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

Hypertension and diabetes mellitus are chronic medical conditions that frequently coexist. In the United States, it is estimated that 10 million persons suffer from diabetes mellitus, 60 million from hypertension, and 3 million from the combination of the two. There may be a causal relationship between hypertension and diabetes. Obesity may be a precipitating factor for both hypertension and non-insulin-dependent diabetes mellitus. Those with insulin-dependent diabetes mellitus generally become hypertensive only with the onset of nephropathy. Glucose tolerance, insulin resistance, and hyperinsulinemia frequently occur with essential hypertension and may be aggravated by hypertension therapy, especially with diuretics and beta-blockers. Hyperinsulinemia may be an important common factor promoting sodium retention, sympathetic nervous system stimulation, and inhibition of the sodium pump. The Working Group on Hypertension in Diabetes has outlined a flexible modified version of the stepped-care approach to the treatment of hypertension in diabetes. Management is complex because diabetes is associated with autonomic neuropathy, sexual dysfunction, hyperlipidemia, and fluid and electrolyte disorders. All these problems can be exacerbated by antihypertensive treatment. Nonpharmacologic measures, which address weight reduction and sodium restriction, are logical, but aggressive antihypertensive medication is invariably necessary. Diuretics and/or beta-blockers were the mainstay of treatment until the introduction of angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers. These newer agents have no deleterious effects on carbohydrate metabolism and are generally better tolerated. Antihypertensive therapy may slow the rate of deterioration in diabetic nephropathy. This was first shown with diuretics, beta-blockers, and hydralazine and more recently with ACE inhibitors, which provide effective blood pressure control and a significant drop in albuminuria without affecting the glomerular filtration rate adversely. ACE inhibition may also lead to increased insulin sensitivity and glucose disposal rate. Long-term trials are needed to assess the effects of these new agents on the treatment of hypertension in the diabetic population.
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PMID:Diabetes mellitus and hypertension. 222 Jul 97

Endogenous factors cross-reacting with antidigoxin antibodies have been found in several tissues and body fluids of animals and humans, using commercially available digoxin radioimmunoassay or enzyme immunoassay methods. The chemical characteristics of these endogenous factors are, at present, unknown, although it has been suggested that they could be substances with low molecular weight. Experimental studies and theoretical considerations indicate that endogenous digitalis-like factors (DDLFs), in addition to the ability to react with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na+/K(+)-ATPase (sodium pump). Therefore, EDLF can be an endogenous modulator of the membrane sodium-potassium pump and several authors have suggested that EDLF could play a role in the regulation of fluids and electrolytes, muscular tone of myocardial and also in the pathogenesis of arterial hypertension. In this review, the authors discuss the hypothesis that, in metabolic diseases such as diabetes mellitus, obesity and acromegaly, the sodium retention and volume expansion, possibly due to exaggerated sodium intake, and/or exogenously induced peripheral hyperinsulinemia and high levels of growth hormone, could trigger a sustained release of EDLF, which in turn increases the blood pressure.
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PMID:Is the endogenous digitalis-like factor the link between hypertension and metabolic disorders as diabetes mellitus, obesity and acromegaly? 222 23

Leucocyte ouabain-sensitive 22Na+ efflux was studied in 35 normal and 12 obese subjects. This efflux rate constant was raised in the obese (2.72 +/- SEM 0.13 vs 2.31 +/- 0.08 h-1, P less than 0.006), indicating a higher activity of the sodium pump in vivo, There was a significant correlation between this efflux rate constant and fasting insulin level in both the whole population and in the normals alone (rs = 0.36, P less than 0.007, and rs = 0.40, P less than 0.009 respectively). A hyperinsulinaemic-euglycaemic clamp was performed on seven normal volunteers. After 2 h, there was a significant stimulation of the leucocyte efflux rate constant (from 2.86 +/- 0.17 to 3.33 +/- 0.18 h-1, P less than 0.01). In-vitro incubation of leucocytes with insulin produced a maximal stimulation of the Na+-K+-ATPase activity of about 35% at 2 h with half-maximal stimulation achieved at 46 mU/l. Insulin (100 mU/l) also stimulated the leucocyte ouabain-sensitive 22Na+ efflux rate constant in vitro by about 11% with or without 1 h of preincubation with the insulin. These findings may explain the hypokalaemic and sodium retaining effects of insulin in man; they may also partially explain the raised Na+ efflux rate constants in obesity.
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PMID:The leucocyte sodium pump in healthy and obese subjects: the association of insulin with its activity. 244 7

