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 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes is a major independent risk factor for cardiovascular disease and stroke; however, the molecular and cellular mechanisms by which diabetes contributes to the development of vascular disease are not fully understood. Our previous studies demonstrated that endoplasmic reticulum (ER) stress-inducing agents, including homocysteine, promote lipid accumulation and activate inflammatory pathways-the hallmark features of atherosclerosis. We hypothesize that the accumulation of intracellular glucosamine observed in diabetes may also promote atherogenesis via a mechanism that involves ER stress. In support of this theory, we demonstrate that glucosamine can induce ER stress in cell types relevant to the development of atherosclerosis, including human aortic smooth muscle cells, monocytes, and hepatocytes. Furthermore, we show that glucosamine-induced ER stress dysregulates lipid metabolism, leading to the accumulation of cholesterol in cultured cells. To examine the relevance of the ER stress pathway in vivo, we used a streptozotocin-induced hyperglycemic apolipoprotein E-deficient mouse model of atherosclerosis. Using molecular biological and histological techniques, we show that hyperglycemia is associated with tissue-specific ER stress, hepatic steatosis, and accelerated atherosclerosis. This novel mechanism may not only explain how diabetes and hyperglycemia promote atherosclerosis, but also provide a potential new target for therapeutic intervention.
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PMID:Glucosamine-induced endoplasmic reticulum dysfunction is associated with accelerated atherosclerosis in a hyperglycemic mouse model. 1638 Apr 81

Researchers are only gradually becoming aware of the gravity of the risk that overweight and obesity pose for children's health. In this article Stephen Daniels documents the heavy toll that the obesity epidemic is taking on the health of the nation's children. He discusses both the immediate risks associated with childhood obesity and the longer-term risk that obese children and adolescents will become obese adults and suffer other health problems as a result. Daniels notes that many obesity-related health conditions once thought applicable only to adults are now being seen in children and with increasing frequency. Examples include high blood pressure, early symptoms of hardening of the arteries, type 2 diabetes, nonalcoholic fatty liver disease, polycystic ovary disorder, and disordered breathing during sleep. He systematically surveys the body's systems, showing how obesity in adulthood can damage each and how childhood obesity exacerbates the damage. He explains that obesity can harm the cardiovascular system and that being overweight during childhood can accelerate the development of heart disease. The processes that lead to a heart attack or stroke start in childhood and often take decades to progress to the point of overt disease. Obesity in childhood, adolescence, and young adulthood may accelerate these processes. Daniels shows how much the same generalization applies to other obesity-related disorders-metabolic, digestive, respiratory, skeletal, and psychosocial-that are appearing in children either for the first time or with greater severity or prevalence. Daniels notes that the possibility has even been raised that the increasing prevalence and severity of childhood obesity may reverse the modern era's steady increase in life expectancy, with today's youth on average living less healthy and ultimately shorter lives than their parents-the first such reversal in lifespan in modern history. Such a possibility, he concludes, makes obesity in children an issue of utmost public health concern.
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PMID:The consequences of childhood overweight and obesity. 1653 58

The cardiometabolic syndrome is a construct associated with an increased risk of type 2 diabetes mellitus, cardiovascular disease (coronary artery disease, peripheral arterial disease, and stroke), chronic kidney disease, and the metabolic hepatopathy referred to as nonalcoholic fatty liver disease or nonalcoholic steatohepatitis. Thus, the term cardiometabolic syndrome includes all of these metabolic, islet, cardiovascular, renal, and hepatic disorders and clustering clinical syndromes. This overview of the cardiometabolic syndrome is designed to review the clinical complications and the end-organ cellular and extracellular matrix remodeling events that occur with the cardiometabolic syndrome. The MINER acronym will serve as an outline, representing: Myocardial and metabolic-hepatopathy, Intimal and islet, Neurovascular, Endothelial, and Renal oxidation-reduction (redox) stress and remodeling.
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PMID:Introduction: organ involvement in the cardiometabolic syndrome. 1767 4

