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Showing papers in "Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy in 2020"


Journal ArticleDOI
TL;DR: This review assesses the cellular components of each physiologic and pathophysiologic factors that are involved in obesity associated insulin resistance, and may encourage further drug development in this field.
Abstract: Obesity is a triggering factor for diabetes associated with insulin resistance. In individuals who are obese, higher amounts of non-esterified fatty acids, glycerol, hormones, and pro-inflammatory cytokines that could participate in the development of insulin resistance are released by adipose tissue. Besides, endoplasmic reticulum stress, adipose tissue hypoxia, oxidative stress, lipodystrophy, and genetic background have a role in insulin resistance. However, no effective drug therapy was developed for type 2 diabetes mellitus targeting these physiological factors. This is might be due to a lack of agreement on the comprehensive mechanism of insulin resistance. Therefore, this review assesses the cellular components of each physiologic and pathophysiologic factors that are involved in obesity associated insulin resistance, and may encourage further drug development in this field.

148 citations


Journal ArticleDOI
TL;DR: The evidence for extra-glycemic effects of SGLT2i and the potential mechanisms driving cardiorenal protection exerted by this class of medications are summarized.
Abstract: Patients with type 2 diabetes (T2D) are often overweight/obese and affected by arterial hypertension, dyslipidaemia, and have high serum levels of uric acid. Moreover, T2D patient have a higher risk of developing cardiovascular or renal complications, which are leading causes of morbidity and mortality in this population. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a new class of glucose-lowering medications that block the reabsorption of glucose in the kidney, thereby increasing urinary glucose excretion, and lowering blood glucose levels. The beneficial effects of SGLT2 inhibition extend beyond glycaemic control, and include improvement in blood pressure, body weight, uric acid concentrations, liver steatosis, oxidative stress, and inflammation. In dedicated cardiovascular outcome trials, SGLT2i treatment was associated with a significant reduction in the rate of cardiovascular events and renal endpoints. In this review, we summarize the evidence for extra-glycemic effects of SGLT2i and the potential mechanisms driving cardiorenal protection exerted by this class of medications.

86 citations


Journal ArticleDOI
TL;DR: It was found that the proportions of some microbiota, such as phyla Bacteroidetes and Verrucomicrobia and genera Akkermansia, Bacteroides and Escherichia, were significantly affected by metformin in several studies.
Abstract: Metformin is a first-line treatment for type 2 diabetes mellitus (T2DM); however, its underlying mechanism is not fully understood. Gut microbiota affect the development and progression of T2DM. In recent years, an increasing number of studies has focused on the relationship between metformin and gut microbiota, suggesting that metformin might exert part of its hypoglycemic effect through these microbes. However, most of these results were not consistent due to the complex composition of the microbiota, the differences between species, the large variation between individuals, and the differences in experimental design, bringing great obstacle for our better understanding of the effects of metformin on the gut microbiota. Here, we reviewed the published papers concerning about the impacts of metformin on the gut microbiota of mice, rats, and humans with obesity or T2DM, and summarized the changes of gut microbiota composition caused by metformin and the possible underlying hypoglycemic mechanism which is related to gut microbiota. It was found that the proportions of some microbiota, such as phyla Bacteroidetes and Verrucomicrobia and genera Akkermansia, Bacteroides and Escherichia, were significantly affected by metformin in several studies. Metformin may exert part of hypoglycemic effects by altering the gut microbiota in ways that maintain the integrity of the intestinal barrier, promote the production of short-chain fatty acids (SCFAs), regulate bile acid metabolism, and improve glucose homeostasis.

75 citations


Journal ArticleDOI
TL;DR: The central principles of the metabolic tests available in order to study glucose and insulin homeostasis in mice are described, focusing on the most widely used – the glucose and diabetes tolerance tests.
Abstract: The epidemic of the century, Diabetes Mellitus (DM) is continuously rising. Intensive research is urgently needed whereby experimental models represent an essential tool to optimise the diagnostic strategy and to improve therapy. In this review, we describe the central principles of the metabolic tests available in order to study glucose and insulin homeostasis in mice, focusing on the most widely used – the glucose and insulin tolerance tests. We provide detailed experimental procedures as well as the practical implementation of these methods and discuss the main factors that should be taken into account when using this methodology.

58 citations


Journal ArticleDOI
TL;DR: Research focused on gaining a better understanding of the dose and duration of treatment with glucocorticoids, which leads to increased triglyceride deposition in the liver, and the reversibility of the condition is highlighted.
Abstract: Glucocorticoids (GCs) are commonly used at high doses and for prolonged periods (weeks to months) in the treatment of a variety of diseases. Among the many side effects are increased insulin resistance with disturbances in glucose/insulin homeostasis and increased deposition of lipids (mostly triglycerides) in the liver. Here, we review the metabolic pathways of lipid deposition and removal from the liver that become altered by excess glucocorticoids. Pathways of lipid deposition stimulated by excess glucocorticoids include 1) increase in appetite and high caloric intake; 2) increased blood glucose levels due to GC-induced stimulation of gluconeogenesis; 3) stimulation of de novo lipogenesis that is augmented by the high glucose and insulin levels and by GC itself; and 4) increased release of free fatty acids from adipose stores and stimulation of their uptake by the liver. Pathways that decrease hepatic lipids affected by glucocorticoids include a modest stimulation of very-low-density lipoprotein synthesis and secretion into the circulation and inhibition of β-oxidation of fatty acids. Role of 11β-hydroxysteroid dehydrogenases-1 and -2 and the reversible conversion of cortisol to cortisone on intracellular levels of cortisol is examined. In addition, GC control of osteocalcin expression and the effect of this bone-derived hormone in increasing insulin sensitivity are discussed. Finally, research focused on gaining a better understanding of the dose and duration of treatment with glucocorticoids, which leads to increased triglyceride deposition in the liver, and the reversibility of the condition is highlighted.

