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Diabetes Mellitus (DM) is amongst the most notable causes of years of life lost worldwide and its prevalence increases perpetually. The disease is characterized as multisystemic dysfunctions attributed to hyperglycemia resulting directly from insulin resistance (IR), inadequate insulin secretion, or enormous glucagon secretion. Insulin is a highly anabolic peptide hormone that regulates blood glucose levels by hastening cellular glucose uptake as well as controlling carbohydrate, protein, and lipid metabolism. In the course of Type 2 Diabetes Mellitus (T2DM), which accounts for nearly 90% of all cases of diabetes, the insulin response is inadequate, and this condition is defined as Insulin Resistance. IR sequela include, but are not limited to, hyperglycemia, cardiovascular system impairment, chronic inflammation, disbalance in oxidative stress status, and metabolic syndrome occurrence. Despite the substantial progress in understanding the molecular and metabolic pathways accounting for injurious effects of IR towards multiple body organs, IR still is recognized as a ferocious enigma. The number of widely available therapeutic approaches is growing, however, the demand for precise, safe, and effective therapy is also increasing. A literature search was carried out using the MEDLINE/PubMed, Google Scholar, SCOPUS and Clinical Trials Registry databases with a combination of keywords and MeSH terms, and papers published from February 2021 to March 2022 were selected as recently published papers. This review paper aims to provide critical, concise, but comprehensive insights into the advances in the treatment of IR that were achieved in the last months. [ABSTRACT FROM AUTHOR]

Background: About 25% of the global population suffers from non-alcoholic fatty liver disease (NAFLD), making it the most prevalent form of liver disease. One form of NAFLD, nonalcoholic steatohepatitis (NASH), can ultimately lead to cirrhosis, hepatocellular carcinoma (HCC), and mortality. The most common causes of fatty liver disease are being overweight or obese, having insulin resistance, leading an inactive lifestyle, consuming a high-fat diet and having a family history of the condition. The pathogenesis of NAFLD is associated with a weaker intestinal barrier caused by an altered gut microbiota, which exposes the host to bacterial components and triggers immunological defense and inflammation pathways via toll-like receptor signalling, ultimately leading to the development of NASH. The objective of the present review article is to discuss the risk factors and pathophysiological pathways that lead to NAFLD. Development: PubMed, Google scholar and Science direct were searched using the following keywords: Steatohepatitis, Steatosis, Hepatocellular carcinoma, Metabolic syndrome, Dysbiosis and Non-alcoholic fatty liver disease. The authors also screened references from the relevant literature, including all the identified studies and reviews, only the most recent or complete study was included between December 2002 and April 2021. Documents in a language apart from English have been excluded as sources for interpretation was not found. Papers apart from main scientific studies had been excluded: documents unavailable as total written text, conversation, conference abstract papers and dissertations. Conclusion: Globally, NAFLD is the most prevalent form of chronic liver disease. The pathophysiology of NAFLD is complex and requires the interaction of multiple factors. Metabolic syndrome, insulin resistance, unhealthy dietary habits and gut microbiota play major roles for the development of NAFLD. [ABSTRACT FROM AUTHOR]

Skeletal muscle serves as the optimal effective organ to balance glucose homeostasis, but insulin resistance (IR) in skeletal muscle breaks this balance by impeding glucose uptake and causes metabolic disorders. IR in skeletal muscle is caused by multiple factors, and it has been reported that systemic low-grade inflammation is related to skeletal muscle IR, though its molecular mechanisms need to be ulteriorly studied. Pyroptosis is a novel inflammatory-mediated type of cell death. It has recently been reported that pyroptosis is associated with a decline in insulin sensitivity in skeletal muscle. The appropriate occurrence of pyroptosis positively eliminates pathogenic factors, whereas its excessive activation may aggravate inflammatory responses and expedite disease progression. The relationship between pyroptosis and IR in skeletal muscle and its underlined mechanism need to be further illustrated. The role of pyroptosis during the process of IR alleviation induced by non-drug interventions, such as exercise, also needs to be clarified. In this paper, we review and describe the molecular mechanisms of pyroptosis and further comb the roles of its relevant key factors in skeletal muscle IR, aiming to propose a novel theoretical basis for the relationship between pyroptosis and muscle IR and provide new research targets for the improvement of IR-related diseases. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is one of the most widely spread metabolic disorder also called as "life style" disease. Due to the alarming number of patients, there is great need to therapies targeting functions which can help in maintaining the homeostasis of glucose levels and improving insulin sensitivity. Detailed analysis was done through various research and review papers which was searched using MEDLINE, BIOSIS, and EMBASE using various keywords. This search retrieved the most appropriate content on these molecules targeting UPP pathway. From this extensive review involving UPP pathway, it was concluded that the role of ubiquitin's is not only limited to neurodegenerative disorders but also plays a critical role in progression of diabetes including obesity, insulin resistance, and various neurogenerative disorders but it also targets proteasomal degradation including mediation of cellular signaling pathways. Thus, drugs targeting UPP not only may show effect against diabetes but also are therapeutically beneficial in the treatment of diabetes-associated complications which may be obtained. Thus, based on the available information and data on UPP functions, it can be concluded that regulation of UPP pathway via downstream regulators mainly E1, E2, and E3 may bring promising results. Drugs targeting these transcriptional factors may emerge as a novel therapy in the treatment of diabetes and diabetes-associated complications. [ABSTRACT FROM AUTHOR]

