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

It has been increasingly recognised in recent years that type 2 (non-insulin-dependent) diabetes is part of a cluster of cardiovascular risk factors known as the metabolic syndrome, but also endorsed with such names as the deadly quartet, syndrome X and the insulin resistance syndrome. Atherosclerosis is the most common complication of type 2 diabetes among Europeans, and coronary artery, cerebrovascular and peripheral vascular disease are 2 to 5 times more common in people with this condition than in those without diabetes. These observations indicate that the treatment of type 2 diabetes requires agents that do more than simply lower blood glucose levels, and a therapy with both antihyperglycaemic effects and beneficial effects on dyslipidaemia, hypertension, obesity, hyperinsulinaemia and insulin resistance is likely to be most useful. In this respect, metformin has an important and established role: this drug has been shown to lower blood glucose and triglyceride levels, and to assist with weight reduction and to reduce hyperinsulinaemia and insulin resistance. Studies in the Israeli sand rat, Psammomys obesus, have indicated hyperinsulinaemia/insulin resistance to be the initial and underlying metabolic disorder in obesity and type 2 diabetes. Thus, the well established effect of metformin in reducing insulin resistance makes this drug an excellent candidate for the prevention of progression of impaired glucose tolerance to type 2 diabetes, and for the reduction of mortality associated with cardiovascular disease.
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PMID:Clinical efficacy of metformin against insulin resistance parameters: sinking the iceberg. 1057 21

We examined the effects of the potassium channel opener KRN4884 (5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine ) on cardiovascular metabolic syndrome (i.e., syndrome X), in rats. High-fructose diet rats developed hypertension, hypertriglyceridemia, increased total cholesterol/HDL (high-density lipoprotein)-cholesterol ratio, and hyperinsulinemia, KRN4884 (0.3-3.0 mg/kg, twice a day for 14 days, p.o.) alleviated the risk factors in fructose-fed rats. Furthermore, fructose-fed rats exhibited impairment of glucose tolerance and excess insulin secretion when loaded with glucose orally. Treatment with KRN4884 (1.0 mg/kg, twice a day for 14 days, p.o.) improved the glucose intolerance and inhibited hypersecretion of insulin in the glucose-loaded, fructose-fed rats. In contrast, KRN4884 (0.3-1.0 mg/kg, twice a day for 10 days, p.o.) did not affect serum triglyceride, cholesterol, glucose, or insulin concentrations in normal rats. LPL (lipoprotein lipase) activities in skeletal muscle and adipose tissue, and HTGL (hepatic triglyceride lipase) activity in liver were measured after administration of KRN4884 or vehicle twice a day for 14 days in fructose-fed rats. KRN4884 caused a significant increase in LPL activity in muscle and tended to increase LPL activity in adipose tissue in fructose-fed rats. HTGL was decreased in fructose-fed rats as compared with normal controls and was unaffected by KRN4884. These findings suggested that KRN4884 enhances insulin sensitivity and LPL activity, which are related to glucose and lipid metabolism and may be useful for the treatment of syndrome X.
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PMID:Effects of the K+ channel opener KRN4884 on the cardiovascular metabolic syndrome model in rats. 1067 63

Multiple metabolic syndrome (MMS) implies a frequent coincidence of four basic serious metabolic risk factors for subsequent manifestation of cardiovascular disease. The latter include: central type obesity, arterial hypertension, dyslipoproteinaemia and diabetes mellitus type II (non-insulin-dependent diabetes mellitus--NIDDM). MMS is also described as syndrome X, Reaven's syndrome, insulin resistance syndrome, metabolic syndrome or as the "deadly quartet". NIDDM in humans is conceived as a syndrome the pathogenesis of which is multifactorial and it is not an unequivocal nosological unit. It many epidemiological studies reliable evidence was provided that in the aetiology of NIDDM a marked genetic influence is involved. Its genetic predisposition is conditioned by the interaction of candidate genes and a complex of influences of the external environment. Evidence was provided that MMS phenotypes cumulate only in members of some families. The mode of genetic transmission of NIDDM remains obscure.
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PMID:[Genetic predisposition for multiple metabolic syndrome. Part 1. Diabetes mellitus type 2--incidence and prevalence]. 1095 28

The insulin resistance syndrome X is related to excess intra-abdominal adipose tissue. With lipectomy of >50% of subcutaneous adipose tissue (SQAT) in nonhibernating, adult female Syrian hamsters on high-fat (HF; 50 calorie%) diet and measurements of oral glucose tolerance, oral [(14)C]oleic acid disposal, serum triglycerides, serum leptin, liver fat, perirenal (PR) adipose tissue cellularity, and body composition, we studied the role of SQAT. Sham-operated (S) animals on HF or low-fat (LF; 12.5 calorie%) diets served as controls. After 3 mo there was no visible regrowth of SQAT but HF diet led to similar levels of body weight and body fat in lipectomized and sham-operated animals. Lipectomized (L) animals had more intra-abdominal fat as a percentage of total body fat, higher insulinemic index, a strong trend toward increased liver fat content, and markedly elevated serum triglycerides compared with S-HF and S-LF. Liver and PR adipose tissue uptake of fatty acid were similar in L-HF and S-HF but reduced vs. S-LF, and were inversely correlated with liver fat content and insulin sums during the oral glucose tolerance test. In summary, lipectomy of SQAT led to compensatory fat accumulation implying regulation of total body fat mass. In conjunction with HF diet these lipectomized hamsters developed a metabolic syndrome with significant hypertriglyceridemia, relative increase in intra-abdominal fat, and insulin resistance. We propose that SQAT, via disposal and storage of excess ingested energy, acts as a metabolic sink and protects against the metabolic syndrome of obesity.
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PMID:Subcutaneous lipectomy causes a metabolic syndrome in hamsters. 1095 51