56 citations


Journal ArticleDOI
TL;DR: It is demonstrated that downregulation of KCNQ1OT1 inhibited the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells by up-regulating the expression of miR-506-3p, which provide new insights into the treatment of DN.
Abstract: Background Long noncoding RNAs (lncRNAs) can regulate the progression of DN. This research aimed to study the effect of lncRNA KCNQ1OT1 on the oxidative stress and pyroptosis of the renal tubular epithelial cells induced by high glucose (HG). Methods RT-qPCR analysis detected the KCNQ1OT1 expression in serum with DN and HG-induced HK-2 cells, detect the expression of NLRP3, cleaved-caspase1, P-caspase1, IL-1β, p-IL-1β and GSDMD-N in HG-induced HK-2 cells, and confirm the transfection effects. The expression of NLRP3, cleaved-caspase1, P-caspase1, IL-1β, p-IL-1β and GSDMD-N in HG-induced HK-2 cells was also analyzed by Western blot analysis. ELISA assay detected the levels of TNF-α, IL-6 and MCP-1. The levels of ROS, MDA and SOD were determined by respective ELISA kits and ROS was also detected by the ROS assay kit (containing DCFH-DA). Results We found that KCNQ1OT1 was increased in the plasma of patients with DN and HG-induced HK-2 cells and KCNQ1OT1 interference could decrease the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells. In addition, KCNQ1OT1 directly targets miR-506-3p. MiR-506-3p was downregulated in the plasma of patients with DN and HG-induced HK-2 cells and KCNQ1OT1 interference promoted the expression of miR-506-3p. MiR-506-3p overexpression suppressed the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells. Conclusion This study demonstrated that downregulation of KCNQ1OT1 inhibited the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells by up-regulating the expression of miR-506-3p, which provide new insights into the treatment of DN.

54 citations


Journal ArticleDOI
TL;DR: It is concluded that miRNA-221-3p is one of the high-expressed miRNAs in EPC-derived exosomes and promoted skin wound healing in diabetic mice and provides a potential novel approach to the clinical treatment of diabetic skin wounds.
Abstract: Background Patients with diabetic cutaneous ulcers experience financial burden and a lower quality of life and life expectancy. Endothelial progenitor cell (EPC)-derived exosomes facilitate skin wound healing by positively modulating vascular endothelial cell function. Exosomes play their important regulatory role through microRNA (miRNA). We explored the potential role and molecular mechanisms of miRNA in EPC-derived exosome healing of diabetic skin wounds. Methods Exosomes were isolated from the media of EPCs derived from mice bone marrow. High-throughput sequencing was used to detect the expression of exosome miRNA, and miRNA target genes were predicted using online databases. A diabetic mouse skin wound model was established, and wounds were treated with exosomes, miRNA-221-3p, or phosphate-buffered saline. Results Exosomes from EPCs accelerated skin wound healing in both control and diabetic mice. High-throughput sequencing showed that miRNA-221-3p was highly expressed in EPC-derived exosomes. Skin wound healing in control and diabetic mice was significantly enhanced by EPC-derived exosomes and miRNA-221-3p administration. Immunohistochemical analyses showed that EPC-derived exosomes and miRNA-221-3p increased protein expression levels of the angiogenesis-related factors VEGF, CD31 and cell proliferation marker Ki67. Bioinformatics analyses indicated that miRNA-221-3p may be involved in the AGE-RAGE signaling pathway in diabetic complications, cell cycle, and the p53 signaling pathway. Conclusion We concluded that miRNA-221-3p is one of the high-expressed miRNAs in EPC-derived exosomes and promoted skin wound healing in diabetic mice. The finding uncovers the molecular mechanism of EPC-derived exosomes and provides a potential novel approach to the clinical treatment of diabetic skin wounds.

52 citations


Journal ArticleDOI
TL;DR: Measurement of the 1‐h PG level could increase the likelihood of identifying high-risk individuals when the pancreatic ß-cell function is substantially more intact with the added practical advantage of potentially replacing the conventional 2‐h OGTT making it more acceptable in the clinical setting.
Abstract: For over 100 years, the oral glucose tolerance test (OGTT) has been the cornerstone for detecting prediabetes and type 2 diabetes (T2DM). In recent decades, controversies have arisen identifying internationally acceptable cut points using fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and/or HbA1c for defining intermediate hyperglycemia (prediabetes). Despite this, there has been a steadfast global consensus of the 2-h PG for defining dysglycemic states during the OGTT. This article reviews the history of the OGTT and recent advances in its application, including the glucose challenge test and mathematical modeling for determining the shape of the glucose curve. Pitfalls of the FPG, 2-h PG during the OGTT, and HbA1c are considered as well. Finally, the associations between the 30-minute and 1-hour plasma glucose (1-h PG) levels derived from the OGTT and incidence of diabetes and its complications will be reviewed. The considerable evidence base supports modifying current screening and diagnostic recommendations with the use of the 1-h PG. Measurement of the 1-h PG level could increase the likelihood of identifying high-risk individuals when the pancreatic s-cell function is substantially more intact with the added practical advantage of potentially replacing the conventional 2-h OGTT making it more acceptable in the clinical setting.