End-stage chronic liver diseases are often associated with insulin resistance (IR) and diabetes mellitus (DM). Indeed, to quantify insulin sensitivity the euglycemic clamp technique was utilized, allowing the following to be stated: in small groups of patients, an IR in almost all cirrhotic patients can be observed, compared with a control group. Additionally, it has been demonstrated that IR in cirrhosis is linked to a decreased peripheral (muscle) glucose uptake rather than an increased liver glucose production. The homoeostasis model of IR (HOMA-IR) technique, devised only later, was then exploited to assess this same phenomenon in a larger sample population. The research established that even in patients with preserved liver function, cirrhosis is associated with significant alterations in glucose homoeostasis levels. The purpose of the present paper is to present the current research around the affiliation of cirrhosis and IR, discuss potential mechanisms explaining the association between cirrhosis and IR (i.e. endocrine perturbation, liver inflammation, altered muscle mass and composition, altered gut microbiota and permeability), complications that can arise as well as treatment options, through a critical review of the literature surrounding this subject. This research will also be investigating the beneficial impact, if there is any, of identifying and curing IR in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Insulin resistance is associated with an increased risk of several metabolic disorders including type 2 diabetes, hypertension and cardiovascular diseases. Advances over the last decade have expanded our understanding of the molecular mechanisms underlying insulin resistance; however, many details of the mechanisms causing insulin resistance remain unknown. Recently, attention has shifted toward the role of epigenetics in insulin resistance. In this regard, acetylation of the histone tails has been widely investigated for its role in influencing both metabolic and mitogenic cascades of insulin signaling. More specifically, histone acetyltransferases and histone deacetylases, as major modulators of chromatin accessibility and gene expression, have been studied to determine a possible interconnectivity between the special effects of lysine acetylation status and tyrosine phosphorylation networks on the target proteins of downstream pathways involved in both metabolic and mitogenic cascades of insulin signaling. There is accumulating evidence for the post-translational modification effects of IGFR, InsR, IRS1/2, PI3K, Akt, GLUT4, FoxO, PGC-1α, PPAR, AMPK and MAPKs on insulin resistance and glucose homeostasis. In this paper, we review the importance of acetylation of these factors in the regulation of insulin signaling and glucose metabolism, with a primary focus on the target proteins of downstream signaling of insulin. We also provide an update on the interplay between epigenetic modification and the cellular genome in the context of insulin signaling and describe the possible effect of the environment on this epigenetic regulation. [ABSTRACT FROM AUTHOR]

Background: Lipid accumulation product (LAP) is an index calculated by waist circumference (WC) and triglyceride (TG), which reflects lipid toxicity. This study aims to investigate the association between the LAP index and nonalcoholic fatty liver disease (NAFLD) in a systematic review and meta-analysis. Methods and results: PubMed, Scopus, and Web of Science online databases were searched for eligible studies that investigated the association of the LAP index and NAFLD. Sixteen observational studies with 96,101 participants, including four cohort studies, one case‒control study and 11 cross-sectional studies with baseline data, were entered into this analysis. Fourteen studies reported a significant association between the LAP index and NAFLD, and two reported that this relation was not significant; two different meta-analyses (1- mean difference (MD) and 2- bivariate diagnostic test accuracy [DTA]) were conducted using Stata version 14. The LAP index was compared in subjects with and without NAFLD, and the difference was significant with 34.90 units (CI 95: 30.59–39.31, P < 0.001) of the LAP index. The DTA meta-analysis was conducted and showed that the LAP index pooled sensitivity and specificity for screening of NAFLD were 94% (CI95: 72%–99%, I2 = 99%, P < 0.001) and 85% (CI95: 62%–96%, I2 = 99%, P < 0.001), respectively. Conclusion: The LAP Index is an inexpensive, sensitive, and specific method to evaluate NAFLD and may be valuable for NAFLD screening. [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]

