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Query: UMLS:C0028754 (obesity)
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Recent research has demonstrated that reduced insulin-stimulated glucose metabolism in skeletal muscle (insulin resistance) and hyperinsulinism are common features in widespread diseases such as essential hypertension, android obesity, non-insulin dependent diabetes mellitus, dyslipidemia (in the form of raised serum triglyceride and reduced serum high-density lipoprotein (HDL) cholesterol) and arteriosclerosis. Simultaneously, investigations in a comprehensive group of healthy middle-aged men have revealed insulin resistance in one fourth. On the basis of these observations, a working hypothesis is suggested which postulates that genetic abnormalities in one or more of the candidate genes in the modes of action of insulin occur in a great proportion of the population. These may result in insulin resistance (primary genetic insulin resistance). Primary insulin resistance may be potentiated by a series of circumstances such as ageing, high-fat diet, lack of physical activity, hormonal and metabolic abnormalities or drugs (secondary insulin resistance). As a consequence of the reduced effect of insulin on muscle tissue, compensatory hyperinsulinism develops. Depending on the remaining vulnerability of the individual the hyperinsulinism is presumed to result in development of one or more phenotypes. For example if the beta-cells of the pancreas are unable to secrete sufficient insulin to compensate the insulin resistance on account of genetic defects, glucose intolerance will develop. In a similar manner, hyperinsulinism in insulin-resistant individuals who are predisposed to essential hypertension is presumed to reveal genetic defects in the blood pressure regulating mechanisms and thus contribute to development of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Insulin resistance--a physiopathological condition with numerous sequelae: non-insulin-dependent diabetes mellitus (NIDDM), android obesity, essential hypertension, dyslipidemia and atherosclerosis]. 163 67

Epidemiological evidence supports a link between hyperinsulinemia and blood pressure. In nondiabetic, normotensive individuals, the male sex, age, obesity, and body fat distribution all are associated with higher systolic and diastolic blood pressure and with higher plasma insulin concentrations. Nevertheless, when accounting for the above physiological variables, blood pressure still is independently related to plasma insulin. In the general population, hypertensive individuals have multiple metabolic abnormalities (glucose intolerance, hyperinsulinemia, and dyslipidemia). A striking pattern of overlap exists among obesity, diabetes, and hypertension. Physiological studies (euglycemic insulin clamp) have shown that essential hypertension per se is a state of insulin resistance: lean, nondiabetic subjects with untreated hypertension have a mean 40% reduction in the ability of physiological hyperinsulinemia to stimulate whole-body glucose uptake. Other insulin actions (suppression of hepatic glucose output, lipolysis, lipid oxidation, and promotion of K+ uptake) are conspicuously preserved. In perfused forearm studies, local (intra-arterial) hyperinsulinemia induces subnormal rates of glucose uptake and glycogen synthesis in the skeletal muscle of individuals with essential hypertension. In the San Antonio Heart Study, parental history of non-insulin-dependent diabetes mellitus (NIDDM) is associated with hyperinsulinemia and higher blood pressure and serum lipid levels in nondiabetic probands. In this biethnic population, however, hyperinsulinemia and NIDDM are more prevalent (approximately threefold) among Mexican-Americans than non-Hispanic whites, but hypertension is more prevalent among the latter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Essential hypertension: an insulin-resistant state. 169 27

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

Twenty-four hour energy expenditure (24EE) can be measured in a respiratory chamber. 24EE is comprised of the basal metabolic rate, the thermic effect of food, and the energy cost of physical activity. The major determinant of 24EE, fat-free mass, accounts for approximately 80% of the variance observed between individuals. Genetic factors seem to be the cause of the familial aggregation of 24EE in man. The variability of 24EE for a given body size and composition is of importance because a low metabolic rate is a major risk factor for weight gain in man. There is increasing evidence that obesity, often an inherited disorder, cannot always be attributed to gluttony and sloth. Similar to the need to treat essential hypertension, there is a need to treat a disorder perhaps best called essential obesity.
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PMID:A brief overview of human energy metabolism and its relationship to essential obesity. 172 37