47 citations


Journal ArticleDOI
TL;DR: Targeting TXNIP is found to be relevant as a unique therapeutic opportunity, not only to improve insulin secretion and sensitivity, but also ameliorating the long term microvascular and macrovascular complications of the disease.
Abstract: Diabetes mellitus (DM) is a common metabolic disorder which is characterized by a persistent increment of blood glucose. Globally, DM affects millions of people and the prevalence is increasing alarmingly. The critical step in the pathophysiology of DM is the loss of β-cells of the pancreas, which are responsible for the secretion of insulin. Thioredoxin-interacting protein (TXNIP) is among the factors that control the production and loss of the pancreatic β-cells. TXNIP is an α-arrestin that can bind and inhibit thioredoxin (the antioxidant protein) which is produced in the pancreatic islet after glucose intake. Numerous studies illustrated that elevated TXNIP levels were found to induce β-cell apoptosis; whereas TXNIP deficiency protects against type I and type II diabetes by promoting β-cell survival. Nowadays, TXNIP depletion is becoming a key factor in pancreatic β-cell survival enhancement. In the present review, targeting TXNIP is found to be relevant as a unique therapeutic opportunity, not only to improve insulin secretion and sensitivity, but also ameliorating the long term microvascular and macrovascular complications of the disease. Thus, TXNIP inhibitors that could reduce the expression and/or activity of TXNIP to non-diabetic levels are promising agents to halt the alarming rate of diabetes and its related complications.

46 citations


Journal ArticleDOI
TL;DR: The purpose of this review is to provide a comprehensive analysis of the disease, by describing the burden of knowledge that has been obtained in the 50 years following its first description, took in 1970, and by highlighting the points that are still unclear in its pathogenesis and management.
Abstract: Insulin autoimmune syndrome (IAS), also named Hirata's disease, is a rare condition characterized by hypoglycemic episodes due to the presence of high titers of insulin autoantibodies (IAA). IAS is a form of immune-mediated hypoglycemia, which develops when a triggering factor (ie, a medication or a viral infection) acts on an underlying predisposing genetic background. IAS pathogenesis involves the formation of insulin-IAA complexes that induce glycemic alterations with a double-phase mechanism: IAA prevent insulin to bind its receptor in the postprandial phase, possibly resulting in mild hyperglycemia; thereafter, insulin is released from the complexes irrespective of blood glucose concentrations, thus inducing hypoglycemia. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. The gold standard for the definitive diagnosis is the finding of IAA in a blood sample. Because IAS is frequently a self-remitting disease, its management mostly consists of supportive measures, such as dietary modifications, aimed at preventing the development of hypoglycemia. Pharmacological therapies may occasionally be necessary for patients presenting with severe manifestations of IAS. Available therapies may include drugs that reduce pancreatic insulin secretion (somatostatin analogues and diazoxide, for instance) and immunosuppressive agents (glucocorticoids, azathioprine and rituximab). The purpose of this review is to provide a comprehensive analysis of the disease, by describing the burden of knowledge that has been obtained in the 50 years following its first description, took in 1970, and by highlighting the points that are still unclear in its pathogenesis and management.

46 citations


Journal ArticleDOI
TL;DR: The prevalence of hypertension is high and the majority have poor blood pressure control, hence, DM care providers and other health sector stakeholders have to work in collaboration to prevent it through designing appropriate strategies especially for those at higher risk of developing hypertension.
Abstract: Background Type 2 diabetes mellitus (T2DM) is associated with a high risk of early mortality and morbidity from hypertension. Even though Ethiopia is Africa's first country among the top five in the prevalence of DM, there is a paucity of data on hypertension and its associated factors among patients with type 2 diabetes mellitus. Therefore, this study aimed to determine the prevalence and associated factors of hypertension among type 2 diabetes mellitus patients at Debre Tabor General Hospital, 2019. Methods and materials An institution-based cross-sectional study was employed on 378 T2DM patients. Data were collected using an interviewer-administered questionnaire and analyzed by Stata 14. A multivariable logistic regression model was used to identify associated factors of hypertension among T2DM patients. Associated factors were declared at p Results The prevalence of hypertension among T2DM patients was 59.5% (95% CI: 54.5-64.5). Stage 1 hypertension was the most common (30.95%). The odds of hypertension was higher among age group of 50-60 years (adjusted odds ratio (AOR)=2.5, 95% confidence interval (CI) (1.27-4.90)), patients from urban area (AOR = 2.8, 95% CI (1.08-7.18)), with longer duration of T2DM (AOR =1.16, 95% CI (1.08-1.25)), with BMI ≥25 kg/m2 (AOR = 3.2, 95% CI (1.71-5.96)), with poor glycemic control (AOR = 3.0, 95% CI (1.75-5.19)), and patients who were current cigarette smokers (AOR = 3.8, 95% CI (1.98-14.96)). Conclusion The prevalence of hypertension is high and the majority have poor blood pressure control. Hence, DM care providers and other health sector stakeholders have to work in collaboration to prevent it through designing appropriate strategies especially for those at higher risk of developing hypertension.

Journal ArticleDOI
TL;DR: The main factors include high BMI, smoking, lack of diabetes control, type of diabetes treatment and older age, and there were other factors that affect severity of DFU such as vascular complications, bacteria isolated, marital status, gender, high levels of cholesterol and triglycerides.
Abstract: Background Diabetic foot ulcer (DFU) is one of the diabetes complications. DFU can be the cause of a high rate of amputation, health-care costs and even death, and this condition occurs in the severity status of DFU. Severity of DFU is the cause of expensive complication incidence. Understanding the factors affecting it can help preventive functions. Adequate evidence for this problem is necessary. The aim of this systematic review is to summarize evidence on severity of diabetic foot ulcer. Methods A literature search was undertaken in Scopus, Pub Med, Elsevier, MEDLINE, Embase, Up To Date and Google Scholar. Observational studies that assessed severity of DFU were included. The data extraction and assessment are on the basis of PRISMA. Results Seven studies were assessed and 25 factors that affect severity of DFU are reported in the studies. The most used score for an estimate of severity was the Wagner scale (n=5). The majority of patients were in G1 and G2 stages (67.5%; basis of Wagner) or have a superficial ulcer (62.84%) on the basis of the Texas Diabetic Wound Classification System. The main factors include high BMI, smoking, lack of diabetes control, type of diabetes treatment and older age. In addition, there were other factors that affect severity of DFU such as vascular complications, bacteria isolated, marital status, gender, high levels of cholesterol and triglycerides. Also, life location, type 2 diabetes, genotype, addiction, long-time DFU and delay to refer patients were other factors. Conclusion Twenty-five factors were reported. The majority of these factors related to life-style and can be prevented by self-care functions. The effect of these factors needs further study and the further studies must be better in quality.