Background: Strokes significantly impair quality of life and incur high economic and societal burdens. The triglyceride and glucose (TyG) index is a biochemical marker of insulin resistance (IR) and may have important value in the prediction of strokes, especially ischemic stroke (IS). Our study aims to investigate the relationship between TyG index and IS and ascertain whether TyG index is independently associated with IS adverse outcomes. Methods: The Cochrane, Embase, Medline, Web of Science, PubMed, and other relevant English databases and related websites were systematically searched for articles on "TyG index" and "stroke" published from inception to April 4, 2022. We reviewed the available literature on the TyG index and its relation to predicting IS occurrence in the general population and adverse clinical outcomes. We calculated odds ratios (OR) of TyG index and its predictability of IS occurrence and adverse outcomes. Statistical analyses were performed using the Meta Package in STATA, version 12.0. Results: A total of 18 studies and 592,635 patients were included in our analysis. The pooled effect values of all stroke types showed that higher TyG index was associated with increased the risk of IS in the general population (OR 1.37; 95% CI 1.22–1.54) in a total sample of 554,334 cases with a high level of heterogeneity (P = 0.000, I2 = 74.10%). In addition, compared to IS patients with a lower TyG index, IS patients with a higher TyG index was associated with higher risk of stroke recurrence (OR: 1.50; 95% CI 1.19–1.89) and increased risk of mortality (OR 1.40 95% CI 1.14–1.71). No correlation was found in the effect value combinations of poor functional outcomes (OR 1.12; 95% CI 0.88–1.43) and neurological worsening (OR: 1.76; 95% CI 0.79–3.95) in a total sample of 38,301 cases with a high level of heterogeneity (P = 0.000; I2 = 77.20%). Conclusions: TyG index has potential value in optimizing risk stratification for IS in the general population. Furthermore, there is a significant association between high TyG index and many adverse outcomes of stroke, especially stroke recurrence and high mortality. Future studies should focus on multi-center and multi-regional designs in order to further explore the relationship between IS and TyG index. [ABSTRACT FROM AUTHOR]

Dementia, especially Alzheimer's Disease (AD) and vascular dementia, is a major public health problem that continues to expand in both economically emerging and hegemonic countries. In 2017, the World Alzheimer Report estimated that over 50 million people were living with dementia globally. Metabolic dysfunctions of brain structures such as the hippocampus and cerebral cortex have been implicated as risk factors for dementia. Several well-defined metabolic risk factors for AD include visceral obesity, chronic inflammation, peripheral and brain insulin resistance, type 2 diabetes mellitus (T2DM), hypercholesterolemia, and others. In this review, we describe the relationship between the dysmetabolic mechanisms, although still unknown, and dementia, particularly AD. Adiponectin (ADPN), the most abundant circulating adipocytokine, acts as a protagonist in the metabolic dysfunction associated with AD, with unexpected and intriguing dual biological functions. This contradictory role of ADPN has been termed the adiponectin paradox. Some evidence suggests that the adiponectin paradox is important in amyloidogenic evolvability in AD. We present cumulative evidence showing that AD and T2DM share many common features. We also review the mechanistic pathways involving brain insulin resistance. We discuss the importance of the evolvability of amyloidogenic proteins (APs), defined as the capacity of a system for adaptive evolution. Finally, we describe potential therapeutic strategies in AD, based on the adiponectin paradox. [ABSTRACT FROM AUTHOR]

