UMLS:C0242339 - FACTA Search

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Obesity has become an increasingly important public health problem. Recent evidence suggests that obesity has become a close second to tobacco use as a preventable cause of death in the United States. During the past decade an increase in the prevalence of type 2 diabetes in adolescents has been observed. The association of type 2 diabetes and obesity is well established and most adolescents with type 2 diabetes have body mass index (BMI) in a range that would already be considered obese in an adult. Childhood overweight is also associated with the atherosclerotic process. In the Bogalusa autopsy study, Berenson et al. found that the extent of fatty streaks and fibrous plaques in the aorta and coronary arteries was associated with BMI. There are three modalities currently available for the treatment of overweight in children and adolescents, including behavioral approaches, pharmacologic approaches, and surgical approaches. Surgical intervention may be considered if the BMI > or = 40 kg/m2 and a severe medical comorbidity including type 2 diabetes, obstructive sleep apnea or pseudotumor cerebri, or if the BMI is > or = 50 kg/m2 and comorbid conditions such as hypertension, dyslipidemia, or the metabolic syndrome are present. Behavioral intervention is usually made by a psychologist, behavioral therapist, dietician, or exercise physiologist. There is evidence that the effect of behavioral therapy for weight loss in childhood will be longer lasting than that seen in adults.
Pediatr Blood Cancer 2005 Jun 15
PMID:Regulation of body mass and management of childhood overweight. 1570 Feb 53

Obesity is the most common nutritional disorder in the Western world. Actually, 250 million adults are obese, and 500 million adults and 22 million children under 5 years of age are overweight. Obesity is a complex trait, depending upon interactions between multiple genes and the environment, but its recent rise and "epidemic proportions" are, above all, the consequences of dramatic changes in lifestyle, socioeconomic progress, and political and cultural trends. Eating behavior has strong extraphysiological determinants, being influenced by neuroendocrine, nutritional, environmental, and cognitive stimuli, able to modify the body weight set-point. Health care professionals should be concerned about obesity, because of the well-established relations between excess body weight and pathologies such as type II diabetes, hypertension, atherosclerosis, osteoarthritis, dyslipidemia, and cancer, which afflict more and more people in the Western world--sort of "well-being syndromes." An overview of modern Western diets--the American, Mediterranean, Atkins, and Zone diets--reveals the contradictions existing about the correct and healthy approach to human nutrition and suggests a "return to Nature." From the actual artificial nutrition systems, based on cereals, milk, and their products, irrespective of our genome and metabolic attitudes, a simple diet based on natural food can be an ally in health maintenance and restoration.
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PMID:A natural diet versus modern Western diets? A new approach to prevent "well-being syndromes". 1571 28

The importance of epigenetic alterations has been acknowledged in cancer for about two decades by an increasing number of molecular oncologists who contributed to deciphering the epigenetic codes and machinery and opened the road for a new generation of drugs now in clinical trials. However, the relevance of epigenetics to common diseases such as metabolic syndrome and cardiovascular disease was less conspicuous. This review focuses on converging data supporting the hypothesis that, in addition to "thrifty genotype" inheritance, individuals with metabolic syndrome (MetS)--combining disturbances in glucose and insulin metabolism, excess of predominantly abdominally distributed weight, mild dyslipidemia and hypertension, with the subsequent development of obesity, type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD)--have suffered improper "epigenetic programming" during their fetal/postnatal development due to maternal inadequate nutrition and metabolic disturbances and also during their lifetime. Moreover, as seen for obesity and T2D, MetS tends to appear earlier in childhood, to be more severe from generation to generation and to affect more pregnant women. Thus, in addition to maternal effects, MetS patients may display "transgenerational effects" via the incomplete erasure of epigenetic marks endured by their parents and grandparents. We highlight the susceptibility of epigenetic mechanisms controlling gene expression to environmental influences due to their inherent malleability, emphasizing the participation of transposable elements and the potential role of imprinted genes during critical time windows in epigenetic programming, from the very beginning of development throughout life. Increasing our understanding on epigenetic patterns significance and small molecules (nutrients, drugs) that reverse epigenetic (in)activation should provide us with the means to "unlock" silenced (enhanced) genes, and to "convert" the obsolete human thrifty genotype into a "squandering" phenotype.
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PMID:[Nutritional epigenomics of metabolic syndrome]. 1581 5

