Trends in insulin resistance: insights into mechanisms and therapeutic strategy

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 6, 2022

The centenary of insulin discovery represents an important opportunity to transform diabetes from a fatal diagnosis into medically manageable chronic condition. Insulin is key peptide hormone and mediates the systemic glucose metabolism in different tissues. resistance (IR) disordered biological response for stimulation through disruption molecular pathways target Acquired conditions genetic factors have been implicated IR. Recent biochemical studies suggest that dysregulated metabolic mediators released by adipose tissue including adipokines, cytokines, chemokines, excess lipids toxic lipid metabolites promote IR other associated with several groups abnormal syndromes include obesity, diabetes, dysfunction-associated fatty liver disease (MAFLD), cardiovascular disease, polycystic ovary syndrome (PCOS), abnormalities. Although no medication specifically approved treat IR, we summarized lifestyle changes pharmacological medications used as efficient intervention improve sensitivity. Ultimately, systematic discussion complex mechanism will help identify potential new targets closely

Language: Английский

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Sex/Gender Differences in Obesity Prevalence, Comorbidities, and Treatment

Current Obesity Reports, Journal Year: 2021, Volume and Issue: 10(4), P. 458 - 466

Published: Oct. 2, 2021

Language: Английский

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Sex differences in type 2 diabetes

Diabetologia, Journal Year: 2023, Volume and Issue: 66(6), P. 986 - 1002

Published: March 10, 2023

Abstract The prevalence of type 2 diabetes mellitus is increasing in both sexes, but men are usually diagnosed at a younger age and lower body fat mass than women. Worldwide, an estimated 17.7 million more women have mellitus. Women appear to bear greater risk factor burden the time their diagnosis, especially obesity. Moreover, psychosocial stress might play prominent role Across lifespan, experience hormone fluctuations changes due reproductive factors men. Pregnancies can unmask pre-existing metabolic abnormalities, resulting diagnosis gestational diabetes, which appears be most for progression Additionally, menopause increases women’s cardiometabolic profile. Due progressive rise obesity, there global increase with pregestational often inadequate preconceptual care. There differences between regarding other cardiovascular respect comorbidities, manifestation complications initiation adherence therapy. show relative CVD mortality young currently less likely receive treatment reduction recommended by guidelines. Current medical recommendations do not provide information on sex-specific or gender-sensitive prevention strategies management. Thus, research sex differences, including underlying mechanisms, necessary evidence future. Nonetheless, intensified efforts screen glucose metabolism disorders factors, as well early establishment prophylactic measures aggressive management strategies, still required increased diabetes. In this narrative review we aim summarise clinical features into screening, treatment. Graphical abstract

Language: Английский

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Sexual dimorphism in cardiometabolic health: the role of adipose tissue, muscle and liver

Nature Reviews Endocrinology, Journal Year: 2020, Volume and Issue: 17(1), P. 47 - 66

Published: Nov. 10, 2020

Language: Английский

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Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease

Journal of Hepatology, Journal Year: 2021, Volume and Issue: 76(2), P. 283 - 293

Published: Oct. 9, 2021

Recent experimental models and epidemiological studies suggest that specific environmental contaminants (ECs) contribute to the initiation pathology of non-alcoholic fatty liver disease (NAFLD). However, underlying mechanisms linking EC exposure with NAFLD remain poorly understood there is no data on their impact human metabolome. Herein, we hypothesized ECs, particularly perfluorinated alkyl substances (PFAS), impacts metabolism, specifically bile acid metabolism.In a well-characterized cohort 105 individuals, investigated effects metabolism. We characterized (via biopsy) circulating metabolomes using 4 mass spectrometry-based analytical platforms, measured PFAS other ECs in serum. subsequently compared these results an study PPARa-humanized mouse model.PFAS appears associated perturbation key hepatic metabolic pathways previously found altered NAFLD, those related lipid identified stronger associations between metabolome, chemical NAFLD-associated clinical variables (liver fat content, HOMA-IR), females than males. Specifically, observed PFAS-associated upregulation acids, triacylglycerols ceramides, association dysregulated glucose metabolism females. The murine further corroborated our findings, vis-à-vis sex-specific changes.Females may be more sensitive harmful PFAS. Lipid-related changes subsequent secondary interplay metabolism.There increasing evidence contaminants, such as progression it how chemicals Here show processes effect different

Language: Английский

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The Role of Estrogen in Insulin Resistance