Obesity and its related co-morbidities, namely type 2 diabetes (T2D), pose a significant global public health problem. Insulin resistance (IR) in muscle and liver is the core pathophysiologic defect that underlies obesity preceding and predicting the onset of T2D in susceptible humans. There is a broad population with IR that has no indication for prescription of medications, who still need medical consultation and specific advice in this respect. This prevalent need can be achieved by appropriate diet, exercise, and other behavioral therapies for lifestyle interventions. Despite a well-recognized role of IR in the progression to metabolic diseases, no specific nutritional recommendations exist to manage this condition, to the best of our knowledge. An international panel of experts reviewed and critically appraised the updated literature published about this topic. This review primarily examines the evidence for areas of consensus and ongoing uncertainty or controversy about diet and exercise approaches for IR. The aim of this article is to present the most common IR states, namely obesity and Polycystic Ovary Syndrome (PCOS), and provide nutritional advice to manage IR, hyperinsulinemia, and reactive hypoglycemia. These nutritional guidelines could prevent progression or worsening of IR with resultant beta-cell failure and, as a result, T2D. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting in inverse body regions. In a systematic review, the role of hormones in HS will be presented to better understand the pathomechanisms of HS. The review is based on the PRISMA criteria. Systematic research was carried out using keywords. Subsequently, the data were analyzed based on the clinical response and other relevant information. The main focus of our systematic review was on HS manifestation, exacerbation, sex hormones, antiandrogen therapy, thyroid function, polycystic ovary syndrome, insulin resistance, and adipokines. In HS, there appears to be a dysregulated adipokine release that is shifted towards pro-inflammatory adipokines. Insulin resistance is significantly more common in HS than in healthy patients regardless of BMI, age, and gender. Insulin resistance in HS patients leads to further cardiovascular disease. The mechanism of insulin resistance and role of adipokines should be investigated in future studies to better provide the pathomechanisms of HS. The role of androgens seems to be important in a certain subgroup of female patients. Anti-androgenic therapy can be useful and helpful in some patients. However, further studies are needed to better understand the hormonal relationship in HS. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite its incidence, the syndrome is poorly understood and remains underdiagnosed, and female patients are diagnosed with a delay. The heterogenous nature of this complex disorder results from the combined occurrence of genetic, environmental, endocrine, and behavioral factors. Primary clinical manifestations of PCOS are derived from the excess of androgens (anovulation, polycystic ovary morphology, lack of or scanty, irregular menstrual periods, acne and hirsutism), whereas the secondary manifestations include multiple metabolic, cardiovascular, and psychological disorders. Dietary and lifestyle factors play important roles in the development and course of PCOS, which suggests strong epigenetic and environmental influences. Many studies have shown a strong association between PCOS and chronic, low-grade inflammation both in the ovarian tissue and throughout the body. In the vast majority of PCOS patients, elevated values of inflammatory markers or their gene markers have been reported. Development of the vicious cycle of the chronic inflammatory state in PCOS is additionally stimulated by hyperinsulinemia and obesity. Changes in DNA methylation, histone acetylation and noncoding RNA levels are presented in this review in the context of oxidative stress, reactive oxygen species, and inflammatory signaling in PCOS. Epigenetic modulation of androgenic activity in response to inflammatory signaling is also discussed. [ABSTRACT FROM AUTHOR]

Background: The triglyceride glucose (TyG) index, which is a new surrogate indicator of insulin resistance (IR), is thought to be associated with many diseases, such as cardiovascular disease, but its relationship with cerebrovascular disease is still controversial. Methods: The PubMed, EMBASE, Cochrane Library, Web of Science and Medline databases were searched until March 2022 to evaluate the association between the TyG index and cerebrovascular disease risk. A random‒effects model was used to calculate the effect estimates and 95% confidence intervals (CIs). Results: A total of 19 cohort studies and 10 case‒control/cross‒sectional studies were included in our study, which included 11,944,688 participants. Compared with a low TyG index, a higher TyG index increased the risk of cerebrovascular disease (RR/HR = 1.22, 95% CI [1.14, 1.30], P< 0.001; OR = 1.15, 95% CI [1.07, 1.23], P< 0.001). Furthermore, the results of the dose-response analysis of the cohort study demonstrated that the risk of cerebrovascular disease increased by 1.19 times per 1 mg/dl increment of the TyG index (relative risk = 1.19, 95% CI [1.13,1.25], P< 0.001). Conclusion: TyG index is related to cerebrovascular disease. More data and basic research are needed to confirm the association. [ABSTRACT FROM AUTHOR]

