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OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially for type 2 diabetes mellitus, show promise in promoting weight loss and improving heart health in obese individuals without diabetes. Our goal was to examine existing research for conclusive evidence on various types of GLP-1 RAs for weight loss and cardiometabolic benefits in obesity without diabetes. METHODS: We conducted an electronic search on PubMed, Scopus, and Cochrane Central using keywords, such as "GLP-1 RA," "obesity," and "weight loss." We considered all available global GLP-1 RAs for inclusion. Our analysis focused on weight loss, blood pressure (BP) changes (systolic and diastolic BPs), and lipid profile effects (high-density lipoprotein, low-density lipoprotein, total cholesterol, and triacylglycerol). We used a random-effects meta-analysis with the standardized mean difference (SMD), mean difference (MD), odds ratio, and relative risk to present the results. RESULTS: Our search yielded a total of 7535 articles. We included 15 trials in our study. GLP-1 RAs led to significant weight loss (MD, -8.77 kg; P <.01) in obese individuals. GLP-1 RAs also improved the systolic BP (MD, -4.13 mm Hg; P <.01), diastolic BP (MD, -1.39 mm Hg; P <.01), and lipid profiles, including improved levels of triacylglycerol (SMD, -0.99 mg/dL; P <.01), total cholesterol (SMD, -0.73 mg/dL; P <.01), very low-density lipoprotein (SMD, -1.11 mg/dL; P <.01), and low-density lipoprotein (SMD, -0.27 mg/dL; P <.01), and significantly increased high-density lipoprotein levels (SMD, 0.11 mg/dL; P <.01). However, GLP-1 RAs were associated with an increased risk of gastrointestinal adverse events. CONCLUSION: GLP-1 RAs were found to be beneficial for not only weight loss but also reduction in risk factors for cardiovascular disease such as BP and lipid profile. Consistent beneficial results were observed across the various subtypes of GLP-1 RAs.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemiantes/efectos adversos , Agonistas Receptor de Péptidos Similares al Glucagón , Péptido 1 Similar al Glucagón/efectos adversos , Obesidad/tratamiento farmacológico , Obesidad/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Pérdida de Peso , Lípidos , Triglicéridos , Lipoproteínas HDL , Lipoproteínas LDL , Colesterol , Receptor del Péptido 1 Similar al Glucagón/agonistasRESUMEN
Deletion of the tryptophan 2,3-dioxygenase ( TDO2 ) gene induces an anxiolytic-like behaviour in mice and TDO inhibition by allopurinol elicits an antidepressant-like effect in rats exposed to restraint stress. Chronic nicotine administration inhibits TDO activity, enhances brain serotonin synthesis and exerts anxiolytic- and antidepressant-like effects in rodent models. There is a strong association between anxiety, depression and tobacco use, which is stronger in women than in men. The present study aimed to examine the relationship between behavioural measures of anxiety and depression with liver TDO activity, brain tryptophan concentration and serotonin synthesis in rats treated chronically with nicotine. Behavioural measures included the elevated plus maze (EPM), open field (OFT) and forced swim (FST) tests. Biochemical measures included TDO activity, serum corticosterone and brain Trp, 5-HT and 5-HIAA concentrations. Anxiolytic-like and antidepressant-like effects of chronic nicotine were confirmed in association with TDO inhibition and elevation of brain Trp and 5-HT. Sex differences in behaviour were independent of the biochemical changes. At baseline, female rats performed better than males in OFT and FST. Nicotine was less anxiolytic in females in the open arm test. Nicotine treatment did not elicit different responses between sexes in the FST. Our findings support the notion that liver TDO activity exhibits a strong association with behavioural measures of anxiety and depression in experimental models, but provide little evidence for sex differences in behavioural response to nicotine. The TDO-anxiety link may be underpinned by kynurenine metabolites as well as serotonin.
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Ansiolíticos , Dioxigenasas , Ratas , Femenino , Ratones , Masculino , Animales , Triptófano/metabolismo , Triptófano Oxigenasa/metabolismo , Triptófano Oxigenasa/farmacología , Serotonina/metabolismo , Nicotina/farmacología , Dioxigenasas/farmacología , Ansiolíticos/farmacología , Antidepresivos/farmacología , Ansiedad , Hígado/metabolismo , Depresión/tratamiento farmacológicoRESUMEN
Nicotine is the principal addictive agent present in Naswar, a smokeless dipping tobacco product. 5-Hydroxytryptamine (5-HT) has been implicated in the reinforcement properties of nicotine. Also, the hypothalamic-pituitary-adrenal (HPA) axis is of vital importance in evaluating the response to stress and nicotine addiction. The study aimed to evaluate serum tryptophan and cortisol levels in Naswar users in relation to addiction. Additionally, serum cotinine levels were also determined to assess daily nicotine exposure. The study comprised 90 healthy Naswar users and 68 non-tobacco users. Estimation of serum cortisol, tryptophan and albumin was carried out. From the Naswar user group, 20 were selected for the estimation of serum cotinine for which blood was drawn twice first in the morning and then in the evening. Serum tryptophan and cortisol levels in Naswar users were significantly raised compared to the control group. However, no difference in the levels of albumin between Naswar users and the control group were found. The mean cotinine values rose from the morning value of 366.0 ± 40.69 ng/ml (mean ± SEM) to an evening value of 503.1 ± 42.96 ng/ml that in turn is equivalent to consumption of 40 cigarettes. Elevated cortisol levels might constitute an important aspect of Naswar addiction. Additionally, raised levels of serum tryptophan in Naswar users could lead to raised concentration of 5-HT which also might be a significant factor contributing to Naswar addiction. Also, serum cotinine concentrations equivalent to an intake of about 40 cigarettes per day is quite alarming.
