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

Obesity-induced hypertension and essential hypertension in lean patients are two different forms of hypertension. The main goal of this study was to test whether there are differences in biochemical parameters between subjects with obesity-associated hypertension and those with essential hypertension. We examined whether the biochemical responses to angiotensin-converting enzyme inhibitor (ACEI) ramipril therapy reveal properties of these two conditions that might explain the differences in clinical outcome. Before ramipril therapy, the hypertensive group exhibited increases in ACE activity (p<0.05), plasma malondialdehyde (MDA) concentration and the malondialdehyde/nitric oxide end-product ratio (MDA/NO(x)) (p<0.05), and decreases in xanthine oxidase (XO) activity (p<0.05) and plasma nitric oxide end-product (NO(x)) level (p<0.01). Before medication, plasma endothelin-1 (ET-1), plasma leptin, and leptin receptor levels were normal. Following ramipril treatment, ACE activity normalized. Before ACE inhibitor treatment, the obese-hypertensive group exhibited elevated levels of plasma ET-1 (p<0.05), plasma leptin (p<0.01), XO activity (p<0.05), plasma MDA and MDA/NO(x) (p<0.05), and reduced levels of plasma NO(x)(p<0.01) and leptin receptors (p<0.001). Following medication, the plasma NO(x) level, MDA/NO(x), and XO activity returned to normal while ACE activity decreased (p<0.001). In patients with essential hypertension, NO availability and ACE activity, and in those with obesity-associated hypertension, hyperleptinemic effects, NO level, endothelin-1 concentration and XO activity, may be important factors in the pathology.
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PMID:Different pathomechanisms of essential and obesity-associated hypertension in adolescents. 1689 99

The prevalence of obesity is steadily increasing. Hypertension is one of the most common co-morbidities of obesity and significantly contributes to morbidity and mortality. Most obese hypertensive patients require antihypertensive drug treatment. However, current guidelines do not give specific recommendations for antihypertensive therapy of obese hypertensive patient. Some antihypertensive agents may have unwanted effects on the metabolic and hemodynamic abnormalities that link obesity and hypertension. Due to the lack of guidelines, this chapter provides recommendations for or against each class of antihypertensive agents mostly based on subjective criteria and pathophysiologic assumptions. Diuretics and betablockers are reported to reduce insulin sensitivity and increase lipid levels, whereas calcium antagonists are metabolically neutral and ACE-inhibitors as well as angiotensin receptor blockers increase insulin sensitivity. Sodium retention plays a central role in the development of obesity-related hypertension. Therefore, treatment with an ACE-inhibitors or a diuretic should be considered as first-line antihypertensive drug therapy in obesity-hypertension.
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PMID:Treatment of arterial hypertension in obese patients. 1692 46

The purpose of the present study was to identify gene polymorphisms for the reliable assessment of genetic factors for obesity. The study population comprised 3906 unrelated Japanese individuals (2286 men, 1620 women), including 1196 subjects (677 men, 519 women) with obesity (body mass index of > or = 25 kg/m2) and 2710 controls (1609 men, 1101 women). The genotypes for 147 polymorphisms of 124 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of smoking revealed that the -30Gright curved arrow A polymorphism of GCK, the -240Aright curved arrow T polymorphism of ACE, and the -482Cright curved arrow T polymorphism of APOC3 were significantly (P < 0.01) associated with the prevalence of obesity, and the -1989Tright curved arrow G polymorphism of ESR1 was almost significantly associated. A stepwise forward selection procedure demonstrated that ACE, GCK, and ESR1 genotypes significantly (P < 0.01) and independently affected the prevalence of obesity. Combined genotype analysis for these three polymorphisms yielded a lowest odds ratio of 0.45 for the combined genotypes of AT or TT for ACE, GG for GCK, and GG for ESR1 in comparison with the combined genotypes of AA for ACE, GG for GCK, and TT or TG for ESR1. Genotypes for ACE, GCK, and ESR1 may prove reliable for the assessment of genetic factors for obesity. Determination of the combined genotypes for these genes may contribute to the personalized prevention of this condition.
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PMID:Genetic factors for obesity. 1701 14

Obesity and insulin resistance are directly associated with the presence of microalbuminuria. However, the prospective relationship between abdominal adiposity and the occurrence of micro-albuminuria has been little studied in a non-diabetic population. From the DESIR cohort, we examined whether waist circumference was associated with the incidence of micro-albuminuria at 6 years (D6). The study evaluated 2738 non-diabetic subjects without micro-albuminuria at inclusion who were then followed prospectively. At 6 years, 254 individuals (9.3%) had developed pathological micro-albuminuria (> or =20 mg/l) measured at micturation. In both sexes, the incidence of micro-albuminuria was associated with increased waist circumference and blood pressure, but not with blood glucose levels, lipid parameters or body mass index. Subjects with a higher waist circumference at inclusion were at a higher risk of having micro-albuminuria at 6 years compared to those with a normal waist circumference. Logical regression analysis showed that waist circumference as a continuous value, or greater than 94 cm for males and 88 cm for females, were predictive factors for the incidence of micro-albuminuria, after adjustment for age, hypertension, ACE inhibitor usage, fibrinogen, and blood glucose level. Abdominal adiposity is thus linked in both sexes to the development of microalbuminuria, which underlines the importance of measuring waist circumference when assessing risk factors for renal lesions in non-diabetic hypertensives.
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PMID:[Larger waist circumference is a predictive factor for the occurrence of microalbuminuria in a non-diabetic population]. 1706 39