Male hypogonadism is a disorder characterized by low levels of the hormone testosterone and patients may also have insulin sensitivity (IS) or insulin resistance (IR), such that they show different clinical complications and different metabolic pathways. In this review, we compare metabonomic differences observed between these two groups before and after testosterone therapy (TRT) in order to obtain information on whether the two hormones testosterone and insulin are synergistic or antagonistic. IS hypogonadism uses glucose as the main biofuel, while IR activates gluconeogenesis by the degradation of branched-chain amino acids. The Krebs (TCA) cycle is active in IS but connected with glutaminolysis, while in IR the TCA cycle stops at citrate, which is used for lipogenesis. In both cases, the utilization of fatty acids for energy (β-oxidation) is hampered by lower amounts of acetylcarnitine, although it is favored by the absence of insulin in IR. Increased free fatty acids (FFAs) are free in the blood in IS, while they are partially incorporated in triglycerides in IR. Thus, upon TRT, the utilization of glucose is increased more in IS than in IR, revealing that in IR there is a switch from preferential glucose oxidation to lipid oxidation. However, in both cases, a high production of lactate and acetyl-CoA is the final result, with these levels being much higher in IR. Lactate is used in IS in the glucose–lactate cycle between the liver and muscle to produce energy, while in IR lactate and acetyl-CoA are biotransformed into ketone bodies, resulting in ketonuria. In conclusion, the restoration of testosterone values in hypogonadism gives better results in IS than in IR patients: in IS, TRT restores most of the metabolic pathways, while in IR TRT impairs insulin, and when insulin is inactive TRT activates an ancestral molecular mechanism to produce energy. This evidence supports the hypothesis that, over time, hypogonadism switches from IS to IR, and in the latter case most of the insulin-related metabolisms are not reactivated, at least within 60 days of TRT. However, testosterone therapy in both IS and IR might be of benefit given supplementation with metabolites that are not completely restored upon TRT, in order to help restore physiological metabolisms. This review underlines the importance of using a systems biology approach to shed light on the molecular mechanisms of related biochemical pathways involving insulin and testosterone. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction has emerged as a central pathomechanism in the setting of obesity and diabetes mellitus, linking these intertwined pathologies that share insulin resistance as a common denominator. High-resolution respirometry (HRR) is a state-of-the-art research method currently used to study mitochondrial respiration and its impairment in health and disease. Tissue samples, cells or isolated mitochondria are exposed to various substrate-uncoupler-inhibitor-titration protocols, which allows the measurement and calculation of several parameters of mitochondrial respiration. In this review, we discuss the alterations of mitochondrial bioenergetics in the main dysfunctional organs that contribute to the development of the obese and diabetic phenotypes in both animal models and human subjects. Herein we review data regarding the impairment of oxidative phosphorylation as integrated mitochondrial function assessed by means of HRR. We acknowledge the critical role of this method in determining the alterations in oxidative phosphorylation occurring in the early stages of metabolic pathologies. We conclude that there is a mutual two-way relationship between mitochondrial dysfunction and insulin insensitivity that characterizes these diseases. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy and has considerable short- and long-term consequences for the health of both the mother and the newborn. Within its pathophysiology, genetic, nutritional, epigenetic, immunological, and hormonal components have been described. Within the last two items, it is known that different hormones and cytokines secreted by adipose tissue, known collectively as adipokines, are involved in the metabolic alterations underlying GDM. Although the maternal circulating profile of adipokines in GDM has been extensively studied, and there are excellent reviews on the subject, it is in recent years that more progress has been made in the study of their expression in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), placenta, and their concentrations in the umbilical circulation. Thus, this review compiles and organizes the most recent findings on the maternal and umbilical circulating profile and the levels of expression of adipokines in VAT, SAT, and placenta in GDM. [ABSTRACT FROM AUTHOR]

Adrenal incidentalomas are incidentally discovered adrenal masses greater than one centimeter in diameter. An association between insulin resistance and adrenal incidentalomas has been established. However, the pathophysiological link between these two conditions remains incompletely characterized. This review examines the literature on the interrelationship between insulin resistance and adrenal masses, their subtypes, and related pathophysiology. Some studies show that functional and non-functional adrenal masses elicit systemic insulin resistance, whereas others conclude the inverse. Insulin resistance, hyperinsulinemia, and the anabolic effects on adrenal gland tissue, which have insulin and insulin-like growth factor-1 receptors, offer possible pathophysiological links. Conversely, autonomous adrenal cortisol secretion generates visceral fat accumulation and insulin resistance. Further investigation into the mechanisms and timing of these two pathologies as they relate to one another is needed and could be valuable in the prevention, detection, and treatment of both conditions. [ABSTRACT FROM AUTHOR]

It is now well established that, beyond its role in nutrient processing and absorption, the intestine and its accompanying gut microbiome constitute a major site of immunological and endocrine regulation that mediates whole-body metabolism. Despite the growing field of host-microbe research, few studies explore what mechani sms govern this relationship in the context of pregnancy. During pregnancy, sig nificant maternal metabolic adaptations are made to accommodate the additional energy demands of the developing fetus and to prevent adverse pregnancy outcomes. Recent data suggest that the maternal gut microbiota may play a role in these adaptations, but changes to maternal gut physiology and the underlying intestinal mechanisms remain unclear. In this review, we discuss selective aspects of intestinal physiology including the role of the incretin hormone, glucagon-like peptide 1 (GLP-1), and the role of the maternal gut microbiome in the maternal metabolic adaptations to pregnancy. Specifically, we discuss how bacterial components and metabolites could mediate the effec ts of the microbiota on host physiology, including nutrient absorption and GLP-1 secretion and action, and whether these mechanisms may change maternal insulin sensitivity and secretion during pregnancy. Finally, we discuss how these pathways could be altered in disease states during pregnancy including maternal obesity and diabetes. [ABSTRACT FROM AUTHOR]

