Incretin Hormones in Obesity and Related Cardiometabolic Disorders: The Clinical Perspective.
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ABSTRACT:
SUBMITTER: Michalowska J
PROVIDER: S-EPMC7910956 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA complex set of perturbations occur in cytokines and hormones in the etiopathogenesis of obesity and related cardiometabolic conditions such as type 2 diabetes (T2D). Evidence for the genetic regulation of these cytokines and hormones is limited, particularly in African-ancestry populations. In order to improve our understanding of the biology of cardiometabolic traits, we investigated the genetic architecture of a large panel of obesity- related cytokines and hormones among Africans with replication analyses in African Americans.MethodsWe performed genome-wide association studies (GWAS) in 4432 continental Africans, enrolled from Ghana, Kenya, and Nigeria as part of the Africa America Diabetes Mellitus (AADM) study, for 13 obesity-related cytokines and hormones, including adipsin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), interleukin-1 receptor antagonist (IL1-RA), interleukin-6 (IL-6), interleukin-10 (IL-10), leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, visfatin, insulin, glucagon, and ghrelin. Exact and local replication analyses were conducted in African Americans (n = 7990). The effects of sex, body mass index (BMI), and T2D on results were investigated through stratified analyses.ResultsGWAS identified 39 significant (P value < 5 × 10-8) loci across all 13 traits. Notably, 14 loci were African-ancestry specific. In this first GWAS for adipsin and ghrelin, we detected 13 and 4 genome-wide significant loci respectively. Stratified analyses by sex, BMI, and T2D showed a strong effect of these variables on detected loci. Eight novel loci were successfully replicated: adipsin (3), GIP (1), GLP-1 (1), and insulin (3). Annotation of these loci revealed promising links between these adipocytokines and cardiometabolic outcomes as illustrated by rs201751833 for adipsin and blood pressure and locus rs759790 for insulin level and T2D in lean individuals.ConclusionsOur study identified genetic variants underlying variation in multiple adipocytokines, including the first loci for adipsin and ghrelin. We identified population differences in variants associated with adipocytokines and highlight the importance of stratification for discovery of loci. The high number of African-specific loci detected emphasizes the need for GWAS in African-ancestry populations, as these loci could not have been detected in other populations. Overall, our work contributes to the understanding of the biology linking adipocytokines to cardiometabolic traits.
| S-EPMC8499470 | biostudies-literature
Project description:BACKGROUND:Sepsis, a complex disorder characterized by a dysregulated immune response to an inciting infection, affects over one million Americans annually. Dysglycemia during sepsis hospitalization confers increased risk of organ dysfunction and death, and novel targets for the treatment of sepsis and maintenance of glucose homeostasis are needed. Incretin hormones are secreted by enteroendocrine cells in response to enteral nutrients and potentiate insulin release from pancreatic ? cells in a glucose-dependent manner, thereby reducing the risk of insulin-induced hypoglycemia. Incretin hormones also reduce systemic inflammation in preclinical studies, but studies of incretins in the setting of sepsis are limited. METHODS:In this bench-to-bedside mini-review, we detail the evidence to support incretin hormones as a therapeutic target in patients with sepsis. We performed a PubMed search using the medical subject headings "incretins," "glucagon-like peptide-1," "gastric inhibitory peptide," "inflammation," and "sepsis." RESULTS:Incretin-based therapies decrease immune cell activation, inhibit proinflammatory cytokine release, and reduce organ dysfunction and mortality in preclinical models of sepsis. Several small clinical trials in critically ill patients have suggested potential benefit in glycemic control using exogenous incretin infusions, but these studies had limited power and were performed in mixed populations. Further clinical studies examining incretins specifically in septic populations are needed. CONCLUSIONS:Targeting the incretin hormone axis in sepsis may provide a means of not only promoting euglycemia in sepsis but also attenuating the proinflammatory response and improving clinical outcomes.
| S-EPMC6763279 | biostudies-literature
Project description:Obesity remains the most prevailing disorder in childhood males and females worldwide. Its high prevalence markedly predisposes children to insulin resistance, hypertension, hyperlipidemia and liver disorders while enhancing the risk of type 2 diabetes and cardiovascular diseases. In this review, the relationship of obesity with genetic and environmental factors will be described and the underlined causes will briefly be reported. As obesity in children constitutes an increasingly health concern, important potential biomarkers have been discussed for the diagnosis, treatment and follow-up of the wide range of overweight-related complications. Awareness about the applicability and limitations of these preventive and predictive biomarkers will intensify the research and medical efforts for new developments in order to efficiently struggle against childhood obesity.