Patients with type 2 diabetes (formerly known as non-insulin-resistant diabetes) have a significantly increased risk of developing cardiovascular disease. Once clinical cardiovascular disease develops, these patients have a poorer prognosis than normoglycemic patients. By inducing endothelial changes, hyperglycemia contributes directly to atherosclerosis. Type 2 diabetes is also associated with atherogenic dyslipidemias. This form of diabetes, or the precursor state of insulin resistance, commonly occurs as a metabolic syndrome (formerly known as syndrome X) consisting of hypertension, atherogenic dyslipidemia and a procoagulant state, in addition to the disorder of glucose metabolism. All cardiovascular risk factors except smoking are more prevalent in patients with type 2 diabetes. In addition to exercise, weight control, aspirin therapy and blood pressure control, therapy to modify lipid profiles is usually necessary. The choice of agent or combination of statin, bile acid sequestrant, fibric acid derivative and nicotinic acid depends on the lipid profile and characteristics of the individual patient.
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PMID:Attenuating cardiovascular risk factors in patients with type 2 diabetes. 1114 70

Allostatic load (AL) has been proposed as a new conceptualization of cumulative biological burden exacted on the body through attempts to adapt to life's demands. Using a multisystem summary measure of AL, we evaluated its capacity to predict four categories of health outcomes, 7 years after a baseline survey of 1,189 men and women age 70-79. Higher baseline AL scores were associated with significantly increased risk for 7-year mortality as well as declines in cognitive and physical functioning and were marginally associated with incident cardiovascular disease events, independent of standard socio-demographic characteristics and baseline health status. The summary AL measure was based on 10 parameters of biological functioning, four of which are primary mediators in the cascade from perceived challenges to downstream health outcomes. Six of the components are secondary mediators reflecting primarily components of the metabolic syndrome (syndrome X). AL was a better predictor of mortality and decline in physical functioning than either the syndrome X or primary mediator components alone. The findings support the concept of AL as a measure of cumulative biological burden.
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PMID:Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging. 1128 59

The definable causes of nonalcoholic steatohepatitis (NASH) include jejunoileal bypass surgery (JIB), other causes of rapid and profound weight loss in obese subjects, total parenteral nutrition, drugs, industrial toxins, copper toxicity, and disorders characterized by extreme insulin resistance. However, the etiopathogenesis in most cases of NASH appears multifactorial. Obesity, type 2 diabetes, and hypertriglyceridemia are often associated with hepatic steatosis, and although this does not invariably lead to NASH, the fatty liver is vulnerable to hepatocellular injury initiated by reactive oxygen species (ROS). It is critical to understand not only the triggers for hepatitis (injury and inflammation) in NASH but also how this is perpetuated as chronic liver disease. The present focus is on whether the biochemical processes that generate oxidative stress lead to hepatocyte injury and secondary recruitment of inflammation or whether inflammation is the primary mediator of liver cell injury. Insulin resistance is a reproducible pathogenic factor in NASH. It favors accumulation of free fatty acids in the liver and predisposes to oxidative stress by stimulating microsomal lipid peroxidases and by the direct effects of high insulin levels in decreasing mitochondrial beta-oxidation. CYP2E1 is normally suppressed by insulin but is invariably increased in the livers of patients with NASH. In rodent dietary models of steatohepatitis, CYP2E1 is the catalyst of microsomal lipid peroxidation, while in Cyp 2e1 nullizygous mice, CYP4A proteins are induced and function as alternative microsomal lipid peroxidases. Other studies implicate activation of peroxisome proliferator-activated receptor-alpha (PPAR alpha) as leading to NASH; PPAR alpha is a transcription factor that governs both microsomal (via CYP4A) and peroxisomal (beta-oxidation) pathways of lipid oxidation and ultimately production of ROS. Increased lipid peroxidation is a crucial difference between the livers of rodents with experimental NASH and those of ob/ob genetically obese mice that have uncomplicated steatosis. Administration of endotoxin, through the release of tumor necrosis factor-alpha (TNF-alpha), provokes liver inflammation with hepatocyte injury in the steatotic liver. This may be particularly relevant in JIB and has been suggested as a pathogenic mechanism in primary NASH. It has been proposed that inheriting one or more copies of the hemochromatosis gene, C282Y, promotes fibrotic progression in NASH because of increased hepatic iron deposition, but recent studies have failed to confirm this. The relationship between the severity of hepatitis in NASH and progression to cirrhosis implies that products of the inflammatory infiltrate play a role in fibrogenesis. In summary, NASH can be regarded as the hepatic consequence of the metabolic syndrome (or syndrome X). Attention should now shift from steatosis, a generally benign process that is less evident in the advanced stages of cirrhosis, to the mechanisms for hepatocellular injury, inflammation, and hepatic fibrosis. In particular, the genetic, molecular, and cellular factors that ordain and moderate fibrosis in the context of steatohepatitis will be of greatest relevance to effective therapy and clinical outcome.
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PMID:Etiopathogenesis of nonalcoholic steatohepatitis. 1129 94