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Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Tabaco sin Humo/efectos adversos , Triptófano/sangre , Adolescente , Adulto , Conducta Adictiva , Estudios de Casos y Controles , Cotinina/sangre , Humanos , Hidrocortisona/análisis , Masculino , Nicotina/efectos adversos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Naswar is a type of finely ground, moistened smokeless dipping tobacco product being commonly used in Pakistan. Although, nicotine is the most important psychoactive agent present in Naswar, it also exerts immunosuppressive effects and could alter the levels of cytokines. Additionally, the effects of Naswar consumption on thyroid hormones are not known. METHODS: Eighty healthy males aged 16-43 years were selected for the study and were divided into a control group comprising 31 healthy subjects with no history of tobacco use in any form, with age matched test group comprising 49 exclusive Naswar users who were consuming Naswar for at least 1 year. Estimation of serum interleukin (IL)-1ß, IL-6, free thyroxine (FT4), free triiodothyronine (FT3) and thyroid stimulating hormone (TSH) was carried out. The data was analyzed by statistical programme (SPSS) using student's independent samples t-test. One way Anova followed by post hoc Tukey test was applied to assess parameters in Naswar users grouped according to duration of Naswar usage. Pearson's correlation coefficient was applied to assess correlations between parameters. RESULTS: IL-1ß was found to be significantly lowered in Naswar users compared to the control group whereas serum FT3 and FT4 levels in Naswar users were significantly raised compared to the control group. However, no differences in the levels of serum IL-6 and TSH between Naswar users and the control group were found. Also, serum FT3 and FT4 were consistently raised whereas IL-1ß was lowered in Naswar users irrespective of duration of Naswar consumption. IL-1ß was negatively correlated with FT3 in Naswar users. CONCLUSION: The findings suggest that Naswar users might be in an immune suppressive state as evident by the lowered levels of interleukin 1ß. Additionally, alterations in the levels of thyroid hormones signify the impact of Naswar consumption on thyroid function.
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Interleucina-1beta/sangre , Interleucina-6/sangre , Glándula Tiroides/efectos de los fármacos , Uso de Tabaco/efectos adversos , Adolescente , Adulto , Humanos , Masculino , Pakistán , Pruebas de Función de la Tiroides , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
Dipping tobacco, traditionally referred to as moist snuff, is a type of finely ground, moistened smokeless tobacco product. Naswar is stuffed in the floor of the mouth under the lower lip, or inside the cheek, for extended periods of time. Tobacco use causes dyslipidemia and also induces oxidative stress, leading to alteration in levels of antioxidant enzymes. Dyslipidemia and oxidative stress in turn play a vital role in the development of cardiovascular disease (CVD). Studies conducted on smokeless tobacco products reveal contradictory findings regarding its effects on lipid profile and antioxidant enzymes. As use of Naswar is quite common in Pakistan, the current study aimed to evaluate levels of the antioxidant enzymes viz glutathione per oxidase (GPx) and super oxide dismutase (SOD), alongside lipid profile parameters such as total cholesterol, triglycerides, High density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) to assess the risk of adverse cardiovascular events in Naswar users.90 Healthy males aged 16-43 years, who consumed Naswar daily, were selected for the study, alongside 68 age-matched non-tobacco users as controls. Both GPx and SOD levels as well as serum HDL-C were significantly reduced (P<0.01) in Naswar users, whereas serum total cholesterol, LDL-C, triglycerides and LDL-C/HDL-C ratio were significantly increased (P<0.01) in Naswar consumers compared to controls. Our findings indicate deleterious effects of Naswar usage on health by causing altered lipid profile and antioxidant enzymes thereby placing its consumers at an increased risk of cardiovascular disease.
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Antioxidantes/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Tabaco sin Humo/efectos adversos , Adolescente , Adulto , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Glutatión Peroxidasa/análisis , Glutatión Peroxidasa/metabolismo , Humanos , Lípidos/sangre , Masculino , Superóxido Dismutasa/análisis , Superóxido Dismutasa/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: To determine the problems faced by thalassemic patients in their personal, psychological and social life. STUDY DESIGN: A cross-sectional multi-centre survey. PLACE AND DURATION OF STUDY: Karachi, Lahore and Quetta Centres of Fatimid Foundation, from October 2009 to October 2010. METHODOLOGY: An indigenously developed Qualifty of Life (QoL) questionnaire modified from SF-36 questionnaire was administered to 101 transfusion dependent subjects suffering from thalassemia major. Variables were analyzed using SPSS version 15 for descriptive statistics. RESULTS: The mean age of the subjects was 10.5 years ranging from 6 - 21 years. Less than one third of the patients felt that their health was slightly worse as compared to last year. Forty five (44%) of the patients felt loneliness due to their disease. Parents of 36 (35.6%) of the children at times did not allow their children to play because of their disease. Twenty eight (27.7%) stated difficulty in mingling with children of their age. Seventy one (70.3%) of the patients reported that at some or all times they were worried about their future life and career while 70 (69.3%) admitted being taken extra care of by their friends and 56 (55.4%) by their teachers. CONCLUSION: The quality of life of surveyed thalassemic patients was immensely affected. Having physical impairments, social stresses, financial burdens and problems with their education and career make them very much vulnerable to psychological trauma very early in their life. All of this creates a hindrance in their way of developing into autonomous functioning adults.