Diabetes mellitus describes a group of metabolic disorders characterized by a prolonged period hyperglycemia with long-lasting detrimental effects on the cardiovascular and nervous systems, kidney, vision, and immunity. Many plant polyphenols are shown to have beneficial activity for the prevention and treatment of diabetes, by different mechanisms. This review article is focused on synthesizing the mechanisms by which polyphenols decrease insulin resistance and inhibit loss of pancreatic islet β-cell mass and function. To achieve the objectives, this review summarizes the results of the researches realized in recent years in clinical trials and in various experimental models, on the effects of foods rich in polyphenols, polyphenolic extracts, and commercially polyphenols on insulin resistance and β-cells death. Dietary polyphenols are able to reduce insulin resistance alleviating the IRS-1/PI3-k/Akt signaling pathway, and to reduce the loss of pancreatic islet β-cell mass and function by several molecular mechanisms, such as protection of the surviving machinery of cells against the oxidative insult; increasing insulin secretion in pancreatic β-cells through activation of the FFAR1; cytoprotective effect on β-cells by activation of autophagy; protection of β-cells to act as activators for anti-apoptotic pathways and inhibitors for apoptotic pathway; stimulating of insulin release, presumably by transient ATP-sensitive K+ channel inhibition and whole-cell Ca2+ stimulation; involvement in insulin release that act on ionic currents and membrane potential as inhibitor of delayed-rectifier K+ current (IK(DR)) and activator of current. dietary polyphenols could be used as potential anti-diabetic agents to prevent and alleviate diabetes and its complications, but further studies are needed. [ABSTRACT FROM AUTHOR]

An update on systematic review and meta-analysis was performed to explore effects of phthalate exposure on insulin resistance. A systematic literature search was performed in MEDLINE, Web of Science, and CNKI until March 2021. A conceptual framework was constructed to guide the organization and presentation of results. Besides, beta coefficients with corresponding confidence intervals were extracted from the most adjusted models. Extracted beta coefficients were transformed into correlation, and z Fisher transformation of correlation with the corresponding standard error was included in meta-analysis. Subgroup analyses were performed by age (adult vs. adolescent) and sex (female vs. male) of participants and site of study (America and Europe vs. Asia) to explore potential sources of heterogeneity. Nineteen literatures with 12,533 participants reporting on the association of exposure to specific phthalates and insulin resistance were selected. The majority of included studies revealed positive relationships of insulin resistance with different phthalate metabolites exposure. Meta-analyses were performed on 16 studies. Exposure to MnBP, MBzP, MCPP, MEHP, MEOHP, MEHHP, ∑DEHP, and high-molecular weight phthalate (∑HMWP) was associated with the increase of the homeostasis model assessment of insulin resistance (HOMA-IR) index. The results of sensitivity analyses stratified by age, sex, and site of study remained stable, suggesting the robustness of these meta-analyses. Most of heterogeneity in sensitivity analyses decreased to moderate or low degree. Exposure to MnBP, MBzP, MCPP, MEHP, MEOHP, MEHHP, ∑DEHP, and ∑HMWP was associated with the increased risk of HOMA-IR. Age, sex, and site of study might provide limited source of heterogeneity. [ABSTRACT FROM AUTHOR]

Inflammasome activity plays a vital role in various non-microbial disease states correlated with prolonged inflammation. NLRP3 inflammasome function and IL-1β formation are augmented in obesity and several obesity-linked metabolic disorders (i.e. diabetes mellitus, hypertension, hepatic steatosis, cancer, arthritis, and sleep apnea). Also, several factors are associated with the progression of diseases viz. increased plasma glucose, fatty acids, and β-amyloid are augmented during obesity and activate NLRP3 inflammasome expression. Prolonged NLRP3 stimulation seems to play significant role in various disorders, though better knowledge of inflammasome regulation and action might result in improved therapeutic tactics. Numerous compounds that mitigate NLRP3 inflammasome expression and suppress its chief effector, IL-1β are presently studied in clinical phases as therapeutics to manage or prevent these common disorders. A deep research on the literature available till date for inflammasome in obesity was conducted using various medical sites like PubMed, HINARI, MEDLINE from the internet, and data was collected simultaneously. The present review aims to examine the prospects of inflammasome as a major progenitor in the progression of obesity via directing their role in regulating appetite. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) in childhood plays a key role in the development of metabolic changes in adulthood, therefore, it is important to diagnose it early. We aimed to investigate studies that evaluated the TyG index for prediction of IR risk and other cardiometabolic risk factors, as well as, the proposed cutoff points in childhood and adolescence. This is a systematic review elaborated according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA). The search was performed in Lilacs, PubMed and CAPES Journal Portal, using the terms "TyG index OR triglyceride-glucose index OR triglyceride and glucose index AND children OR adolescent*". Eight articles were included in this review. All were cross-sectional studies with individuals aged ≥2 and ≤20 years old, from the United States, Korea, Mexico, Brazil, and Iran. We concluded that the TyG index was positively associated with other IR prediction methods and appears to be advantageous for predicting IR risk and other cardiometabolic risk factors in children and adolescents (review registration: PROSPERO CRD42018100726). [ABSTRACT FROM AUTHOR]