This study was designed to examine whether abnormalities that comprise the metabolic syndrome, including insulin resistance, hyperinsulinemia, hypertension, hyperlipidemia, and obesity, are reversible by diet. Female Fischer rats were placed on either a high-fat, refined-carbohydrate (HFS) diet or low-fat, complex-carbohydrate (LFCC) diet for a period of 20 months. After 20 months, a group of HFS rats were switched to the LFCC diet (HFS/LFCC) for a period of 2 months. Skeletal muscle glucose transport, plasma insulin, systolic blood pressure, and plasma lipids were measured in all groups after 22 months. Energy intake and body weight were measured weekly. In the HFS group, insulin-stimulated glucose transport was significantly reduced (67+/-4 versus 98+/-4 pmol. mg(-)(1). 15 s(-)(1)), whereas plasma insulin (300+/-49 versus 82+/-8 pmol/L), blood pressure (147+/-4 versus 123+/-4 mm Hg), plasma triglycerides (2.58+/-0.31 versus 0.39+/-0.04 mmol/L), LDL cholesterol (C) (3.45+/-0.40 versus 0.89+/-0.06 mmol/L), LDL-C to HDL-C ratio (2.9+/-0.1 versus 2.2+/-0.1), VLDL-C (1.53+/-0.23 versus 0.37+/-0.07 mmol/l), Total-C (5.56+/-0.58 versus 1.49+/-0.10 mmol/L), and body weight (360+/-11 versus 260+/-5 g) were all significantly elevated compared with the LFCC. Energy intake did not differ significantly; however, the LFCC had a much poorer feed efficiency. Conversion to a LFCC diet for 2 months led to normalization of glucose transport, blood pressure, plasma insulin, and VLDL-C and significant amelioration of obesity and other lipid abnormalities. These results demonstrate that syndrome X induced by an inappropriate diet is reversed with implementation of a low-fat, unrefined-carbohydrate diet without caloric restriction and suggest that diet may be a possible treatment for multiple simultaneous cardiovascular risk factors.
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PMID:Reversibility of chronic experimental syndrome X by diet modification. 1135 48

Hypertension and diabetes are the basic risk factors of atherosclerosis and its complications. At present new associations are sought which will enable us to describe more satisfactorily the mutual relationship of hypertension, metabolic disorders and cardiovascular disease. One of the systems involved in all substantial physiological processes is the autonomic nervous system. Stimulation of the sympathetic nervous system by chronic stress causes in addition to an elevated pulse rate and cardiac minute output also activation of another important pressor mechanism--the renin-angiotensin-aldosterone system. Increased activity of the sympathetic nervous system plays a part also in the development of impaired glucose and lipid metabolism, which are very frequent in hypertonic subjects. Hyperinsulinaemia, hypertriglyceridaemia and reduced HDL-cholesterol concentration are associated with a decline of the insulin capacity to take up glucose and deposit glycogen and together with a raised blood pressure create the so-called metabolic syndrome of insulin resistance (syndrome X, Reaven's syndrome).
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PMID:[Stress-induced hypertension and diabetes mellitus]. 1139 76

Insulin resistance was already suspected in the thirties from clinical observations in diabetic patients, then better appreciated in the early sixties with the development of insulin radioimmunoassay, and finally confirmed in the last 20 years by using various sophisticated methods able to quantify insulin action. First demonstrated in obese and/or type 2 diabetic patients, the diminution of insulin sensitivity may in fact concern a much larger population. The concept of insulin sensitivity gained a considerable importance when Reaven, in 1988, emphasized the role of insulin resistance in different human diseases. The metabolic syndrome or syndrome X is characterized by the association of various cardiovascular risk factors (among which impaired glucose tolerance, arterial hypertension and dyslipidaemias), all closely linked to insulin resistance which is indeed the core of the syndrome. Even if insulin action signalling appears to be rather complex and the mechanisms leading to insulin resistance still largely unknown, it is essential to develop pharmacological or non pharmacological strategies to improve insulin sensitivity for treating insulin-resistant individuals. Such an approach should allow not only to provide a better blood glucose control in patients with type 2 diabetes, but also to improve the cardiovascular prognosis of numerous patients, with or without diabetes mellitus, who have the metabolic syndrome.
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PMID:[The insulin sensitivity concept]. 1145 10


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