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Obesity has reached epidemic proportions in the United States: more than 20% of adults are clinically obese as defined by a body mass index of 30 kg/m(2) or higher, and an additional 30% are overweight. Environmental, behavioral, and genetic factors have been shown to contribute to the development of obesity. Elevated body mass index, particularly caused by abdominal or upper-body obesity, has been associated with a number of diseases and metabolic abnormalities, many of which have high morbidity and mortality. These include hyperinsulinemia, insulin resistance, type 2 diabetes, hypertension, dyslipidemia, coronary heart disease, gallbladder disease, and certain malignancies. This underscores the importance of identifying people at risk for obesity and its related disease states.
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PMID:The obesity epidemic: pathophysiology and consequences of obesity. 1249 Jun 58

The prevalence of obesity is increasing worldwide. In the United States, in 1999, 27% of adults had a body mass index >30 kg/m(2), almost double the prevalence of 20 years earlier. The estimated mortality from obesity-related diseases in the United States is approximately 300,000 annually and growing. In the future, mortality related to obesity is expected to exceed that of smoking. Numerous diseases are caused or made worse by obesity. These include type 2 diabetes; hypertension; dyslipidemia; ischemic heart disease; stroke; obstructive sleep apnea; asthma; nonalcoholic steatohepatitis; gastroesophageal reflux disease; degenerative joint disease of the back, hips, knees, and feet; infertility and polycystic ovary syndrome; various malignancies; and depression. Type 2 diabetes is perhaps the most visible obesity-related problem. Present in at least 14 million Americans, it leads to serious complications and premature death. It is largely caused by obesity, and is generally cured by weight loss. The quality of life of the obese is markedly reduced, and the costs to health care systems are great. Preventive programs have yet to affect the rising prevalence. An effective solution is needed.
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PMID:The extent of the problem of obesity. 1252 43

Despite a rapid improvement in dialysis technology during the last 20 years, the mortality rate is still very high in patients with end-stage renal disease (ESRD), and the death rate is comparable with that of many cancer patients with metastases. The main cause of mortality in ESRD is cardiovascular disease (CVD), and cardiac mortality for dialysis patients aged 45 years or younger is more than 100-fold greater than in the general population. The high cardiovascular mortality rate suggests that ESRD patients are subjected to a process of accelerated atherogenesis. Because factors proven to contribute to atherosclerosis in the general population, such as dyslipidemia, smoking, diabetes mellitus, and hypertension are highly prevalent in ESRD patients, it is reasonable to assume that such risk factors also apply to these patients. However, as it has been shown that the high cardiovascular risk in ESRD is incompletely accounted for by traditional risk factors, it may be speculated that nontraditional risk factors, seemingly more difficult to reconcile, also contribute. Among several putative nontraditional risk factors, chronic inflammation has attracted a lot of interest recently because it seems to be associated to both increased vascular oxidative stress and endothelial dysfunction, both of which are important predictors of cardiovascular events in nonrenal patient groups.
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PMID:Interactions between inflammation, oxidative stress, and endothelial dysfunction in end-stage renal disease. 1267 39

Beyond the already well-established strong causative relationship with cancer, smoking increases the risk for vascular disease. Smoking may act directly or adversely influence risk factors contributing to the development of vascular disease. Smoking causes endothelial dysfunction, dyslipidemia (decreased high-density lipoprotein cholesterol levels, hypertriglyceridemia and increased oxidation of low-density lipoprotein cholesterol) and platelet activation leading to a prothrombotic state. Smoking increases emerging risk factors (eg, fibrinogen, homocysteine, and high-sensitivity C-reactive protein) and increases insulin resistance and the risk of developing type 2 diabetes mellitus. The beneficial effects of statins and antioxidants (eg, vitamins C and E, beta-carotene) are counteracted by smoking. Smoking-induced alterations in growth factors, adhesion molecules, and even in genes can accelerate the progression of atherosclerosis. The aim of this review is to consider the adverse consequences of smoking on the factors predisposing to vascular disease and to emphasize the beneficial effects of smoking cessation.
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PMID:Influence of smoking on predictors of vascular disease. 1456 27