As cellular sodium pumping is an energy consuming process and differences in the obese may account for their energetic efficiency, leucocyte sodium-22 efflux was studied in obese and normal volunteers both in the fasting state and after a test meal or infusion of glucose and insulin intravenously. The 22Na ouabain sensitive efflux rate constant was significantly higher in obese subjects than normal (mean (1 SD) 2.69 (0.40)/h v 2.35 (0.49)/h). Two hours after a 4.2 MJ (1000 kcal) meal there was an increase in the efflux rate constant from its fasting value in normal weight subjects (2.39 (0.33)/h to 2.71 (0.40)/h) but not in obese subjects (2.65 (0.54)/h to 2.61 (0.58)/h). The rise in ouabain sensitive efflux rates was significantly higher in normal than obese subjects. Both groups showed a rise in intracellular sodium concentrations. The euglycaemic clamp produced similar results. Feeding or infusion of insulin increases sodium pump activity more in normal than obese subjects. This difference may contribute to any defective dietary thermogenesis in obesity, which may lead to energetic efficiency and a tendency to gain weight.
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PMID:Leucocyte sodium pump activity after meals or insulin in normal and obese subjects: cause for increased energetic efficiency in obesity? 244 97

The effect of oral glucose (40 g/m2 body surface area) on the leucocyte 22Na efflux rate constants (ERC) was studied in 13 normal weight and 10 obese subjects. The ouabain-sensitive 22Na ERC was higher in leucocytes isolated from fasting obese subjects (median [range] for obese 2.77 [2.33-3.11] vs normals 1.91 [1.57-2.77] h-1, P less than 0.001). There was no difference in the ouabain-resistant 22Na ERC. Oral glucose raised the ouabain-sensitive 22Na ERC after 2 h in normal subjects (1.91 [1.57-2.77] to 2.41 [2.11-3.02] h-1, P less than 0.001). The ouabain-resistant 22Na ERC fell from 0.71 [0.32-1.10] to 0.46 [0.35-0.68] h-1, P less than 0.008. Conversely, in obese subjects, the ouabain-sensitive ERC fell (2.77 [2.33-3.11] to 2.59 [2.11-2.92] h-1, P less than 0.06). There was no significant change in ouabain-resistant 22Na ERC 2 h after oral glucose. The fasting leucocyte 22Na ouabain-sensitive ERC correlated with fasting plasma insulin levels and insulin resistance (rs = 0.48, P less than 0.01 for both). The change in this ERC with oral glucose correlated with the incremental insulin response over 2 h (rs = -0.53, P less than 0.006) and to the insulin resistance (rs = -0.56, P less than 0.003). The failure of oral glucose to stimulate the leucocyte sodium pump in obesity could partially account for the defect in dietary thermogenesis in obesity. This defect in stimulation of the sodium pump is related to insulin resistance.
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PMID:The effect of oral glucose on the leucocyte sodium pump in normal and obese subjects. 244 70

The number of sodium pump sites on erythrocytes was measured on 1,847 individuals in 80 Utah kindreds ascertained through probands with cardiovascular disease. Likelihood analysis supported recessive inheritance of high pump number. The major locus explained 14.0% of the variance in pump number; polygenic inheritance explained another 63.4%. Homozygotes for the recessive allele occurred with a frequency of 1.74% and had a mean pump number estimated as 566.0 sites/red blood cell (RBC) versus a mean of 312.2 sites/RBC for the other genotypes. Young individuals with the high pump number genotype were leaner, and older adults with the high pump number genotype were heavier. Diabetes and early hypertension were more prevalent in women with the high pump number genotype. Although not significant, obesity in adults of both sexes and early coronary heart disease in men were more prevalent in individuals with the high pump number genotype.
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PMID:Recessive inheritance of a high number of sodium pump sites. 255 21

