy, while in humans it has helped to alleviate metabolic syndrome, asthma, rheumatoid arthritis, Alzheimer's disease, and many other disorders. IF involves a series of coordinated metabolic and hormonal changes to maintain the organism's metabolic balance and cellular homeostasis. More importantly, IF can activate hepatic autophagy, which is important for maintaining cellular homeostasis and energy balance, quality control, cell and tissue remodeling, and defense against extracellular damage and pathogens. IF affects hepatic autophagy through multiple interacting pathways and molecular mechanisms, including adenosine monophosphate (AMP)-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), silent mating-type information regulatory 2 homolog-1 (SIRT1), peroxisomal proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR), as well as signaling pathways and molecular mechanisms such as glucagon and fibroblast growth factor 21 (FGF21). These pathways can stimulate the pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), play a cytoprotective role, downregulate the expression of aging-related molecules, and prevent the development of steatosis-associated liver tumors. By influencing the metabolism of energy and oxygen radicals as well as cellular stress response systems, IF protects hepatocytes from genetic and environmental factors. By activating hepatic autophagy, IF has a potential role in treating a variety of liver diseases, including non-alcoholic fatty liver disease, drug-induced liver injury, viral hepatitis, hepatic fibrosis, and hepatocellular carcinoma. A better understanding of the effects of IF on liver autophagy may lead to new approaches for the prevention and treatment of liver disease.
Topics: Humans; Intermittent Fasting; Liver; Fatty Liver; Hepatocytes; Autophagy
PubMed: 37661370
DOI: 10.5582/bst.2023.01207 -
Pharmacological Research Oct 2023There is an increasing interest in the use of nutraceuticals and plant-derived bioactive compounds from foods for their potential health benefits. For example, as a... (Review)
Review
There is an increasing interest in the use of nutraceuticals and plant-derived bioactive compounds from foods for their potential health benefits. For example, as a major active ingredient found from cruciferous vegetables like broccoli, there has been growing interest in understanding the therapeutic effects of sulforaphane against diverse metabolic complications. The past decade has seen an extensive growth in literature reporting on the potential health benefits of sulforaphane to neutralize pathological consequences of oxidative stress and inflammation, which may be essential in protecting against diabetes-related complications. In fact, preclinical evidence summarized within this review supports an active role of sulforaphane in activating nuclear factor erythroid 2-related factor 2 or effectively modulating AMP-activated protein kinase to protect against diabetic complications, including diabetic cardiomyopathy, diabetic neuropathy, diabetic nephropathy, as well as other metabolic complications involving non-alcoholic fatty liver disease and skeletal muscle insulin resistance. With clinical evidence suggesting that foods rich in sulforaphane like broccoli can improve the metabolic status and lower cardiovascular disease risk by reducing biomarkers of oxidative stress and inflammation in patients with type 2 diabetes. This information remains essential in determining the therapeutic value of sulforaphane or its potential use as a nutraceutical to manage diabetes and its related complications. Finally, this review discusses essential information on the bioavailability profile of sulforaphane, while also covering information on the pathological consequences of oxidative stress and inflammation that drive the development and progression of diabetes.
PubMed: 37703962
DOI: 10.1016/j.phrs.2023.106918 -
Frontiers in Endocrinology 2023Worldwide, diabetes and its complications have seriously affected people's quality of life and become a serious public health problem. C-peptide is not only an indicator... (Review)
Review
Worldwide, diabetes and its complications have seriously affected people's quality of life and become a serious public health problem. C-peptide is not only an indicator of pancreatic β-cell function, but also a biologically active peptide that can bind to cell membrane surface signaling molecules and activate downstream signaling pathways to play antioxidant, anti-apoptotic and inflammatory roles, or regulate cellular transcription through internalization. It is complex how C-peptide is related to diabetic complications. Both deficiencies and overproduction can lead to complications, but their mechanisms of action may be different. C-peptide replacement therapy has shown beneficial effects on diabetic complications in animal models when C-peptide is deficient, but results from clinical trials have been unsatisfactory. The complex pattern of the relationship between C-peptide and diabetic chronic complications has not yet been fully understood. Future basic and clinical studies of C-peptide replacement therapies will need to focus on baseline levels of C-peptide in addition to more attention also needs to be paid to post-treatment C-peptide levels to explore the optimal range of fasting C-peptide and postprandial C-peptide maintenance.
Topics: Animals; Humans; C-Peptide; Quality of Life; Diabetes Complications; Diabetes Mellitus
PubMed: 37745697
DOI: 10.3389/fendo.2023.1256093 -
Bone Nov 2023Multiple pathogenetic mechanisms are involved in the genesis of various microvascular and macrovascular complications of diabetes mellitus. Of all these, advanced... (Review)
Review
BACKGROUND
Multiple pathogenetic mechanisms are involved in the genesis of various microvascular and macrovascular complications of diabetes mellitus. Of all these, advanced glycation end products (AGEs) have been strongly implicated.
OBJECTIVES
The present narrative review aims to summarize the available literature on the genesis of AGEs and their potential role in the causation of both micro- and macrovascular complications of diabetes mellitus.