Relationships between fatty liver and coronary heart disease (CHD) and stroke risk remain ill defined. We investigated whether fatty liver is a predictor of CHD and stroke risk. Until December 2000 we followed 2,024 atomic bomb survivors (775 men: 62.0 +/- 9.9 years old; 1,249 women: 63.2 +/- 8.4 years old) who had basic examinations between November 1990 and October 1992 for clinical and laboratory CHD risk factors and fatty liver and who were initially free of CHD and stroke. Forty-nine cases of CHD and 84 cases of stroke were observed. At the time of the baseline examinations, significant clinical associations were found between fatty liver and obesity (p<0.001), hypertension (p<0.001), dyslipidemia (p<0.001), and glucose intolerance (p<0.001). A slight but nonsignificant association was found between fatty liver and hyperuricemia (p=0.07) as well. By using multiple Cox regression analyses, age (relative risk [RR] 1.05, 95% confidence interval [CI] 1.01-1.08), smoking (RR 2.20, 95% CI 1.02-4.74), hyperuricemia (RR 2.30, 95% CI 1.08-4.89), and fatty liver (RR 2.53, 95% CI 1.06-6.06) were shown to be significant predictors of CHD, whereas age (RR 1.08, 95% CI 1.06-1.10), smoking (RR 2.06, 95% CI 1.14-3.72), and hypertension (RR 2.14, 95% CI 1.38-3.30) predicted stroke risk. Fatty liver, which clusters clinical and laboratory CHD risk factors, is an independent predictor of CHD, but not of stroke. Fatty liver should be followed as a feature of metabolic syndrome, with the aim of preventing CHD.
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PMID:Fatty liver and uric acid levels predict incident coronary heart disease but not stroke among atomic bomb survivors in Nagasaki. 1803 75

Over the past 20 years obesity has become a worldwide concern of frightening proportion. The World Health Organization estimates that there are over 400 million obese and over 1.6 billion overweight adults, a figure which is projected to almost double by 2015. This is not a disease restricted to adults - at least 20 million children under the age of 5 years were overweight in 2005 (WHO 2006). Overweight and obesity lead to serious health consequences including coronary artery disease, stroke, type-2 diabetes, heart failure, dyslipidemia, hypertension, reproductive and gastrointestinal cancers, gallstones, fatty liver disease, osteoarthritis and sleep apnea (Padwal et al 2003). Modest weight loss in the obese of between 5% and 10% of bodyweight is associated with improvements in cardiovascular risk profiles and reduced incidence of type 2 diabetes (Goldstein 1992; Avenell et al 2004; Padwal and Majumdar 2007). Orlistat, a gastric and pancreatic lipase inhibitor that reduces dietary fat absorption by approximately 30%, has been approved for use for around ten years (Zhi et al 1994; Hauptman 2000). There is now a growing body of evidence to suggest that Orlistat assists weight loss and that it may also have additional benefits. The aim of this review is to provide a brief update on the current literature studying the efficacy, safety and significance of the use of Orlistat in clinical practice.
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PMID:Obesity management: update on orlistat. 1820 Aug 2

Nonalcoholic fatty liver disease (NAFLD) is a group of diseases with excess fat in liver in the absence of a poorly defined limit of alcohol consumption. Most common variety, a universal public health problem, is associated with insulin resistance caused by a host of genetic and epigenetic defects modulated by life style and environmental factors. In fact the term NAFLD is loose to incorporate so many etiologies except alcoholism and few other etiologies, presenting as fat in liver. However as a sign fatty liver is very important in predicting the risk of diabetes, cardiovascular disease, stroke, cirrhosis and cancer. Abnormal fat accumulation can result from several defects in nuclear receptors associated with lipid sensing, synthesis and oxidation like LXR, FXR, SREBP, ChREBP and PPAR; defects in the lipid influx-efflux channels, insulin signaling, proteins involved in fatty acid catabolism, defects in adipose tissue development and function, inappropriate nutrition and finally defects in neural regulatory mechanisms. The progress of the disease is determined by the basic defects which results in fat accumulation, an individual's immunological response to the accumulated fat and its derivatives and the oxidant stress response. Congregation of unrelated genetic defects under same diagnosis 'NAFLD' can result in inefficient patient management. Further studies are required to understand the molecular basis of fatty liver to enable a personalized management of diseases presenting as fatty liver in the absence of alcohol abuse.
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PMID:The blind men 'see' the elephant-the many faces of fatty liver disease. 1824 Mar 40

Abdominal obesity is often associated with a constellation of comorbidities that include central adiposity, insulin resistance, dyslipidemia, and hypertension. Clinical evaluations should include a measurement of waist circumference, which is a good marker of abdominal obesity. Abdominal obesity is closely associated with an elevated outflow of free fatty acids from the visceral fat compartment and dysregulation of adipokine expression, accompanied by increased inflammation. The most serious consequences of abdominal obesity are coronary heart disease and stroke. It is also associated, however, with polycystic ovary syndrome and hepatic steatosis. Weight reduction and increased physical activity should be recommended to patients with a high waist circumference. Patients with abdominal obesity and other classic risk factors are at high cardiovascular risk and require strict monitoring of their blood pressure, LDL-c, and blood glucose. New pharmacological strategies might help manage both abdominal obesity and its metabolic consequences.
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PMID:[Abdominal obesity: a health threat]. 1841 15

