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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is the result of ancient evolutionary survival mechanisms in a modern environment of affluence. When pressures from this environment generate a long-term or chronic hypothalamic arousal, neuroendocrine-endocrine and autonomic nervous systems are activated, leading to disease-generating 'risk factors' including the metabolic syndrome, with visceral fat accumulation as a conveniently observable marker. The susceptibility to develop these co-morbidities is probably dependent on a functional defect of the inhibitory feedback control of the hypothalamus-pituitary-adrenal axis by central glucocorticoid receptors, often based on a prevalent polymorphism of the gene locus for this receptor. This means that moderate ('peripheral') obesity is a fairly innocent condition while, when hypothalamic arousal is added, as indicated by the internalization of excess body fat ('central' obesity), a highly malignant condition develops in genetically susceptible individuals. Obesity research would benefit from a distinction between these two types of condition.
Baillieres Best Pract Res Clin Endocrinol Metab 1999 Apr
PMID:Overweight is risking fate. 1093 76

Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance. It is frequently associated with obesity, especially visceral fat, and is intimately related to fatty liver and markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. The identification of obese patients who may progress from steatosis to NASH and from NASH to fibrosis/cirrhosis is an important clinical challenge. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by a remarkable regression of liver steatosis in most patients, although increased inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome, and perhaps being part of it, especially in obese patients.
Best Pract Res Clin Endocrinol Metab 2002 Dec
PMID:Obesity and liver disease. 1246 16

Hyperuricemia (HU) is present in 5-30% of the general population, although the prevalence is higher among some ethnic groups and seems to be increasing worldwide. Classically, chronic HU has been considered a risk factor for gout or lithiasis and is associated with alcoholism, obesity, hypertension, dyslipidemia, hyperglycemia/diabetes mellitus, renal failure and intake of certain drugs. HU is also associated with cardiovascular diseases such as hypertension, vascular disease, pre-eclampsia, pulmonary arterial hypertension, stroke, heart failure, ischemic heart disease and also metabolic syndrome, renal disease and increased mortality. It is uncertain if these associations are dependent or not, especially cardiovascular and renal diseases. Patients with chronic HU and also those with gout require both medical investigation for associated diseases or drugs as well as nutritional counseling and life-style changes. HU should alert physicians to possible complications.
Best Pract Res Clin Rheumatol 2004 Apr
PMID:Primary prevention in rheumatology: the importance of hyperuricemia. 1512 Oct 34

The prevalence of childhood obesity is increasing worldwide, as is the prevalence of obesity-related co-morbidity. Altered glucose metabolism, manifested as impaired glucose tolerance (IGT), appears early in obese children and adolescents. Obese young people with IGT are characterized by marked peripheral insulin resistance and a relative beta-cell failure. Lipid deposition in muscle and the visceral compartment, and not only adiposity per se, is related to increased peripheral insulin resistance, the "driving force" of the metabolic syndrome. Other elements of the metabolic syndrome, such as dyslipidemia and hypertension, are already present in obese youngsters and worsen with the degree of obesity. Similarly, markers of systemic "low-grade inflammation" worsen with increasing adiposity. The long-term impact on cardiovascular and liver morbidity of obesity-related insulin resistance in young people is expected to emerge as these youngsters become young adults.
Best Pract Res Clin Endocrinol Metab 2005 Sep
PMID:The metabolic consequences of childhood obesity. 1615 Mar 83

In recent years, the thiazolidinediones (e.g. rosiglitazone, pioglitazone) have emerged as an exciting novel class of therapeutic agent for the treatment of type 2 diabetes mellitus and the human metabolic syndrome. At first glance, the use of these high-affinity peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, that promote adipogenesis, to treat a group of disorders that typically have their origins in obesity seems counter-intuitive. However, to view PPARgamma simply as a regulator of fat mass, and adipocytes themselves as passive vessels for energy storage, is to ignore an extensive body of data that speaks of the diverse roles of both this receptor and adipose tissue in the maintenance of normal metabolic homeostasis. This article highlights the important clinical and laboratory observations made in human subjects harbouring genetic variations in PPARgamma that have confirmed its pivotal role in the regulation of adipocyte endocrine function, and thus our metabolic response to the environment.
Best Pract Res Clin Endocrinol Metab 2005 Dec
PMID:Peroxisome proliferator-activated receptor gamma and the regulation of adipocyte function: lessons from human genetic studies. 1631 Dec 14

Gallstone disease is common: >700,000 cholecystectomies and costs of approximately 6.5 billion dollars annually in the U.S. The burden of disease is epidemic in American Indians (60-70%); a corresponding decrease occurs in Hispanics of mixed Indian origin. Ten to fifteen per cent of white adults in developed countries harbour gallstones. Frequency is further reduced in Black Americans, East Asia and sub-Saharan Africa. In developed countries, cholesterol gallstones predominate; 15% are black pigment. East Asians develop brown pigment stones in bile ducts, associated with biliary infection or parasites, or in intrahepatic ducts (hepatolithiasis). Certain risk factors for gallstones are immutable: female gender, increasing age and ethnicity/family (genetic traits). Others are modifiable: obesity, the metabolic syndrome, rapid weight loss, certain diseases (cirrhosis, Crohn's disease) and gallbladder stasis (from spinal cord injury or drugs like somatostatin). The only established dietary risk is a high caloric intake. Protective factors include diets containing fibre, vegetable protein, nuts, calcium, vitamin C, coffee and alcohol, plus physical activity.
Best Pract Res Clin Gastroenterol 2006
PMID:Gallstone disease: Epidemiology of gallbladder stone disease. 1712 83

