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Introduction: Topical corticosteroids (TCS), used to treat atopic dermatitis (AD), have been associated with type 2 diabetes and osteoporosis in epidemiological studies, possibly explained by systemic absorption., Objectives: We examined whether intensive daily whole-body TCS treatment over 2 weeks followed by twice weekly application for 4 weeks could elicit insulin resistance and increase bone resorption in adults with AD., Methods: A randomized parallel-group double-blind double-dummy non-corticosteroid-based active comparator study design was completed in Copenhagen, Denmark. Thirty-six non-obese, non-diabetic adults with moderate-to-severe AD were randomized to whole-body treatment with betamethasone 17-valerate 0.1% plus a vehicle once daily or tacrolimus 0.1% twice daily after washout. Insulin sensitivity assessed by the hyperinsulinemic-euglycemic clamp combined with tracer infusions and biomarkers of bone formation (P1NP) and resorption (CTX) were evaluated at baseline, after 2 weeks of daily treatment and after further 4 weeks of twice-weekly maintenance treatment., Results: AD severity improved with both treatments and systemic inflammation was reduced. After 2 weeks, we observed similar increase in peripheral insulin sensitivity with use of betamethasone (n = 18) and tacrolimus (n = 18). Bone resorption biomarker, CTX, was unchanged, while bone formation marker, P1NP, decreased after betamethasone treatment after both 2 and 6 weeks but remained unchanged in the tacrolimus arm., Conclusions: Whole-body treatment with TCS leads to systemic exposure but appears not to compromise glucose metabolism during short-term use, which may be a result of reduced systemic inflammatory activity. The negative impact on bone formation could be regarded an adverse effect of TCS., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Acanthosis nigricans is associated with numerous systemic disorders. These include endocrinological conditions such as, diabetes, acromegaly, Cushing's syndrome, thyroid dysfunction, as well as metabolic abnormalities like obesity and polycystic ovarian disease. Its association with visceral malignancy is known. Moreover, Acanthosis nigricans is known to be a cutaneous marker of insulin resistance (IR) and hyperinsulinemia. The primary aim of this study was to study clinical and histopathological patterns of acanthosis nigricans and its correlation with dermoscopic patterns and treatment implications. 103 patients clinically diagnosed as acanthosis nigricans were enrolled in the study. Clinical evaluation, dermoscopy, and skin biopsy was done for histopathological evaluation. Consistency was observed in the changes seen on dermoscopy with clinical and histopathological findings. Common dermoscopy findings were Crista Cutis, Sulcus Cutis, Papillary projections, hyperpigmented dots, crypts, and blotching Dermoscopic findings can be correlated with histopathological features. Dermoscopy allows visualization on higher magnification which helps to pick up subtle changes which are not visible to naked eye. Dermoscopy can be a useful tool to distinguish acanthosis nigricans from other pigmentary disorders in patients who are not willing for histopathological examination and helps in treatment making decisions., (© 2020 Wiley Periodicals LLC.)

Background: Despite numerous studies confirming the association between insulin resistance (IR) and macrophage polarization, there is a lack of bibliometric analysis in this area. Therefore, our objective is to conduct a comprehensive analysis of published literature and identify potential future research trends using bibliometrics. Method: Publications on the topic of macrophage polarization in IR were gathered from the Web of Science Core Collection database (WoSCC) spanning the years 1999–2023. Bibliometric analysis and visualization were conducted using VOSviewers, CiteSpace, the R package "bibliometrix" and Tableau Public. Result: A total of 3435 articles published between 1999 and 2023 were included in the analysis. These articles originated from 75 countries, with the United States and China leading in contributions. The top five research institutions are the University of California, San Diego, Harvard University, the University of Michigan, Shanghai Jiao Tong University, and Huazhong University of Science and Technology. In this research domain, Diabetes is the most frequently published journal, and the Journal of Clinical Investigation is the most co‐cited. Among the 19,398 authors contributing to these publications, Lumeng CN. not only authored the most papers but also received the highest number of co‐citations. "Insulin resistance" emerges as a primary keyword in the analysis of emerging research hotspots. Conclusion: For the first time, bibliometric methods have been employed to conduct a comprehensive summary of papers relevant to macrophage polarization in IR. This study aims to identify the current research direction and future research hotspots, offering valuable guidance and insights for scholars in the field. [ABSTRACT FROM AUTHOR]

Background: Acanthosis nigricans (AN) is a common skin disease characterized by clear pigmented patches on the folds of the skin. However, the AN research field lacks scientific and comprehensive bibliometric analysis. This article aims to use bibliometric methods to summarize and visualize the distribution patterns, research hotspots, and development trends of AN literature. Methods: Literature from 1900 to 2024 was retrieved from the Web of Science Core Collection database through AN's thematic search. Using CiteSpace, VOSviewer, and Excel 2019, conduct a comprehensive analysis of the number of publications, countries/regions, institutions, authors, journals, highly cited literature, keywords, and so on, and sort out the hotspots and directions of AN. Results: From 1900 to 2024, 1675 publications were included in the bibliometric analysis, showing a steady annual increase in the number of publications. The United States leads in this research field, with the University of Texas System being a key research institution. The Journal of Clinical Endocrinology & Metabolism has the highest number of published papers. The most cited article is "Syndromes of Insulin Resistance and Acanthosis Nigricans: Insulin‐Receptor Disorders in Man" (1976). The author Taylor, SI, has published the most papers. "Acanthosis nigricans" is the most frequently occurring keyword. The main research hotspots and frontier areas in AN research are as follows: (1) The relationship between AN and other diseases is a popular research topic; (2) The connection between AN and insulin resistance (IR) is a current research focus; (3) Treatment of AN, with an emphasis on addressing the underlying causes and improving local skin conditions, represents the cutting edge of this field. Conclusion: This study summarizes the research trends and hotspots in the field of AN, offering valuable information and insights for scholars focused on AN scientific research, and providing a reference for future research directions. [ABSTRACT FROM AUTHOR]

The article presents abstracts on equine veterinary which includes the insulin sensitivity from dexamethasone, the equine midge-borne disease in Great Britain, and the surgical treatment for cryptorchidism among horses.

The global prevalence of diabetes has increased significantly, leading to various complications and a negative impact on quality of life. Hyperglycemia hyperglycemic‐induced oxidative stress (OS) and inflammation are closely associated with the development and progression of type 2 diabetes mellitus (T2D) and its complications. This review explores the effect of T2D on target organ damage and potential treatments to minimize this damage. The paper examines the pathophysiology of T2D, focusing on low‐grade chronic inflammation and OS and on their impact on insulin resistance. The review discusses the role of inflammation and OS in the development of microvascular and macrovascular complications. The findings highlight the mechanisms by which inflammatory cytokines, stress kinases, and reactive oxygen species (ROS) interfere with insulin signaling pathways, leading to impaired glucose metabolism and organ dysfunction. Lifestyle interventions, including a balanced diet and exercise, can help reduce chronic inflammation and OS, thereby preventing and controlling T2D and its associated complications. Additionally, various antioxidants and anti‐inflammatory agents show potential in reducing OS and inflammation. Some anti‐diabetic drugs, like pioglitazone, metformin, and glucagon‐like peptide‐1 (GLP‐1) agonists, may also have anti‐inflammatory effects. Further research, including randomized controlled trials, is needed to evaluate the efficacy of these interventions. [ABSTRACT FROM AUTHOR]

