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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Most ischemic heart disease in associated with severe coronary atherosclerosis. A small subset of patients, however, had angina pectoris despite angiographically normal coronary arteries and absence of inducible coronary spasm. Coronary microcirculation (i.e. arteries too small to be visualized by current angiographic techniques) has been identified as the weak point of these patients. Small coronary vessel involvement may be due to organic conditions (such as diabetes, vasculitis, systemic collagen-vascular diseases, infectious processes) that act through coronary thrombosis or embolism and related alteration in coronary vasomotion; alternatively, the vascular abnormality appears to be entirely functional (no ultrastructural myocardial changes) such as the case of hypertension, hypertrophic cardiomyopathy and syndrome X. Whatever the cause(s) and mechanism(s) of the small coronary artery involvement, this leads to myocardial ischemia and to the related complications as in classic atherosclerotic heart disease. Syndrome X is characterized by effort-induced angina pectoris, ST-segment changes during exercise testing, negative ergonovine test and reduced coronary reserve. A pre-arteriolar hypersensitivity to vasoconstrictor influences (elicited by cold pressor test or ergonovine) and a reduced vasodilator capacity (unmasked by metabolic and pharmacological studies) have been proposed as potential pathogenetic substrate. This dynamic alteration in vasomotion would answer for both symptoms and signs of myocardial ischemia, that, however, appear to be contemporarily elicitable in a minority of patients. Treatment with beta-blockers and calcium-antagonists has been found to be effective. The long-term follow-up shows favorable outcome with a high survival rate and a low incidence of cardiovascular events.
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PMID:[Angina due to microvascular pathology]. 184 63

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

Acute cardiac rejection, syndrome X, and arterial hypertension can induce small vessel damage and, therefore, restriction of coronary reserve in the presence of normal epicardial coronary arteries. A characteristic response pattern to dipyridamole (DIP) infusion has been previously described in syndrome X and arterial hypertension: ST segment depression without any measurable systolic dysfunction. The aim of this study was to establish whether acute cardiac rejection might induce electrocardiographic alterations during DIP infusion. Changes in the 12-lead electrocardiogram and two-dimensional echocardiogram during high-dose DIP infusion (up to 0.84 mg/kg in 10 minutes) were evaluated within 24 hours of endomyocardial biopsy in 14 transplanted patients. A total of 47 biopsy-controlled DIP studies were performed within 5 weeks after cardiac transplantation. For each patient, at least 7 days elapsed between two consecutive studies. Electrocardiographic and echocardiographic tracings were analyzed without prior knowledge of endomyocardial biopsy findings. No remarkable side effects occurred in any case, so that the DIP study could be completed in all patients. A diagnostic (greater than 0.1 mV) ST segment depression was found in 11 studies. The sensitivity and specificity of DIP-induced ST segment depression for the detection of biopsy-proven acute rejection were 72% and 94%, respectively. These data show that DIP stress is feasible and safe in transplanted patients and that acute cardiac rejection can be accompanied by DIP-induced ST segment depression without detectable impairment in systolic function. These changes might provide noninvasive markers for surveillance of rejection.
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PMID:Electrocardiographic changes suggestive of myocardial ischemia elicited by dipyridamole infusion in acute rejection early after heart transplantation. 229 50

Minimal forearm vascular resistances during maximal postischaemic vasodilation were measured in normotensive subjects with syndrome X, a condition characterized by angina and normal coronary arteries, in which a reduced coronary and systemic vasodilatory capacity has been reported. Age- and sex-matched normals and essential hypertensives constituted the control groups. The syndrome X patients had a significantly higher minimal forearm vascular resistance than the normals, indicating that arteriolar alterations may occur in the normotensive state and therefore cannot be considered solely as a consequence of hypertension.
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PMID:Forearm vasodilatory capacity in patients with syndrome X: a comparison with normal and hypertensive subjects. 263 58

The ability of insulin to stimulate glucose uptake varies widely from person to person, and these differences, as well as how the individual attempts to compensate for them, are of fundamental importance in the development and clinical course of what are often designated as diseases of Western civilization. Evidence is presented that non-insulin-dependent diabetes mellitus (NIDDM) results from a failure on the part of pancreatic beta-cells to compensate adequately for the defect in insulin action in insulin-resistant individuals. In addition, a coherent formulation of the physiological changes that lead from the defect in cellular insulin action to the loss in glucose homeostasis is presented. However, the ability to maintain the degree of compensatory hyperinsulinemia necessary to prevent loss of glucose tolerance in insulin-resistant individuals does not represent an unqualified homeostatic victory. In contrast, evidence is presented supporting the view that the combination of insulin resistance and compensatory hyperinsulinemia predisposes to the development of a cluster of abnormalities, including some degree of glucose intolerance, an increase in plasma triglyceride and a decrease in high-density lipoprotein cholesterol concentrations, high blood pressure, hyperuricemia, smaller denser low-density lipoprotein particles, and higher circulating levels of plaminogen activator inhibitor 1. The cluster of changes associated with insulin resistance has been said to comprise syndrome X, and all of the manifestations of syndrome X have been shown to increase risk of coronary heart disease. Thus it is concluded that insulin resistance and its associated abnormalities are of utmost importance in the pathogenesis of NIDDM, hypertension, and coronary heart disease.
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PMID:Pathophysiology of insulin resistance in human disease. 762 91