RESULTS
Uncontrolled hyperglycemia triggers the formation of AGEs through non-enzymatic glycation reactions between reducing sugars and proteins, lipids, or nucleic acids. AGEs accumulate in bloodstream and bodily tissues under chronic hyperglycemia. AGEs create irreversible cross-linkages of various intra- and extracellular molecules and activate the receptor for advanced glycation end products (RAGE), which stimulates downstream signaling pathways that generate reactive oxygen species (ROS) and contribute to oxidative stress. Additionally, intracellular glycation of mitochondrial respiratory chain proteins by AGEs contributes to the further generation of ROS, which, in turn, sets a vicious cycle that further promotes the production of endogenous AGEs. Through these pathways, AGEs play a principal role in the pathogenesis of various diabetic complications, including diabetic retinopathy, nephropathy, neuropathy, bone disease, atherosclerosis and non-alcoholic fatty liver disease. Multiple clinical studies and meta-analyses have revealed a positive association between tissue or circulating levels of AGEs and development of various diabetic complications. Besides, exogenous AGEs, primarily those derived from diets, promote insulin resistance, obesity, and metabolic syndrome.
CONCLUSIONS
AGEs, triggered by chronic hyperglycemia, play a pivotal role in the pathogenesis of various complications of diabetes mellitus.
Topics: Humans; Metabolic Syndrome; Glycemic Control; Reactive Oxygen Species; Hyperglycemia; Cardiovascular Diseases; Glycation End Products, Advanced
PubMed: 37598920
DOI: 10.1016/j.bone.2023.116884 -
Journal of Internal Medicine Aug 2023Nonalcoholic fatty liver disease (NAFLD) is considered a multisystem disease, as it is bidirectionally linked to other cardiometabolic disorders, such as type 2 diabetes...
INTRODUCTION
Nonalcoholic fatty liver disease (NAFLD) is considered a multisystem disease, as it is bidirectionally linked to other cardiometabolic disorders, such as type 2 diabetes (T2D). However, the long-term risk for microvascular outcomes in NAFLD is unclear.
METHODS
Using the outpatient part of the nationwide Swedish Patient Register in the time period between 01/01/2002 and 12/31/2019, we identified all individuals with a first NAFLD diagnosis (N = 6785) and matched these (age, sex, and municipality) with up to 10 reference individuals from the general population (N = 61,136). Using population-based registers, we ascertained the development of microvascular diseases. The primary outcome was defined as a composite outcome of any diagnosis representative of microvascular disease (chronic kidney disease, retinopathy, or neuropathy). As secondary outcomes, we separately examined the risk of each specific microvascular outcome. Hazard ratios (aHR, adjusted for cirrhosis and time-varying T2D, hypertension, and hyperlipidemia) for the outcomes were calculated by Cox proportional-hazards models.
RESULTS
Median follow-up was 5.7 years. The incidence rate of microvascular diseases was >twofold higher in patients with NAFLD (10.8 per 1000 person-years [95% confidence interval (CI) = 9.9-11.8]) versus reference individuals (4.7 per 1000 person-years [95%CI = 4.5-4.9]). NAFLD was independently and positively associated with the development of microvascular diseases compared to non-NAFLD subjects (aHR = 1.45 [95%CI = 1.28-1.63]). When stratifying the analysis by follow-up time, sex, or age categories, results remain virtually unchanged.
CONCLUSIONS
NAFLD is positively and independently associated with the development of microvascular diseases. The risk for development of microvascular diseases should be taken into account in the personalized risk assessment of individuals with NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Cohort Studies; Diabetes Mellitus, Type 2; Liver Cirrhosis; Risk Assessment; Risk Factors
PubMed: 37259481
DOI: 10.1111/joim.13673 -
European Review For Medical and... Aug 2023The aim of this study was to investigate the prevalence of microvascular and macrovascular diabetic complications and the associated comorbidities in newly diagnosed...
OBJECTIVE
The aim of this study was to investigate the prevalence of microvascular and macrovascular diabetic complications and the associated comorbidities in newly diagnosed pre-diabetic individuals.
PATIENTS AND METHODS
This cross-sectional study includes 100 newly diagnosed pre-diabetic individuals. Fasting plasma glucose, HbA1c, and oral glucose tolerance (OGTT) were tested according to the American Diabetes Association's diagnostic criteria for pre-diabetes, besides anthropometric measurements, lipid profiles, and demographic and biochemical parameters. Comorbidities like hypertension, obesity, dyslipidemia etc., were evaluated. All participants were screened for microvascular (retinopathy, nephropathy, neuropathy) and macrovascular [coronary artery disease (CAD) and cerebrovascular event-peripheral artery disease] complications.
RESULTS
Microvascular complications were found in 12% of the participants (neuropathy: 4%, nephropathy: 8%) and 19% had macrovascular complications. Of the participants, 21% of the cases presented hypertension, 21% dyslipidemia and 48% obesity. A high probability of developing non-alcoholic fatty liver disease-related fibrosis [estimated using non-alcoholic fatty liver disease fibrosis score (NFS)] was found in 68% of cases. History of dyslipidemia (OR: 5.00, 95% CI: 1.10-22.56; p=0.037) was an independent risk factor for the development of vascular complications.