Periodontal disease is a chronic infection of the gums characterized by a loss of attachment between the tooth and bone, and by bone loss. We evaluated cross-sectionally the association between periodontal disease and C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (t-PA), LDL-C, von Willebrand factor, and soluble tumor necrosis factor receptors 1 and 2. The final sample consisted of 468 men (ages 47-80 yrs), participating in the Health Professional Follow-up Study, who provided blood and were free of CVD, diabetes, and cancer. In multivariate regression models controlling for age, cigarette smoking, alcohol intake, physical activity, and aspirin intake, self-reported periodontal disease was associated with significantly higher levels of CRP (30% higher among periodontal cases compared with non-cases), t-PA (11% higher), and LDL-C (11% higher). Based on our data, periodontal disease showed significant associations with biomarkers of endothelial dysfunction and dyslipidemia, which may potentially mediate the association between periodontal and cardiovascular disease.
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PMID:Periodontal disease and biomarkers related to cardiovascular disease. 1474 54

The ability of insulin to stimulate glucose disposal varies more than six-fold in apparently healthy individuals. The one third of the population that is most insulin resistant is at greatly increased risk to develop cardiovascular disease (CVD), type 2 diabetes, hypertension, stroke, nonalcoholic fatty liver disease, polycystic ovary disease, and certain forms of cancer. Between 25-35% of the variability in insulin action is related to being overweight. The importance of the adverse effects of excess adiposity is apparent in light of the evidence that more than half of the adult population in the United States is classified as being overweight/obese, as defined by a body mass index greater than 25.0 kg/m(2). The current epidemic of overweight/obesity is most-likely related to a combination of increased caloric intake and decreased energy expenditure. In either instance, the fact that CVD risk is increased as individuals gain weight emphasizes the gravity of the health care dilemma posed by the explosive increase in the prevalence of overweight/obesity in the population at large. Given the enormity of the problem, it is necessary to differentiate between the CVD risk related to obesity per se, as distinct from the fact that the prevalence of insulin resistance and compensatory hyperinsulinemia are increased in overweight/obese individuals. Although the majority of individuals in the general population that can be considered insulin resistant are also overweight/obese, not all overweight/obese persons are insulin resistant. Furthermore, the cluster of abnormalities associated with insulin resistance - namely, glucose intolerance, hyperinsulinemia, dyslipidemia, and elevated plasma C-reactive protein concentrations -- is limited to the subset of overweight/obese individuals that are also insulin resistant. Of greater clinical relevance is the fact that significant improvement in these metabolic abnormalities following weight loss is seen only in the subset of overweight/obese individuals that are also insulin resistant. In view of the large number of overweight/obese subjects at potential risk to be insulin resistant/hyperinsulinemic (and at increased CVD risk), and the difficulty in achieving weight loss, it seems essential to identify those overweight/obese individuals who are also insulin resistant and will benefit the most from weight loss, then target this population for the most-intensive efforts to bring about weight loss.
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PMID:Obesity, insulin resistance, and cardiovascular disease. 1474 3

The issue of a possible relationship between type 2 diabetes and cancer is still debated. Such chronic diseases show a high incidence in the general population. In their pathophysiology both genetic and environmental factors are involved, inducing important modifications of metabolism. Diabetes is associated to profound metabolic alterations, such as hyperinsulinemia and insulin resistance, which are common in various diseases, i.e. obesity, hypertension, dyslipidemia and hyperuricemia. Those illnesses form the so-called metabolic syndrome. Insulin resistance, hyperestrinism and the associated hyperandrogenism may play a role in the onset of some malignancies, such as endometrium cancer, breast cancer and prostate cancer. Low plasma levels of IGF-1 are able to reduce the risk of cancer in type 2 diabetes patients. This goal can be obtained with preventive measures, as physical activity, diet and drugs that can reduce insulin resistance (metformin and thiazolidinediones).
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PMID:Evidence for a putative relationship between type 2 diabetes and neoplasia with particular reference to breast cancer: role of hormones, growth factors and specific receptors. 1503 27