Background: While there have been several school‐based physical activity (PA) interventions targeting improvement in cardiovascular disease (CVD) risk factors, few have assessed long‐term effects. The aim of this paper was therefore to determine intervention effects on CVD risk factors 5 years after cessation. Methods: Two schools were assigned to intervention (n = 125) or control (n = 134). The intervention school offered 210 min/week more PA than the control school over two consecutive years (fourth and fifth grades). Follow‐up assessment was conducted 5‐year post‐intervention (10th grade) where 180–210 (73%–85%) children provided valid data. Outcomes were CVD risk factors: triglyceride, total‐to‐high‐density‐lipoprotein‐cholesterol ratio (TC:HDL ratio), insulin resistance, blood pressure (BP), waist circumference, and cardiorespiratory fitness (VO2peak). Variables were analyzed individually and as a composite score through linear mixed models, including random intercepts for children. Results: Analyses revealed significant sustained 5‐year intervention effects for HDL (effect sizes [ES] = 0.22), diastolic BP (ES = 0.48), VO2peak (ES = 0.29), and composite risk score (ES = 0.38). These effects were similar to the immediate results following the intervention. In contrast, while TC:HDL ratio initially decreased post‐intervention (ES = 0.27), this decrease was not maintained at 5‐year follow‐up (ES = 0.09), whereas WC was initially unchanged post‐intervention (ES = 0.02), but decreased at 5‐year follow‐up (ES = 0.44). Conclusion: The significant effects of a 2‐year school‐based PA intervention remained for CVD risk factors 5 years after cessation of the intervention. As cardiometabolic health can be maintained long‐term after school‐based PA, this paper demonstrates the sustainability and potential of schools in the primary prevention of future CVD risk in children. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions Many review articles have explored data regarding the coexistence of specific types of pituitary adenomas (PAs) and polycystic ovary syndrome (PCOS), particularly focusing on the potential pathogenesis of this intersection and overlapping features. However, a comprehensive evaluation encompassing the full spectrum of PAs and their association with PCOS remains lacking. This review aims to provide a broad assessment of the interactions between these entities, emphasizing pathophysiological mechanisms, clinical presentations, diagnostic challenges and therapeutic implications.A comprehensive literature search was conducted in the PubMed/MEDLINE database, focusing primarily on publications from the years 2000 to 2024, while also including seminal papers from the 1950s. The reference lists of selected articles were also manually searched. Inclusion criteria encompassed review articles, retrospective studies, clinical trials, case reports and meta‐analyses providing data on the pathogenesis, clinical features, diagnostic challenges and therapeutic approaches related to PCOS and different PAs.PCOS and functioning PAs often exhibit overlapping clinical features, complicating diagnosis and management. PCOS may precede and delay the diagnosis of growth hormone (GH)‐secreting adenomas. The prevalence of PCOS or its features in acromegaly is influenced by disease activity, while approximating 13% in cases with controlled disease. Excess GH and insulin‐like growth factor 1 (IGF‐1) adversely affect ovarian function through direct pathways and by inducing insulin resistance, contributing to acromegaly‐associated PCOS. In Cushing's syndrome (CS), findings consistent with PCOS may be present in 46% of patients, with cortisol excess contributing to menstrual dysfunction, hyperandrogenism and insulin resistance. While the prevalence of PCOS in patients with prolactinomas remains under‐researched, recent studies indicate a 2.8%–10% prevalence of prolactinomas in PCOS. Elevated prolactin (PRL) levels in these patients may promote insulin resistance, further contributing to PCOS pathogenesis. Moreover, increased androgen bioavailability may be observed in all three aforementioned adenomas. To date, no studies have provided prevalence data for PCOS in other types of PAs.Distinct clinical features, along with biochemical evaluations and imaging, can help differentiate the presence of both PAs and PCOS. Moreover, excluding other mimicking disorders is essential for an accurate diagnosis of PCOS. The persistence or recurrence of menstrual dysfunction, hyperandrogenism and metabolic disturbances in patients with controlled functioning adenomas may indicate a coexisting PCOS diagnosis. Timely diagnosis may optimize management and improve long‐term outcomes for both conditions. Future studies should focus on investigating the clinical differences between patients with co‐occurring PCOS and PAs compared to those with PCOS alone, ideally in larger cohorts, to better understand unique diagnostic and therapeutic considerations. [ABSTRACT FROM AUTHOR]

Could shift nurses develop overactive bladder (OAB) as a result of metabolic syndrome (MetS)? Shift work and consequent sleep disorders are risk factors of developing MetS. The aim of this literature review was to describe the correlation between MetS OAB and shift work. Search terms (free terms, MeSH): 'metabolic syndrome', 'urologic diseases'; papers published in the last 10 years (2009–2019) were searched in major medical databases (PubMed, CINAHL, Scopus, Embase and Cochrane Database of Systematic Review). We included all randomized controlled trials, observational studies, reviews and we included papers studying MetS and OAB. Quality assessment of the papers was conducted according to the Dixon‐Woods checklist. Seven articles were analysed. The literature review pointed out that insulin resistance, hypertension, obesity, high‐density lipoproteins (HDL), cholesterol and triglycerides have a relationship with MetS. The prevalence of obesity and insulin resistance increases the risk of urolithiasis especially in women. Nurses are an occupational category at risk for MetS, due mainly to shift work. All this could therefore put nurses in a position to develop OAB, but studies are needed that analyse the urinary habits of this professional category to prevent bad habits and reduce absenteeism. Nurses are an occupational category at risk for MetS.Shift nurses tend to hold urine too long during working hours and this could lead to the development of OAB.This review suggests that there may be important links between MetS and OAB and its complex symptoms. [ABSTRACT FROM AUTHOR]

Summary: Psychological distress has a demonstrable impact on cardiovascular diseases (CVD) and risk factors. Transcendental Meditation (TM) has been shown to reduce stress and improve health and well‐being. The current review aimed to synthesize the evidence on the effects of TM on cardiometabolic outcomes and identify gaps for future research. We searched PubMed/MEDLINE, EMBASE, SCOPUS, and Web of Science databases for relevant literature. Forty‐five papers that reported studies of TM on cardiometabolic risk factors and diseases were included. Evidence shows that TM is effective in reducing blood pressure (BP). We found some evidence that TM can improve insulin resistance and may play a role in improving dyslipidemia, exercise tolerance, and myocardial blood flow, and in reducing carotid intima‐media thickness and left ventricular mass. Studies show that long‐term TM practice can reduce the risk of myocardial infarction, stroke, and CVD mortality. This review identified that certain studies have high participant drop‐out rates, and fewer studies targeted comprehensive cardiometabolic outcomes beyond BP with longer follow‐up periods. We found that most studies were conducted in specific populations, which may limit generalizability. In conclusion, TM has the potential to improve cardiometabolic health; however, research gaps highlight the need for larger phase III multicenter clinical trials with long‐term follow‐ups. [ABSTRACT FROM AUTHOR]

Diabetic encephalopathy (DE) is a severe complication that occurs in the central nervous system (CNS) and leads to cognitive impairment. DE involves various pathophysiological processes, and its pathogenesis is still unclear. This review summarised current research on the pathogenesis of diabetic encephalopathy, which involves neuroinflammation, oxidative stress, iron homoeostasis, blood‐brain barrier disruption, altered gut microbiota, insulin resistance, etc. Among these pathological mechanisms, neuroinflammation has been focused on. This paper summarises some of the molecular mechanisms involved in neuroinflammation, including the Mammalian Target of Rapamycin (mTOR), Lipocalin‐2 (LCN‐2), Pyroptosis, Advanced Glycosylation End Products (AGEs), and some common pro‐inflammatory factors. In addition, we discuss recent advances in the study of potential therapeutic targets for the treatment of DE against neuroinflammation. The current research on the pathogenesis of DE is progressing slowly, and more research is needed in the future. Further study of neuroinflammation as a mechanism is conducive to the discovery of more effective treatments for DE in the future. [ABSTRACT FROM AUTHOR]