The introduction of novel antipsychotics for the treatment of patients with serious psychiatric illness has alleviated the burden of managing some of the side effects of conventional agents. However, the novel agents may also cause adverse events. The long-term adverse events of concern include weight gain, diabetes, tardive dyskinesia (TD), and those associated with hyperprolactinemia. Recent studies with the novel agents have prompted clinicians to revisit antipsychotic-induced weight gain. Clinically significant weight gain puts patients at risk for coronary heart disease, hypertension, type II diabetes, dyslipidemia, and some types of cancer. More recently, case reports of glucose abnormalities and diabetes have emerged, indicating that some novel antipsychotics may be associated with altered glucose metabolism or insulin sensitivity. The novel antipsychotics may also have a lower propensity for causing TD than the conventional antipsychotics. Side effects associated with hyperprolactinemia include galactorrhea, gynecomastia, and menstrual and sexual dysfunction. All of these adverse events can cause patients to become non-compliant and may thus predispose them to relapse. In this review, the authors summarize the literature on the long-term side effects of the novel antipsychotics and examine the severity of the problem, with recommendations for management. When selecting treatments, clinicians should consider the side-effect profiles of the various antipsychotic agents.
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PMID:Long-term adverse effects of novel antipsychotics. 1599 Apr 91

Studies published before the introduction of highly active antiretroviral therapy (HAART) have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac disease.The introduction of HAART regimens, by preventing opportunistic infections and reducing the incidence of myocarditis, has reduced the prevalence of HIV-associated cardiomyopathy of about 30% and the prevalence of cardiac involvement of AIDS-associated malignancies of about 50%. However, HAART regimens, especially those including protease inhibitors have been shown to cause, in a high proportion of HIV-infected patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease (approximately 1.4 cardiac events per 1000 years of therapy according to the Framingham score). A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART according to the most recent clinical guidelines is needed.
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PMID:Reviewing the cardiovascular complications of HIV infection after the introduction of highly active antiretroviral therapy. 1610 66

Obesity is a known cause of metabolic syndrome which includes Type II diabetes, hypertension, and dyslipidemia. It is well documented that insulin resistance contributes to the mortality and the incidence of metabolic syndromes including central obesity, dyslipidemia, hyperglycemia and hypertension. Both obesity and diabetes are emerging topics for researchers to consider as having a possible causal association with cancer since the two factors have been viewed as risk factors for cancer. The present paper introduced the hypothesis of a possible causal relationship between obesity, insulin resistance and cancer and reviews relevant existing studies in this area. More efforts and studies are needed to clarify the mechanisms and the common risk factors which might be incorporated into interventions to prevent cancer and cardiovascular diseases as top causes of death.
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PMID:Obesity, insulin resistance and cancer risk. 1612 67

Metabolism, in part, is regulated by the peroxisome proliferator-activated receptors (PPARs). The PPARs act as nutritional lipid sensors and three mammalian PPAR subtypes designated PPARalpha (NR1C1), PPARgamma (NR1C3) and PPARdelta (NR1C2) have been identified. This subgroup of nuclear hormone receptors binds DNA and controls gene expression at the nexus of pathways that regulate lipid and glucose homeostasis, energy storage and expenditure in an organ-specific manner. Recent evidence has demonstrated activation of PPARdelta in the major mass peripheral tissue (ie, adipose and skeletal muscle). It enhances glucose tolerance, insulin-stimulated glucose disposal, lipid catabolism, energy expenditure, cholesterol efflux and oxygen consumption. These effects positively influence the blood-lipid profile. Furthermore, PPARdelta activation produces a predominant type I/slow twitch/oxidative muscle fiber phenotype that leads to increased endurance, insulin sensitivity and resistance to obesity. PPARdelta has rapidly emerged as a potential target in the battle against dyslipidemia, insulin insensitivity, type II diabetes and obesity, with therapeutic efficacy in the treatment of cardiovascular disease risk factors. GW-501516 is currently undergoing phase II safety and efficacy trials in human volunteers for the treatment of dyslipidemia. The outcome of these clinical trials are eagerly awaited against a background of conflicting reports about cancer risks in genetically predisposed animal models. This review focuses on the potential pharmacological utility of selective PPARdelta agonists in the context of risk factors associated with metabolic and cardiovascular disease.
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PMID:Cardiovascular disease and PPARdelta: targeting the risk factors. 1618 88