Hypertension is often associated with an impairment of glucose tolerance and is a risk factor for the development of type 2 diabetes mellitus. The occurrence of diabetes may be also influenced by the selection of the type of antihypertensive treatment. While it has been shown that the use of older type antihypertensives - diuretics and beta-blockers - may precipitate diabetes, newer drugs which inhibit the renin-angiotensin system have a positive effect on glucose tolerance. Several recent clinical trials of ACE-inhibitors and AT1-blockers have demonstrated a decreased risk of the occurrence of diabetes in comparison with placebo or conventional antihypertensive drugs. The mechanisms responsible for the antidiabetic effect of these newer antihypertensive agents remain largely speculative. Insulin resistance may be improved in several ways, e.g. by changes in microcirculation or direct effects on insulin response and glucose transport in target organ cells. However, as shown in experimental studies, improved islet function and insulin secretion may also have role due to an inhibitory effect on the local renin-angiotensin system in the pancreas. Ongoing prospective clinical trials having the occurrence of diabetes as a primary specified endpoint should confirm the preventive potential of the inhibitors of the renin-angiotensin system. Since direct comparisons are lacking, current data are inconclusive as to the superiority of one of the two classes of these inhibitors or of any single drug. Nevertheless, inhibitors of the renin-angiotensin system should definitely represent first choice antihypertensive agents for persons with additional risk factors such as family history of diabetes, obesity or impaired glucose tolerance.
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PMID:[Prevention of type 2 diabetes mellitus due to antihypertensive treatment affecting renin-angiotensin system]. 1709 2

Arterial hypertension is frequently associated with type 2 diabetes mellitus, and both of these diseases are the major risk factors for cardiovascular complications. During the past few years, a number of large randomized clinical trials examined the frequency of new onset diabetes mellitus during administration of antihypertensive drugs. Application of ACE inhibitors or angiotensin receptor blockers reduces the risk for the onset of diabetes mellitus by 20-27%, and calcium channel blockers by 16%. Despite some uncertainties, novel studies have demonstrated an increased risk for cardiovascular complications related to new onset diabetes mellitus. The duration of patient monitoring is also an important factor, as the onset of diabetes-related complications is closely associated with the duration of this disease. Considering all above, the aim of preventing the onset of diabetes is to recognize patients with an increased risk. The risk factors include basal glycemia, positive family history for diabetes mellitus, obesity, metabolic syndrome, and some ethnic groups (South Asia, the Caribbeans). Therefore, increased-risk patients should be subjected to therapy with ACE inhibitor, angiotensin receptor blocker, or calcium channel blocker as the first drug of choice. For these patients, application of thiazides and beta blockers or the combination of these two drugs is not advantageous. However, such a view poses a dilemma whether thiazide diuretics should be the first choice in the treatment of hypertension.
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PMID:[Antihypertensive agents and the risk of new onset diabetes mellitus]. 1721 94

The pathological role of obesity has rarely been studied in primary glomerular diseases. The purpose of this study is to examine the clinicopathological influence of obesity in IgA nephropathy (IgAN). 74 patients with IgA nephropathy in our institution from October 2000 to January 2004 were retrospectively divided into two groups according to body mass index (BMI): the non-obese group (group N) with BMI < 25 kg/m(2), and the obese group (group O) with BMI > or = 25 kg/m(2). There were 50 patients in group N and 24 patients in group O. Clinical analysis showed no significant difference between these two groups in blood pressure, serum cholesterol, creatinine clearances or grade of hematuria. However, urinary protein excretion and serum creatinine were significantly greater in group O than in group N. Although semiquantitative analysis of light-microscopical findings showed no significant differences in the severity of mesangial proliferation, matrix expansion, glomerulosclerosis or crescent formation, image analysis showed that total glomerular area and tuft area were significantly larger in group O. In addition, ultrastructural study revealed significantly higher glomerular basement membrane thickness in group O. 62 patients (46 patients, group N; 16 patients, group O) were followed in our institution for one year. Urinary protein was significantly decreased only in patients who received steroid in both groups. Although administration of ACE inhibitor or ARB tended to decrease urinary protein in group O, the change was not statistically significant. Our findings indicate that obesity may accelerate the increase of proteinuria in IgAN through ultrastructural modification of the glomerular basement membrane.
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PMID:Clinicopathological influence of obesity in IgA nephropathy: comparative study of 74 patients. 1749 42