Summary: This study aims to determine the association between social jetlag and parameters of metabolic syndrome and type 2 diabetes (T2D) in a systematic review and meta‐analysis. A systematic literature search was conducted in PubMed/Embase/Scopus until May 2022. Included studies described an association between social jetlag and parameters of the metabolic syndrome and/or T2D, were available full text and written in English or Dutch. Data extraction and quality assessment were performed on pre‐piloted forms independently by two reviewers. Results were meta‐analysed using random‐effects analysis. A total of 6,290 titles/abstracts were screened, 176 papers were read full‐text, 68 studies were included. Three studies were rated as low quality, 27 were moderate, and 38 were high quality. High quality studies showed that having social jetlag compared to no social jetlag was significantly associated with higher body mass index in 20 studies (0.49 kg/m2, 95% confidence interval [CI] 0.21–0.77; I2 = 100%), higher waist circumference in seven studies (1.11 cm, 95% CI 0.42–1.80; I2 = 25%), higher systolic blood pressure in 10 studies (0.37 mmHg, 95% CI 0.00–0.74; I2 = 94%) and higher glycated haemoglobin in 12 studies (0.42%, 95% CI 0.12– 0.72; I2 = 100%). No statistically significant associations were found for obesity, abdominal obesity, high‐ and low‐density lipoprotein levels, cholesterol, triglycerides, diastolic blood pressure, hypertension, fasting glucose, homeostatic model assessment for insulin resistance, metabolic syndrome or T2D. Sensitivity analyses did not reduce heterogeneity. Despite substantial heterogeneity, social jetlag is associated with certain parameters of the metabolic syndrome and T2D, but not with prevalent metabolic syndrome or T2D. These findings should be interpreted with caution as the level of evidence is low and mostly based on cross‐sectional data. Longitudinal studies are needed to further assess the direction of causality. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is currently a public health problem worldwide and a threat to human health and social development. The incidence rate of the disease is steadily increasing. Various genetic and environmental factors have been established as influencing the pathogenesis of this disease. However, the influence of social factors and the natural environment on DM incidence should also be considered. Low-grade inflammation could represent a central point of connection integrating all these potential triggers, being partly responsible for the development of insulin resistance. This paper aims to elaborate on the impact of the natural environment and social factors on DM development, with a special focus on six aspects of the pathogenesis of DM: pollution, radiation, psychology, drink, sleep, and exercise. We identified a two-way relationship between T2DM and social and natural environments. Changes in these environments may lead to low-grade inflammation, which in turn induces or aggravates T2DM and vice versa. Poor lifestyle may lead to increased insulin resistance and promote DM development. Improvements in blood glucose control can be achieved through nonenvironmental and behavioral interventions. [ABSTRACT FROM AUTHOR]

Key points: Adipocyte enlargement is a key feature of obesity and associated with insulin resistance and metabolic diseaseThe cause and consequences of adipocyte enlargement have remained hard to study in vitro due to a lack of human cell models with representative morphologyThis paper provides an easily set up spheroid culture method, HUVAS (human unilocular vascularized adipocyte spheroids), for the differentiation and culturing of human adipocytes with a more unilocular morphologyWe show that providing adipocyte progenitors with a vascular differentiation niche is key for achieving in vitro differentiated adipocytes with large lipid dropletsLipid treatment of the HUVAS spheroids can further adipocyte enlargement and induce cellular dysfunction, mimicking the in vivo effects of weight gainThe model will allow a wider research community to perform mechanistic studies of the factors impacting on human adipocyte differentiation and growth, increasing our understanding of how obesity develops and why it has such detrimental consequences on whole body metabolism The rise in obesity prevalence has created an urgent need for new and improved methods to study human adipocytes and the pathogenic effects of weight gain in vitro. Despite the proven advantage of culturing adipocyte progenitors as 3D structures, the majority of studies continue to use traditional 2D cultures which result in small, multilocular adipocytes with poor representability. We hypothesized that providing differentiating pre‐adipocytes with a vascular growth niche would mimic in vivo adipogenesis and improve the differentiation into unilocular adipocytes. Here we present HUVAS (human unilocular vascularized adipocyte spheroids), a simple, easily applicable culture protocol that allows for the differentiation of human adipocytes with a more unilocular morphology and larger lipid droplets than previous protocols. Moreover, we offer a protocol for inducing adipocyte enlargement in vitro, resulting in larger lipid droplets and development of several key features of adipocyte dysfunction, including altered adipokine secretion, impaired lipolysis and insulin resistance. Taken together, our HUVAS model offers an improved culture system for studying the cellular and molecular mechanisms causing metabolic dysfunction and inflammation in human adipose tissue during weight gain. [ABSTRACT FROM AUTHOR]

Aim: The occurrence of acanthosis nigricans (AN) in childhood should not be underestimated since it acts as a cutaneous marker of underlying diseases, such as insulin resistance, endocrinopathy, syndromes and malignancy. The purpose of this review was to highlight the clinical significance of AN in childhood and draw attention to its possible role as early marker of alterations in glucose metabolism in obese children., Methods: The Cochrane Library and PubMed databases were searched for papers published in English up to April 2019. Observational studies, case reports and reviews from 1994 to 2019 were included., Results: Most of the cases of AN are associated with obesity. The prevalence of obesity is rising worldwide and is paralleled by global increases in the prevalence of metabolic syndrome in children. Insulin resistance and AN are closely associated. Evidence indicates that AN is a useful clinical marker for the identification of obese and overweight children and adolescents with insulin resistance who are susceptible to type 2 diabetes mellitus and metabolic syndrome., Conclusion: In clinical practice, the recognition of AN is useful for an early identification of children and adolescents, prone to the insulin-resistant obese phenotype, who could benefit from early interventions., (© 2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Diabetes is a chronic inflammatory state, and several studies have shown that the mechanisms of insulin resistance and abnormal islet β-cell function in diabetes are closely related to inflammatory reactions. Inflammation plays a critical role in diabetic complications. Long noncoding RNAs (lncRNAs), a new area of genomic research for gene regulation, have complex biological functions in various aspects of cellular biological activity. Recent studies have shown that lncRNAs are associated with the regulation of inflammatory responses in various ways, including at the epigenetic, transcriptional, and posttranscriptional levels. This paper presents a brief review of studies on the mechanisms of lncRNAs in diabetic inflammation. The purpose of this article is to determine the role of lncRNAs in the process of diabetic inflammation and to provide new strategies for the use of lncRNAs in the treatments for diabetic inflammation. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is an unprecedented health crisis as entire populations have been asked to self-isolate and live in home-confinement for several weeks to months, which in itself represents a physiological challenge with significant health risks. This paper describes the impact of sedentarism on the human body at the level of the muscular, cardiovascular, metabolic, endocrine and nervous systems and is based on evidence from several models of inactivity, including bed rest, unilateral limb suspension, and step-reduction. Data form these studies show that muscle wasting occurs rapidly, being detectable within two days of inactivity. This loss of muscle mass is associated with fibre denervation, neuromuscular junction damage and upregulation of protein breakdown, but is mostly explained by the suppression of muscle protein synthesis. Inactivity also affects glucose homeostasis as just few days of step reduction or bed rest, reduce insulin sensitivity, principally in muscle. Additionally, aerobic capacity is impaired at all levels of the O2 cascade, from the cardiovascular system, including peripheral circulation, to skeletal muscle oxidative function. Positive energy balance during physical inactivity is associated with fat deposition, associated with systemic inflammation and activation of antioxidant defences, exacerbating muscle loss. Importantly, these deleterious effects of inactivity can be diminished by routine exercise practice, but the exercise dose–response relationship is currently unknown. Nevertheless, low to medium-intensity high volume resistive exercise, easily implementable in home-settings, will have positive effects, particularly if combined with a 15–25% reduction in daily energy intake. This combined regimen seems ideal for preserving neuromuscular, metabolic and cardiovascular health. [ABSTRACT FROM AUTHOR]