CONCLUSIONS
Diabetic vascular complications were found in approximately one-third of pre-diabetic cases. Dyslipidaemia was found to be an important risk factor for the development of vascular complications in these individuals.
Topics: Humans; Prediabetic State; Cross-Sectional Studies; Non-alcoholic Fatty Liver Disease; Cardiovascular Diseases; Hypertension; Obesity; Fibrosis
PubMed: 37667932
DOI: 10.26355/eurrev_202308_33407 -
Alcohol (Fayetteville, N.Y.) Jun 2024Alcohol overconsumption is well known to cause damage to the peripheral nervous system, affecting both small and large nerve fibers. The aim of this descriptive study...
Alcohol-related peripheral neuropathy: Clinico-neurophysiological characteristics and diagnostic utility of the neuropathy symptoms score and the neuropathy impairment score.
Alcohol overconsumption is well known to cause damage to the peripheral nervous system, affecting both small and large nerve fibers. The aim of this descriptive study was to investigate peripheral nerve damage, and to correlate clinical, epidemiological and neurophysiological findings, in patients diagnosed with Alcohol Use Disorder (AUD). Ninety alcohol-dependent subjects on inpatient basis were enrolled in this prospective study over a 3-year period. Every subject was assessed by the Neuropathy Symptoms Score (NSS) questionnaire and the Neuropathy Impairment Score (NIS) clinical examination grading scale, followed by Nerve Conduction Studies, Quantitative Sensory Testing and Sympathetic Skin Response (SSR) testing. Peripheral neuropathy was diagnosed in 54 subjects (60%), by abnormal neurophysiological tests and presence of clinical signs or symptoms. Among them, pure large fiber neuropathy (LFN) was found in 18 subjects, pure small fiber neuropathy (SFN) in 12 subjects, and both large and small fiber neuropathy was diagnosed in 24 subjects. Using linear regression, we found that higher NSS and NIS scores correlated with lower amplitudes of the sural sensory nerve action potential and of the SSR. We also found a significant longer duration of alcohol abuse in subjects with neuropathy, using Student's t-test (p = 0.024). Additionally, applying NIS abnormal cut-off score ≥4, using ROC analysis, we predicted the majority of subjects with LFN, confirming 95.23% sensitivity and 93.75% specificity. Our study confirmed that peripheral neuropathy involving large and small nerve fibers, with a symmetrical length-dependent pattern, is common between patients with AUD and related to the duration of the disorder. We suggest that NSS and NIS scales could be used for the assessment of neuropathy in clinical practice, when the essential neurophysiological testing is not available.
Topics: Humans; Male; Female; Middle Aged; Adult; Prospective Studies; Alcoholic Neuropathy; Neural Conduction; Alcoholism; Severity of Illness Index; Peripheral Nervous System Diseases; Surveys and Questionnaires
PubMed: 38580031
DOI: 10.1016/j.alcohol.2024.04.001 -
World Journal of Diabetes May 2024In this editorial, we comment on the article by Liu published in the recent issue of the (Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with...
In this editorial, we comment on the article by Liu published in the recent issue of the (Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria). Type 2 diabetes mellitus (T2DM) is a chronic disorder characterized by dysregulated glucose homeostasis. The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications, including cardiovascular disease, re-tinopathy, neuropathy, and nephropathy. T2DM arises from a complex interplay between genetic, epigenetic, and environmental factors. Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM. Specifically, variations within the glucokinase regulatory protein (GCKR) gene have been linked to heightened susceptibility to T2DM and its associated complications. The clinical trial by Liu further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development. Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype. These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.
PubMed: 38766433
DOI: 10.4239/wjd.v15.i5.814 -
Diabetes/metabolism Research and Reviews Jan 2024The mammalian target of rapamycin complex 1 syndrome (Tors), paradigm implies an exhaustive cohesive disease entity driven by a hyperactive mTORC1, and which includes... (Review)
Review
The mammalian target of rapamycin complex 1 syndrome (Tors), paradigm implies an exhaustive cohesive disease entity driven by a hyperactive mTORC1, and which includes obesity, type 2 diabetic hyperglycemia, diabetic dyslipidemia, diabetic cardiomyopathy, diabetic nephropathy, diabetic peripheral neuropathy, hypertension, atherosclerotic cardiovascular disease, non-alcoholic fatty liver disease, some cancers, neurodegeneration, polycystic ovary syndrome, psoriasis and other. The TorS paradigm may account for the efficacy of standard-of-care treatments of type 2 diabetes (T2D) in alleviating the glycaemic and non-glycaemic diseases of TorS in T2D and non-T2D patients. The TorS paradigm may generate novel treatments for TorS diseases.
Topics: Female; Humans; Diabetes Mellitus, Type 2; Risk Factors; Obesity; Non-alcoholic Fatty Liver Disease; Polycystic Ovary Syndrome; Metabolic Syndrome
PubMed: 37615286
DOI: 10.1002/dmrr.3712