Exogenous obesity is characterized hemodynamically by expanded intravascular (plasma) volume associated with an increased cardiopulmonary volume and cardiac output. In contrast, essential hypertension is related to an increased total peripheral resistance that is more or less uniformly distributed throughout the component organ circulations associated with a contracted plasma volume in proportion to the height of arterial pressure. Thus, both cardiac output and total peripheral resistance are elevated in obesity hypertension, and both impose a load on the left ventricle, resulting in both a volume and a pressure overload left ventricular hypertrophy. Although renal vascular resistance is not as increased as it is in lean hypertensive patients, these patients are subjected to hyperfiltration and proteinuria. Additionally, these hemodynamic alterations coexist with carbohydrate intolerance, hyperinsulinemia, hyperlipidemia, and hyperuricemia. With weight reduction and associated pressure reduction, the hemodynamic and metabolic changes reverse toward normal. However, should this not be achievable, the angiotensin converting enzyme inhibitors and calcium antagonists provide rational physiological approaches to drug therapy. With these agents pressure reduction is achieved through a fall in vascular resistance without intravascular volume expansion, and this is associated with reduced left ventricular mass and preserved cardiac and renal function, and without exacerbation of preexisting metabolic perturbations. Hence, these two classes of antihypertensive agents may provide a rational and physiological means for reversing the pathophysiological alterations of hypertensive disease in those obese patients in whom weight control is not possible.
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PMID:Obesity hypertension. Converting enzyme inhibitors and calcium antagonists. 173 Apr 48

Late diabetic effects are the sequelae of for a long time super elevated blood sugar levels. The diabetic nephropathy is the cause of the secondary arterial hypertension. The investigation seeks for the connections between the diabetes mellitus and the essential, that is primary hypertension. The two diseases frequently appear and clearly increase in the second half of life. Moreover, they are above average frequently associated with each other. Among brothers and sisters of diabetic hypertensives in comparison to normal cohorts clearly increased high blood pressure prevalences were found. The insulin resistance which could be proved in a great number of hypertensive and which has been known since more than two decades might be the connecting link between hypertension and diabetes mellitus. Like the obesity the essential hypertension can be associated with all degrees of an insulin hyposensitiveness. The sodium-retaining effect of the insulin might explain the increased sodium content of the body in hypertensives. The differential diagnostics of the essential hypertension should therefore seek for conditions of an insulin resistance. The type II diabetic lacks a release of bradykinin during muscle work. Thus the glucose uptake into the cell is unfavourable influenced and demands an increased insulin excretion. This genetically (?) fixed defect is found also in essential hypertensives. It could be the connecting link between the two diseases. ACE-inhibitors have via a kininase II inhibition an effect also on the bradykinin decomposition and can favourable influence the glucose uptake into the muscle. An improved insulin effect among the ACE-inhibitors was described. Therefore, they should be preferred in the treatment of hypertensive diabetics.
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PMID:[Diabetes mellitus and arterial hypertension. In search of the connecting link]. 177 26

Insulin resistance is the cornerstone for the development of non-insulin-dependent diabetes mellitus (NIDDM). Free fatty acids (FFAs) cause insulin resistance in muscle and liver and increase hepatic gluconeogenesis and lipoprotein production and perhaps decrease hepatic clearance of insulin. It is suggested that the depressing effect of insulin on circulating FFA concentration is dependent on the fraction derived from visceral adipocytes, which have a low responsiveness to the antilipolytic effect of insulin. Elevated secretion of cortisol and/or testosterone induces insulin resistance in muscle. This also seems to be the case for low testosterone concentrations in men. In addition, cortisol increases hepatic gluconeogenesis. Cortisol and testosterone have "permissive" effect on adipose lipolysis and therefore amplify lipolytic stimulation; FFA, cortisol, and testosterone thus have powerful combined effects, resulting in insulin resistance and increased hepatic gluconeogenesis. All these factors promoting insulin resistance are active in abdominal visceral obesity, which is closely associated with insulin resistance, NIDDM, and the "metabolic syndrome." In addition, the endocrine aberrations may provide a cause for visceral fat accumulation, probably due to regional differences in steroid-hormone-receptor density. In addition to the increased activity along the adrenocorticosteroid axis, there also seem to be signs of increased activity from the central sympathetic nervous system. These are the established endocrine consequences of hypothalamic arousal in the defeat and defense reactions. There is some evidence that suggests an increased prevalence of psychosocial stress factors is associated with visceral distribution of body fat. Therefore, it is hypothesized that such factors might provide a background not only to a defense reaction and primary hypertension, suggested previously, but also to a defeat reaction, which contributes to an endocrine aberration leading to metabolic aberrations and visceral fat accumulation, which in turn leads to disease.
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PMID:Metabolic implications of body fat distribution. 177

