Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin action starts with binding to a membrane receptor (insulin receptor-tyrosine kinase) and with activating an insulin receptor substrate 1 (IRS-1) and substrate 2 (IRS-2). Insulin receptors interact at least with three cascade reactions, phosphorylating G proteins and IRS-1, that activate PLC "ras" and PI-3-K. NIDDM can be defined as a disease caused by defective transduction of insulin signals and IR as a complex phenotype manifesting itself, emphasized by individual and environmental factors, in the cellular systems of signal transduction. IRS is a syndrome characterized by NIDDM, hypertension, visceral obesity, CHD: the X syndrome. Up to day the described mutations of the insulin-receptor gene are rare (e.g. the leprechaunism): genetic IR. Obesity is the principal cause of IR by receptorial and post-receptorial defects: metabolic IR. The obese skeletal muscle shows a reduction of insulin receptor and IRS-1 phosphorylation and of PI-3-K activation; the scarce expression of these proteins would determine the muscular IR. IR is a pattern of essential hypertension. Hypertension, dyslipidemia and abnormality of glucose metabolism are linked by IR. The so called high erythrocyte Na(+)-Li+ counter-transport is a new biochemical marker for IR and hypertension. These drugs can reduce IR: metformin, sulphonilureas, fibrats, dexfenfluramine, troglitazone, doxazosin, ACE-inhibitors.
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PMID:[Insulin resistance. Receptor and post-receptor abnormalities]. 984 54

The tissue-specific expression of the mitochondrial pyruvate dehydrogenase complex (PDHc) has been studied in an animal model of obesity with hyperinsulinemia, the obese (fa/fa) Zucker rat. Liver and heart were obtained from 4 and 8 week-old obese rats and age-matched lean animals, and in each tissue the following parameters were analyzed: (1) total activity of the mitochondrial PDHc; (2) abundance of the mitochondrial PDHc subunits on Western blots; and (3) abundance of the E1alpha and E1beta subunit mRNAs on Northern blots and semi-quantitative RT-PCR. Regardless of age, obese rats showed an increase in liver total PDHc activity and a coordinate increase in liver E1alpha and E1beta PDHc subunit abundance. At 4 weeks, obese rats also showed an increase in liver PDH E1alpha mRNA level, but regardless of age E1beta mRNA level was unchanged. In contrast, neither total PDHc activity nor the concentration of its protein subunits were increased in heart of obese rats. Thus, obese Zucker rats display a liver-specific early increase in PDHc which results from a selective up-regulation of the E1alpha gene expression.
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PMID:Longitudinal study of tissue- and subunit-specific obesity-induced regulation of the pyruvate dehydrogenase complex. 986 34

This study compares the effects of a calcium channel blocker (amlodipine) and an angiotensin converting enzyme inhibitor (enalapril) on in vivo insulin sensitivity in patients with essential hypertension. Forty-six patients with mild and moderate hypertension were studied. After a 2-week single-blind placebo phase, they were randomly assigned to double-blind therapy with either amlodipine (2.5 to 10 mg/day) or enalapril (5 to 40 mg/day) for 16 weeks. Both groups were comparable in terms of demographic characteristics, degree of obesity, metabolic parameters, and arterial blood pressure. Insulin sensitivity was measured at baseline and at week 16 during the active phase using euglycemic hyperinsulinemic clamps. Arterial blood pressure decreased similarly in both groups. Whole body glucose uptake (M-value) increased with amlodipine from 3.63 +/- 0.32 (mean +/- SEM) to 3.97 +/- 0.31 mg/kg/min (P = .02). A similar tendency was observed with enalapril: from 3.59 +/- 0.32 to 3.94 +/- 0.30 mg/kg/min (P = .09). A trend to lower steady-state insulin level during the second clamp (compared to baseline) was observed in both groups. The clamp-derived insulin sensitivity index (that corrects for steady-state insulin levels and glucose levels during the clamp) increased similarly in both groups: from 1.15 +/- 0.11 to 1.39 +/- 0.13 with amlodipine (P = .03) and from 1.25 +/- 0.13 to 1.49 +/- 0.16 with enalapril (P = .01). LDL cholesterol decreased with amlodipine (mean change, -11.3 mg/dL, P = .004). Amlodipine and enalapril were associated with increments in insulin sensitivity. Amlodipine provided an additional benefit with decreased low density lipoprotein cholesterol levels.
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PMID:A double blind comparison of the effects of amlodipine and enalapril on insulin sensitivity in hypertensive patients. 1019 33

