Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 diabetes mellitus (DM) has traditionally been considered a disease of adults. However, in the last 2 decades, it is increasingly being reported in children and adolescents. Obesity is a strong correlate, and the increasing prevalence of obesity and poor physical activity is precipitating type 2 DM at younger ages in the ethnic groups at risk. Indians and other South Asians are among the ethnic groups particularly prone to insulin resistance and type 2 DM, the other racial groups being some American Indian tribes like the Pima Indians, Mexican Americans,Pacific Islanders and African Americans,among others. The WHO has predicted that India will have the greatest number of diabetic individuals in the world by the year 2025. Type 2 DM starting during adolescence puts the individual at risk for major morbidity and even mortality right during the productive years of life. The microvascular complications of DM (nephropathy, retinopathy, neuropathy) are brought on at an early age. In addition, type 2 DM and obesity are two components of a metabolic syndrome of insulin resistance, the other features of which include hypertension, dyslipidemia and hypercoagulability of blood. All these conditions together increase the risk for cardiovascular and cerebrovascular mortality and morbidity (i.e., myocardial infarction and stroke). The resulting economic burden will be enormous. Type 2 DM and the insulin resistance syndrome are to a large extent preventable. Adoption of a healthy eating and physical activity pattern has resulted in decreasing the development of DM in a few recent studies from various parts of the world. A concerted,multi-pronged effort is needed, involving the general public, pediatricians and general physicians, teachers and schools, the media,the government and professional medical bodies, to generate a momentum towards the goal of prevention of type 2 DM and the insulin resistance syndrome in the young population of India.
 ...
PMID:IAP National Task Force for Childhood Prevention of Adult Diseases: insulin resistance and Type 2 diabetes mellitus in childhood. 1518 Dec 95

Insulin resistance is a characteristic feature of obesity and type 2 diabetes mellitus, but it is also present in up to 25% of healthy nonobese individuals. The molecular mechanisms causing insulin resistance are not yet fully understood. Recently, overexpression of several potential inhibitors of the insulin receptor tyrosine-kinase activity, a key step in insulin signaling, has been described in insulin-resistant subjects . PC-1 is expressed in many tissues and inhibits insulin signaling either at the level of the insulin receptor or downstream at a postreceptor site. An elevated PC-1 content in insulin target tissues may play an important role in the development of insulin resistance in obesity and type 2 diabetes mellitus. A polymorphism in PC-1 has been demonstrated to be associated with insulin resistance. This was a DNA polymorphism in exon 4 that causes an amino acid change from lysine to glutamine at codon 121 (K121Q). PC-1 121Q allele might predispose independently of other well established risk factors for early myocardial infarction. Testing for the PC-1 K121Q polymorphism might be valuable in patients with a family history of atherosclerotic vascular disease and myocardial infarction. There is growing evidence that genetic factors play an important role in the development of diabetic nephropathy (DN). Efforts to identify these factors rely primarily on the candidate gene approach; candidate genes for insulin resistance may be considered candidates for DN as well. In a stratified analysis according to duration of diabetes, the risk of early-onset end-stage renal disease (ESRD) for carriers of the Q variant was 2.3 times that for noncarriers. The cellular mechanisms for the insulin resistance of pregnancy and gestational diabetes mellitus (GDM) are unknown. Women with GDM have an increased PC-1 content and excessive phosphorylation of serine/threonine residues in muscle insulin receptors. The postreceptor defects in insulin signaling may contribute to the pathogenesis of GDM and the increased risk for type 2 diabetes later in life. Although widely explored, the true cause of insulin resistance in uremic patients is not entirely elucidated yet. During the last decade it was found that erythropoietin (EPO) therapy, used for correction of anemia in patients with end stage renal failure, ameliorates insulin resistance. An increased lymphocyte PC-1 activity over control was found in hemodialysis patients. A two-month EPO therapy significantly decreased PC-1 activity to the control values, suggesting that an effect on PC-1 expression could be implicated in the amelioration of insulin resistance in uremic patients treated with EPO. Current investigations implicate that therapeutic modification of PC-1 expression would be of great benefit for insulin-resistant type 2 diabetics. Metformin, a biguanide oral antidiabetic agent, was shown to affect insulin resistance by decreasing enzymatic activity of overexpressed PC-1 molecules in obese type 2 diabetics. Thiazolidinedione (TZD) insulin-sensitizing drugs are a class of compounds that improve insulin action in vivo. Treatment of patients with TZDs seems to have a beneficial effect on most, if not all, components of metabolic syndrome. TZDs have also been used in the treatment of nondiabetic human insulin-resistant states, and have demonstrated an improvement in insulin sensitivity. Although much remains to be learned about PPAR gamma receptor and TZD action, the advent of TZD insulin-sensitizing agents has an enormous impact on our understanding of insulin resistance. The great potential of insulin resistance therapy illuminated by the TZDs will continue to catalyze research in this area directed toward the discovery of new insulin-sensitizing agents that work through other mechanisms.
 ...
PMID:Plasma cell membrane glycoprotein 1 (PC-1): a marker of insulin resistance in obesity, uremia and diabetes mellitus. 1520 35