Non-insulin dependent diabetes mellitus (NIDDM) is an important cause of morbidity and mortality, both in developed as well as in developing countries. The eyes, kidneys, and cardiovascular and neurological systems are predominantly affected by this chronic disease, leading to loss of employment and sometimes life. The most common setting is uncontrolled glycaemia after dietary restriction, exercise and oral hypoglycaemic drug therapy. Insulin may be needed for treating NIDDM some time during the course of the disease. Insulin therapy results in improved beta-cell function, a decrease in the hepatic glucose output and an improvement of the lipoprotein profile. Some of these beneficial effects are due to nullification of 'glucose toxicity'. Objective evidence of a link between tight metabolic control and chronic complications of NIDDM is still not established, despite the results of recent trials. Many insulin regimes have been tried. Recently, attention has been focused on combination therapy with sulphonylureas and insulin, using long-acting insulin at bedtime only. This regime improves the glycaemic profile (due to a reduction of hepatic glucose output), using lower doses of insulin and sulphonylureas. However, experience with this regime suggests that it is only suitable for a subset of NIDDM patients. Adverse effects of insulin therapy include weight gain and hypoglycaemia, which can usually be easily managed. It is hyperinsulinaemia, with its complex array of adverse metabolic effects, that has recently concerned physicians. Acceleration of atherosclerosis, hypertension and worsening of the lipoprotein profile have been cited as possible adverse effects. The presence of such dysregulation is included in the recently described syndrome X.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin treatment in non-insulin dependent diabetes mellitus. 763 12

The author summarizes mechanisms by which insulin resistance and compensatory hyperinsulinism are manifested in the clinical picture. He divides the mechanisms into prereceptor, receptor and postreceptor mechanisms. The latter dominate in the population quantitatively and thus also by their impact because they create the so-called 5H syndrome (association of hyperinsulinism with hyperglycaemia (NIDDM), hyperlipoproteinaemia, hypertension, hirsutism and the polycystic ovary syndrome) or the so-called hormonal metabolic syndrome X, lethal tetrad, metabolic syndrome, syndrome of insulin resistance). The term syndrome X does not appear suitable as it is frequently mistaken for coronary X syndrome which probably is also conditioned by hyperinsulinism, for the hormonal metabolic X syndrome and probably also fot the "fragile X syndrome" in genetics. The 5H syndrome is caused by a postreceptor disorder of insulin efficiency for which so far the molecular basis and dominating organ site have not yet been defined adequately. Hyperinsulinism is conceived as an insulin resistance compensating phenomenon. In its development participates, however, in addition to compensatory hypersecretion also impaired insulin utilization (liver, muscles) and an impaired primary secretory response caused probably by a disorder of blood sugar control (glucokinase, GLUT 2). This is suggested by the frequently inadequate response of the blood sugar level, IRI and C-peptide during the oral glucose tolerance test (OGGT). A hyperinsulinaemic response may be encountered when the blood sugar curve is normal, flat, in impaired glucose tolerance and in diabetes. Thus OGGT alone is not suited for the early detection of the 5H syndrome unless concurrently the IRI and C-peptide response is recorded.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical manifestations of the insulin resistance syndrome. The hormonal-metabolic syndrome X, the 5H syndrome and their etiopathogenesis]. 772 46

The general practitioner man be confronted with the X syndrome, which includes central obesity, impaired glucose tolerance or type II diabetes mellitus, dyslipidemia and eventually hypertension. Insulinoresistance and hyperinsulinaemia contribute to the pathogenesis of these disorders. The syndrome X, which leads to important cardiovascular morbidity, needs appropriate treatment, which has to take into account the actions of drugs on glucose and lipid profiles. Syndrome X is rarely treated as a whole, but to treat separately each of its manifestations would be a mistake. The necessity of a global approach, a complete understanding of the familial environment and also the duration of the development of syndrome X justify the prominent part of the family doctor in the follow-up.
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PMID:[Syndrome X and general medicine]. 778 42

Syndrome X is a constellation of abnormalities; it appears to be strongly linked to insulin resistance and the risk of atherosclerosis. It consists of hypertension, glucose intolerance, obesity, dyslipidemia and, observed more recently, coagulation abnormalities. It is possible that treating blood pressure levels alone while ignoring or worsening other strongly associated risk factors has resulted in minimal effects on the incidence of coronary heart disease (CHD). Syndrome X has raised the awareness of these associated risk factors and has further led to the consideration of hypertension as a metabolic disease. The epidemiologic evidence in support of the link between insulin resistance and hypertension is reviewed, and the public health implications of these data are outlined.
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PMID:Reducing the incidence of coronary heart disease by managing hypertension: implications of syndrome X. 780 51


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