A retrospective review of the cases of congestive heart failure admitted to Holberton Hospital in Antigua in 1995 and 1996 was undertaken. Two hundred and ninety-three (293) patients were identified by International Statistical Classification of Diseases, 10th revision (ICD-10) coding as having congestive cardiac failure in the period but only 138 charts were either available or fitted the definition of congestive cardiac failure and these provided the basis for this analysis. The average age of patients admitted for congestive cardiac failure was 69 years (range: 5 months to 99 years), and 63% were female. the aetiology of congestive cardiac failure was hypertension (41%), ischaemia (33%), valvular (12%), alcohol related (2%), idiopathic (5%) and mixed (7%). Treatment included diuretics (95%), angiotensin converting enzyme inhibitors (78%), digoxin (75%), nitrates (34%), calcium channel blockers (25%), other vasodilators (7%) and antiarrhythmics (5%). Of those with congestive heart failure, diabetes was present in 38%, atrial fibrillation in 19%, renal insufficiency in 17%, elevated cholesterol in 11%, obesity in 9% and tobacco use in 7%. The in-hospital mortality in the 2-year period was 17.4% (females 15%, males 22%, 11% < 65 years, 20% > 65 years, 14% for those with 1 to 3 admissions and 83% for those with > 3 admissions, 19% for those with atrial fibrillation and 16% for those without). The prevalence of congestive cardiac failure utilizing the data analysed in this study (138 patients) was 0.21% of the population of the island state but based on the discharge diagnosis using ICD-10 coding it was 0.5%; it was 1% in the 40 to 65-year-age group and 4% in those > 65 years of age. The patients in this study represented only those with New York Heart Association (NYHA) classes III and IV, hence the true prevalence would be higher than recorded here. Congestive cardiac failure is emerging as a significant health problem in Antigua and Barbuda.
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PMID:The prevalence, aetiology and treatment of congestive cardiac failure in Antigua and Barbuda. 1055 60

In the C57BL/6J mice model, we investigated whether obesity affects the function or expression of components of the tissue renin-angiotensin system and whether endothelin (ET)-1 contributes to these changes. ACE activity (nmol. L His-Leu. mg protein(-1)) was measured in lung, kidney, and liver in control (receiving standard chow) and obese animals treated for 30 weeks with a high-fat, low cholesterol diet alone or in combination with LU135252, an orally active ET(A) receptor antagonist. ACE mRNA expression was measured in the kidney, and the effects of LU135252 on purified human ACE were determined. Aortic and renal tissue ET-1 protein content was measured, and the vascular contractility to angiotensin II was assessed. Obesity was associated with a tissue-specific increase in ACE activity in the kidney (55+/-4 versus 33+/-3 nmol/L) but not in the lung (34+/-2 versus 32+/-2 nmol/L). Long-term LU135252 treatment completely prevented this activation (13.3+/-0.3 versus 55+/-4 nmol/L, P<0.05) independent of ACE mRNA expression, body weight, or renal ET-1 protein but did not affect pulmonary or hepatic ACE activity. Obesity potentiated contractions in response to angiotensin II in the aorta (from 6+/-2% to 33+/-5% KCl) but not in the carotid artery (4+/-1% to 3.6+/-1% KCl), an effect that was completely prevented with LU135252 treatment (6+/-0.4% versus 33+/-5% KCl). No effect of LU135252 on purified ACE was observed. Thus, obesity is associated with the activation of renal ACE in vivo independent of its mRNA expression and enhanced vascular contractility to angiotensin II. These effects are regulated by ET in an organ-specific manner, providing novel mechanisms by which ET antagonists may exert organ protection.
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PMID:Obesity is associated with tissue-specific activation of renal angiotensin-converting enzyme in vivo: evidence for a regulatory role of endothelin. 1064 20