Journal ArticleDOI
Yi Zhou1
TL;DR: The blood glucose level, iron content, accumulation of lipid peroxides and islet injury in diabetic model were all improved by CCA via a concentration-dependent manner, so it may be a promising agent for diabetes therapy, providing a new avenue for diabetes treatment.
Abstract: Purpose Mulberry leaf extract has exerted better antidiabetic activities, while the effects of major active components in mulberry leaf extract are still unclear. Cryptochlorogenic acid (CCA) as the major active component in mulberry leaf extracts was investigated herein. Materials and methods Rats were treated with 50mg/kg streptozotocin for the establishment of diabetic model in vivo, and cells were treated with 33.3 mM glucose for the establishment of cell model in vitro. HE staining assay was performed for observation of pancreatic pathology and aldehyde fuchsin staining assay for examining islet cell numbers. The iron content was detected via Perls staining assay with iron assay kit (ab83366). The malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG) were detected by corresponding kits. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed for assessment of gene level and Western blot for measurement of protein expression level. The cell survival was detected via CCK-8 assay. Results The blood glucose level, iron content, accumulation of lipid peroxides and islet injury in diabetic model were all improved by CCA via a concentration-dependent manner. CCA functions via inhibition of ferroptosis by activation of cystine/glutamate transporter system (XC-)/glutathione peroxidase 4(GPX4)/Nrf2 and inhibition of nuclear receptor coactivator 4 (NCOA4) in diabetes. Conclusion CCA exerted excellent antidiabetic effects via inhibition of ferroptosis, so it may be a promising agent for diabetes therapy, providing a new avenue for diabetes treatment.

Journal ArticleDOI
TL;DR: A randomized, double-blinded, placebo-controlled trial in 60 subjects with metabolic syndrome was conducted in this article, where 60 subjects were randomized to either placebo or high-concentration molecular hydrogen (H2)-rich water (HRW) for 24 weeks.
Abstract: Purpose Metabolic syndrome is associated with several medical risk factors including dyslipidemia, hyperglycemia, and obesity, which has become a worldwide pandemic. The sequelae of this condition increase the risk of cardiovascular and neurological disease and increased mortality. Its pathophysiology is associated with redox dysregulation, excessive inflammation, and perturbation of cellular homeostasis. Molecular hydrogen (H2) may attenuate oxidative stress, improve cellular function, and reduce chronic inflammation. Pre-clinical and clinical studies have shown promising effects of H2-rich water (HRW) on specific features of metabolic syndrome, yet the effects of long-term, high-concentration HRW in this prevalent condition remain poorly addressed. Methods We conducted a randomized, double-blinded, placebo-controlled trial in 60 subjects (30 men and 30 women) with metabolic syndrome. An initial observation period of one week was used to acquire baseline clinical data followed by randomization to either placebo or high-concentration HRW (> 5.5 millimoles of H2 per day) for 24 weeks. Results Supplementation with high-concentration HRW significantly reduced blood cholesterol and glucose levels, attenuated serum hemoglobin A1c, and improved biomarkers of inflammation and redox homeostasis as compared to placebo (P < 0.05). Furthermore, H2 tended to promote a mild reduction in body mass index and waist-to-hip ratio. Conclusion Our results give further credence that high-concentration HRW might have promising effects as a therapeutic modality for attenuating risk factors of metabolic syndrome.

Journal ArticleDOI
TL;DR: DSME programs are highly effective inimproving glycemic control, lipid profile and BMI, and modestly effective in improving BP, and can reduce the risks of developing diabetes complications.
Abstract: Aim This review study aimed to determine the effectiveness and factors affecting the success of DSME programs in T2DM patients living in ME countries. Methods An extensive manual literature search was conducted using PubMed and Google Scholar for clinical trials assessing the effect of diabetes self-management education (DSME) for type 2 diabetes mellitus patients in Middle East countries. Information from the included studies was summarized in relation to study population, sample size, duration of follow-up, characteristics of DSME program, and follow-up time, besides in addition to parameters used in assessment, results, and conclusions. The risk of bias in the included studies was assessed using the Cochrane risk of bias tool. The effect of DSME on clinical and patient-reported outcomes was measured by calculation of the percentage of DSME studies that produce a significant improvement in these outcomes for patients in intervention group as compared to those in control group. Additionally, the effect of DSME on each clinical outcome was assessed by calculating the mean for the absolute effect of DSME on that outcome. Results Twelve studies were included in this review. Heterogeneity was found among included studies in terms of DSME program characteristics, the enrolled patients, duration of follow-up, assessment methods, and obtained outcomes. All clinical glycemic outcomes (glycosylated hemoglobin, fasting, and non-fasting blood glucose), lipid profile (total cholesterol and triglycerides), and body mass index were significantly improved for patients in intervention group as compared to those in control group in at least 60% of the included studies. All patients' reported outcomes (medication adherence, self-management behavior, knowledge, self-efficacy, health belief and quality of life) were significantly improved by the DSME program. Conclusion DSME programs are highly effective in improving glycemic control, lipid profile and BMI, and modestly effective in improving BP. Thus, they can reduce the risks of developing diabetes complications. Patient diabetes knowledge, DSM behaviors, adherence to medications, self-efficacy, and quality of life can also be significantly improved by DSME.