Zucker diabetic fat (ZDF) rats with the metabolic syndrome and hyperlipidemia develop focal and segmental sclerosis. The role of oxidative and nitrosative stress in the nephropathy in ZDF was studied. Renal histology, function, and immunohistologic and biochemical parameters of oxidative and nitrosative stress were evaluated at 8 and 22 wk of age in ZDF and Zucker lean (ZL) rats and after chronic treatment with ebselen, an antioxidant and peroxinitrite scavenger. At 8 wk, ZDF rats showed hyperglycemia, no proteinuria or nephropathy, but higher levels of dihydrobiopterin and 3-nitrotyrosine (3-NT)-modified proteins compared with age-matched ZL rats. At 22 wk, ZDF rats developed focal and segmental sclerosis, proteinuria, decreased creatinine clearance, and renal tissue levels of glutathione and tetrahydrobiopterin with further elevation in dihydrobiopterin and 3-NT-modified proteins, in contrast to age-matched ZL rats. Renal immunohistologic expression of lipid peroxidation products and 3-NT-modified proteins also increased in 22-wk-old ZDF but not in ZL rats. Chronic ebselen treatment of ZDF rats restored renal tissue levels of glutathione and tetrahydrobiopterin; prevented significant accumulation of dihydrobiopterin, lipid peroxidation products, and 3-NT-modified proteins; and ameliorated focal and segmental sclerosis, proteinuria, and fall in creatinine clearance without affecting mean BP, body weight, and blood glucose, compared with the untreated ZDF rats. Chronic ebselen therapy also ameliorated vasculopathy with lipid deposits and tubulointerstitial scarring, inflammation, and upregulated alpha-smooth muscle actin expression. These findings suggest that ZDF rats develop a progressive nephropathy with glomerular, vascular, and tubulointerstitial pathology. Oxidative and nitrosative stress predates the nephropathy, which is improved by peroxinitrite scavenger ebselen, and thus considered its cause and not consequence.
 ...
PMID:Nephropathy in Zucker diabetic fat rat is associated with oxidative and nitrosative stress: prevention by chronic therapy with a peroxynitrite scavenger ebselen. 1533 88

Patients with end-stage renal disease have markedly increased risk for death from cardiovascular disease. Renal failure is associated with multiple metabolic and endocrinologic abnormalities, and these alterations are involved in advanced atherosclerosis and high cardiovascular risk. Increased insulin resistance index by homeostasis model assessment (HOMA-IR), a simple index of insulin resistance, was an independent predictor of cardiovascular mortality in nondiabetic patients on maintenance hemodialysis. Renal failure impairs lipoprotein metabolism leading to the atherogenic lipoprotein profile characterized by increased triglyceride-rich remnant lipoproteins such as intermediate-density lipoprotein, an independent factor of increased aortic stiffness. Non-high-density lipoprotein cholesterol, the sum of cholesterol of intermediate-density lipoprotein and other apoB-containing lipoproteins, is an independent factor associated with increased arterial thickness and a predictor of cardiovascular death in hemodialysis patients. The risk for cardiovascular death in hemodialysis patients is associated closely with hypertension and malnutrition, but not with obesity. The constellation of insulin resistance, dyslipidemia, hypertension, and malnutrition in renal failure suggests the presence of another type of metabolic syndrome promoting cardiovascular disease. In addition, vitamin D deficiency and abnormalities in calcium, phosphate, and parathyroid hormone levels increase the death risk from cardiovascular disease in renal failure. It is expected that treatment of these metabolic and endocrinologic alterations would improve the survival of patients with renal failure.
 ...
PMID:Roles of metabolic and endocrinological alterations in atherosclerosis and cardiovascular disease in renal failure: another form of metabolic syndrome. 1549 Apr 3