Hypertension is currently defined in terms of levels of blood pressure associated with increased cardiovascular risk. A cut-off of 140/90 mm Hg is accepted as a threshold level above which treatment should at least be considered. This would give a prevalence of hypertension of about 20% of the adult population in most developed countries. Hypertension is associated with increased risk of stroke, myocardial infarction, atrial fibrillation, heart failure, peripheral vascular disease and renal impairment. Hypertension results from the complex interaction of genetic factors and environmental influences. Many of the genetic factors remain to be discovered, but environmental influences such as salt intake, diet and alcohol form the basis of nonpharmacological methods of blood pressure reduction. Investigation of the individual hypertensive patient aims to identify possible secondary causes of hypertension and also to assess the individual's overall cardiovascular risk, which determines the need for prompt and aggressive therapy. Cardiovascular risk can be determined from (i) target organ damage to the eyes, heart and kidneys; (ii) other medical conditions associated with increased risk; and (iii) lifestyle factors such as obesity and smoking. Secondary causes of hypertension are individually rare. Screening tests should be initially simple, with more expensive and invasive tests reserved for those in whom a secondary cause is suspected or who have atypical features to their presentation. The main determinants of blood pressure are cardiac output and peripheral resistance. The typical haemodynamic finding in patients with established hypertension is of normal cardiac output and increased peripheral resistance. Treatment of hypertension should initially use nonpharmacological methods. Selection of initial drug therapy should be based upon the strength of evidence for reduction of cardiovascular mortality in controlled clinical trials, and should also take into account coexisting medical conditions that favour or limit the usefulness of any given drug. Given this approach, it would be reasonable to use a thiazide diuretic and/or a beta-blocker as first-line therapy unless there are indications to the contrary. Individual response to given drug classes is highly variable and is related to the underlying variability in the abnormal pathophysiology. There are data to suggest that the renin-angiotensin system is more important in young patients. The targeting of this system in patients under the age of 50 years with a beta-blocker (or ACE inhibitor), and the use of a thiazide diuretic (or calcium antagonist) in patients over 50 years, may enable blood pressure to be controlled more quickly.
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PMID:Pathoaetiology, epidemiology and diagnosis of hypertension. 1067 92

Some 44% of all patients with elevated blood pressure are overweight. In obesity-related hypertension, sympathicotonia is regularly found, together with elevated intracellular calcium, sodium retention, increased cardiac output (per minute) and a sensitivity to salt. The role played by hyperinsulinemia has apparently been overstated. A primary rise in the minimal vascular resistance suffices to reduce the perfusion of the skeletal musculature and, solely on this basis, to induce insulin resistance. For the treatment of obesity-related hypertension, non-medicinal approaches to weight reduction predominate. Reducing the daily salt intake to 5 g can also bring about a measurable reduction in blood pressure. For the treatment with antihypertensive drugs, beta blockers and diuretics are the initial choice; in the case of pronounced metabolic syndrome, ACE-inhibitors and alpha-1 receptors.
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PMID:[Fat control--an effective antihypertensive strategy. Special recommendations for therapy of the overweight patient]. 1079 42

