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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is associated with a spectrum of metabolic and cardiovascular disorders, including hypertension. Both the degree and the distribution of excess adipose tissue impact on the risk of hypertension and associated cardiovascular diseases. The mechanisms that may lead to hypertension in obese individuals include increased SNS activity, insulin resistance and hyperinsulinemia, sodium retention, and enhanced vascular reactivity. These abnormalities are interrelated in a complex fashion, making it difficult to determine which, if any, of them is the primary process leading to elevated blood pressure in obese individuals. Nonetheless, the metabolic abnormalities and hypertension diminish with weight loss and chronic exercise, providing a strong rationale for hypocaloric diets and aerobic exercise in the treatment of obesity-related hypertension. Patients who fail to achieve acceptable blood pressure control with diet and exercise therapy require pharmacologic treatment. Of the available antihypertensive agents, calcium entry blockers, ACE inhibitors, and alpha 1-receptor blockers appear to offer good blood pressure control without worsening--and sometimes while improving--the lipid and carbohydrate abnormalities that often occur in obese patients. New drugs developed to ameliorate insulin resistance show promise as antihypertensive agents as well, and may prove to be ideal in reversing multiple cardiovascular risk factors in obese, hypertensive patients.
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PMID:Obesity and hypertension. 807 Apr 30

Hypertension is the commonest cardiovascular disease in Africans occurring in more than 15% of the adult population in some studies. It occurs in the lower as much as in the higher socio-economic groups. Recent studies have confirmed earlier findings that essential hypertension in Africans is characterised by volume loading, low plasma renin activity, high salt taste threshold, high urinary sodium and low potassium excretion and high plasma aldosterone. The commonest complication of hypertension in Africans is congestive cardiac failure followed by cerebrovascular accidents. Coronary heart disease is rare. Even in the absence of overt heart failure and compounding factors like obesity, alcoholism, cigarette smoking, diabetes mellitus and myocarditis, evidence of abnormal left ventricular morphology and function is often present in newly diagnosed patients with moderate or severe hypertension. Response to monotherapy with beta-blockers or ACE inhibitors is usually poor but is good with thiazide diuretics or calcium channel blockers. The diuretics are an essential component of a two or three drug regime containing other classes of antihypertensive drugs. Cost of drugs is the most important determinant of compliance with drug treatment and consequently the likelihood of progression of the diseases to more severe forms in long term follow-up.
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PMID:Hypertension in Africa and effectiveness of its management with various classes of antihypertensive drugs and in different socio-economic and cultural environments. 826 3

Hyperinsulinemia is very much in the spotlight. Debate rages as to its significance and role in the etiology not only of NIDDM, but also other morphological and metabolic risk factors for atherosclerotic cardiovascular disease, including upper-body obesity, dyslipidemia, hypertension, and hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in these disorders but it is far from conclusive except for the fact that hyperinsulinemia and insulin resistance may be present many years before the onset of impaired glucose tolerance and NIDDM, and clearly play a role in their etiology. The thrifty genotype hypothesis provides a plausible basis for a better understanding of how hyperinsulinemia and insulin resistance could lead to glucose intolerance and atherosclerotic cardiovascular disease, but the detailed biochemical mechanisms remain elusive. A role for increased sympathetic nervous system activity, resulting from hypothalamic stimulation as a primary event causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The current focus on hyperinsulinemia also has resulted in closer examination of the therapy of diabetes and hypertension, emphasizing the need to avoid hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk of atherosclerotic cardiovascular disease and hypertension. There is still a paucity of epidemiological data to support a role for hyperinsulinemia in the etiology of hypertension. However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies. The research reviewed here, particularly that relating to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors, has opened new vistas for the treatment and prevention of NIDDM and atherosclerotic cardiovascular disease. Appropriate exercise clearly is associated with improved insulin sensitivity, modification of CVD risk factors, and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance can be detected in children, adolescents, and young adults. NIDDM can be prevented, but clearly, intervention needs to commence in childhood, and intensive risk factor intervention in subjects with NIDDM can reduce the risk of atherosclerotic cardiovascular disease. It seems paradoxical that prevention of NIDDM and atherosclerotic cardiovascular disease are now possible even though the biochemical and molecular basis of these disorders is not fully understood.
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PMID:Hyperinsulinemia--how innocent a bystander? 829 79