Obesity is a chronic multisystem disease associated with increased morbidity and mortality. The increasing prevalence of obesity makes it a major healthcare challenge across both developed and developing countries. Traditional measures such as body mass index do not always identify individuals at increased risk of comorbidities, yet continue to be used in deciding who qualifies for weight loss treatment. A better understanding of how obesity is associated with comorbidities, in particular non‐metabolic conditions, is needed to identify individuals at risk in order to prioritize treatment. For metabolic disorders such as type 2 diabetes (T2D), weight loss can prevent T2D in individuals with prediabetes. It can improve and reverse T2D if weight loss is achieved early in the course of the disease. However, access to effective weight loss treatments is a significant barrier to improved health for people with obesity. In the present paper, we review the rising prevalence of obesity and why it should be classed as a multisystem disease. We will discuss potential mechanisms underlying its association with various comorbidities and how these respond to treatment, with a particular focus on cardiometabolic disease, malignancy and mental health. [ABSTRACT FROM AUTHOR]

We systematically reviewed papers published in English between 1994 and October 2015 on how postnatal weight gain and growth affect neurodevelopment and metabolic outcomes in term-born small-for-gestational-age (SGA) infants. Two randomised trials reported that enriched infant formulas that promoted early growth also increased fat mass, lean mass and blood pressure (BP), but had no effect on early neurocognitive outcomes. Meanwhile, 31 observational studies reported consistent positive associations between postnatal weight gain and growth with neurocognitive outcomes, adiposity, insulin resistance and BP.Conclusion: Few intervention studies exist, despite consistent positive associations between early growth and neurocognition in term-born SGA infants. [ABSTRACT FROM AUTHOR]

GLP-1 and GLP-2 are gut-derived hormones used in the treatment of diabetes type-2 and short bowel syndrome, respectively. GLP-1 attenuates insulin resistance and GLP-2 reduces enterocyte apoptosis and enhances crypt cell proliferation in the small intestine. In addition, both hormones have vasoactive effects and may be useful in situations with impaired microcirculation. The aim of this systematic review was to provide an overview of the potential effects of GLP-1 and GLP-2 on microcirculation. A systematic search was performed independently by two authors in the following databases: PubMed, EMBASE, Cochrane library, Scopus, and Web of Science. Of 1111 screened papers, 20 studies were included in this review: 16 studies in animals, three in humans, and one in humans and rats. The studies were few and heterogeneous and had a high risk of bias. However, it seems that GLP-1 regulates the pancreatic, skeletal, and cardiac muscle flow, indicating a role in the glucose homeostasis, while GLP-2 acts primarily in the regulation of the microcirculation of the mid-intestine. These findings may be useful in gastrointestinal surgery and in situations with impaired microcirculation of the gut., (© 2017 John Wiley & Sons Ltd.)

Summary: The association between plasma endothelin‐1 (ET‐1) and obesity has been documented for decades, yet the contribution of ET‐1 to risk factors associated with obesity is not fully understood. In 1994, one of first papers to document this association also noted a positive correlation between plasma insulin and ET‐1, suggesting a potential contribution of ET‐1 to the development of insulin resistance. Both endogenous receptors for ET‐1, ETA and ETB are present in all insulin‐sensitive tissues including adipose, liver and muscle, and ET‐1 actions within these tissues suggest that ET‐1 may be playing a role in the pathogenesis of insulin resistance. Further, antagonists for ET‐1 receptors are clinically approved making these sites attractive therapeutic targets. This review focuses on known mechanisms through which ET‐1 affects plasma lipid profiles and insulin signalling in these metabolically important tissues and also identifies gaps in our understanding of ET‐1 in obesity‐related pathophysiology. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of four peptides, VLP, LLP, LL, and LL from pea on regulating glucose metabolism and antioxidant through IRS‐1/PI3K/AKT and p38MAPK signal pathway in IR‐HepG2 cell induced by 10‐6M insulin. The genes expression of PEPCK, G6Pase, GLUT2, and IRS‐1 and proteins of IRS‐1, p(Ser307)‐IRS‐1, AKT, p(Ser473)‐AKT, p38MAPK, and p‐p38MAPK were determined by RT‐PCR and western blotting, respectively. Results show that they displayed highly potent on stimulation glucose metabolism and relief oxidative stress in IR‐HepG2 cells. VLP, LLP, VA, and LL reduced Ser307 phosphorylation of IRS‐1 and promoted Ser473 phosphorylation of AKT. Among them, LLP, VA, and LL increased the expression both gene and protein of GLUT2, and VLP and LL reduced p38MAPK phosphorylation showing strong antioxidant capacity. Therefore, pea oligopeptides have considerable potential for reversing the metabolic abnormalities associated with type 2 diabetes. Practical applications: This paper examined the intervention effect of VLP, LLP, VA, and LL that from pea on insulin resistance, and the mechanisms were detected by western blotting. The results provide a theoretical knowledge for the prevention of insulin resistance in T2D of pea‐derived peptides and lay the foundation for the development of functional products and drugs in the future. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is the most common type of diabetes, and insulin resistance (IR) is its core pathological mechanism. Proteomics is an ingenious and promising Omics technology that can comprehensively describe the global protein expression profiling of body or specific tissue, and is widely applied to the study of molecular mechanisms of diseases. In this paper, we focused on insulin target organs: adipose tissue, liver, and skeletal muscle, and analyzed the different pathological processes of IR in these three tissues based on proteomics research. By literature studies, we proposed that the main pathological processes of IR among target organs were diverse, which showed unique characteristics and focuses. We further summarized the differential proteins in target organs which were verified to be related to IR, and discussed the proteins that may play key roles in the emphasized pathological processes, aiming at discovering potentially specific differential proteins of IR, and providing new ideas for pathological mechanism research of IR. [ABSTRACT FROM AUTHOR]