The peroxisome proliferator-activated receptor gamma (PPARgamma) is an important therapeutic drug target for several conditions, including diabetes, inflammation, dyslipidemia, hypertension, and cancer. It is shown that an antagonist or partial agonist of PPARgamma has attractive potential applications in the discovery of novel antidiabetic agents that may retain efficacious insulin-sensitizing properties and minimize potential side effects. In this work, the dipeptide H-Trp-Glu-OH (G3335) was discovered to be a novel PPARgamma antagonist. Biacore 3000 results based on the surface plasmon resonance (SPR) technique showed that G3335 exhibits a highly specific binding affinity against PPARgamma (K(D) = 8.34 microM) and is able to block rosiglitazone, a potent PPARgamma agonist, in the stimulation of the interaction between the PPARgamma ligand-binding domain (LBD) and RXRalpha-LBD. Yeast two-hybrid assays demonstrated that G3335 exhibits strong antagonistic activity (IC50 = 8.67 microM) in perturbing rosiglitazone in the promotion of the PPARgamma-LBD-CBP interaction. Moreover, in transactivation assays, G3335 was further confirmed as an antagonist of PPARgamma in that G3335 could competitively bind to PPARgamma against 0.1 microM rosiglitazone to repress reporter-gene expression with an IC50 value of 31.9 muM. In addition, homology modeling and molecular-docking analyses were performed to investigate the binding mode of PPARgamma-LBD with G3335 at the atomic level. The results suggested that residues Cys285, Arg288, Ser289, and His449 in PPARgamma play vital roles in PPARgamma-LBD-G3335 binding. The significance of Cys285 for PPARgamma-LBD-G3335 interaction was further demonstrated by PPARgamma point mutation (PPARgamma-LBD-Cys285Ala). It is hoped our current work will provide a powerful approach for the discovery of PPARgamma antagonists, and that G3335 might be developed as a possible lead compound in diabetes research.
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PMID:The dipeptide H-Trp-Glu-OH shows highly antagonistic activity against PPARgamma: bioassay with molecular modeling simulation. 1631 83

Evidence suggests that hypertension may share a similar pathophysiology with cardiovascular disease (CVD). Thus, dyslipidemia, a strong predictor of CVD, may also predict incident hypertension. We analyzed 3110 men free of hypertension, CVD, and cancer from the Physicians' Health Study, who provided baseline blood samples from which we measured total cholesterol (TC) and HDL cholesterol (HDL-C), and calculated non-HDL-C and the TC/HDL-C ratio. We categorized each lipid parameter into quintiles and considered National Cholesterol Education Project clinical cut points. Other risk factor information was provided from self-reports on the baseline questionnaire. Incident hypertension was defined as either the initiation of antihypertensive treatment, self-reported systolic blood pressure > or =140 mm Hg, or diastolic blood pressure > or =90 mm Hg. Over a mean follow-up of 14.1 years, 1019 men developed hypertension. In Cox proportional hazards models adjusted for lifestyle and clinical risk factors, men in the highest quintile of TC, non-HDL-C, and TC/HDL-C ratio had increased risks of developing hypertension of 23%, 39%, and 54%, respectively, compared with participants in the lowest quintile. Furthermore, men in the highest quintile of HDL-C had a 32% decreased risk of developing hypertension compared with those in the lowest quintile. Models using National Cholesterol Education Project cut points demonstrated similar associations with hypertension. Models excluding men with diabetes and obesity maintained an independent association between baseline lipids and hypertension. These prospective cohort data suggest that dyslipidemias may lead to the subsequent development of hypertension. Thus, plasma lipids may be useful in the identification of men at risk for hypertension.
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PMID:Dyslipidemia and the risk of incident hypertension in men. 1634 75