Insulin resistance is a feature of a number of clinical disorders, including type 2 diabetes/glucose intolerance, obesity, dyslipidaemia and hypertension clustering in the so-called metabolic syndrome. Insulin resistance in skeletal muscle manifests itself primarily as a reduction in insulin-stimulated glycogen synthesis due to reduced glucose transport. Ectopic lipid accumulation plays an important role in inducing insulin resistance. Multiple defects in insulin signalling are responsible for impaired glucose metabolism in target tissues of subjects with features of insulin resistance. Inflammatory molecules and lipid metabolites inhibit insulin signalling by stimulating a number of different serine kinases which are responsible for serine phosphorylation of Insulin Receptor Substrate-1 (IRS-1).
Best Pract Res Clin Endocrinol Metab 2006 Dec
PMID:Pathophysiology of insulin resistance. 1716 38

The global epidemic of obesity and type-2 diabetes has heightened the need to understand the mechanisms that contribute to its pathogenesis and also to design and trial novel treatments. Patients with glucocorticoid (GC) excess--'Cushing's syndrome'--are phenotypically similar to patients with simple obesity. As such, much research has focused on the manipulation of local GC action as a therapeutic strategy. The majority of the classical actions of GCs are mediated via activation of the glucocorticoid receptor (GR). 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inactive cortisone to cortisol and therefore amplifies local GC action. There is now a wealth of data from rodent and clinical studies implicating this conversion in the pathogenesis of obesity, type-2 diabetes, and the metabolic syndrome. Selective 11beta-HSD1 inhibitors (selective in that they block the activity of 11beta-HSD1 and not 11beta-HSD2 which inactivates cortisone to cortisol in mineralocorticoid target tissues) are currently in development although not yet available for use in clinical studies. Rodent studies utilizing these compounds have shown dramatic improvements in insulin sensitivity as well as improvements in lipid profiles and atherogenesis. A further experimental approach has been to design drugs that antagonize GR activation, and again these compounds appear to improve insulin sensitivity and lower glucose production rates. The key test for both of these research strategies is whether they will translate into clinical studies, and results from these trials are now eagerly awaited.
Best Pract Res Clin Endocrinol Metab 2007 Dec
PMID:Modulation of glucocorticoid action and the treatment of type-2 diabetes. 1805 38

As men age, testosterone levels decline, and decreased testosterone levels are associated with increased risks of osteoporosis, metabolic syndrome, type 2 diabetes mellitus and mortality. Nevertheless, it is still uncertain whether reduced testosterone level is a cause of ill-health or a marker of pre-existing disease, as systemic illness lowers testosterone levels. Most circulating testosterone is bound to sex-hormone-binding globulin (SHBG) and albumin, whereas a small proportion circulates as free testosterone. Decreased SHBG level is associated with increased risks for insulin resistance and metabolic syndrome, although it would also be expected to be associated with increased free testosterone level. During male aging, total and free testosterone levels fall while SHBG level rises. Thus, associations between decreasing androgens and negative health outcomes might differ across men of various ages. Trials of testosterone therapy report benefits for body composition and BMD, but there are limited data on the effect of testosterone supplementation on cardiovascular risk. Whereas men who have androgen deficiency should be considered for testosterone therapy, the role of testosterone supplementation in older men who are not clearly hypogonadal requires further clarification. Further studies are also needed to establish whether the age-related decline in circulating testosterone level in men can be modified or prevented.
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PMID:Testosterone and ill-health in aging men. 1916 23

The relationship of infertility, endocrinology and cancer has become clearer in recent years. Polycystic ovaries (PCO) increase the risk of endometrial cancer. Prolonged amenorrhoea, therefore, should be prevented in such cases with the use of cyclical progestogens, in order for regular withdrawal bleeds to be induced and the endometrium protected from long-term unopposed oestrogen stimulation. There is no secure evidence base on which a relationship between PCO and breast cancer can be based. No specific breast screening for women with PCO is, therefore, recommended. Hyperandrogenaemia and hyperinsulinaemia are conditions whose significance in terms of increasing both endometrial and breast cancer risks is increasingly recognised. The exact mechanism with which they influence carcinogenesis is still far from clear. Whether they act in isolation or as expressions of the common background of the metabolic syndrome - in interaction with other components of this syndrome - is still the subject of research.
Best Pract Res Clin Obstet Gynaecol 2010 Feb
PMID:Anovulation with or without PCO, hyperandrogenaemia and hyperinsulinaemia as promoters of endometrial and breast cancer. 1926 56


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