Non-insulin-dependent or type 2 diabetes is a heterogeneous disorder, characterized by defects in insulin secretion as well as in insulin action; these defects are worsened by the developing hyperglycaemia. Diabetes is an independent risk factor for the development of cardiovascular disease. In addition to hypertension, which is encountered in almost 50% of patients, lipid abnormalities, comprising elevations of both LDL-cholesterol and VLDL-triglycerides, as well as decreases in the levels of HDL-cholesterol, contribute to the high prevalence of vascular disease. Elevated levels of serum lipoprotein(a) may add to this increased risk. Considering the apparent clustering of risk factors such as poor metabolic control, obesity, hypertension and dyslipidaemia, the attainment of optimal blood glucose control forms only one of the aims of treatment to prevent the neurological and vascular complications, which severely affect the quality of life. Dietary advice comprises the adoption of healthy eating habits and reducing the intake of refined sugars and saturated fat. The long-term metabolic effects of intensive dietary therapy, however, have been disappointing. This necessitates early pharmacological treatment in a considerable number of patients. With mild hyperglycaemia, the metabolic effects of sulphonylurea and insulin treatment were comparable, but insulin is superior to sulphonylurea in patients who are more hyperglycaemic (fasting blood glucose > 11 mmol/l). In addition to its effects on blood glucose control, insulin therapy favourably affects dyslipidaemia. Treatment can be safely instituted on an outpatient basis, and hypoglycaemic side-effects are infrequent. Combination therapy of insulin and sulphonylurea results in similar metabolic improvement when compared with insulin treatment alone, but with a lower dose of insulin and the need for only one injection in two-thirds of patients. Drugs such as ACE inhibitors, which have no metabolic side-effects, have become the therapy of choice when treating hypertension in diabetic patients.
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PMID:Type 2 diabetes mellitus. Aspects of complications and treatment. 830 99

A 46-year-old man with known arterial hypertension for 10 years had, over the last two years, developed increasing obesity, particularly of the trunk, with other symptoms typical of Cushing's syndrome. Hormone analysis demonstrated hypercortisolism and decreased plasma ACTH concentration. The dexamethasone inhibition test failed to show any significant suppression of serum cortisol. Plasma ACTH was not increased in the corticotrophin-releasing hormone and the metyrapone tests. In the short ACTH test there was an excessive cortisol increase. Abdominal computed tomography revealed both adrenals to be enlarged (6 x 4 cm) and coarsely nodular. Adrenolytic treatment with ketoconazole (400 mg daily) caused symptoms of adrenal insufficiency, but a reduced dosage of 200 mg daily lowered the cortisol level to between 5 and 11 micrograms/dl and normalized the blood pressure and clinical signs of Cushing's syndrome disappeared. Subsequent bilateral adrenalectomy confirmed the diagnosis of massive macronodular adrenal hyperplasia. Substitution treatment with twice daily 25 mg cortisone acetate and 0.05 mg fludrocortisone was started postoperatively.
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PMID:[Bilateral massive macronodular adrenal gland hyperplasia. A rare cause of Cushing's syndrome]. 830 53

Hyperinsulinaemia and insulin resistance are associated with essential hypertension irrespective of obesity and non-insulin-dependent diabetes mellitus. One of the mechanisms whereby hyperinsulinaemia may play a role in the increase in blood pressure, is an increased activity of the sympathetic nervous system. The authors studied the incidence of hyperinsulinaemia, and the possibility of modulating it by 12-week administration of the ACE inhibitor (ACEI) lisinopril (Prinivil by MSD) at a dose of 20-40 mg/day. Compared with normotensive subjects, hypertensives showed a degree of hyperinsulinaemia and insulin resistance (higher blood glucose at higher immunoreactive insulin and C-peptide concentrations, and a higher IRI/blood glucose ratio) as well as manifestations of enhanced sympathetic activity (higher adrenaline levels). Lisinopril had a favourable effect not only on blood pressure but, also, on hyperinsulinaemia and adrenaline levels. It can be reasonably concluded that therapy with ACEI, in addition to its antihypertensive effect, may also favourably modulate some pathogenic and metabolic factors in essential hypertension.
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PMID:[Control of hyperinsulinemia in essential hypertension using the angiotensin-converting enzyme inhibitor, lisinopril]. 838 86

To investigate the effects on glucose and insulin metabolism of the slightly E-dominant, monophasic, low-dose oral contraceptive (OC) Diane-35, which contains 35 mcg ethinyl estradiol and 2 mg cyproterone acetate, a 17 alpha-hydroxyprogesterone derivative, the euglycemic hyperinsulinemic glucose clamp technique test was performed in 7 health young women after a one-year trial. The 7 subjects had a mean age of 22 years, a body mass index of 20.4 kg/m sq., had either never used OCs or had discontinued use at least 8 weeks before the study, were not taking medication, had no history of obesity or diabetes, and had normal glucose tolerance. The metabolic test was performed within the last 7 days before the presumed onset of menstruation during the last pretreatment cycle and within the last 5 days of OC intake during the sixth and twelfth cycle of continuous treatment with the OC. It was found that the glucose infusion rate, glucose metabolic clearance rate, and glucose infusion rate divided by plasma insulin plateau levels were not significantly affected by the OC. The metabolic clearance rate of the exogenous insulin infused during the clamp technique test was significantly increased after 6 cycles but not after 12. It was concluded that a 1-year treatment with Diane-35 does not alter peripheral (and presumable muscular) insulin sensitivity significantly, but increases insulin (presumably hepatic) clearance slightly.
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PMID:Effects of a 1-year treatment with a low-dose combined oral contraceptive containing ethinyl estradiol and cyproterone acetate on glucose and insulin metabolism. 845 99