Journal ArticleDOI
TL;DR: The results suggest that plant-based diets may improve weight status in some patient groups, and should aim to include a representative study population and apply study diets without dietary restrictions.
Abstract: There is an increasing number of people who convert to a plant-based diet. The desire for health benefits, including weight management, is often a contributing factor behind this dietary choice. The purpose of this review was to evaluate intervention studies assessing the effects of different plant-based diets on body mass index and weight. A literature search was conducted in PubMed until December 2019. Twenty-two publications from 19 studies were included. The majority of them were randomized controlled trials comparing a low-fat vegan diet to an omnivore diet in participants with overweight, type 2 diabetes mellitus and/or cardiovascular disease. All studies reported weight reductions, of which seven revealed significant differences, and four revealed non-significant differences between the intervention and the control groups. The results suggest that plant-based diets may improve weight status in some patient groups. Due to restrictions in fat intake in many studies, followed by reduced energy intake, the effects of the different interventions differ depending on the specific plant-based diets investigated. Future research should aim to include a representative study population and apply study diets without dietary restrictions.

Journal ArticleDOI
Min Gong1, Song Wen1, Thiquynhnga Nguyen1, Chaoxun Wang1, Jianlan Jin1, Ligang Zhou1 
TL;DR: The metabolic relationships between obesity and hyperuricemia in terms of pathophysiology, complications, and treatments are delineated, and the therapeutic targets for the management of metabolic syndromes are provided.
Abstract: Background Obesity and hyperuricemia mutually influence metabolic syndrome. This study discusses the metabolic relationships between obesity and hyperuricemia in terms of pathophysiology, complications, and treatments. Methods We searched for preclinical or clinical studies on the pathophysiology, complications, and therapy of obesity and hyperuricemia on the PubMed database. Results In this systemic review, we summarized our searching results on topics of pathophysiology, complications and therapeutic strategy. In pathophysiology, we firstly introduce genetic variations for obesity, hyperuricemia and their relationships by genetic studies. Secondly, we talk about the epigenetic influences on obesity and hyperuricemia. Thirdly, we describe the central metabolic regulation and the role of hyperuricemia. Then, we refer to the character of adipose tissue inflammation and oxidative stress in the obesity and hyperuricemia. In the last part of this topic, we reviewed the critical links of gut microbiota in the obesity and hyperuricemia. In the following part, we review the pathophysiology of major complications in obesity and hyperuricemia including insulin resistance and type 2 diabetes mellitus, chronic kidney disease, cardiovascular diseases, and cancers. Finally, we recapitulate the therapeutic strategies especially the novel pharmaceutic interventions for obesity and hyperuricemia, which concurrently show the mutual metabolic influences between two diseases. Conclusion The data reviewed here delineate the metabolic relationships between obesity and hyperuricemia, and provide a comprehensive overview of the therapeutic targets for the management of metabolic syndromes.

Journal ArticleDOI
TL;DR: It is demonstrated that SGLT-2 is expressed in CNS tissues involved in autonomic control and possibly influence cardiovascular function, and Dapagliflozin influences central autonomic activity via unidentified pathways by inhibiting central or peripheral SGLt-2.
Abstract: Purpose This study investigates the possible effect and central mechanism of novel antidiabetic medication sodium glucose transporter-2 (SGLT-2i) on the cardiovascular activity. Material and methods Thirty-four normal male C57BL/6 mice were randomly assigned to 2 groups to receive single Dapagliflozin (1.52mg/kg) dose via intragastric gavage or a comparable dose of saline. Glycemic level (BG), blood pressure (BP) and heart rate (HR) were measured 2 hours after administration of the respective treatments. Immunohistochemical tests were performed to determine the effect of SGLT-2i on neural localization of SGLT-2 and c-Fos, a neural activator. The distributional relationships of SGLT-2 and c-Fos were examined by immunofluorescence. Results Administration of SGLT-2i significantly decreased BP but did not affect the HR. There was no difference in BG between the two groups. Results showed that SGLT-2 was localized to specific regions involved in autonomic control. Expression of c-Fos was significantly higher in major critical nuclei in the aforementioned regions in groups treated with Dapagliflozin. Conclusion This study demonstrates that SGLT-2 is expressed in CNS tissues involved in autonomic control and possibly influence cardiovascular function. Dapagliflozin influences central autonomic activity via unidentified pathways by inhibiting central or peripheral SGLT-2. These results provide a new concept that sympathetic inhibition by SGLT-2i can be mediated by central autonomic system, a mechanism that explains how SGLT-2i improves the cardiovascular function.

Journal ArticleDOI
Jia Feng1, Shiyin Lu1, Biqian Ou1, Qian Liu1, Jiaxin Dai1, Chunyan Ji1, Haiqing Zhou1, Hongke Huang1, Yi Ma1 
TL;DR: An overview of the composition of the JNK signaling pathways, its regulation of insulin signaling pathway, and the relationship between the J NK signaling pathway and other pathways in insulin resistance is provided.
Abstract: Obesity is not only closely related to insulin resistance but is one of the main factors leading to the formation of Type 2 Diabetes (T2D) too. The c-Jun N-terminal kinase (JNK) family is a member of the mitogen-activated protein kinase (MAPK) superfamily. JNK is also one of the most investigated signal transducers in obesity and insulin resistance. JNK-centric JNK signaling pathway can be activated by growth factors, cytokines, stress responses, and other factors. Many researches have identified that the activated phosphorylation JNK negatively regulates insulin signaling pathway in insulin resistance which can be simultaneously regulated by multiple signaling pathways related to the JNK signaling pathway. In this review, we provide an overview of the composition of the JNK signaling pathway, its regulation of insulin signaling pathway, and the relationship between the JNK signaling pathway and other pathways in insulin resistance.