In this paper, we sought to explore the relationship between apolipoprotein AV (APOAV) overexpression and insulin resistance in hepatocytes. The insulin-resistant HepG2 cell model was constructed, and then, APOAV-overexpressed HepG2 cells (B-M) were induced by infecting with a recombinant adenovirus vector. Microarray data were developed from B-M samples compared with negative controls (A-con), and the microarray data were analyzed by bioinformatic methods. APOAV-overexpression induced 313 upregulated genes and 563 downregulated ones in B-M sample. The differentially expressed genes (DEGs) were significantly classified in fat digestion and absorption pathway. Protein-protein interaction network was constructed, and AGTR1 (angiotensin II receptor type 1) and P2RY2 (purinergic receptor P2Y, G-protein coupled 2) were found to be the significant nodes closely related with G-protein related signaling. Additionally, overexpression of APOAV could change the expression of Glut4 and release the insulin resistance of hepatic cells. Thus, APOAV overexpression may prevent the insulin resistance in liver cells by mediating the genes such as AGTR1 and P2RY2. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Bansal et al. papers. To view these articles, visit https://doi.org/10.1111/apt.17930 and https://doi.org/10.1111/apt.18124. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Lin et al papers. To view these articles, visit https://doi.org/10.1111/apt.17930 and https://doi.org/10.1111/apt.18182. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM), a metabolic disorder, has the hallmarks of persistent hyperglycemia, insulin resistance, and dyslipidemia. Protein‐tyrosine phosphatase 1B (PTP1B) was found to be overexpressed in many tissues in the case of T2DM and involved in the negative regulation of insulin signaling. So, PTP1B inhibition can act as a therapeutic target for T2DM. Numerous studies claimed the anti‐inflammatory, hypoglycemic, hepatoprotective, and hypolipidemic activities of Dodonaea viscosa. Previously, we generated the high‐fat diet (HFD)‐low dose streptozotocin (STZ)–induced diabetic male mice model and treated it with a PTP1B inhibitor (5, 7‐dihydroxy‐3, 6‐dimethoxy‐2‐ (4‐methoxy‐3‐ (3‐methyl‐2‐enyl) phenyl)‐4H‐chromen‐4‐one), isolated from Dodonaea viscosa. In the current study, we aimed to investigate the De novo lipogenesis, adipocyte differentiation, augmentation of lipoproteins clearance, fatty acid uptake, antilipolysis activity, and hepatic steatosis of PTP1B inhibition in adipose and liver tissues of the HFD‐STZ–induced diabetic mice model. We found the retrieval of normal morphology of adipocytes and hepatocytes in the compound‐treated group. The biochemical parameters showed the gradual reduction of LDL, VLDL, TC, and TG in the serum of the compound‐treated group. To further test our hypothesis, real‐time PCR was performed, and data revealed the reduction of PTP1B and other inflammatory markers in both tissues, showing enhanced expression of insulin signaling markers (INSR, IRS1, IRS2, and PI3K). Our compound upregulated the adipogenic (PPARγ), lipogenic (SREBP1c, FAS, ACC, and DGAT2), lipoprotein clearance (LPL, LDLR, and VLDLR), fatty acid uptake (CD36 and FATP1), and lipid droplet forming (FSP27 and perilipin‐1) markers expressions in adipocytes and downregulated in hepatocytes. Furthermore, we found elevated cholesterol efflux (in adipose and liver) and decreased lipolysis in adipocytes and elevated in hepatocytes. Hence, we can conclude that our compound protects the adipocytes from abrupt lipolysis and stimulates adipocyte differentiation. In addition, it plays a hepatic protective role by shifting clearance and uptake of lipoproteins and fatty acids to the peripheral tissues and retrieving the fatty liver condition. [ABSTRACT FROM AUTHOR]

Over the past decades, the global prevalence of Type 2 diabetes mellitus (T2D) and impaired glucose tolerance (IGT) has been increasing at an epidemic rate, yet the exact cause remains unknown. It is widely accepted that glucose metabolism can be impaired by circadian rhythms and sleep disturbances. Concurrently, exposures to light at night have been closely linked to circadian and sleep disturbances. However, there is no direct experiment on primates to demonstrate the precise extent of how serious light pollution impairs glucose metabolism, whether people will eventually become accustomed to this environment, and whether the pollution has synergistic impairing effects with aging and weight on glucose metabolism. To quantitatively address these questions, 137 cynomolgus were exposed to three distinct nocturnal light intensities for consecutive 10 months. Monthly glucose metabolism assessments were conducted. Data pertaining to the mortality rate of preexisting diabetes, incidence of light‐induced diabetes and IGT, and alterations in insulin secretion were collected and analyzed. The results show that nocturnal light (1) caused premature deaths in individuals with preexisting diabetes; (2) intensity‐dependently induced diabetes and IGT in previous healthy monkeys; (3) intensity‐dependently reduced melatonin secretion; (4) had a synergistic impairing effect on glucose metabolism with aging and weight; and (5) although monkeys would eventually adapt to the environment, the disrupted glucose metabolism would not fully recover in most individuals. In conclusion, nocturnal light is associated with the global high prevalence of T2D and IGT. The harmful effects of light pollution on glucose metabolism are synergistic with age and weight. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a chronic metabolic disorder that can cause elevated blood glucose levels due to impaired insulin secretion or resistance. Different parts of Musa balbisiana have been used widely in traditional medicine to treat many disorders. The present study aims to evaluate the antidiabetic ability of the corm, pseudostem, inflorescence, fruit, peel, and seed of M. balbisiana via in vitro experiments by inhibiting α‐amylase and α‐glucosidase enzymes as well as in vivo models on diabetic alloxan‐induced mice. The results show that all investigated parts have performed potential inhibition on two investigated digestive enzymes. Seed poses the highest capacity among surveyed parts on α‐amylase (IC50:f μg/mL) and α‐glucosidase (IC50: 21.63 μg/mL) as well as effectively lowers the blood glucose index (IG) in alloxan‐induced mice. In addition, fruit, corm, and inflorescence are considered essential parts that have high hypoglycemic effects via in vivo experiments. These findings indicate that all M. balbisiana parts are possibly a potential source for hypoglycemic agents; further clinical studies are needed to evaluate the safety of human beings before applying them in functional food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a chronic metabolic disorder caused by defective insulin signaling, insulin resistance, and impairment of insulin secretion. Autophagy is a conserved lysosomal‐dependent catabolic cellular pathway involved in the pathogenesis of T2D and its complications. Basal autophagy regulates pancreatic β‐cell function by enhancing insulin release and peripheral insulin sensitivity. Therefore, defective autophagy is associated with impairment of pancreatic β‐cell function and the development of insulin rersistance (IR). However, over‐activated autophagy increases apoptosis of pancreatic β‐cells leading to pancreatic β‐cell dysfunction. Hence, autophagy plays a double‐edged sword role in T2D. Therefore, the use of autophagy modulators including inhibitors and activators may affect the pathogenesis of T2D. Hence, this review aims to clarify the potential role of autophagy inhibitors and activators in T2D. [ABSTRACT FROM AUTHOR]

Aims: To assess the risk of difference between 2 h post‐load plasma glucose (2 h‐PG) and fasting plasma glucose (FPG) on incident prediabetes/type 2 diabetes (T2DM) among normoglycemic individuals. Methods: Among 4,971 individuals aged ≥20 years, the associations of the difference between 2 h‐PG and FPG with outcomes were examined using multivariable‐adjusted Cox regression analysis. Participants were categorized into three groups: a low post‐load group (2 h‐PG ≤ FPG, as the reference group); a high post‐load group (2 h‐PG > FPG and ≥75th percentile of the difference); and a medium post‐load group (2 h‐PG > FPG and <75th percentile of the difference), which was further categorized into three groups by equal ranges. Results: Over a median of 11.5 years of follow‐up, 2,331 new cases of prediabetes/type 2 diabetes and 360 cases of type 2 diabetes occurred. Greater risks of incident prediabetes/type 2 diabetes in second (9–16 mg/dL) and third (17–24 mg/dL) medium post‐load, as well as high post‐load (≥25 mg/dL) categories, were found, with hazard ratios (95% confidence intervals) of 1.26 (1.11–1.44), 1.32 (1.15–1.51), and 1.69 (1.51–1.90), respectively; the issue was more prominent among women (P for interaction = 0.005). The risk of incident type 2 diabetes was also higher for these categories. After further adjustment for the homeostasis model assessment of insulin resistance, result remained essentially unchanged. Even among individuals with low normal FPG (i.e., <90 mg/dL), ≥9 mg/dL difference between 2 h‐PG and FPG increased the risk of composite prediabetes/ type 2 diabetes. Conclusions: Greater levels of 2 h‐PG as low as 9 mg/dL than FPG among normoglycemic individuals is a harbinger of prediabetes/type 2 diabetes development. [ABSTRACT FROM AUTHOR]