This study aimed at analysing an effect of the coronary risk factors and pharmacotherapy on the long-term outcome in women following the coronary artery by-pass. In 1004-1997, 253 female patients, aged between 33 and 82 years (mean [+/- SD] 57.0 +/- 8 years) were treated surgically. The follow-up period lasted for 7 to 60 months (mean 32.0 +/- 14 months). Ten patients (3.9%) died. Answers to the questionnaire and personal interviews assessed physical fitness based on CCS classification, pharmacotherapy, and presence of risk factors. According to CCS scale, significant improvement has been seen in 195 (82.6%; p < .0001) patients. Health state did not change in 34 (14.4%) patients, and deteriorated in 7 (3.0%). Analysisn coronary risk factors, hypertension proved prevailing (60.3%), followed by diabetes mellitus (25.5%) and obesity (22.9%). Eleven percent of patients returned to cigarettes smoking after surgery. Postoperatively, 74.1% of patients received nitrates as a constant, medication, 58.2%--beta-blockers, 53.4%--ACE inhibitors, and 19.8% of patients received calcium antagonists. Lipid abnormalities have been treated in 49.1% of patients whereas antiplatelet therapy has been carried out in 74.1%. Only 9.9% of patients received hormones. The lower CCS class before surgery, the more significant improvement after it. As pharmacotherapy was used according to the European guidelines, an improvement in the long-term outcome required some modifications in patients' life style.
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PMID:[An influence of cardiovascular risk factors and pharmacotherapy on the long-term results in women undergoing coronary artery bypass]. 1080 40

More women than men eventually develop hypertension in the United States due to their higher numbers and longer longevity. The white coat hypertension is also more common in women. Alcohol, obesity and oral contraceptives are important causes of rise in blood pressure among women. On the other hand, hormone replacement therapy may decrease cardiovascular mortality in the postmenopausal woman. Women with left ventricular hypertrophy are at a greater risk of death than men. Fibromuscular hyperplasia and primary aldosteronism are more common as causes of secondary hypertension in women. Nonpharmacologic therapy, such as weight reduction, exercise, salt and alcohol reduction, should always be tried prior to medical treatment of hypertension and are very useful adjunctive measures in controlling hypertension. ACE inhibitors and angiotensin receptor blockers are contraindicated in pregnancy and should be avoided in women with childbearing potential. Hypertension remains a major public health problem among black women. Although the antihypertensive drug therapy seems to benefit white women the least, proportionately more of them comply with their antihypertensive therapy. Hypertension is the most common chronic medical condition requiring visits to the physicians, as well as prescription medications, in the United States. The epidemiology, clinical course, response to treatment and ultimate outcome of essential hypertension may vary with gender. More women than men eventually develop hypertension in the US due to their higher numbers and longer longevity.
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PMID:Hypertension in women. 1092 86

A cross-sectional study in a sample of 3,291 healthy workers was performed in May 1997 to assess the prevalence of obesity (BMI > or = 30 kg/m2) in a working population, and to compare prescription of antihypertensive drugs in obese and non obese subjects. Obesity was found in 7.4% (245) subjects and morbid obesity concerned 0.4% of the total sample (mean age 37.6 +/- 9.7 [SD] years, 52.4% of males). Risk of obesity was significantly associated with age, male sex, professional classes (higher in blue collars workers, lower in senior executive), business travels, atypical schedules, professional and private difficulties. Albeit the prevalence of drug users (49.7%) was similar whatever the BMI, obese subjects used a higher number of drugs than non obese (2.0 +/- 1.2 versus 1.6 +/- 0.9, p < 0.001). Risk of consumption of cardiovascular drugs was higher in obese than in non obese subjects (OR 2.9, 95% CI [2.2-4.1]). After adjustment on confounding factors, obesity increased specific drug use such as angiotensin converting enzyme inhibitors (OR 3.3, 95% CI [1.7-6.4]), beta-blocking agents (OR 2.83, 95% CI [1.01-8.01]), calcium channel blockers (OR 2.44, 95% CI [1.06-5.63]) or diuretics only in women (OR 5.7, 95% CI [2.1-16.3]). Prescribed antihypertensive drugs were different in obese (beta-blockers = angiotensin converting enzyme inhibitors > diuretics > calcium channels blockers) and non obese (angiotensin converting enzyme inhibitors > calcium channel blockers > diuretics > beta-blockers) subjects.
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PMID:[Consumption of antihypertensive agents in obese patients: a cross-sectional study in a sample of 3,291 wage-earners in the Toulous region]. 1098 31


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