BACKGROUND: The topical role of uric acid and its relation to cardiovascular disease, renal disease, and hypertension is rapidly evolving. Its important role both historically and currently in the clinical clustering phenomenon of the metabolic syndrome (MS), type 2 diabetes mellitus (T2DM), atheroscleropathy, and non-diabetic atherosclerosis is of great importance. RESULTS: Uric acid is a marker of risk and it remains controversial as to its importance as a risk factor (causative role). In this review we will attempt to justify its important role as one of the many risk factors in the development of accelerated atherosclerosis and discuss its importance of being one of the multiple injurious stimuli to the endothelium, the arterial vessel wall, and capillaries. The role of uric acid, oxidative - redox stress, reactive oxygen species, and decreased endothelial nitric oxide and endothelial dysfunction cannot be over emphasized.In the atherosclerotic prooxidative environmental milieu the original antioxidant properties of uric acid paradoxically becomes prooxidant, thus contributing to the oxidation of lipoproteins within atherosclerotic plaques, regardless of their origins in the MS, T2DM, accelerated atherosclerosis (atheroscleropathy), or non-diabetic vulnerable atherosclerotic plaques. In this milieu there exists an antioxidant - prooxidant urate redox shuttle. CONCLUSION: Elevations of uric acid > 4 mg/dl should be considered a "red flag" in those patients at risk for cardiovascular disease and should alert the clinician to strive to utilize a global risk reduction program in a team effort to reduce the complications of the atherogenic process resulting in the morbid - mortal outcomes of cardiovascular disease.
 ...
PMID:Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: The urate redox shuttle. 1550 32

Uric acid, a weak organic acid, has very low pH-dependent solubility in aqueous solutions. About 70% of urate elimination occurs in urine, the kidney standing as a major determinant of plasma levels. The complex renal handling results in a fractional clearance of less than 10%. Recently identified urate-specific transporter/channels are involved in tubular handling and extracellular transport. Extracellular fluid, rather than urine output, is the main regulator of urate excretion. A number of interfering agents, including widely used drugs such as aspirin, losartan, diuretics, may decrease or increase urate elimination. Hyperuricemia induced by hypouricosuria often accompanies the metabolic syndrome, and insulin resistance has been hypothesized as the common underlying defect. Hyperuricosuria, associated with dehydration or exercise, results in acute uric acid nephropathy, and causes an obstructive acute renal failure (ARF). This reversible ARF can be prevented by forced hydration with bicarbonate or saline solutions. Renal hypouricemia, due to mutations of urate transporter, is a rare cause of exercise-induced ARF. The existence of chronic urate nephropathy, gouty nephropathy, is still under discussion. Uric acid nephrolithiasis results from supersaturation, strongly influenced by low urine pH, rather than altered urate turnover. Alkali and fluid intake prove successful in managing uric acid stones.
 ...
PMID:Uric acid elimination in the urine. Pathophysiological implications. 1560 13