Introduction: Wound healing in diabetes may be delayed by persistent wound infection due to deficient immune and cellular response to tissue injury. Hyperglycemia due to decreased insulin availability and increased insulin resistance affects the immune response of the body. Accumulation of inflammatory immune cells and pro-inflammatory cytokines results in chronic inflammation and an altered resolution and remodeling phase of wound healing. Areas covered: Pro-resolving mediators called 'resolvins' target the resolution phase of wound healing and are becoming an area of increased interest. Resolvins stimulate self-limited innate immune responses and enhance innate microbial killing and clearance. Resolvins resolve inflammation by decreasing neutrophil infiltration and transmigration, increasing the phagocytic activity of macrophages, decreasing adipose tissue macrophages, downregulating platelet activation, suppressing nuclear factor-kappa beta activation, promoting the apoptosis of polymorphonuclear leukocytes, and improving insulin sensitivity. This review discusses the role of resolvins in diabetic wound healing and potential therapeutic strategies. The review is based on a literature search of PubMed and the Web of Science restricted to publications between January 2001 and October 2020. Expert opinion: There is increasing support for the use of resolvins in clinical applications related to diabetes and wound healing. Further research will help clarify this potential. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance has been demonstrated to be involved in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVDs). This study evaluated the association between the triglyceride–glucose (TyG) index, a novel surrogate indicator of insulin resistance, and the incidence of ASCVDs in people without ASCVDs at baseline by performing a meta-analysis. Methods: Cohort studies reporting the multivariate-adjusted association between the TyG index and the incidence of ASCVDs were obtained by searching the PubMed and Embase databases. A random-effects model incorporating intra-study heterogeneity was applied to combine the results. Results: Eight cohort studies comprising 5,731,294 participants were included in this meta-analysis. The results showed that compared to those with the lowest TyG index category, participants with the highest TyG index category were independently associated with a higher risk of ASCVDs [hazard ratio (HR): 1.61, 95% confidence interval (CI) 1.29–2.01, I2 = 80%, P < 0.001]. This finding was consistent with the meta-analysis results with the TyG index analyzed as a continuous variable (HR per 1-unit increment of the TyG index: 1.39, 95% CI 1.18–1.64, I2 = 89%, P < 0.001). Subgroup analyses suggested that the age, sex, and diabetic status did not significantly affect the association (for subgroup analyses, all P > 0.05). Moreover, participants with the highest TyG index category were independently associated with a higher risk of coronary artery disease [(CAD), HR: 1.95, 95% CI 1.47–2.58, I2 = 92%, P < 0.001] and stroke (HR: 1.26, 95% CI 1.23–1.29, I2 = 0%, P < 0.001). Conclusions: A higher TyG index may be independently associated with a higher incidence of ASCVDs, CAD, and stroke in people without ASCVDs at baseline. [ABSTRACT FROM AUTHOR]

The disease (COVID-19) novel coronavirus pandemic has so far infected millions resulting in the death of over a million people as of Oct 2020. More than 90% of those infected with COVID-19 show mild or no symptoms but the rest of the infected cases show severe symptoms resulting in significant mortality. Age has emerged as a major factor to predict the severity of the disease and mortality rates are significantly higher in elderly patients. Besides, patients with underlying conditions like Type 2 diabetes, cardiovascular diseases, hypertension, and cancer have an increased risk of severe disease and death due to COVID-19 infection. Obesity has emerged as a novel risk factor for hospitalization and death due to COVID-19. Several independent studies have observed that people with obesity are at a greater risk of severe disease and death due to COVID-19. Here we review the published data related to obesity and overweight to assess the possible risk and outcome in Covid-19 patients based on their body weight. Besides, we explore how the obese host provides a unique microenvironment for disease pathogenesis, resulting in increased severity of the disease and poor outcome. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic progressive systemic disease caused by a metabolic disorder. In recent years, a large number of studies have shown that certain traditional Chinese medicines and their bioactive ingredients have obvious hypoglycemic effects. This literature review focuses on medicine food homology (MFH) and medicinal health food (MHF) species used in China with a hypoglycemic function and emphasizes the bioactive ingredients and their pharmacological effects. The bioactive ingredients of MFH and MHF have been divided into six categories: saponins, flavonoids, terpenoids, alkaloids, polysaccharides, and others; and their sources, models, efficacy, and mechanisms of action have been described. It is noteworthy that the mechanisms of the bioactive ingredients of MFH and MHF with hypoglycemic effects have been summarized as follows: a) insulin-mimetic effects and restoration of the damaged pancreas; b) effect on glucose metabolism; c) increased insulin sensitivity and improved insulin resistance; and d) regulation of intestinal flora. We conclude that this review provides useful data and information to support the further investigation and application of MFH and MHF to treat DM. [ABSTRACT FROM AUTHOR]