| S-EPMC5387697 | biostudies-literature
Project description: Not available
| S-EPMC3809929 | biostudies-literature
Project description:ObjectivesThis study aimed to evaluate the cardiometabolic abnormalities in women with normal-weight obesity (NWO) in comparison with lean, overweight, and obese women.MethodsThis cross-sectional study evaluated the assessment of cardiometabolic abnormalities of women with NWO compared to lean, overweight, and obese women. NWO was defined as a BMI < 25 kg.m-2 and a BFP higher than 30%. Anthropometric variables, cardiometabolic abnormality markers (fasting blood glucose (FBG), blood pressure (BP), lipid profile, insulin resistance, and high-sensitivity C-reactive protein (hs-CRP)), and liver enzymes were also examined.ResultsSignificant differences were observed in HDL concentrations between NWO, lean, and obese participants (p < 0.05). There were no significant differences in FBG, insulin resistance, liver enzymes, or cholesterol between groups (p > 0.05). The prevalence of the abnormal metabolic phenotype was higher in NWO compared to the lean group (4.0% and 24.1%, respectively; p < 0.05). Women with type 2 and 3 obesity had abnormal metabolic profiles (60.9% and 73.9%, respectively) compared to NWO participants (p < 0.01). The NWO group had a significantly higher incidence of cardiometabolic abnormalities compared to the lean participants (p < 0.05), while the type 2 and 3 obese individuals had significantly higher incidences compared to the NWO group (p < 0.001 and p < 0.001, respectively).ConclusionsIndividuals with NWO had a significantly higher incidence of cardiometabolic abnormalities when compared to lean participants. These abnormalities strongly relate to BFP and waist circumferences.
| S-EPMC9953250 | biostudies-literature
Project description:Incretin hormones, such as glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, are secreted on oral nutrient ingestion and regulate postprandial glucose homeostasis by conveying the signal of intestinal glucose flux. In East Asians, the secretion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 is not reduced in type 2 diabetes relative to normal glucose tolerance. Although the incretin effect is blunted in European patients with type 2 diabetes, a few East Asian studies showed no difference in the incretin effect between type 2 diabetes and normal glucose tolerance. Interestingly, the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 receptor agonists was reported to be greater in Asians than in non-Asians. The difference in the treatment responses could be ascribed to a different pathophysiology of type 2 diabetes (lower insulin secretory function and less insulin resistance), lower body mass index, different genetic makeups, preserved incretin effect and different food compositions in East Asians compared with other ethnic groups. Based on the currently available data, incretin-based therapies appear to be safe and well tolerated in East Asians. Nevertheless, continuous pharmacovigilance is required. The characteristics of incretin biology and treatment responses to incretin-based therapies should be considered in developing ethnicity-specific treatment guidelines and making patient-centered decisions for patients with type 2 diabetes.
| S-EPMC4578486 | biostudies-literature
Project description:There is considerable evidence that some dietary patterns contribute to obesity and metabolic disorders but there is less data on diet's association with different health parameters. We investigated the interaction between different dietary patterns and anthropometric, biochemical, lifestyle, and psychological health parameters in a Greek population with obesity and metabolic disorders. To the best of our knowledge, this is the first study in Greece with a thorough and holistic approach in analyzing such relationships. For assessing food patterns, revealing underlying structures, and reducing the number of variables we applied exploratory factor analysis (EFA). Principal Component Analysis was chosen as the extraction method using Varimax rotation, and three regression sets were computed. The study involved 146 Greek metabolically unhealthy obese adults, both men and women. Our cohort was categorized into four dietary patterns: "Western type diet", "Mediterranean-like diet", "Healthy diet", and "Animal meat and sauces diet". Dietary patterns characterized by a high consumption of energy-dense and animal-derived foods were positively associated with anthropometric and biochemical parameters related to metabolic disorders. Plant-based, healthier dietary patterns, on the other hand, were associated with better biochemical and mental health profiles among metabolically unhealthy obese individuals.