Journal ArticleDOI
Chunhong Shi1, Haili Zhu, Jun Liu, Jian Zhou, Weihong Tang 
TL;DR: Perceived barriers to diabetes self-management described by diabetes patients indicated a lack of environmental resources and support strategies to meet their needs, which is important in assisting patients with diabetes to improve their quality of life and health outcomes.
Abstract: Purpose Diabetes self-management behaviors are necessary to obtain optimum glycemic control, reduce the risk of complications, and improve health outcomes. The COVID-19 pandemic imposes an additional struggle for self-management by diabetes patients. Although previous studies have reported socio-demographic, behavioral, psychological, and cultural barriers to diabetes self-management, little is known about perceived barriers to diabetes self-management among patients during isolation following their recovery from COVID-19. The purpose of this study was to explore perceived barriers among type 2 diabetes patients during isolation following their recovery from COVID-19. Patients and methods A qualitative, exploratory, and descriptive research design was utilized. Semi-structured telephonic interviews were conducted with 12 patients with diabetes who had been discharged from one COVID-19 designated hospital and underwent isolation in the designated facilities in Wuhan City, Hubei Province, China. Data were analyzed using Colaizzi's seven steps. Results Barriers to diabetes self-management identified by patients with diabetes during isolation were categorized into five major themes: inadequate knowledge and behavioral beliefs, shortage of resources, suffering from health problems, negative emotions, and lack of support. Conclusion Perceived barriers to diabetes self-management described by diabetes patients indicated a lack of environmental resources and support strategies to meet their needs. Efforts to remove barriers are important in assisting patients with diabetes to improve their quality of life and health outcomes.

Journal ArticleDOI
TL;DR: Although VAI might not be very cost-beneficial compared to IDF, the study showed VAI is a better predictor of MetS than BRI in adults and ABSI was not a suitable predictor for MetS.
Abstract: Background The use of anthropometric indices is one of the new and low-cost diagnostic methods of metabolic syndrome (MetS). The present study aimed to determine optimal cutoff points for the visceral adiposity index (VAI), body roundness index (BRI), and a body shape index (ABSI) in the prediction of MetS. Methods This cross-sectional study was performed on 10,000 individuals aged from 35 to 65 years, recruited in Ravansar Non-Communicable Diseases (RaNCD) cohort study, in the west region of Iran, in 2019. MetS was defined according to International Diabetes Federation (IDF) criteria. The receiver operating characteristic (ROC) curve analysis was used to assess predictive anthropometric indices and determine optimal cutoff values. Results The optimal cutoff points for VAI were 4.11 (AUC: 0.82; 95% CI: 0.81-0.84) in men and 4.28 (AUC: 0.86; 95% CI: 0.85-0.87) in women to prediction of MetS. The optimal cutoff points for BRI were 4.75 (AUC: 0.75; 95% CI: 0.74-0.77) in men and 6.17 (AUC: 0.62; 95% CI: 0.61-0.64) in women to prediction of MetS. The optimal cutoff points for ABSI were 0.12 (AUC: 0.49; 95% CI: 0.47-0.51) in men and 0.13 (AUC: 0.49; 95% CI: 0.47-0.51) in women to prediction of MetS. The risk of MetS in men and women with a VAI higher than the optimal cutoff point was, respectively, 9.82 and 11.44 times higher than that in those with a VAI lower than the cutoff point. Conclusion Although VAI might not be very cost-beneficial compared to IDF, our study showed VAI is a better predictor of MetS than BRI in adults. ABSI was not a suitable predictor for MetS.

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TL;DR: Curcumin significantly decreased the progress of DN possibly via increasing autophagy and inhibiting apoptosis of renal cell in DN mice and showed that curcumin exerted significantly protective effects in DN.
Abstract: Introduction Curcumin has various biological properties including being anti-inflammatory and antidiabetic. Podocyte apoptosis and autophagy dysfunction have been found to be responsible for the development of diabetic nephropathy (DN). Thus, the aim of the study was to investigate the effects of curcumin on the podocyte apoptosis and autophagy in DN and clarify its potential mechanisms. Methods The mice with DN induced by injection of streptozotocin were treated with curcumin by gavage at a dose of 200 mg/kg/day for 8 weeks. The serum lipid levels were detected by total cholesterol (TC) and triglyceride (TG) kits at different time points. Renal damage was assessed by detecting urine albumin, serum creatinine (Scr), HE staining and PAS staining. The renal impairment was detected by immunohistochemical staining and TUNEL staining. Western blot assay tested the expression of autophagy-related and apoptotic-related proteins in vivo and vitro. The viabilities and apoptosis of MPC5 cells exposed to high glucose (HG) or curcumin were respectively detected by CCK-8 assay and flow cytometry. Results The results showed that curcumin significantly decreased the progress of DN possibly via increasing autophagy and inhibiting apoptosis of renal cell in DN mice. Besides, podocyte marker proteins (podocalyxin and nephrin) were markedly increased in DN mice by curcumin treatment. The autophagy-related proteins LC3, p62, Beclin1, UVRAG and ATG5 were significantly affected in DN mice by curcumin, along with reducing expression of pro-apoptotic protein Bax and caspase-3 and increasing anti-apoptotic protein Bcl-2. In vitro, curcumin increased the viabilities and inhibited apoptosis of MPC5 cells exposed to high glucose (HG). In addition, the podocyte autophagy was enhanced partly via regulating beclin1/UVRAG. Discussion Together, the results showed that curcumin inhibited podocyte apoptosis and accelerated cell autophagy via regulating Beclin1/UVRAG/Bcl2. Thus, the study showed that curcumin exerted significantly protective effects in DN.