There is strong evidence for the presence of a functional renin-angiotensin system in diabetogenic tissues, and ACE (angiotensin-converting enzyme) inhibitors may improve glucose metabolism in those individuals at high risk of developing T2DM (Type 2 diabetes). In the present study, we tested the hypothesis that subjects with genetically lower plasma and tissue ACE activity, because of their ACE [I/D (insertion/deletion)] genotype, would have a lower risk of T2DM in 2642 healthy middle-aged Caucasian men (mean age, 56 years) followed-up for 15 years. Obesity was the strongest predictor of T2DM, with an HR (95% CI) [hazard ratio (95% confidence interval)] of 3.74 (2.66-5.26) (P<0.0001). Overall there was no association between ACE genotype (II homozygotes, n=623; and D allele carriers, n=2019) and risk of T2DM, and although in lean men there was no genotype difference in risk in D allele carriers compared with II homozygotes [adjusted HR=0.75 (95% CI, 0.46-1.22)], in obese (body mass index >30 kg/m(2)) men the risk of T2DM was higher [adjusted HR=4.26 (95% CI, 1.30-13.93)] with a genotype-obesity interaction of P=0.01. A similar pattern of risk was seen by re-analysis of a previously published case-control study, where D allele carriers had a non-significant 1.30 (0.97-1.74)-fold higher risk of developing T2DM than II homozygotes when non-obese, but a 1.79 (1.17-2.72) (P=0.007)-fold higher risk when obese. Further prospective studies are needed to confirm these findings. The ACE D allele may worsen glucose metabolism, which could raise the prospective T2DM risk in obese men, but not in lean men. In obesity, adipose tissue undergoes inflammatory infiltration and the subsequent higher levels of pro-inflammatory angiotensin II may explain this association.
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PMID:Is the influence of variation in the ACE gene on the prospective risk of Type 2 diabetes in middle-aged men modified by obesity? 1762 39

At present, thrombolytic agents represent the only direct way of augmenting fibrinolytic activity in humans. While these agents are proven to be efficacious in the treatment of acute thrombotic events, they are not a viable option for long-term administration. There are numerous drugs available that indirectly to increase fibrinolytic activity by reducing plasma levels of plasminogen activator inhibitor-1 (PAI-1), including ACE inhibitors, insulin-sensitizing agents, and hormone replacement therapy in women. At present, efforts are underway to develop and test synthetic, selective PAI-1 antagonists. The potential applications of PAI-1 antagonists include thrombotic disorders (arterial and venous), amyloidosis, obesity, polycystic ovarian syndrome, and perhaps even type 2 diabetes mellitus. The availability of specific PAI-1 antagonists promises to expand the limits of understanding the role the fibrinolytic system plays in human disease and break through the current confines of therapeutic options that can effectively restore and augment the activity of the fibrinolytic system.
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PMID:PAI-1 antagonists: predictable indications and unconventional applications. 1789 47

We aimed to (i) determine the relative importance of childhood gain in upper body adiposity for insulin resistance (IR) and triglyceridemia (TG); (ii) examine whether the associations between adiposity and metabolic indices were more evident in those with the ACE DD genotype. We examined a birth cohort study of 292 children with measures in the neonatal period (day 4) including subscapular and triceps skinfolds; repeat skinfold measures at age 8, cardiorespiratory (CR) fitness, IR by the homeostasis model assessment (HOMA) equation (HOMA-IR) and serum triglyceride (TG) concentrations and measures of ACE I/D gene variants. A multiple linear regression analysis incorporating a life course approach was undertaken. Childhood gain in upper body adiposity was positively associated with HOMA-IR and TG independently of neonatal skinfolds (P < or = 0.02). The magnitude of these associations was higher among those of the ACE DD genotype. For example, subscapular skinfold gain was not strongly associated with HOMA-IR or TG among those with II or ID genotype (b = 0.03, P = 0.05; b = 0.02, P = 0.18 respectively) but was positively associated among those with the DD genotype (b = 0.11, P = 0.001; b = 0.08, P = 0.003); difference in effect P = 0.05; P = 0.01 respectively. Upper body fat accumulation during childhood was positively associated with HOMA-IR and TG independently of neonatal skinfolds. Further, the stronger associations for those with the ACE DD genotype is consistent with randomised controlled trial findings that ACE inhibition is associated with a reduced risk of developing type 2 diabetes. Further work is required to confirm and extend these findings.
Obesity (Silver Spring) 2008 Sep
PMID:Adiposity gain during childhood, ACE I/D polymorphisms and metabolic outcomes. 1855 Nov 23


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