Obesity paradox refers to the clinical observation that when acute cardiovascular decompensation occurs, patients with obesity may have a survival benefit. This apparently runs counter to the epidemiology of obesity, which may increase the risk for non‐communicable diseases (NCDs). The scientific community is split on obesity paradox, with some supporting it, while others call it BMI paradox. This review: (a) defines the obesity paradox, and its proposed role in overall mortality in NCDs; (b) delineates evidence for and against obesity paradox; (c) presents the importance of using different indices of body mass to assess the risk in NCDs; (d) examines the role of metabolically healthy obesity in obesity paradox, and emerging importance of cardio‐respiratory fitness (CRF) as an independent predictor of CVD risk and all‐cause mortality in patients with/without obesity. Evidence suggests that the development of obesity and insulin resistance are influenced by genetic (or ethnic) make up and dietary habits (culture) of the individuals. Hence, this review presents lean diabetes, which has higher total CVD and non‐CVD mortality as compared to diabetics with obesity and the possibility of maternal factors programming cardiometabolic risk during fetal development, which may lead to a paradigm shift in our understanding of obesity. [ABSTRACT FROM AUTHOR]

Sirtuin 6 (Sirt6), a NAD+‐dependent protein deacetylase, is involved in hepatic glucose metabolism and insulin sensitivity, which impact metabolic homeostasis. In this paper, we discover that Sirt6 affects the insulin sensitivity of mice in a gender‐dependent manner; few studies have been conducted on this issue. Based on reports revealing the influences of sex hormones on insulin signaling, this investigation explores the mechanism by which Sirt6 regulates the estrogen pathway and disrupts insulin signal transduction. Hepatocyte‐specific Sirt6 knockout (Sirt6HKO) mice were generated to investigate the function of Sirt6 in hepatocytes. Mice were castrated or spayed to eliminate sex hormones. Insulin sensitivity was assessed via an insulin tolerance test (ITT) in vivo. The interaction of Sirt6 with the estrogen pathway and their impacts on insulin signal transduction were revealed by immunoblot and immunoprecipitation. Sirt6 deletion in hepatocytes significantly enhanced insulin sensitivity and signal transduction in female mice but not in male or spayed female mice as demonstrated by ITT and the phosphorylation level of Akt in the liver. We also identified upregulation of p300, ERα, and interaction of ERα with p85 in the liver of female Sirt6HKO mice. Additionally, Sirt6 was found to inhibit ERα protein stability in a p300‐dependent manner without interacting directly with ERα. Our findings show that hepatic Sirt6 downregulates the ERα protein level in a p300‐dependent manner and thus disturbs estrogen‐induced improvement in insulin sensitivity in the liver, which may partially explain the gender difference in insulin sensitivity. [ABSTRACT FROM AUTHOR]

The article discusses papers in the January 2012 issue of "Experimental Diabetes Research," about the pathophysiology of metabolic syndrome and its cardiovascular complications, including a paper on the association between HIV and metabolic syndrome, a paper on the role of low plasma concentrations of paraoxonase (PON1) in metabolic syndrome and a paper on the higher prevalence of diabetes in periodontitis patients.

Abstract: Non‐alcoholic steatohepatitis (NASH) is strongly associated with overnutrition, insulin resistance, and predisposition to type 2 diabetes. To critically analyze the translational significance of currently used animal models of NASH, we reviewed articles published during the last 3 years that studied NASH pathogenesis using mouse models. Among 146 articles, 34 (23%) used models in which overnutrition was reported, and 36 (25%) demonstrated insulin resistance, with or without glucose intolerance. Half the articles contained no information on whether mice exhibited overnutrition or insulin resistance. While 75 papers (52%) reported > 2‐fold increase of serum/plasma alanine aminotransferase (ALT) compared with controls, ALT levels were near normal or not reported in 48%. Liver pathology was assessed by a pathologist with an interest in liver pathology in 53% of articles published in gastroenterology/hepatology journals, versus 43–44% in other journals. While there appears to be a trend to use models that are potentially relevant to the pathogenesis of human NASH, journals currently publish data on mouse models in which overnutrition and insulin resistance do not occur, without ALT increase or appropriate analysis of NASH pathology. We recommend that investigators, reviewers, and journal editors carefully consider the validity of NASH models in current use and that moves are made to reach a consensus on what the minimal criteria should be. [ABSTRACT FROM AUTHOR]

The recently published Lancet Diabetes and Endocrinology paper that identifies five subtypes of adult‐onset diabetes associated with differing risk of complications has sparked new debate on the classification of diabetes and may help bring precision medicine a step closer. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2D) is a disorder of glucose metabolism. It is a complex process involving the regulation of insulin secretion, insulin sensitivity, gluconeogenesis, and glucose uptake at the cellular level. Diabetic peripheral neuropathy (DPN) is one of the debilitating complications that is present in approximately 50% of diabetic patients. It is the primary cause of diabetes-related hospital admissions and nontraumatic foot amputations. The pathogenesis of diabetic neuropathy is a complex process that involves hyperglycemia-induced oxidative stress and altered polyol metabolism that changes the nerve microvasculature, altered growth factor support, and deregulated lipid metabolism. Recent literature has reported that there are several heterogeneous groups of susceptible genetic loci which clearly contribute to the development of DPN. Several studies have reported that some patients with prediabetes develop neuropathic complications, whereas others demonstrated little evidence of neuropathy even after long-standing diabetes. There is emerging evidence that genetic factors may contribute to the development of DPN. This paper aims to provide an up-to-date review of the susceptible and prognostic genetic factors associated with DPN. An extensive survey of the scientific literature published in PubMed using the search terms “Diabetic peripheral neuropathy/genetics” and “genome-wide association study” was carried out, and the most recent and relevant literature were included in this review. [ABSTRACT FROM AUTHOR]

Pannexins, which contain three subtypes: pannexin-1, -2, and -3, are vertebrate glycoproteins that form non-junctional plasma membrane intracellular hemichannels via oligomerization. Oxidative stress refers to an imbalance of the generation and elimination of reactive oxygen species (ROS). Studies have shown that elevated ROS levels are pivotal in the development of a variety of diseases. Recent studies indicate that the occurrence of these oxidative stress related diseases is associated with pannexin hemichannels. It is also reported that pannexins regulate the production of ROS which in turn may increase the opening of pannexin hemichannels. In this paper, we review recent researches about the important role of pannexin hemichannels in oxidative stress related diseases. Thus, pannexin hemichannels, novel therapeutic targets, hold promise in managing oxidative stress related diseases such as the tumor, inflammatory bowel diseases (IBD), pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), cardiovascular disease, insulin resistance (IR), and neural degeneration diseases. [ABSTRACT FROM AUTHOR]

