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Recent studies have indicated that the waist/hip circumference ratio (WHR), an index of abdominal fat distribution, is a risk factor for cardiovascular disease and diabetes, in parallel with other previously established risk factors. Obesity, without taking fat distribution into account, seems to be associated with WHR in its relationship to the metabolic risk factors for these diseases. The important component of the WHR is probably the mass of visceral fat. This cluster of phenomena constitute what has recently been called the metabolic syndrome or syndrome X. Visceral fat mass is probably increased by a multiple endocrine aberration, where steroid hormones are important. This seems to cause insulin resistance by direct effects on the periphery, which may be amplified by the metabolism of the enlarged visceral adipose tissues.
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PMID:Abdominal fat distribution and the metabolic syndrome. 128 66

Coronary heart disease is the most frequent cause of death in Western, industrialized countries. Coronary risk factors are prevalent in such countries and sometimes combine to constitute the so-called syndrome X--hypertension, central obesity, serum lipid and clotting disturbances, and insulin resistance. beta-Blockers, unlike calcium antagonists, have proved highly effective in secondary prevention of myocardial infarction. If present at the time of the myocardial infarction, beta-blockers (unlike calcium antagonists and diuretics) probably decrease mortality 1 month later. Early intervention (within 12 h) of chest pain with intravenous beta-blockers results in a 15% reduction in cardiovascular mortality at 1 week. Later intervention (3-28 days) with oral non-ISA beta-blockers results in a 30% reduction in mortality after 1 year; ISA-containing beta-blockers are probably less effective (less decrease in heart rate). Hydrophilicity/lipophilicity of beta-blockers is unimportant in terms of decreased mortality. Primary prevention of myocardial infarction, unlike stroke, in hypertensive patients has been disappointing, possibly due to treatment-induced biochemical/lipid changes or inappropriate lowering of diastolic blood pressure in high-risk subjects (J-curve effect). beta-Blockers should be first-line therapy for hypertensive patients up to the age of 65 years, particularly men (and nonsmokers) as Q-wave myocardial infarction is significantly decreased by beta-blockers and significantly increased by diuretics. However, in elderly hypertensive subjects, beta-blockers have not significantly decreased myocardial infarction (unlike stroke), whereas diuretics have. The effects of beta-blockers and diuretics on heart size (and thus coronary flow reserve) in the elderly may be important. Thus, beta-blockers should be second-line therapy for the elderly hypertensive individual but first-line if overt ischemia (e.g., angina or recent myocardial infarction) also is present. In patients with angina but normal blood pressure, beta-blockers tend to decrease and calcium antagonists increase cardiovascular events. Thus, beta-blockers are highly effective agents in the secondary prevention of myocardial infarction and are moderately effective in primary prevention of myocardial infarction in hypertensive patients (particularly men) under the age of 65 years.
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PMID:Beta-blockers: primary and secondary prevention. 128 45

The obvious syntropy of obesity and type II (non-insulin dependent) diabetes mellitus has always suggested a causal inter-relationship between the two diseases. However, the actual pathophysiological connection still remains to be elucidated. Recent findings have suggested that insulin resistance and hyperinsulinaemia might link glucose intolerance/type II diabetes mellitus, hypertension and hyperlipoproteinaemia in the context of a hypothetical 'syndrome X' characterized by an excessive risk constellation for the development of atherosclerosis. However, as to the practical consequences of the ('diabesity') syndrome of type II diabetes mellitus and structured programmes for effective therapy, very little new information has been gathered during the past 100 years.
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PMID:Risk of obesity in type II diabetes mellitus. 133 84

The metabolic syndrome (syndrome X) is characterised by an association of elevated insulin levels, a tendency to obesity of the android type, a disturbance of lipid metabolism with elevated triglyceride levels and commonly associated hypertension. The underlying common cause of this syndrome appears to be insulin resistance of the skeletal muscles, which is related in particular to the non-oxidative glucose utilization on the part of the muscle. The molecular cause of this syndrome has not been clarified, but a defect in the signal transduction chain between the insulin receptor and glycogen synthase is suspected. Epidemiological studies have shown that the metabolic syndrome may be considered a preliminary stage of manifest type II diabetes. In addition, it appears to play a major role in the development of cardiovascular complications in certain high-risk groups.
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PMID:[Pathophysiologic principles of metabolic syndrome. Consequences for early diagnosis and prevention]. 148 14