American Journal Of Pathology, Journal Year: 2021, Volume and Issue: 191(9), P. 1490 - 1498

Published: June 5, 2021

Language: Английский

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Sexual Dimorphism in Colon Cancer

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: Dec. 9, 2020

A higher incidence of colorectal cancer (CRC) is found in males compared to females. Young women (18-44 years) with CRC have a better survival outcome men the same age or older (over 50 years), indicating global sexual dimorphism rates and survival. This suggests protective role for sex steroid hormone estrogen development. Key proliferative pathways tumorigenesis exhibit dimorphism, which confer females through regulated genes cell signaling. Estrogen regulates activity class Kv channels (KCNQ1:KCNE3), control fundamental ion transport functions colon epithelial mesenchymal transition bi-directional interactions Wnt/β-catenin signalling pathway. also modulates responses hypoxia

Language: Английский

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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Jan. 5, 2021

Abstract Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence impaired men tolerance women, however, genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women 67,506/47,806 men) sex-combined (151,188/105,056 individuals) glucose/fasting insulin effects via genome-wide association study meta-analyses individuals European descent without diabetes. Here we report sex dimorphism allelic on at IRS1 ZNF12 loci, latter showing RNA expression whole blood compared men. also observe sex-homogeneous seven novel loci. Fasting shows stronger correlations than with waist-to-hip ratio anorexia nervosa. Furthermore, causally related resistance but These results position dissection metabolic glycemic health as steppingstone for understanding differences phenotypes.

Language: Английский

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Influence of Gender in Diabetes Mellitus and Its Complication

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 8850 - 8850

Published: Aug. 9, 2022

In medicine, there is growing evidence that gender differences are important and lead to variations in the pathophysiology treatment of many diseases with traits appear be particularly relevant influencing outcomes morbid forms. Today, inclusion biomedical research, improve scientific quality relevance knowledge, technology an increasingly present element precisely due practical implications derive from it. Gender describe biological variability between women men, which is, turn, related information contained sex chromosomes, specific gene expression autosomes linked sex, different number hormones, their effects on systems organs, without neglecting fact each sexes has target organs these hormones act. Additionally, both genders undergo metabolic changes throughout lives, this especially true for who show more dramatic role reproduction. not only result our genetic makeup but also mixed socio-cultural habits, behaviors, lifestyles, exposure environmental influences, food lifestyle styles or stress, attitude compliance treatments disease prevention campaigns. affect behavior life, physical can have lifestyle, social roles, mental health. Therefore, determinism therapeutic outcome chronic influenced by a complex combination factors, forgetting interactions factors men. This review will address management various forms diabetes its complications considering functions difference body composition, physiological glucose fat metabolism, microbiota. intestinal, as well description gestational possible pathophysiological events typical

Language: Английский

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Potential screening indicators for early diagnosis of NAFLD/MAFLD and liver fibrosis: Triglyceride glucose index–related parameters

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 2, 2022

Importance Homeostatic model assessment for insulin resistance (HOMA-IR) and triglyceride glucose (TyG) index–related parameters [TyG index, glucose–waist circumference (TyG-WC), glucose–waist-to-height ratio (TyG-WHtR), glucose–body mass index (TyG-BMI)] are gradually considered as convenient alternative indicators in various metabolic diseases, but the specific diagnostic capacity comparison of non-alcoholic fatty liver disease (NAFLD), metabolic-associated (MAFLD), fibrosis remain uncertain. Objective To comprehensively assess compare accuracy above NAFLD, MAFLD, identify appropriate indicators. Methods A total 1,727 adults were enrolled from 2017–2018 National Health Nutrition Examination Surveys. Logistic regressions used to significantly associated with fibrosis; receiver operating characteristic (ROC) curves evaluate their capacity. Subgroup analyses conducted validate concordance, optimal cutoff values determined according Youden’s indexes. Results Significant differences observed between quartile-stratified HOMA-IR TyG across ( P < 0.05). All variables predictive different states The top three AUC TyG-WC, TyG-WHtR, TyG-BMI AUCs 0.815, 0.809, 0.804 NAFLD. 822.34, 4.94, 237.77, respectively. Similar same trend indexes could be MAFLD fibrosis. showed consistent results primary research, despite some heterogeneity. Conclusions can early screening NAFLD MAFLD. These more suitable assessing risks monitoring progression patients

Language: Английский

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