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

Insulin resistance has been implicated in the pathogenesis of essential hypertension. Studies from other countries discovered insulin resistance; in people with essential hypertension in was also associated with obesity, however, insulin resistance was found in lean people too. In obesity, insulin resistance occurs secondarily to many physiopathological states and circulating factors which adversely affects insulin action. The metabolic abnormality in this action was mainly found in relation to abdominal fat; in other cases, insulin resistance was found to be inherited. Hyperinsulinaemia can actually increase blood pressure and is associated with venous and arterial thrombosis and it also rises lipid levels. It is interesting too that insulin resistance and hyperinsulinaemia are associated with impaired fibrinolysis through high levels of fibrinogen and plasminogen activator inhibitor of endothelial type and in identifying individuals prone to myocardial infarction. Some antihypertensive drugs like beta-blockers, methyl-dopa and diuretics increase insulin resistance, while angiotensin converting enzyme-inhibitors have not shown any adverse metabolic affects. Alfa-1-blocker were beneficial and alfa-2-agonists were neutral, whereas calcium channel-antagonists are still in controversy. Treatment should be designed to improve the metabolic state; physical exercise, a diet rich in fruit, vegetable and rott vegetables, the reduction of abdominal fat and, finally, the use of antihypertensive drugs which decrease insulin resistance would be expected to reverse hyperinsulinaemia. Biguanides like metformin have also been found to reduce insulin resistance.
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PMID:[Insulin resistance: an etiological factor in essential arterial hypertension and coronary cardiopathy]. 792 20

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

Secondary causes of hyperlipidemia are important to recognize. In fact, hyperlipidemia may be a clue to the presence of an underlying systemic disorder. It may greatly heighten the risk of atherosclerosis with a raised LDL-c, triglyceride-rich lipoprotein excess, and increased lipoprotein(a) as well as lowered HDL-c. The search for secondary causes may provide a clue as to why patients with primary lipid disorders suddenly develop worsening lipid profiles. The point is a crucial one because some acquired causes of hyperlipidemia, such as alcohol, estrogens, steroids, or pregnancy, when superimposed on a primary familial form of hypertriglyceridemia can result in a saturated removal system and a buildup of chylomicrons, which can lead to life-threatening pancreatitis. A convenient way to remember secondary causes is to think of the four D's of diet, drugs, disorders of metabolism, and diseases. Although diets rich in saturated fats and cholesterol are a common cause of the mild hypercholesterolemia seen in our society, alcohol excess and weight gain can explain much of the tendency toward hypertriglyceridemia. Interestingly anorexia nervosa has long been associated with severe but reversible hypercholesterolemia. Several classes of drugs need to be considered as common causes of altered lipid profiles. Glucocorticoids and estrogens elevate triglycerides and raise levels of HDL-c. Anabolic steroids taken orally markedly reduce levels of HDL-c in contrast to injectable testosterone, which does not adversely affect the LDL-to-HDL ratio. Oral contraceptives affect atherosclerotic risk depending on the kind and doses of progestin/estrogen. In those with an underlying primary hypertriglyceridemia and associated obesity, estrogenic medications can depress triglyceride removal mechanisms, leading to the chylomicronemia syndrome and pancreatitis. Antihypertensives have variable effects on lipids and lipoproteins. Although short-term thiazide usage raises cholesterol, triglycerides, and LDL-c, long-term usage is not necessarily associated with significant alterations in lipid levels. Alpha blockers may cause an increase in HDL-c, whereas beta blockers raise triglycerides and lower HDL-c. Sympatholytics, angiotensin converting enzyme inhibitors, and calcium channel blockers are essentially lipid neutral. Retinoids can be associated with increased LDL-to-HDL ratios and occasionally striking elevations in triglycerides. Cyclosporine raises LDL-c and lipoprotein(a). Classes of drugs that may raise HDL-c include cimetidine, antiepileptic drugs, and tamoxifen, but the effect may be seen primarily in women. Hypothyroidism is the most common secondary cause of hyperlipidemia after dietary causes are considered. A thyroxine and TSH level should be obtained on all new cases of clinically important hyperlipidemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Secondary causes of hyperlipidemia. 828 27

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

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

1. The gene for dipeptidyl carboxypeptidase 1 (angiotensin I-converting enzyme, kininase II; DCP1), located on chromosome 17q23, has been implicated in hypertension in rats. In humans associations have been found for the insertion allele of a bi-allelic insertion/deletion polymorphism of DCP1 with hypertension and the deletion allele with myocardial infarction. Other hypertension studies have, however, failed to find a relationship. 2. Mathematical predictions based on DCP1 association data suggest that high sib-pair numbers may be needed to achieve statistical significance by this approach, although differences in the severity of hypertension in different study groups could account for the disparate findings. 3. No association was found between DCP1 allele or genotype frequencies and obesity in essential hypertensives.
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PMID:Chromosome 17q23: a locus for cardiovascular disease. 839 42

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

To assess the effects of angiotensin converting enzyme (ACE) inhibitor on insulin action in obesity, five normotensive non-diabetic obese women were examined on two occasions as part of a double-blind, randomized, cross-over study involving ten days of treatment with either 1.25 mg ramipril or placebo. The study consisted of a euglycaemic hyperinsulinaemic clamp (two periods of insulin infusion at rates of 0.4 and 1 mU/kg/min, 2 h for each step) combined with indirect calorimetry. The most notable results involved a significantly faster time-course of glucose infusion rates during the first 30 min of each insulin infusion period [analysed by calculating slopes (S1 and S2)] after ramipril than placebo administration. The mean glucose infusion rates reached during the last 30 min of each insulin infusion period (G1 and G2), as well as the increases in carbohydrate oxidation rates during the clamp (C1-C0 and C2-C0) and the decreases in plasma nonesterified fatty acids (A0-A1 and A0-A2), were not significantly different after ramipril and placebo. According to robust principal component analysis of S1, S2, G1, G2, C1, C2, A1 and A2 (orthogonally to C0 and A0), insulin sensitivity was improved with ramipril as compared to placebo (p = 0.013). This study strongly suggests that a low dose of an ACE inhibitor increases the activation phase of insulin action in normotensive nondiabetic obese patients and may accelerate insulin action.
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PMID:Effect of ramipril on insulin sensitivity in obese patients. Time-course study of glucose infusion rate during euglycaemic hyperinsulinaemic clamp. 869 8


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