It is a general impression that the blood pressure (BP) response during monotherapy in hypertensive subjects is highly variable. As decreased insulin sensitivity is a frequent finding in hypertensive patients, the following study was performed to evaluate if the degree of insulin sensitivity could predict the BP response to different types of anti-hypertensive treatments. Insulin sensitivity was evaluated by the hyperinsulinaemic euglycaemic clamp technique before initiation of treatment with beta-adrenergic blockers (n = 181), thiazide diuretics (n = 60), ACE inhibitors (n = 73), non-dihydropyridine calcium antagonists (n = 38), dihydropyridine calcium antagonists (n = 26) or alpha-1 antagonists (n = 39) over periods of 3-6 months in hypertensive patients. The proportion of poor responders, defined as a reduction in the diastolic blood pressure (DBP) of < 3 mm Hg ranged between 8% and 30% in the different groups despite similar pretreatment DBPs (100-102 mm Hg). A decreased pretreatment insulin sensitivity was related to a poor DBP treatment response in the thiazide-treated group only (r = -0.33, P < 0.05). In this group also obesity, as evaluated by body mass index (BMI), was associated with a poor BP response (r = 0.28, P < 0.05), while obesity was a predictor of a favourable reduction in DBP in the group treated with non-dihydropyridine calcium antagonists (r = -0.34, P < 0.05). These associations were still significant when pretreatment DBP was taken into account in multiple regression analysis. Neither age nor sex were found to be significant predictors of BP response in any of the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is insulin resistance a predictor of the blood pressure response to anti-hypertensive treatment? 855 91

The Ca(2+)-insensitive protein kinase C (PKC) isoforms epsilon, eta, delta and zeta are possible direct downstream targets of phosphatidylinositol 3-kinase (P13-K), and might therefore be involved in insulin signalling. Although isoform-specific changes in PKC expression have been reported for skeletal muscle and liver in insulin-resistant states, little is known about these isoforms in adipocytes. Therefore we studied (1) expression and subcellular localization of these isoforms in murine adipocytes, (2) translocation of specific isoforms to membranes in response to treatment with insulin and phorbol 12-myristate 13-acetate (PMA) and (3) regulation of expression in insulin-resistant states. The PKC isoforms epsilon, eta, delta and zeta are expressed in adipocytes. Immunoreactivity for all isoforms is higher in the membranes than in the cytosol, but subcellular fractionation by differential centrifugation shows an isoform-specific distribution within the membrane fractions. PMA treatment of adipocytes induces translocation of PKC-epsilon and -delta from the cytosol to the membrane fractions. Insulin treatment does not alter the subcellular distribution of any of the isoforms. 3T3-L1 adipocytes express PKC-epsilon and -zeta, and PKC-epsilon expression increases with differentiation from preadipocytes to adipocytes. PKC-epsilon expression decreases in an adipose-specific and age/obesity-dependent manner in two insulin-resistant models, the brown-adipose-tissue-deficient mouse and db/db mouse compared with control mice. We conclude that, although none of the isoforms investigated seems to be activated by insulin, the decrease in PKC-epsilon expression might contribute to metabolic alterations in adipocytes associated with insulin resistance and obesity.
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PMID:Protein kinase C isoforms epsilon, eta, delta and zeta in murine adipocytes: expression, subcellular localization and tissue-specific regulation in insulin-resistant states. 867 Jan 64

In the present paper we report the results of a study in which we compared 2 different approaches to the computation of biological age (BA) in a sample of 322 Japanese men (age range 20 to 79 years). In the first approach, 4 commonly used measures of health-related fitness (VO2peak, trunk flexion from a standing position, body fat, and grip strength) were reduced to a single BA score (HRF Age) using principal component analysis. In contrast, in the second approach, 3 commonly used measures of skilled motor performance and agility (vertical jump, stepping side-to-side, and balancing on one leg with eyes closed) were reduced to a single BA score (SMP Age) using similar multivariate procedures. The criterion-related validity of both of the BA measures was examined by assessing each measure's ability to discriminate between healthy and active groups of subjects. This was achieved by classifying the original subject pool into regularly active (ACT; n = 108) and healthy (HLTH; n = 169) subgroups on the basis of self-reported activity levels. Analyses revealed that HRF Age was a more powerful discriminator between the two activity groups than SMP Age. While HRF Age of HLTH subjects was very close to their chronological age (CA), in the ACT group, HRF Age was on average 15 years less than their CA (P < 0.05). In a separate analysis, we assessed the HRF Age of patients with ischemic heart disease, hypertension, obesity, or diabetes (PAT; n = 45). The HRF Age of these subjects averaged 10 years above their CA. Our data suggest that commonly used measures of health-related fitness can be usefully employed as indices of BA which differentiate between individuals of similar ages but differing health and physical activity status. In contrast, measures of skilled motor performance were found to be less valuable measures of BA. The implication of our findings for future experimental design in exercise and aging research is discussed.
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PMID:The relative utility of health-related fitness tests and skilled motor performance tests as measures of biological age in Japanese men. 871 21


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