Studies on erythrocyte sodium pump activity in obesity have yielded conflicting results probably because the erythrocyte is an atypical cell, and it may not reflect ATPase activity of other cells in the body. This study was undertaken to establish a reproducible procedure to measure sodium transport in human diploid fibroblasts, and apply this method to explore any differences in the cells from obese and nonobese humans. Cell cultures were established from 12 nonobese (body mass index (BMI) = wt in kg/height in m2 (Khosla and Lowe, Br J Prev Soc Med 1967; 21: 122-128); less than 27 kg/m2) and 10 obese (BMI) greater than 35 kg/m2) subjects. Triplicate measurements of sodium efflux rate constant were made with and without ouabain (1 mmol/l) to determine the total, active (ouabain-sensitive) and passive (ouabain-insensitive) components. Reproducible results were obtained as suggested by a coefficient of variation (CV) of less 10% on successive experiments on the same cell-line, and 11 and 15% of the active sodium efflux rate constant measured in fibroblasts from nonobese and obese subjects, respectively. The active sodium efflux rate constant in fibroblasts from nonobese (0.202 +/- 0.023 (SD)) was not significantly different from that obtained in the cells from obese subjects (0.21 +/- 0.030; p greater than 0.10). These results suggest that there is no intrinsic differences in basal sodium pump activity in fibroblasts related to obesity.
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PMID:A reproducible procedure for measuring sodium transport in cultured human fibroblasts from normal and obese donors. 407 28

In an attempt to resolve the prevailing confusion about erythrocyte sodium pump activity in obesity, we measured sodium-potassium-ATPase, ouabain-inhibitable (active) sodium efflux rate constant and intracellular sodium concentration in erythrocytes from 107 non-obese and obese subjects, with a body-mass index ranging from 17 to 54 kg X m-2. All the three independently measured variables were not significantly different between the two groups and no correlations were found between these three indices and body-mass index. The expression of ATPase activity in units of membrane protein allowed our previous data to be compared with this study and other reports. Our studies and most of the published reports suggest that there is no difference in erythrocyte sodium-potassium-ATPase and sodium transport between the vast majority of obese and non-obese subjects, but there is a subgroup of obese subjects (about 5%) with abnormally high erythrocyte sodium pump activity. The variable treatment of data from this subgroup and the small numbers of obese subjects studied by various investigators are largely responsible for the conflicting results about erythrocyte sodium pump activity.
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PMID:Erythrocyte sodium pump activity in human obesity. 609 47

Looking for evidence of reduced energy use in the cells of obese persons, we measured the numbers of sodium-potassium-pump units in erythrocytes from a group of 21 obese human subjects and found them to be reduced by 22 per cent as compared with those of nonobese controls (P <0.001). The cation-transport activity of the pump, as measured by 86rubidium uptake by the cells, we also reduced in parallel with decrease in pump units. An increased concentration of sodium in the red cells of obese subjectes was also found (9.6 +/- 0.7 vs. 7.1 +/- 0.6 mmol per liter of cells; P<0.01). This finding demonstrates independently the physiologic importance of reduced numbers of sodium-pump units and reduced pump activity as measured by ouabain binding and rubidium transport, respectively. The magnitude of the reduction in the number of pump units was found to be negatively correlated with the percentage of ideal body weight (r = 0.56, P<0.001); this observation suggests a possible role of abnormalities of the sodium pump in the pathophysiology of obesity.
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PMID:Reduced activity of the red-cell sodium-potassium pump in human obesity. 625 62

Na+, K+ -ATPase activity was measured in red blood cells from 20 nondiabetic euthyroid male Pima Indians with varying degrees of obesity; their body mass indices ranged from 22-60 kg/m2. The na+, K+ -ATPase, measured both by 86Rb uptake in intact cells and ATP hydrolysis by purified membranes, was inversely correlated with body mass index (r = -0.62; P less than 0.005 and r = -0.75; P less than 0.0001, respectively). These results confirm that obesity is associated with decreased Na+, K+ -ATPase in intact red blood cells, and provide the first demonstration of a reduced sodium pump in isolated red cell membrane preparations from obese men.
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PMID:Reduced Na+, K+ -ATPase activity in intact red cells and isolated membranes from obese man. 627 81


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