Dietary fat has a dual role in human physiology: a) it functions as a source of energy and structural components for cells; b) it functions as a regulator of gene expression that impacts lipid, carbohydrate, and protein metabolism, as well as cell growth and differentiation. Fatty acid effects on gene expression are cell-specific and influenced by fatty acid structure and metabolism. Fatty acids interact with the genome through several mechanisms. They regulate the activity or nuclear abundance of several transcription factors, including PPAR, LXR, HNF-4, NFkappaB, and SREBP. Fatty acids or their metabolites bind directly to specific transcription factors to regulate gene transcription. Alternatively, fatty acids indirectly act on gene expression through their effects on a) specific enzyme-mediated pathways, such as cyclooxygenase, lipoxygenase, protein kinase C, or sphingomyelinase signal transduction pathways; or b) pathways that involve changes in membrane lipid/lipid raft composition that affect G-protein receptor or tyrosine kinase-linked receptor signaling. Further definition of these fatty acid-regulated pathways will provide insight into the role dietary fat plays in human health and the onset and progression of several chronic diseases, like coronary artery disease and atherosclerosis, dyslipidemia and inflammation, obesity and diabetes, cancer, major depressive disorders, and schizophrenia.
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PMID:Fatty acid regulation of gene transcription. 1507 23

BACKGROUND: The pharmacological treatment of bipolar disorder has dramatically improved with multiple classes of agents being used as mood-stabilizers, including lithium, anticonvulsants, and atypical antipsychotics. However, the use of these medications is not without risk, particularly when a patient with bipolar disorder also has comorbid medical illness. As the physician who likely has the most contact with patients with bipolar disorder, psychiatrists must have a high index of suspicion for medical illness, as well as a basic knowledge of the risks associated with the use of medications in this patient population. METHODS: A review of the literature was conducted and papers addressing this topic were selected by the authors. RESULTS AND DISCUSSION: Common medical comorbidities and treatment-emergent illnesses, including obesity, diabetes mellitus, dyslipidemia, cardiac disease, hepatic disease, renal disease, pulmonary disease and cancer are reviewed with respect to concomitant use of mood stabilizers. Guidance to clinicians regarding effective monitoring and treatment is offered. CONCLUSIONS: Mood-stabilizing medications are necessary in treating patients with bipolar disorder and often must be used in the face of medical illness. Their safe use is possible, but requires increased vigilance in monitoring for treatment-emergent illnesses and effects on comorbid medical illness.
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PMID:Special considerations in the treatment of patients with bipolar disorder and medical co-morbidities. 1510 99

A few past clinical and recent case-control studies of statin use, for example, in patients with and without prostate cancer have not demonstrated its potential for reducing or preventing the risk for this disease, and the potential for benefit may have been a confounding coincidence. Data from larger continuing and future studies will be needed to resolve this issue, but the recent data on cholesterol or dyslipidemia and risk increase or reduction with treatment are interesting, especially because of other potential improvements with therapy in nonprostate cancers. In addition, the finding that some available cancer treatments improve some parameters of the lipid profile is fascinating, and some cancer drugs are being used in a specific cardiovascular disease treatment setting to improve outcome. Even if CHD, dyslipidemia, and the treatment of these conditions has no role in preventing prostate cancer or its progression, what has been lost? CVD is still the leading cause of death of men, and a heart-healthy program for the patient concerned about prostate disease would reduce this primary cause of death. Patients would take a step forward in improving all-cause mortality. Recent data from surveys, however, continue to demonstrate that men have an inadequate understanding of cholesterol and heart disease. Crisis creates opportunity, and individuals working in urology have ample reasons not only to discuss the overall benefits of reducing lipid markers, but to improve cholesterol and CHD awareness as much as health professionals working in other fields of medicine. The marriage between general preventive medicine and urology seems to be inevitable, and in the authors' opinion, this merger will provide the foundation for novel research that could affect patients' lives dramatically.
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PMID:Prostate cancer and coronary heart disease: correlation or coincidence? 1512


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