Objective: To determine the associations between triglyceride‐glucose (TyG) index and mortality from all causes and cardiovascular causes in diabetic population. Methods: 3349 participants with diabetes mellitus (DM) from the 1999–2014 National Health and Nutrition Examination Surveys (NHANES), aged 18–85 years were included and grouped based on the TyG index in quintiles. Mortality was followed up through December 31th, 2015. Cox proportional hazards models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs). We clarified the shape of association between TyG index and mortality using restricted cubic splines and piecewise linear regression. Results: After a median follow‐up period of 82 months, 800 (23.9%) deaths occurred, of which 190 (5.7%) were due to cardiovascular causes. Participants in the top quintile had higher risks of all‐cause mortality (HR, 1.38; 95% CI, 1.04–1.48) and cardiovascular mortality (HR, 2.43; 95% CI, 1.32–4.45) than those in the lowest quintile. TyG index and all‐cause mortality had a J‐shaped relationship with a threshold value of 9.32, while TyG index and cardiovascular mortality had a reversed L‐shaped relationship with a threshold value of 9.37. Higher TyG index was associated with increased risks of all‐cause mortality (per SD increment, HR, 1.52; 95% CI, 1.27–1.82) and cardiovascular mortality (per SD increment, HR, 2.17; 95% CI, 1.54–3.04) when above the threshold values. The sensitivity analyses demonstrated similar findings. Conclusions: TyG index in diabetic patients was nonlinearly correlated with mortality risks, potentially predicting all‐cause and cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Aims: Insulin resistance (IR) is an important risk factor for obesity and cardiometabolic diseases, and our previous findings have demonstrated that visceral fat area to skeletal muscle mass ratio (VSR) is significantly and positively associated with the risk of cardiometabolic diseases. Hence, this study aimed to investigate the relationship between VSR and multiorgan IR, provide a new approach to improve body composition, and set the basis for VSR to increase the incidence of cardiometabolic diseases. Materials and Methods: The study included 398 patients who underwent anthropometric and biochemical measurements, and body composition assessment. Spearman correlation analysis was used to investigate the correlation between VSR and homeostatic model assessment for insulin resistance (HOMA‐IR) as well as multiorgan IR, including homeostasis model assessment adiponectin (HOMA‐AD), adipose tissue insulin resistance (ADIPO‐IR), and hepatic insulin sensitivity (HISI). The new model that incorporated into the present study is made up of easily measured biochemical indicators and is used to predict IR. Logistic regression was used to analyze the odds ratio (OR) of VSR on the risk of multiorgan IR. The predictive value of VSR for HOMA‐IR and new model was evaluated using the receiver operating characteristic (ROC) curve. Results: VSR was significantly associated with HOMA‐IR, HOMA‐AD, ADIPO‐IR, 1/HISI, and new model (p < 0.001). With the increase of VSR, the OR increased significantly for HOMA‐IR and new model (p < 0.001). Then, multiorgan IR indicators were quantified, compared to the lowest quartile group, and increased VSR exacerbated the risk of IR in the highest quartile (ptrend < 0.001). The area under the curve for predicting IR using VSR for HOMA‐IR and new model was 0.88 for men, 0.85 for women and 0.73 for men, 0.76 for women, respectively. Conclusions: There was significant correlation between VSR and multiorgan IR, and the risk of multiorgan IR increased with increasing VSR. Trial Registration: Clinical Trial Registry identifier: ChiCTR2100044305. [ABSTRACT FROM AUTHOR]

Fenugreek (Trigonella foenum‐graecum) is a widely grown dietary herb in Asia, and its seeds are traditionally used for several diseases, including diabetes. The seeds and leaves possess a variety of compounds that play an important role in regulating their hypoglycemic effect. However, so far, no extensive systematic review exists on its antidiabetic effect, highlighting the molecular mechanisms and isolated compounds. The purpose of this review is to summarize the preclinical and clinical antidiabetic properties of fenugreek and its isolated compounds by focusing on underlying mechanisms. PubMed, Google Scholar, Science Direct, and Scopus databases were searched to retrieve articles until June, 2024. Preclinical studies demonstrated that the antidiabetic effect of fenugreek was mostly associated with enhanced glucose transporter type‐4 (GLUT4) translocation and hexokinase activity, decreased glucose‐6‐phosphatase and fructose‐1,6‐bisphosphatase activities, inhibited α‐amylase and maltase activities, protected β cells, and increased insulin release. Furthermore, few studies have reported its role as a glucagon‐like peptide‐1 (GLP‐1) modulator, 5′‐AMP‐activated kinase (AMPK) activator, and dipeptidyl peptidase‐IV (DPP‐IV) inhibitor. Further clinical trials showed that fenugreek seeds improved blood glucose levels, insulin resistance, insulin sensitivity, and lipid profiles. This study highlights significant evidence of the antidiabetic effect of fenugreek and its isolated compounds; therefore, it could be a potential therapy for diabetes. [ABSTRACT FROM AUTHOR]

The coexistence of diabetes mellitus (DM) and tuberculosis (TB) presents a significant global burden, with DM being recognized as a major risk factor for TB. This review comprehensively analyzes the immunological aspects of DM‐TB comorbidity, shedding light on the impact of DM on TB pathogenesis and immune responses. It reveals that high blood glucose levels in TB patients contribute to reduced innate immune cell count, compromised phagocytic function, and delayed antigen presentation. These factors ultimately impair the clearance of Mycobacterium tuberculosis (MTB) and delay adaptive immune responses. With the interaction between TB and DM, there is an increase in inflammation and elevated secretion of pro‐inflammatory cytokines by immune cells. This exacerbates the inflammatory response and contributes to poor treatment outcomes in TB. Moreover, the review explores the effects of DM on TB prevention, diagnosis, and treatment. It highlights how poor glycemic control, insulin resistance (IR), DM complications, and genetic factors increase the risk of MTB infection in individuals with DM. Additionally, DM‐related immune suppression adversely affects the sensitivity of traditional diagnostic tests for TB, potentially resulting in underdiagnosis and delayed intervention. To mitigate the burden of TB in DM patients, the review emphasizes the need for further research on the mechanisms underlying DM reactivation in latent TB infection (LTBI). It shows how important it is to find and treat LTBI in DM patients as soon as possible and suggests looking into biomarkers that are specific to DM to make diagnosis more accurate. [ABSTRACT FROM AUTHOR]

Background: Not many large‐sample investigations are available that compare the potency of the relationship of remnant cholesterol (RC) and other lipid parameters with diabetes and prediabetes. The goals of our study are to discover the relationship between RC and prediabetes, diabetes, and insulin resistance (IR) and to investigate RC, high‐density lipoprotein cholesterol (HDL‐C), non‐HDL‐C, triglycerides (TG), low‐density lipoprotein cholesterol (LDL‐C), total cholesterol (TC), TC/HDL‐C, LDL‐C/HDL‐C, and TG/HDL‐C, which are the lipid parameters that are most positively related to diabetes, prediabetes, and IR. Methods: This research enrolled 36 684 subjects from China's eight provinces. We employed multiple logistic regression analysis for testing the relationship between lipid parameters and diabetes, prediabetes, and IR. Results: After adjusting for potential confounders, and comparing the results with other lipid parameters, the positive relationship between RC and diabetes (odds ratio [OR] 1.417, 95% confidence interval [CI]: 1.345–1.492), prediabetes (OR 1.555, 95% CI: 1.438–1.628), and IR (OR 1.488, 95% CI: 1.404–1.577) was highest. RC was still related to diabetes, prediabetes, and IR even when TG <2.3 mmol/L (diabetes: OR 1.256, 95% CI: 1.135–1.390; prediabetes: OR 1.503, 95% CI: 1.342–1.684; and IR: OR 1.278, 95% CI: 1.140–1.433), LDL‐C <2.6 mmol/L (diabetes: OR 1.306, 95% CI: 1.203–1.418; prediabetes: OR 1.597, 95% CI: 1.418–1.798; and IR: OR 1.552, 95% CI: 1.416–1.701), or HDL‐C ≥1 mmol/L (diabetes: OR 1.456, 95% CI: 1.366–1.550; prediabetes: OR 1.553, 95% CI: 1.421–1.697; and IR: OR 1.490, 95% CI: 1.389–1.598). Conclusion: RC is more positively related to diabetes, prediabetes, and IR than conventional lipids and lipid ratios in the general population, the relationships between RC and diabetes, prediabetes, and IR are stable, even if HDL‐C, LDL‐C, or TG are at appropriate levels. [ABSTRACT FROM AUTHOR]