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TL;DR: Preliminary data on the use of glucagon-like peptide 1 receptor agonists (GLP1 Ras) and sodium-glucose co-transporter 2 (SGLT2) inhibitors in cases of FPLD have shown promising results with reduction in total insulin requirements and improvement in glycemic control.
Abstract: Lipodystrophies are a heterogeneous group of congenital or acquired disorders, characterized by partial or generalized loss of adipose tissue. Familial partial lipodystrophy (FPLD) presents with genetic and phenotypic variability with insulin resistance, hypertriglyceridemia and hepatic steatosis being the cardinal metabolic features. The severity of the metabolic derangements is in proportion with the degree of lipoatrophy. The underpinning pathogenetic mechanism is the limited capacity of adipose tissue to store lipids leading to lipotoxicity, low-grade inflammation, altered adipokine secretion and ectopic fat tissue accumulation. Advances in molecular genetics have led to the discovery of new genes and improved our knowledge of the regulation of adipose tissue biology. Diagnosis relies predominantly on clinical findings, such as abnormal fat tissue topography and signs of insulin resistance and is confirmed by genetic analysis. In addition to anthropometry and conventional imaging, new techniques such as color-coded imaging of fat depots allow more accurate assessment of the regional fat distribution and differentiation of lipodystrophic syndromes from common metabolic syndrome phenotype. The treatment of patients with lipodystrophy has proven to be challenging. The use of a human leptin analogue, metreleptin, has recently been approved in the management of FPLD with evidence suggesting improved metabolic profile, satiety, reproductive function and self-perception. Preliminary data on the use of glucagon-like peptide 1 receptor agonists (GLP1 Ras) and sodium-glucose co-transporter 2 (SGLT2) inhibitors in cases of FPLD have shown promising results with reduction in total insulin requirements and improvement in glycemic control. Finally, investigational trials for new therapeutic agents in the management of FPLD are underway.

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TL;DR: Evidence of the effects of topical insulin on wound healing, including on diabetic and non-diabetic wounds, is reviewed to support that topical insulin improves wound healing through several mechanisms without causing side effects.
Abstract: Wound healing is a complex biological process that repairs damaged tissues and restores skin integrity. Insulin, a potent factor of wound healing, has been reported for nearly a century to induce rapid recovery of various wounds, as shown by numerous human and animal studies. Although many studies have addressed the healing effect of systemic insulin on burn wound, only few have investigated the efficacy of topical insulin. Thus, this study aimed to review evidence of the effects of topical insulin on wound healing, including on diabetic and non-diabetic wounds. The presented animal and clinical studies support that topical insulin improves wound healing through several mechanisms without causing side effects. Additionally, various wound dressings accelerate the wound healing with controlled and sustained delivery of bioactive insulin. Therefore, topical insulin has been appreciated in field of wound healing, and further studies are needed to improve our understanding of the role of insulin in the healing of various wounds.

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TL;DR: The 8-week synbiotic supplementation in T1DM patients may be effective in improvement of FBG, HbA1c, insulin, hs-CRP, and TAC.
Abstract: Background and Objective The aim of the present study was to evaluate the effects of synbiotic on glycemic status, lipid profile, and biomarkers of oxidative stress in type 1 diabetes mellitus (T1DM) patients. Materials and Methods In this double-blind clinical trial, 50 T1DM patients were randomly allocated to intervention (n = 25) and control (n = 25) groups and received either synbiotic powder (Lactobacillus sporogenes GBI-30 (probiotic), maltodextrin and fructooligosaccharide (prebiotic)) or placebo 2 g per day for 8 weeks. Fasting blood samples were collected before and after the intervention to measure fasting blood glucose (FBG), insulin concentration, hemoglobin A1c (HbA1c), lipid profile, and biomarkers of oxidative stress such as total antioxidant capacity (TAC) and hs-C-reactive protein (hs-CRP). Results Supplementation with synbiotic resulted in a significant decrease in the mean serum levels of HbA1c and hs-CRP (p = 0.01 and p = 0.004, respectively), and marginally significant decrease in FBG (p = 0.05) in the intervention group post- intervention. Also, the mean changes of FBG and hs-CRP were significantly lower in the intervention group compared with the control group (p = 0.03 and p = 0.005, respectively). There were no significant changes found in lipid profile in intervention group post-intervention (p≥ 0.05). The mean serum levels of insulin and TAC were significantly increased in the intervention group post-intervention (p = 0.001). There was a significant increase in the mean changes of TAC (p = 0.005) in the intervention group compared with the control group. Conclusion The 8-week synbiotic supplementation in T1DM patients may be effective in improvement of FBG, HbA1c, insulin, hs-CRP, and TAC.

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TL;DR: Twelve potential biomarkers of intestinal microbial flora and 357 differential metabolites were found in ZDF fa/fa rats, among which there are three flora that contributed the most to the perturbation of metabolites, including genus Phocea, Pseudoflavonifractor and species Lactobacillus intestinalis.
Abstract: Purpose The purpose of this study was to explore the difference and association between intestinal microbiota and plasma metabolomics between type 2 diabetes mellitus (T2DM) and normal group and to identify potential microbiota biomarkers that contribute the most to the difference in metabolites. Methods Six male ZDF model (fa/fa) rats were fed by a Purina #5008 Lab Diet (crude protein 23.5%, crude fat 6.5%) for 3 weeks and their age-matched 6 ZDF control (fa/+) rats were fed by normal rodent diet. Their stool and blood samples were collected at 12 weeks. To analyze the microbial populations in these samples, we used a 16S rRNA gene sequencing approach. Liquid chromatography-mass spectrometry (LC-MS) followed by multivariate statistical analysis was applied to the plasma metabolites profiling. Correlation analysis of them was calculated by Pearson statistical method. Results Twelve potential biomarkers of intestinal microbial flora and 357 differential metabolites were found in ZDF fa/fa rats, among which there are three flora that contributed the most to the perturbation of metabolites, including genus Phocea, Pseudoflavonifractor and species Lactobacillus intestinalis. Conclusion Our study demonstrates the alterations of the abundance and diversity of the intestinal microbiota and the perturbation of metabolites in ZDF rats (fa/fa). We found three potential biomarkers of intestinal microbiota that may lead to perturbation in plasma metabolites. This may prompt new pathogenesis of obesity-related T2DM, but we also need to study further about the causal relationship between intestinal microbe and T2DM, so as to find the target of T2DM treatment or preventive measures.