Bisphenol-A (BPA) has been reported to be associated to female infertility. Indeed, BPA has been found to be more frequently detected in infertile women thus leading to hypothesize a possible effect of BPA on natural conception and spontaneous fecundity. In addition, in procedures of medically assisted reproduction BPA exposure has been found to be negatively associated with peak serum estradiol levels during gonadotropin stimulation, number of retrieved oocytes, number of normally fertilized oocytes and implantation. BPA deleterious effects are more critical during perinatal exposure, causing dysregulation of hypothalamic-pituitary-ovarian axis in pups and adults, with a precocious maturation of the axis through a damage of GnRH pulsatility, gonadotropin signaling and sex steroid hormone production. Further, BPA exposure during early lifestage may have a transgenerational effect predisposing the subsequent generations to the risk of developing BPA related disease. Experimental studies suggested that prenatal, perinatal and postnatal exposure to BPA can impair several steps of ovarian development, induce ovarian morphology rearrangement and impair ovarian function, particularly folliculogenesis, as well as can impair uterus morphology and function, in female adult animal and offspring. Finally, studies carried out in animal models have been reported the occurrence of endometriosis-like lesions after BPA exposure. Moreover, BPA exposure has been described to encourage the genesis of PCOS-like abnormalities through the impairment of the secretion of sex hormones affecting ovarian morphology and functions, particularly folliculogenesis. The current manuscript summarizes the evidence regarding the association between BPA exposure and female infertility, reviewing both clinical and preclinical studies. [ABSTRACT FROM AUTHOR]

Introduction: Sweeteners are substances used to replace sugar. They can either be chemically produced (artificial sweeteners) or extracted from plants (natural sweeteners). In the last two decades, there is an increased popularity in their role as sugar substitutes in individuals to promote weight loss or maintain glycemic control. However, despite their favorable effects, there is concern regarding their side effects and especially their influence in the development of nonalcoholic fatty liver disease (NAFLD). Areas covered: A comprehensive literature search was conducted on Medline including systematic reviews, longitudinal controlled studies, and retrospective cohort studies. We present an up-to-date systematic review of the current literature regarding the safety in artificial and natural sweeteners use as a means of weight loss or diabetes control. Expert opinion: Natural sweeteners have not been associated directly with NAFLD, and on the contrary, some, such as stevia, and trehalose, may have a protective effect. Rare sugars and polyols can be used safely and have significant benefits that include anti-oxidant effect and optimal glycemic control. Artificial sweeteners, due to their effect on NAFLD development and insulin resistance, are not indicated in patients with obesity or diabetes. Further studies in human subjects are required to verify the above findings. [ABSTRACT FROM AUTHOR]

Introduction: Lipodystrophy is a heterogeneous group of rare diseases characterized by various degrees of fat loss which leads to serious morbidity due to metabolic abnormalities associated with insulin resistance and subtype-specific clinical features associated with underlying molecular etiology. Areas covered: This article aims to help physicians address challenges in diagnosing and managing lipodystrophy. We systematically reviewed the literature on PubMed and Google Scholar databases to summarize the current knowledge in lipodystrophy management. Expert opinion: Adipose tissue is a highly active endocrine organ that regulates metabolic homeostasis in the human body through a comprehensive communication network with other organ systems such as the central nervous system, liver, digestive system, and the immune system. The adipose tissue is capable of producing and secreting numerous factors with important endocrine functions such as leptin that regulates energy homeostasis. Recent developments in the field have helped to solve some of the mysteries behind lipodystrophy that allowed us to get a better understanding of adipocyte function and differentiation. From a clinical standpoint, physicians who suspect lipodystrophy should distinguish the disease from several others that may present with similar clinical features. It is also important for physicians to carefully interpret clinical features, laboratory, and imaging results before moving to more sophisticated tests and making decisions about therapy. [ABSTRACT FROM AUTHOR]

The prevalence of sarcopenic obesity is increasing worldwide, particularly amongst aging populations. Insulin resistance is the core mechanism of sarcopenic obesity and is also associated with variable cardiometabolic diseases such as cardiovascular disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Fat accumulation in muscle tissue promotes a proinflammatory cascade and oxidative stress, leading to mitochondrial dysfunction, impaired insulin signaling, and muscle atrophy. To compound the problem, decreased muscle mass aggravates insulin resistance. In addition, the crosstalk between myokines and adipokines leads to negative feedback, which in turn aggravates sarcopenic obesity and insulin resistance. In this review, we focus on the molecular mechanisms linking sarcopenic obesity and insulin resistance with various biological pathways. We also discuss the impact and mechanism of sarcopenic obesity and insulin resistance on cardiometabolic disease. [ABSTRACT FROM AUTHOR]

Reviews the book `Blood Sugar Blues: Overcoming the Hidden Dangers of Insulin Resistance,' by Miryam Ehrlich Williamson.