The Restoring Insulin Secretion ( RISE) study was initiated to evaluate interventions to slow or reverse the progression of β-cell failure in type 2 diabetes ( T2D). To design the RISE study, we undertook an evaluation of methods for measurement of β-cell function and changes in β-cell function in response to interventions. In the present paper, we review approaches for measurement of β-cell function, focusing on methodologic and feasibility considerations. Methodologic considerations included: (1) the utility of each technique for evaluating key aspects of β-cell function (first- and second-phase insulin secretion, maximum insulin secretion, glucose sensitivity, incretin effects) and (2) tactics for incorporating a measurement of insulin sensitivity in order to adjust insulin secretion measures for insulin sensitivity appropriately. Of particular concern were the capacity to measure β-cell function accurately in those with poor function, as is seen in established T2D, and the capacity of each method for demonstrating treatment-induced changes in β-cell function. Feasibility considerations included: staff burden, including time and required methodological expertise; participant burden, including time and number of study visits; and ease of standardizing methods across a multicentre consortium. After this evaluation, we selected a 2-day measurement procedure, combining a 3-hour 75-g oral glucose tolerance test and a 2-stage hyperglycaemic clamp procedure, augmented with arginine. [ABSTRACT FROM AUTHOR]

Diabetes is considered a major public health problem affecting millions of individuals worldwide. Remarkably, scientific reports regarding salivary glands sphingolipid metabolism in diabetes are virtually non-existent. This is odd given the well-established link between the both in other tissues (e.g., skeletal muscles, liver) and the key role of these glands in oral health preservation. The aim of this paper is to examine sphingolipids metabolism in the salivary glands in (pre)diabetes (evoked by high fat diet feeding or streptozotocin). Wistar rats were allocated into three groups: control, HFD-, or STZ-diabetes. The content of major sphingolipid classes in the parotid (PSG) and submandibular (SMSG) glands was assessed via chromatography. Additionally, Western blot analyses were employed for the evaluation of key sphingolipid signaling pathway enzyme levels. No changes in ceramide content in the PSG were found, whereas an increase in ceramide concentration for SMSG of the STZ group was observed. This was accompanied by an elevation in SPT1 level. Probably also sphingomyelin hydrolysis was increased in the SMSG of the STZ-diabetic rats, since we observed a significant drop in the amount of SM. PSG and SMSG respond differently to (pre)diabetes, with clearer pattern presented by the later gland. An activation of sphingomyelin signaling pathway was observed in the course of STZ-diabetes, that is, metabolic condition with rapid onset/progression. Whereas, chronic HFD lead to an inhibition of sphingomyelin signaling pathway in the salivary glands (manifested in an inhibition of ceramide de novo synthesis and accumulation of S1P). [ABSTRACT FROM AUTHOR]

Background A high prevalence of cancers in metabolic disorders, like metabolic syndrome (MetS) and type 2 diabetes mellitus (T2 DM), recently has been noted, including prostate cancer ( PC), which is androgen-sensitive. However, the pathological relationship among testosterone and insulin and insulin-like growth factor ( IGF)-1 signaling in relation to MetS and T2 DM with PC remains unclear. Methods Papers were reviewed, including those by the authors. Results In MetS or the initial stage of T2 DM accompanying insulin resistance, insulin and IGF-1 signaling could be essential for PC growth. In the advanced stage of T2 DM, the decrease in insulin secretion might work against PC growth. A decrease in testosterone concentration with T2 DM also might suppress PC proliferation. Androgen deprivation therapy in patients with PC might increase the risk of MetS and/or T2 DM and consequently cardiovascular events. Certain drugs for T2 DM treatment, such as metformin and glucagon-like peptide-1 analog, potentially might be useful for the treatment of PC. Conclusion The improvement of insulin resistance appears to be essential for the prevention of PC growth. Further studies are needed to clarify the complicated pathophysiology of metabolic disorders in PC growth. [ABSTRACT FROM AUTHOR]

Summary: Objectives: The aim of this paper is to test whether α‐defensins and bacterial/permeability‐increasing protein were related to obesity and cardiovascular risk factors in prepubertal children. Methods: Plasma α‐defensins and bacterial/permeability‐increasing protein, body mass index (BMI), waist circumference, systolic blood pressure (SBP), carotid intima media thickness (cIMT), HOMA‐IR and HMW‐adiponectin were assessed. Results: In a cross‐sectional study (N = 250), higher α‐defensins concentrations were positively associated with BMI, waist, SBP, cIMT, HOMA‐IR and negative correlated with HMW‐adiponectin (all between r = 0.191 and r = 0.377, p ≤ 0.01 and p ≤ 0.0001). Conversely, plasma bacterial/permeability‐increasing protein concentrations presented inversed associated with the same parameters (all between r = −0.124 and r = −0.329; p ≤ 0.05 and p ≤ 0.0001). In a longitudinal study (N = 91), α‐defensins at age 7 were associated with BMI (β = 0.189, p = 0.002; model R2 = 0.847) and waist (β = 0.241, pthinsp;= 0.001; model R2 = 0.754) at age 10. Conclusions: α‐Defensins and bacterial/permeability‐increasing protein may be the markers of childhood obesity. Increased concentrations of α‐defensins may predict BMI and abdominal fat deposition in children. [ABSTRACT FROM AUTHOR]

Unlabelled: Insulin resistance (IR) occurs in a transient manner during puberty. Obese adolescents may be at risk for persistent IR during puberty. The objective of the study is to review the literature on the association of the anthropometry and lifestyle characteristics with insulin sensitivity in overweight and obese adolescents, and include data from a new study. Relevant papers were selected and reviewed. In addition, 137 overweight and obese adolescents (42 male/95 female, age 14.4 ± 2.3 years, BMI z-score +3.3 ± 0.7, HOMA-IR 3.4 ± 1.8) from the Centre for Overweight Adolescent and Children's Healthcare (MUMC+) were included in this study. Anthropometrics, Tanner stages, sleep characteristics, food intake behaviour and physical activity were determined, and possible associations with homeostasis model assessment of insulin resistance (HOMA-IR) were tested., Results: Overweight and obese adolescents with unfavourable fat partitioning and family history of NIDDM are at risk for persistent IR. Overweight and obese adolescents from the new cohort showed a higher HOMA-IR postpubertally. BMI z-score, age, pubertal stage and prepubertally total sleeping time (TST) and sleep efficiency (SE) were identified as significant contributors. Overweight and obese adolescents showed a persistently higher instead of transiently higher HOMA-IR during puberty, associated with BMI z-score, age, pubertal stage and prepubertally less TST and SE., (© 2015 John Wiley & Sons Ltd.)