The metabolic syndrome is strongly associated with insulin resistance and consists of a constellation of factors such as hypertension and hyperlipidemia that raise the risk for cardiovascular diseases and diabetes mellitus. Indeed, hypertension occurs approximately twice as frequently in patients with diabetes compared with in non-diabetic controls. Conversely, hypertensive patients are more likely than normotensive persons to develop diabetes. In addition, up to 75% of CVD in diabetic patients can be attributed to hypertension. Therefore, the primary goals of treating hypertensive patients with insulin resistance are prevention of type 2 diabetes and cardiovascular events. Then, what is the optimal anti-hypertensive approach to target organ protection in these patients? Several clinical trials suggest that the renin-angiotensin system (RAS) plays a pivotal role in the pathogensis of insulin resistance and CVD in diabetes. Interruption of the RAS with angiotensin-coverting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) has been shown to prevent the onset of diabetes in hypertensive patients and to reduce cardiovascular and renal disease progression in diabetic patients with hypertension. However, whether we should recommend ARBs for insulin resistant-hypertensive patients or type 2 diabetic patients without nephropathy due to its insulin-sensitizing property remains to be clarified. Recently, telmisartan, an ARB, was found to act as a patrtial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). PPAR-gamma influences the gene expression involved in carbohydrate metabolism, and pioglitazone and rosiglitazone, ligands for PPAR-gamma, improve insulin resistance in diabetic patients. Furthermore, there is a growing body of evidence that activators of PPAR-gamma exert anti-inflammatory, anti-oxidative and anti-proliferative effects on vascular wall cells, thus decreasing the risks for atherosclerosis. We hypothesize here that due to its unique PPAR-gamma-modulating activity, telmisartan will become a promising 'cardiometabolic sartan', that targets both diabetes and CVD in hypertensive patients. In this paper, we would like to propose the possible ways of testing our hypothesis. Does telmisartan reduce the development of diabetes and CVD in insulin resistant patients pretreated with maximal doses of other ARBs? Does co-treatment with an activator of PPAR-gamma attenuate the effects of telmisartan in these patients? These clinical studies will provide further information whether the beneficial cardiometabolic actions of telmisartan could be ascribed to its PPAR-gamma-inducing property.
 ...
PMID:Telmisartan is a promising cardiometabolic sartan due to its unique PPAR-gamma-inducing property. 1561 52

The prevalence of end-stage renal disease (ESRD) is rising throughout the developed and developing world, although the rate of increase may be attenuating in some regions. Type 2 diabetes mellitus, often a consequence of obesity and accompanied by the metabolic syndrome, is a major cause of progressive renal disease and the increasing global burden of ESRD. Strategies that are cost-effective and applicable at the community level are urgently needed to stem the tide of both type 2 diabetes and the resulting ESRD. Primary and secondary prevention measures, involving screening and interventions, have demonstrated beneficial effects when appropriately designed and targeted to "high-risk" groups. If these strategies can be implemented at the societal level and compliance with the interventions is robust, it is entirely possible that the rising tide of ESRD can be converted into a receding tide of ESRD in the future.
 ...
PMID:The rising tide of end-stage renal disease: what can be done? 1561 26

Chronic renal disease is generally appreciated as a major and rapidly growing health problem. In the United States alone, as many as 19.5 million people may have markers of early renal disease, and more than 660,000 people are expected to require renal replacement therapy by the year 2010. By contrast, the presence and pathological role of renal disease in patients with cardiovascular disease are somewhat underrecognized. Evidence now shows that even minor impairments in renal function, as indicated by measures including glomerular filtration rate and microalbuminuria, are common in cardiovascular disease states and predictive of cardiovascular events. Indeed, microalbuminuria may be a marker of systemic vascular disease rather than kidney dysfunction alone. In patients with hypertension, diabetes, metabolic syndrome, acute coronary syndromes, and stroke, markers of renal disease have proved to be at least as predictive of morbidity and mortality as conventional risk factors. Yet, chart reviews in a variety of clinical settings reflect poor recognition and management of renal disease in at-risk patients. Models for renal protection are based on the control of risk factors, particularly blood pressure, that are associated with renal and cardiovascular outcomes. Screening protocols for markers of renal disease should recognize the potential inaccuracy of serum creatinine concentrations and the preferability of glomerular filtration rate estimates that take age and gender into account. Pilot programs for screening high-risk populations have shown efficacy in detecting renal disease.
 ...
PMID:Renal disease in cardiovascular disorders: an underrecognized problem. 1578 15

When risk factors such as dyslipidemia and hypertension are inadequately controlled in subjects with the metabolic syndrome by lifestyle interventions, pharmacologic approaches are warranted. Statins are first-line pharmacotherapy for dyslipidemia due to their efficacy for lowering low-density lipoprotein (LDL) cholesterol and may also improve high-density lipoprotein (HDL) cholesterol and triglyceride levels. Fibrates and niacin may be useful in combination with a statin for additionally lowering triglycerides or raising HDL cholesterol. Adequate control of hypertension will usually require two or more drugs; agents that block the renin-angiotensin system are particularly useful in this population, given their demonstrated benefits for reducing the burden of cardiovascular events and end-stage renal disease independent of blood-pressure lowering. A multifaceted approach to risk factor management for the metabolic syndrome will have benefits for prevention of type 2 diabetes and cardiovascular disease.
 ...
PMID:New approaches in the intensive management of cardiovascular risk in the metabolic syndrome. 1582 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>