Mean platelet volume (MPV) is increased in patients with coronary heart disease or at risk for stroke. However, MPV determinants have never been assessed in a population study. The present investigation is a cross-sectional study involving 366 non-selected subjects (both sexes, mean age 72.9 +/- 5.5 [1 SD] years). The main cardiovascular risk factors, several indexes of adiposity (including percent body fat as estimated by skinfold measurement, and ultrasound detection of hepatic steatosis and thickness of abdominal subcutaneous and visceral fat) and ischaemic electrocardiographic (ECG) changes were assessed in all subjects. Platelet parameters were determined by a Bayer ADVIA 120 counter. In addition to being associated directly with platelet distribution width (PDW) and inversely with platelet count (p < 0.0001 for both), MPV values were associated with subcutaneous abdominal fat (p = 0.02), fasting blood glucose (p = 0.002) and the prevalence of ischaemic ECG changes (p = 0.004), and tended to be higher in the subjects with a greater prevalence of hepatic steatosis (p = 0.07) and higher Homeostasis Model Assessment (HOMA) index (p = 0.09). In multiple logistic regression, of the non-platelet parameters only percent body fat (p = 0.006), ischaemic ECG changes (p = 0.01) and blood glucose (p = 0.03) remained independently associated with an MPV < or =8.4 fl (high tertile). The relative risk (odds ratio) of having ischaemic ECG changes for the subjects with MPV < or =8.4 fl was 4.2 (95% confidence interval: 2.5-7.1; p = 0.006) with respect to the subjects with lower MPV values. Blood glucose, percent body fat and ischaemic ECG changes were the main MPV determinants in our elderly population.
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PMID:Determinants of mean platelet volume (MPV) in an elderly population: relevance of body fat, blood glucose and ischaemic electrocardiographic changes. 1861 26

Most seizures during pregnancy occur in women who already have epilepsy. During pregnancy most women will continue their previous level of seizure control, although 15-30% may experience an increase in seizures. Pregnancy-induced changes in antiepileptic drug pharmacokinetics are a major factor affecting changes in seizure control during pregnancy, although compliance is also a significant factor. Status epilepticus occurs in only 1-2% of pregnancies, and if treated appropriately and aggressively carries a fairly low risk of morbidity and mortality. Structural and metabolic changes may precipitate new-onset seizures during pregnancy. The structural causes include intracranial hemorrhage of multiple types, cerebral venous sinus thrombosis, and ischemic stroke. Metabolic causes include hyperemesis gravidarum; acute hepatitis (due to fatty liver of pregnancy or viral hepatitis); metabolic diseases, such as acute intermittent porphyria; infections, such as malaria; and eclampsia.
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PMID:Seizures in pregnancy: diagnosis and management. 1892 87

Being the metabolic syndrome a multifactorial condition, it is difficult to find adequate experimental models to study this pathology. The obese Zucker rats, which are homozygous for the fa allele, present abnormalities similar to those seen in human metabolic syndrome and are a widely extended model of insulin resistance. The usefulness of these rats as a model of non-insulin-dependent diabetes mellitus is nevertheless questionable, and they neither can be considered a clear experimental model of hypertension. Some experimental models different from the obese Zucker rats have also been used to study the metabolic syndrome. Some derive from the spontaneously hypertensive rats (SHR). In this context, the most important are the obese SHR, usually named Koletsky rats. Hyperinsulinism, associated with either normal or slightly elevated levels of blood glucose, is present in these animals, but SHR/N-corpulent rats are a more appropriated model of non-insulin-dependent diabetes mellitus. The SHR/NDmc corpulent rats, a subline of SHR/N-corpulent rats, also exhibit metabolic and histopathologic characteristics associated with human metabolic disorders. A new animal model of the metabolic syndrome, stroke-prone-SHR (SHRSP) fatty rats, was obtained by introducing a segment of the mutant leptin receptor gene from the Zucker line heterozygous for the fa gene mutation into the genetic background of the SHRSP. Very recently, it has been developed as a non-obese rat model with hypertension, fatty liver and characteristics of the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein in the SHR rats. The Wistar Ottawa Karlsburg W rats are also a new strain that develops a nearly complete metabolic syndrome. Moreover, a new experimental model of low-capacity runner rats has also been developed with elevated blood pressure levels together with the other hallmarks of the metabolic syndrome.
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PMID:Experimental rat models to study the metabolic syndrome. 1963 Oct 25


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