Weight gain is associated with the use of many psychotropic medications, including antidepressants, mood stabilizers, antipsychotic drugs, and may have serious long term consequences: it can increase health risks, specifically from overweight (BMI = 25-29.9 kg/m2) to obesity (BMI > or =30 kg/m2), according to Body Mass Index (BMI), and the morbidity associated therewith in a substantial part of patients (hypertension, coronary heart desease, ischemic stroke, impaired glucose tolerance, diabetes mellitus, dyslipidemia, respiratory problems, osteoarthritis, cancer); according to patients, psychosocial consequences such as a sense of demoralization, physical discomfort and being the target of substantial social stigma are so intolerable that they may discontinue the treatment even if it is effective. The paper reviews actual epidemiological data concerning drug induced weight gain and associated health problems in psychiatric patients : there is a high risk of overweight, obesity, impaired glucose tolerance, diabetes mellitus, premature death, in patients with schizophrenia or bipolar disorder; and the effects of specific drugs on body weight: Tricyclic Antidepressants (TCA) induced weight gain correlated positively with dosage and duration of treatment, more pronounced with amitriptyline ; Selective Serotonin Reuptake Inhibitors (SSRI) decrease transiently bodyweight during the first few weeks of treatment and may then increase bodyweight; weight gain appears to be most prominent with some mood stabilizers (lithium, valproate); atypical antipsychotics tend to cause more weight gain than conventional ones and weight gain, diabetes, dyslipidemia, seem to be most severe with clozapine and olanzapine. Conceming the underlying mechanisms of drug induced weight gain, medications might interfere with central nervous functions regulating energy balance; patients report about: increase of appetite for sweet and fatty foods or "food craving" (antidepressants, mood stabilizers, antipsychotic drugs) and weight gain despite reduced appetite which can be explained by an altered resting metabolic rate (TCA, SSRI, Monoaminoxidase Inhibitors MAO I). According to current concepts, appetite and feeding are regulated by a complex of neurotransmitters, neuromodulators, cytokines and hormones interacting with the hypothalamus, including the leptin and the tumor necrosis factor system. The pharmacologic mechanisms underlying weight gain are presently poorly understood: maybe the different activities at some receptor systems may induce it, but also genetic predisposition. Understanding of the metabolic consequences of psychotropic drugs (weight gain, diabetes, dyslipidemia) is essential: the insulin-like effect of lithium is known; treatment with antipsychotic medications increases the risk of impaired glucose tolerance and diabetes mellitus. Several management options of weight gain are available from choosing or switching to another drug, dietary advices, increasing physical activities, behavioural treatment, but the best approach seems to attempt to prevent the weight gain : patients beginning maintenance therapy should be informed of that risk, and nutritional assessment and counselling should be a routine part of treatment management, associated with monitoring of weight, BMI, blood pressure, biological parameters (baseline and three months monitoring of fasting glucose level, fasting cholesterol and triglyceride levels, glycosylated haemoglobin). Psychiatrics must pay attention to concomitant medications and individual factors underlying overweight and obesity. Weight gain has been described since the discovery and the use of the firstpsychotropic drugs, but seems to intensify with especially some of the second generation antipsychotic medications ; understanding of the side effects of psychotropic drugs, including their metabolic consequences (weight gain, diabetes, dyslipidemia) is essential for the psychiatrics to avoid on the one hand a risk of lack of compliance, a discontinuation of the pharmacological medication and also a risk of relapse and rehospitalization, and on the other hand to avoid acute life threatening events (diabetic ketoacidocetosis and non ketotic hyperosmolar coma, long term risk complications of diabetes and overweight).
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PMID:[Psychotropic drugs induced weight gain: a review of the literature concerning epidemiological data, mechanisms and management]. 1638 18

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