Obesity, essential hypertension, and diabetes mellitus share certain metabolic disturbances. The predictive value of disordered glucose metabolism and insulin action for hypertension are discussed. Several studies have examined the relationship between hypertension and glucose metabolism in diverse populations, and tend to indicate a predictive role for insulin and glucose metabolism disturbances in the development of hypertension.
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PMID:Glucose, insulin, and insulin resistance as biochemical predictors of hypertension. 178 48

Evidence of old cerebral infarction of magnetic resonance imaging (MRI) is common in acute stroke patients without a prior history of stroke. This experience led us to investigate the incidence of silent cerebral infarction (SCI) in the patients with essential hypertension, as well-known major predisposing factor for stroke. The incidence, number, size and localization of SCI on MRI (MARK-J, 0.1 T) and the prevalence of risk factors for stroke were investigated both in 66 hypertensive patients (WHO stage I or II; 63 +/- 9 (mean +/- S.D.) years old) and in 42 age-matched normotensive patients (61 +/- 9 years old). Risk factors selected were as follows: diabetes mellitus, hypercholesterolemia, daily alcohol intake, cigarette smoking, obesity, cardiac disease (arrhythmia and ischemic heart disease), hyperuricemia and high hematocrit. In hypertensive patients, the relationships between the incidence of SCI and hypertensive damages in major organs were also investigated. SCI was found in 45 out of the 108 subjects studied and a total of 216 SCI lesions were detected. All of the SCI lesions were localized in the subcortical white matter or in the basal ganglia. All SCI lesions were smaller than 3 cm in diameter and 201 lesions (93%) were smaller than 1 cm. The incidence of SCI tended to be higher in hypertensive patients (47%) than that in normotensives (33%) and increased significantly with advancing age in hypertensives from 26.9% in the 50s to 86.7% in the 70s, while no significant increase was noted in normotensives.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Silent cerebral infarction in the patients with essential hypertension]. 179 35

Hyperinsulinemia has been implicated in the pathogenesis of the blood pressure elevation in patients with noninsulin-dependent diabetes mellitus, obesity, but also essential hypertension. In these conditions an increased cardiovascular reactivity to noradrenaline (NA) and angiotensin II (AII) can be observed. Using the euglycemic clamp technique, we determined the cardiovascular reactivity to graded infusions of NA and AII in nine healthy males before (Bas), and 1 and 6 h after infusion of insulin (50 mU/kg per h) was started. On separate days control experiments were carried out to control for any circadian variation. Insulin led to a decrease of the amount of circulating NA necessary to increase the diastolic blood pressure (DBP) 20 mmHg (actual experiment [mean +/- SEM]: Bas, 23.1 +/- 5.0; 1 h, 14.8 +/- 3.0; and 6 h, 12.3 +/- 3.1; and control experiment: Bas, 20.7 +/- 5.0; 1 h, 18.6 +/- 3.5; and 6 h, 17.3 +/- 3.3 nmol/liter; Bas vs. 1 and 6 h: P less than 0.05). Although the amount of NA infused to raise DBP 20 mmHg showed a similar decline after 1 h of insulin infusion, no such change from baseline could be observed at 6 h. This appeared to be due to an increase in NA clearance with more prolonged insulin infusion. Insulin exerted no effect on the amount of AII infused to increase DBP 20 mmHg (actual experiment: Bas, 27.6 +/- 6.4; 1 h, 28.8 +/- 10.0; and 6 h, 21.2 +/- 5.3; and control experiment: Bas, 33.6 +/- 5.7; 1 h, 34.2 +/- 6.1; and 6 h, 23.4 +/- 4.7 ng/kg/min; NS). We did observe a circadian variation in AII reactivity. Whether the increase in cardiovascular responsiveness to NA after administration of insulin contributes to the elevation in blood pressure frequently observed in patients with insulin resistance remains to be proven.
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PMID:Exogenous insulin augments in healthy volunteers the cardiovascular reactivity to noradrenaline but not to angiotensin II. 186 61


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