Data from several different studies are reviewed suggesting that a subset of hypertension is associated with metabolic abnormalities involving lipids, insulin, and often obesity, all aggregating strongly in families. Persons with 'familial dyslipidaemic hypertension (FDH)' have an especially high risk of early coronary disease. The clinical and biochemical features of FDH are compared with Reaven's Syndrome X, familial combined hyperlipidaemia, dense LDL subfractions, diabetes, impaired glucose tolerance, central and general obesity, pre-diabetes, pre-hypertension, and heterozygous lipoprotein lipase deficiency. Some contribution from major gene effects is suggested in specific subsets reported in several different genetic studies reviewed in this report. It seems likely that multiple metabolic abnormalities are genetically heterogeneous. The data also suggest significant contributions from environmental factors such as diet and physical activity.
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PMID:Familial dyslipidaemic hypertension and other multiple metabolic syndromes. 148 41

The aim of this study was to compare the causes of death and parameters related to alcohol consumption, between subjects diagnosed as diabetic, clinically by their general practitioner, or glucose intolerant and in particular as diabetic, using the epidemiological criteria of an abnormal glucose level following an oral glucose tolerance test. The subjects in this study were 7035 working men, aged between 44 and 55 years, who attended the first follow-up examination of the Paris Prospective Study, between 1968 and 1973. They were classified as 'clinically diagnosed diabetic' or, following an oral glucose tolerance test and the World Health Organisation criteria, as having 'oral glucose tolerance test diagnosed diabetes', impaired glucose tolerance or normoglycaemia. The relative risk of death by cirrhosis, in comparison with the normoglycaemic group, was 21 (95% confidence interval: 9.1-49) in the group diagnosed diabetic by the oral glucose tolerance test, significantly different (p less than 0.02) from the group diagnosed diabetic clinically 3.1 (0.41-24); factors indicative of excessive alcohol consumption at baseline differed accordingly. In contrast, the relative risks for death by coronary heart disease were similar, 2.1 (1.0-4.1) and 2.7 (1.4-5.4) respectively; all of the factors defining the insulin resistance 'Syndrome X' (hyperglycaemia, hyperinsulinaemia, hypertension, hyperlipidaemia and also central obesity) and predictive of coronary heart disease were elevated in both groups of diabetic subjects. 'Diabetes', as diagnosed by the oral glucose tolerance test, might be the consequence of excessive alcohol consumption which could lead to insulin resistance, then to coronary heart disease, as well as to alcohol-related diseases.
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PMID:Cardiovascular and alcohol-related deaths in abnormal glucose tolerant and diabetic subjects. 154 80

Many studies have shown that hyperinsulinemia and/or insulin resistance are related to various metabolic and physiological disorders including hypertension, dyslipidemia, and non-insulin-dependent diabetes mellitus. This syndrome has been termed Syndrome X. An important limitation of previous studies has been that they all have been cross sectional, and thus the presence of insulin resistance could be a consequence of the underlying metabolic disorders rather than its cause. We examined the relationship of fasting insulin concentration (as an indicator of insulin resistance) to the incidence of multiple metabolic abnormalities in the 8-yr follow-up of the cohort enrolled in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease in Mexican Americans and non-Hispanic whites. In univariate analyses, fasting insulin was related to the incidence of the following conditions: hypertension, decreased high-density lipoprotein cholesterol concentration, increased triglyceride concentration, and non-insulin-dependent diabetes mellitus. Hyperinsulinemia was not related to increased low-density lipoprotein or total cholesterol concentration. In multivariate analyses, after adjustment for obesity and body fat distribution, fasting insulin continued to be significantly related to the incidence of decreased high-density lipoprotein cholesterol and increased triglyceride concentrations and to the incidence of non-insulin-dependent diabetes mellitus. Baseline insulin concentrations were higher in subjects who subsequently developed multiple metabolic disorders. These results were not attributable to differences in baseline obesity and were similar in Mexican Americans and non-Hispanic whites. These results support the existence of a metabolic syndrome and the relationship of that syndrome to multiple metabolic disorders by showing that elevations of insulin concentration precede the development of numerous metabolic disorders.
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PMID:Prospective analysis of the insulin-resistance syndrome (syndrome X). 158 98

