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 124,988 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

Silent myocardial ischemia (SI), an asymptomatic manifestation of coronary artery disease (CAD), was identified in 10% of apparently healthy nonsmoking, nondiabetic older (60 +/- 7 years, mean +/- SD) men with normal plasma cholesterol levels. We hypothesized that in the absence of other major risk factors for CAD, the men with SI would have reduced plasma levels of high density lipoprotein (HDL) and HDL2 subspecies due to an upper-body fat distribution (waist-to-hip ratio [WHR]), hyperinsulinemia, and abnormal postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities. Compared with 47 normal control subjects of similar age, obesity, and maximal aerobic capacity, the 18 men with SI had higher plasma triglyceride (TG) (162 +/- 71 versus 102 +/- 39 mg/dl, p less than 0.001) and lower HDL-C (33 +/- 6 versus 37 +/- 7 mg/dl, p less than 0.02) levels with no difference in low density lipoprotein cholesterol level. The HDL2b and HDL2a subspecies measured by gradient gel electrophoresis were also lower in the men with SI (p less than 0.01). The plasma glucose and insulin responses during an oral glucose tolerance test were the same in both groups. Postheparin plasma HL activity was significantly higher in 12 men with SI than in 41 control subjects (34 +/- 8 versus 27 +/- 10 mumol/ml.hr-1, p less than 0.03) and was correlated with log insulin area (r = 0.36, p less than 0.05) and WHR (r = 0.32, p less than 0.05) in the control subjects but not in the men with SI. In the control group, the percent HDL2b subspecies was correlated inversely with postheparin plasma HL activity (r = -0.46, p less than 0.01, n = 41) as well as WHR (r = -0.49, p less than 0.001, n = 47) and log insulin area (r = -0.37, p less than 0.05, n = 47) but not in the men with SI. Postheparin LPL activity was the same in both groups of men and did not correlate with HDL, WHR, insulin, or plasma TG levels. As the control subjects and men with SI had comparable degrees of abdominal obesity and hyperinsulinemia, these results suggest that the reduced HDL-C levels in men with SI may be related to elevations in HL activity. Thus, abdominal obesity, hyperinsulinemia, elevated TG levels, and low HDL-C and HDL2 subspecies levels may predispose these older men to atherosclerosis.
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PMID:Reduced HDL2 cholesterol subspecies and elevated postheparin hepatic lipase activity in older men with abdominal obesity and asymptomatic myocardial ischemia. 161 6

Since the time that coronary artery disease was first described in the transplanted human heart, attempts have been made to define risk factors for its development. Although recent reports have emphasized immunologic and infectious (i.e., cytomegalovirus) mechanisms in the development of transplant coronary disease, the influence of several nonimmunologic risk factors has also been studied. Some of the nonimmunologic risk factors that have been evaluated include recipient characteristics (age, sex, obesity, hyperlipidemia, hypertension, smoking, diabetes mellitus, pretransplantation heart disease), donor characteristics (age, sex), immunosuppressive agents/protocols, and nonimmune mechanisms of endothelial injury (cyclosporine, ischemic time). Studies evaluating the role of these risk factors have produced variable results. One or more studies, however, have suggested an effect of recipient age and sex, donor age and sex, obesity, hyperlipidemia, pretransplantation diagnosis, and ischemic time on the development of transplant coronary disease. The most consistently described relationship has been between hyperlipidemia and transplant coronary disease. Hyperlipidemia is common after heart transplantation, with elevations noted in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. The cause of posttransplantation hyperlipidemia is not well defined, but obesity and the immunosuppressive agents prednisone and cyclosporine play a role. Treatment of posttransplantation hyperlipidemia can be difficult because commonly used lipid-lowering agents have side effects and interactions with immunosuppressive drugs that necessitate caution in their use in the posttransplantation population. Transplant coronary disease almost certainly has a multifactorial cause, with endothelial injury and nonimmunologic risk factors, particularly hyperlipidemia, playing contributory roles. Because hyperlipidemia and the obesity that commonly accompany it are modifiable risk factors, weight loss and treatment of hyperlipidemia are recommended.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transplant coronary disease: nonimmunologic risk factors. 162 91

Regular exercise is an effective nonpharmacologic therapy for stress, sleep disorders, depression, and anxiety, as well as such chronic conditions of aging as hypertension, obesity, diabetes mellitus, coronary artery disease, hyperlipidemia, and constipation. Pre-exercise office assessment of cardiac risk, possible limitations, and contraindications is advised. A balanced fitness training program includes activities to increase flexibility, strength, and cardiovascular endurance. The most effective exercise prescription begins with a type of aerobic activity the patient enjoys. A prescribed schedule of stepwise increments in frequency, duration, and intensity gradually leads to a maintenance level of fitness.
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PMID:Prescribing physical activity for older patients. 163 24

Coronary artery disease is a very common disorder for which hypertension is a well-recognized risk factor. However many trials of antihypertensive therapy have failed to demonstrate a reduction in the incidence of coronary events. One explanation is that hypertension is a disorder associated with hyperinsulinaemia, obesity and non-insulin dependent diabetes. Furthermore certain antihypertensive drugs, notably thiazide diuretics, increase the hyperinsulinaemia and thereby increase one of the other coronary risk factors. In this review the links between hypertension and hyperinsulinaemia are explored and the mechanisms whereby an increased plasma insulin can lead to the more rapid development of coronary artery disease are explained. These observations may influence the choice of drugs used to treat hypertension.
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PMID:Hypertension, coronary artery disease and insulin resistance--linked disorders with an impact on treatment. 163 76