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TL;DR: Hematological parameters showed the correlation with the occurrence of MetS and LHR and NHR may become valuable makers and have strong predictive power for predicting MetS, especially in females.
Abstract: Background This study aimed to determine the optimal cutoff values and evaluate the associations of neutrophil to high-density lipoprotein cholesterol ratio (NHR) and lymphocyte to high-density lipoprotein cholesterol ratio (LHR) with metabolic syndrome (MetS), stratified by sex. Methods A large-scale cross-sectional survey was conducted among 1401 adults from January to April 2018 in six communities in Wanzhai Town, Zhuhai City, on the southern coast of China. Receiver operating characteristics (ROC) analyses and logistic regression analysis were conducted to assess the optimal cutoff and value of NHR and LHR for predicting MetS. Results Hematological parameters showed the correlation with the occurrence of MetS (red blood cells, hemoglobin, and white blood cells and subtypes). Binomial logistic regression analysis found that LHR (OR: 3.671; 95% CI: 2.385-5.651; p<0.001) and NHR (OR: 1.728; 95% CI: 1.353-2.207; p<0.001) can predict MetS in females, independent of confounding factors. Although LHR (OR: 1.571; 95% CI: 1.001-2.468; p=0.05) and NHR (OR: 1.163; 95% CI: 0.909-1.48; p<0.01) were independent risk factors for MetS in males after adjustment for age, current smoking, current alcohol use, physical activity, educational attainment, waist circumference, systolic pressure, diastolic pressure and hypersensitive C-reactive protein (hs-CRP), when further adjusted for fasting plasma glucose level, LHR and NHR, both lost their independence. ROC curves showed that LHR had the highest AUC for predicting MetS in females and NHR had the highest AUC in males. The cutoff points of LHR and NHR were 1.36 and 2.31 in females, and 1.96 and 3.38 in males. Conclusion LHR and NHR may become valuable makers and have strong predictive power for predicting MetS, especially in females.

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TL;DR: Current perspectives on BED in the context of T2DM with implications for screening and management of these highly comorbid conditions are discussed.
Abstract: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of disordered eating behaviors including binge eating disorder (BED). Comorbid BED in patients with T2DM has been associated with adverse clinical outcomes such as higher body mass index (BMI) and depressive symptoms. Identifying and addressing this disorder in patients with T2DM is a significant challenge for health-care providers. The purpose of this narrative review is to discuss current perspectives on BED in the context of T2DM with implications for screening and management of these highly comorbid conditions. BED continues to be underrecognized and underdiagnosed. However, there are established tools that providers can use to screen for BED such as the SCOFF Questionnaire and Questionnaire on Eating and Weight Patterns-5. There are several effective treatments for BED including cognitive behavioral therapy, interpersonal therapy, and lisdexamfetamine dimesylate. However, few studies have examined the effects of these treatments in patients with co-morbid T2DM and BED.

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TL;DR: H. pylori positivity, total cholesterol, degree of fatty liver by ultrasound, fasting blood sugar and diastolic blood pressure were independent risk factors for NAFLD and correlated with increased degree of steatosis.
Abstract: Background Non-alcoholic fatty liver disease (NAFLD) is a very common disease that affects 25-30% of the population in western countries. Many studies have observed the importance of H. pylori infection in the development of insulin resistance, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and liver fibrosis and cirrhosis. However, the evidence from different studies was controversial. The present study aimed to investigate the relationship between H. pylori infection and NAFLD in a developing country. Patients and methods This cross-sectional study included all the attending outpatient clinics at four Major University hospitals and two research and clinical institutes in a developing country in the period between June and October 2019. Patients were assessed for the diagnosis of H. pylori infection as detected by H. pylori antigen in stool; they were also assessed for the diagnosis of NAFLD by ultrasound, fibroscan, and CAP. Results The study was conducted on 646 patients; H. pylori infection was found to be present in 538 patients (83.3%). NAFLD (diagnosed by both U/S and Fibroscan with CAP), ALT, AST, hepatomegaly, hypertension, fasting blood sugar were significantly higher in H. pylori +ve group than H. pylori -ve group. After performing Linear regression of independent risk factors of NAFLD to prove or to refute the role of Helicobacter; H. pylori positivity, total cholesterol, degree of fatty liver by ultrasound, fasting blood sugar and diastolic blood pressure were independent risk factors for NAFLD. Conclusion Helicobacter pylori infection was independent risk factors for NAFLD and correlated with increased degree of steatosis.

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TL;DR: Evidence on reach, effectiveness, and sustainability of the NDPP is summarized, while highlighting opportunities to overcome challenges in these areas and revisiting pay-for-performance reimbursement models may be critical to sustainability.
Abstract: To address the public health and economic burden of type 2 diabetes, the Centers for Disease Control and Prevention (CDC) began dissemination of the National Diabetes Prevention Program (NDPP) in the United States in 2010. Based on the intensive lifestyle intervention from a large efficacy trial, the NDPP aims to reduce incidence through lifestyle change and weight loss. This narrative review summarizes evidence on reach, effectiveness, and sustainability of the NDPP, while highlighting opportunities to overcome challenges in these areas. Major successes include reaching hundreds of thousands of at-risk individuals across the nation, with notable effectiveness upon full participation and widespread insurance coverage. Yet, more work is needed to ensure greater public health impact, particularly among priority populations at heightened risk who also experience disparities in program outcomes. Preliminary evidence suggests a number of strategies may improve reach and effectiveness of the NDPP, often with more rigorous study needed prior to widespread uptake. Updating the NDPP to better match the current evidence-base may also be important, such as directly targeting glycemia with a patient-centered approach and promoting metformin as an adjunct or second-line treatment. Finally, revisiting pay-for-performance reimbursement models may be critical to sustainability by ensuring adequate availability of suppliers and ultimately reducing diabetes prevalence.