| S-EPMC9738070 | biostudies-literature
Project description:The baroreflex represents a rapid negative feedback system implicated in blood pressure regulation, which aims to prevent blood pressure variations by regulating peripheral vascular tone and cardiac output. The aim of the present review was to highlight the association between baroreflex sensitivity (BRS) and obesity, including factors associated with obesity, such as metabolic syndrome, hypertension, cardiovascular disease and diabetes. For the present review, a literature search was conducted using the PubMed database until August 21, 2021. The searched terms included 'baroreflex', and other terms such as 'sensitivity', 'obesity', 'metabolic syndrome', 'hypertension', 'diabetes', 'gender', 'aging', 'children', 'adolescents', 'physical activity', 'bariatric surgery', 'autonomous nervous system' and 'cardiometabolic risk factors'. Obesity and its related metabolic disorders can influence baroreflex functionality and decrease BRS, mostly by potentiating sympathetic nervous system activity. Obesity induces inflammation, which can increase sympathetic system activity and lead to a higher incidence of cardiovascular events. Obesity also represents an important risk factor for hypertension through numerous mechanisms; in this setting, dysfunctional baroreceptors are not able to protect against constantly elevated blood pressure. Furthermore, diabetes mellitus and oxidative stress result in deterioration of BRS, whereas aging is also generally related to reduced cardiovagal BRS. Differences in BRS have also been observed between men and women, and overall cardiovagal BRS in healthy women is less intense compared with that in men. BRS appears lower in children with obesity compared with that in children of a healthy weight. Notably, physical exercise can increase BRS in both hypertensive and normotensive subjects, and BRS can also be significantly improved following bariatric surgery and weight loss. In conclusion, obesity and its related metabolic disorders may influence baroreflex functionality and decrease BRS, and baroreceptors cannot protect against the constantly elevated blood pressure in obesity. However, following bariatric surgery and weight loss, BRS can be significantly improved. The present review summarizes the role of obesity and related metabolic risk factors in BRS, providing details on possible mechanisms and shedding light on their interplay leading to autonomic neuropathy.
| S-EPMC8649854 | biostudies-literature
Project description:Background:Noncommunicable diseases (NCDs) are considered as a global health problem and considered as a public health priority with the more considerable increasing trend of obesity and cardiometabolic disorders rates in the Middle Eastern countries. This systematic review aims at assessing the prevalence, incidence rates, and trends, as well as the cost of obesity and related cardiometabolic disorders in the United Arab Emirates (UAE). Methods:A highly sensitive strategy was used to retrieve original observational studies, addressing the epidemiology and cost of obesity and related cardiometabolic disorders in the UAE, irrespective of nationality (nationals and expatriates). The search was conducted on April 4, 2017, within numerous electronic databases and the grey literature. Standardized and validated methods were used for data extraction and analysis as well as quality assessment. Results:6789 records were retrieved, of which 36 were deemed eligible. High prevalence rates were reported for obesity, diabetes, hypertension, and metabolic syndrome in all studies. However, the definitions and methods employed by the studies were highly variable. The risk of bias in the epidemiological studies ranged between low and medium. Only one study reported the cost of illness for diabetes. In this study, the estimated cost per patient was $2,015 (adjusted to the year 2015), and it became twofold and sixfold higher in patients with microvascular and macrovascular complications, respectively. Conclusions:Obesity and related cardiometabolic disorders are highly prevalent in the UAE, but quoting a precise prevalence for them is difficult given the methodological heterogeneity of the epidemiological studies addressing them. Nonetheless, we detected a 2-3-fold increase in the prevalence of overweight and obesity in the UAE between 1989 and 2017. It is hopeful that this systematic review will provide an insight into direct future studies, especially longitudinal studies exploring obesity and cardiometabolic risks and their costs.
| S-EPMC6311818 | biostudies-literature
Project description:Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role.We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE.Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review.We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a central action of estrogens to increase the satiating potency of the gastrointestinal hormone cholecystokinin. Another mechanism involves a decrease in the preference for sweet foods during the follicular phase. Genetic defects in brain ?-melanocycte-stimulating hormone-melanocortin receptor (melanocortin 4 receptor, MC4R) signaling lead to a syndrome of overeating and obesity that is particularly pronounced in women and in female animals. The syndrome appears around puberty in mice with genetic deletions of MC4R, suggesting a role of ovarian hormones. Emerging functional brain-imaging data indicates that fluctuations in ovarian hormones affect eating by influencing striatal dopaminergic processing of flavor hedonics and lateral prefrontal cortex processing of cognitive inhibitory controls of eating. There is a dearth of research on the neuroendocrine control of eating after menopause. There is also comparatively little research on the effects of ovarian hormones on EE, although changes in ovarian hormone levels during the menstrual cycle do affect resting EE.The markedly greater obesity burden in women makes understanding the diverse effects of ovarian hormones on eating, EE and body adiposity urgent research challenges. A variety of research modalities can be used to investigate these effects in women, and most of the mechanisms reviewed are accessible in animal models. Therefore, human and translational research on the roles of ovarian hormones in women's obesity and its causes should be intensified to gain further mechanistic insights that may ultimately be translated into novel anti-obesity therapies and thereby improve women's health.
| S-EPMC5850121 | biostudies-literature