A conference convened by the NIH in 1985 officially designated obesity a health hazard, stopping short of calling it a disease; yet its characteristic progressive, debilitating and refractory nature is impressively disease-like. Long-term weight loss occurs in only 5% of patients. Group office visits led by physicians have been used in a number of life-style conditions. In diabetes this format enhances blood sugar control and in obesity it improves five-year weight loss success to 20%. In patients with coronary artery disease risk factor a 21% decrease in angina, 55% improvement of exercise tolerance, and 21% decrease in cholesterol occurred in a pilot study. Group office physician-led visits offer encouraging results for the mitigation of life-style conditions.
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PMID:Group office visits in obesity. 164 Feb 12

Hypertension is one of the primary risk factors for cardiovascular disease, especially coronary artery disease (CAD), cerebrovascular disease, and congestive heart failure. Recent analysis of the numerous prospective clinical trials of the efficacy of antihypertensive therapy performed during the past quarter century has shown that active treatment reduces mortality and cerebrovascular disease but has not prevented CAD. The reason for this paradox--that lowering blood pressure does not reduce CAD mortality or morbidity--is uncertain. During the past several years, it has become clear that hyperinsulinemia and peripheral insulin resistance constitute the link between hypertension, obesity, and non-insulin-dependent diabetes mellitus, three conditions in which the rate of CAD is very high. Other studies have shown that hyperinsulinemia is a potent cardiovascular risk factor. Epidemiologic surveys and retrospective reviews of clinical experience have pointed out the surprising fact that when hypertension and non-insulin-dependent diabetes mellitus occur in the same patient, hypertension is likely to be diagnosed first and the risk of developing diabetes is much higher if antihypertensive drugs (thiazide diuretics or beta-adrenoreceptor blockers) were given. Recently, careful studies have shown that both thiazide diuretic and beta-adrenoreceptor blockers worsen insulin sensitivity, whereas angiotensin converting enzyme inhibitors (captopril) and peripheral alpha 1-blockers (prazosin) improve it and also favorably affect the levels of other atherogenic risk factors. Although it is too early to be certain, this information suggests that, pending the results of long-term clinical trials that measure clinical events, treatment of hypertension might be better able to reduce CAD if it were directed at improving insulin sensitivity. Nonpharmacologic measures that reduce hyperinsulinemia, weight loss, and exercise should be vigorously recommended, and pharmacologic therapy should be aimed at avoiding drugs that worsen insulin sensitivity, as long as blood pressure is successfully reduced.
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PMID:The coronary artery disease paradox: the role of hyperinsulinemia and insulin resistance and implications for therapy. 169 28

The coexistence of the syndromes of essential hypertension and coronary artery disease (CAD) poses a major but common therapeutic challenge. High blood pressure is one of the most potent risk factors for the early development of CAD. Conversely, the presence of CAD significantly worsens the predictive prognosis associated with high blood pressure. Moreover, metabolic risk factors for the acceleration of both syndromes are similar, particularly with regard to abnormalities of the blood lipid profile, carbohydrate intolerance, and obesity. It is clinically crucial, therefore, to direct drug therapy not only at the immediate alleviation of the symptoms and signs of each syndrome but also to control the cardiac and vascular risk factors common to both syndromes. Carvedilol is a third-generation vasodilating beta-adrenoceptor antagonist with advantageous ancillary pharmacologic properties for the treatment of the patient with high blood pressure complicated by CAD. The immediate advantages of the drug in the treatment of both syndromes are distinct. In the patient with high blood pressure, carvedilol controls the pressure throughout the 24 h of the day and suppresses the increase associated with exercise. In the patient with CAD, the drug is efficacious in relieving anginal pain and electrocardiographic signs of myocardial ischemia. By reducing blood pressure and heart rate and retarding their increases during exercise, the drug exhibits a potent ability to reduce left ventricular work, wall stress, myocardial oxygen consumption, and left ventricular myocardial ischemia. In the patient in whom both syndromes coexist, carvedilol affords a remedy for both.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypertension and coronary artery disease: a therapeutic challenge. 172 78

Severe obesity is associated with abnormalities of cardiac structure and function. These include an increased cardiac workload and ventricular hypertrophy. Hypertension in combination with severe obesity seriously burdens the heart because the increased preload and afterload compound cardiac work. Weight reduction induced by gastric operations for severe obesity is associated with resolution of hypertension, reduction in ventricular wall thickness and cardiac chamber size, as well as improved systolic function. Additional data are needed to predict when in the course of development of obese cardiomyopathy the changes in contractile function become irreversible. Additionally, the impact of coronary artery disease on the progression of obese cardiomyopathy and the effects of surgical weight reduction on cardiac structure and function need to be further clarified. Studies of the association between obesity, its treatment, and modification of cardiovascular risk are a major focus of preventive cardiology today.
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PMID:Heart disease and hypertension in severe obesity: the benefits of weight reduction. 173 33

Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors. 173 2


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