Non-insulin-dependent diabetes (NIDDM) has long been recognized as being associated with a cluster of disorders including obesity, hypertension, dyslipidemia, and atherosclerotic heart disease. It was only recently, however, that Reaven, DeFronzo, and Ferrannini with techniques to quantitate insulin resistance suggested that this represents a common factor in this group of disorders and that hyperinsulinemia resulting from insulin resistance could be the cause of the hypertension, dyslipidemia, and atherosclerosis. The names syndrome X or the insulin-resistance syndrome have been used to identify this pathological entity, and considerable investigations have been done and are in progress to establish whether or not these coexisting disorders represent an as yet unexplained association of cardiovascular risk factors or if, indeed, insulin resistance and hyperinsulinism represent the primary cause for most of the other disorders. To paraphrase a philosophical comment, if syndrome X did not exist, we probably would have had to invent it. In addition to the intellectual satisfaction of being able to "lump" these diverse ills under a single etiology, the main value of grouping these disorders as a syndrome is to continually remind physicians that the therapeutic goals are not only to correct hyperglycemia in NIDDM but also to manage the elevated blood pressure and dyslipidemia that cause cerebrovascular and cardiac morbidity as well as mortality in these patients. Having a syndrome X reduces the fragmentation of medical care among subspecialties and decreases the likelihood of prescribing drugs that correct hypertension but raise lipids or drugs that lower lipids but raise blood glucose. Finally, it encourages the selection of drugs that reduce hyperglycemia without increasing insulin secretion and to the development of new drugs for this purpose. Unfortunately, the concept of insulin resistance with hyperinsulinism being a cause of the other associated disorders is still unproved but continues to be open to experimental investigation. The remainder of this article reviewed the use of sulfonylureas in the management of NIDDM, discussed new molecular and cellular mechanisms by which they promote insulin secretion, and reviewed the controversy as to whether an extrapancreatic action contributes to their glucose-lowering effects in NIDDM. A closing section listed some other oral drugs that can lower blood glucose without stimulating the pancreatic beta cell. Their insulin-sparing hypoglycemic effect makes them potentially useful in NIDDM therapy, particularly if the fundamental premise of syndrome X is substantiated, which implicates hyperinsulinemia as contributing to the morbidity and mortality from atherosclerotic vascular disease.
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PMID:Type II diabetes and syndrome X. Pathogenesis and glycemic management. 161 69

Macrovascular disease, especially coronary heart diseases, have been found to be linked to glucose intolerance. Insulin resistance in respect to glucose uptake in peripheral tissues seems to play an important role in the development of glucose intolerance, since subjects with coronary heart disease mainly are hyperinsulinemic. Insulin resistance may induce not only glucose intolerance but also hypertension, obesity, and dyslipoproteinemia (high very low-density lipoprotein and low high-density lipoprotein values), all variables that add to the risk of coronary heart disease. On the basis of these findings, a new syndrome has been postulated-syndrome X. This syndrome may be caused by inherited insulin resistance in skeletal muscles, and secondary to that arterial hypertension, obesity, and dyslipoproteinemia may develop. Insulin resistance in noninsulin-dependent diabetic persons and in hypertensive subjects is located in skeletal muscles, where insulin's ability to promote nonoxidative glucose metabolism is reduced. The key enzyme in this pathway, glycogen synthase, is proposed as the causal defect responsible for the insulin resistance state, at least in noninsulin-dependent diabetic patients. The pill (sex steroids) may induce a clinical situation that is similar to syndrome X. However, it is important to emphasize that many more studies are needed to substantiate these hypothetical mechanisms behind coronary heart disease.
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PMID:Impairment of glucose tolerance: mechanism of action and impact on the cardiovascular system. 211 96

The prevention of cardiovascular diseases has been considered the first cause in diminishing coronary heart disease mortality. The main objective is the control of risk factors in primary as well as in secondary prevention. The correlation between diet rich in saturated fat and plasma cholesterol was the first milestone in this field followed by the improvement in cholesterol levels and subsequently in CHD mortality. Smoking cessation, physical exercise and control of blood pressure have shown to be efficacious. May be that Syndrome X that corresponds to insulin resistance, central obesity and low levels of HDL among other characteristics, reaches in the future a greater importance in CVD epidemiology. Other risk factors like those of psychosocial origin, thrombogenesis or hormones need more research in order to know their actual importance.
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PMID:[The epidemiology and risk factors of ischemic cardiopathy]. 749 37


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