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

To determine quantitative and qualitative differences in insulin secretion equimolar amounts of glucose and arginine were infused in 9 healthy subjects, in 8 individuals each with obesity without and with impaired glucose tolerance, and in non-obese and obese non-insulin-dependent diabetic patients (NIDDM). Insulin secretion was calculated after individual determination of metabolic clearance rate of C-peptide (MCRcp) both as the area under the C-peptide concentration curve times MCRcp, and by a mono-compartment mathematical model, both yielding identical results. MCRcp fell consistently with increasing C-peptide infusion rate (e.g.: healthy subjects: C-peptide, 10 nmol/h, 4.2 +/- 0.4; 20 nmol/h, 3.3 +/- 0.3; 30 nmol/h, 3.1 +/- 0.2 ml/kg.min; p less than 0.05 to p less than 0.01). Basal insulin secretion was 2.1-fold greater in the obese with impaired glucose tolerance than in healthy subjects, but was unchanged in non-obese NIDDM. Glucose and arginine triggered insulin release was greater than in healthy subjects at almost identical area under the respective substrate concentration curve (AUC/kg body weight) in obese subjects without (2-fold) and with impaired glucose tolerance (4-fold), and in NIDDMs following i.v. arginine (2-fold). The mean ratio of incremental insulin release to i.v. glucose and arginine was smaller in NIDDM (normal weight, 1.3 +/- 0.4; obese, 1.0 +/- 0.2) than in healthy (2.0 +/- 0.3), or obese subjects with impaired glucose tolerance (2.8 +/- 0.7). Stimulated C-peptide/insulin ratio was reduced in all patients vs that in healthy subjects (p less than 0.05). We conclude that (a) MCR of C-peptide is in part a saturable process; (b) insulin clearance may be impaired in obesity and NIDDM; and (c) insulin secretion differs in obese states and NIDDM both quantitatively and qualitatively, and thereby separates the two disorders as different entities. In addition, quantitation of insulin release in obese states may also help (d) to better define primary algorithms for insulin replacement in normal- and overweight insulin-dependent diabetic patients.
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PMID:Quantitative and qualitative differences in basal and glucose- and arginine-stimulated insulin secretion in healthy subjects and different stages of NIDDM. 207 83

Excess body fat has been clearly associated with an increased risk of oligo-ovulation and endometrial/breast carcinoma. The connection has been assumed to lie within derangements of the metabolic/endocrine compartments, particularly of estrogens and androgens. To differentiate the effect of obesity from its related disease process, an attempt has been made to define the reproductive-endocrinologic alterations encountered in otherwise asymptomatic obese women. Androgen metabolism is accelerated in obesity. It is not clear whether the increased clearance precedes or follows the accelerated production of androgens. A servocontrol mechanism appears to be operative in these asymptomatic individuals, maintaining plasma steroid levels normal. The unbound fraction of T may be somewhat increased in overweight women with predominantly upper body fat deposition. The increased clearance of androgen may arise from an obesity-related depression in SHBG concentration (e.g., for T, E2, delta 5-diol, etc.). Adipose tissue, by virtue of the lipid solubility of most of these steroids, concentrates androgens, estrogens, and progesterone. This steroid sequestration not only contributes to the obesity-related increase in androgen clearance but also leads to an extremely enlarged total body steroid pool. Fat tissue sequestration also increases the concentration of androgens in the vicinity of adipose stromal cells, possibly encouraging their aromatization. Adipose tissue also has a moderate degree of 17-hydroxysteroid dehydrogenase activity, which appears to stimulate the conversion of A to T. Finally, alterations in peripheral and hepatic conjugation and an accelerated urinary excretion may contribute to the elevated clearance of androgens. The accelerated PR of androgens may simply result as compensation for the elevated MCR in obesity. Nonetheless, evidence of alteration(s) in adrenocortical steroidogenesis has been presented suggesting a selective obesity-related enhancement in adrenal androgen secretion. These remain to be confirmed. Nonetheless, adrenocortical abnormalities may arise secondary to the influence of other circulating and intra-adrenal factors, including insulin, prolactin, estrogens, and androgens. It is not known whether the accelerated androgen metabolism or the aberrant adrenal steroidogenesis improve with weight reduction. Excess body fat increases androgen aromatization which, together with an obesity-related decrease in SHBG, is associated with mildly elevated levels of E1 and free E2 in postmenopausal women. Although premenopausal obese individuals have the same tendency, the far greater ovarian estrogen secretion overshadows any differences. The bulk of aromatization activity in fat lies in the stromal comportment. The major substrate for peripheral estrogen production is A. Testosterone also contributes to the estrogen pool via its conversion to E2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reproductive endocrinologic alterations in female asymptomatic obesity. 268 Jun 25

To study the effect of obesity on the metabolism of adrenal androgens not bound to testosterone-estradiol-binding globulin, the MCRs of delta 4-androstenedione (A) and dehydroepiandrosterone (DHEA) were determined using constant infusion of unlabeled steroids to steady state in 8 normal weight and 19 obese nonhirsute eumenorrheic women. The blood production rates (PR) were calculated as the product of the MCR and the 24-h integrated serum concentrations (IC). The mean MCR and PR of A and DHEA were significantly higher in the obese women than in the normal weight women. There was, however, no difference in the mean IC of each androgen in the 2 groups. The MCR and PR of A and DHEA were each correlated with the body mass index (BMI; kilograms per m2). The MCR and PR of A and the MCR of DHEA were also correlated with the ratio of waist circumference to hip circumference (WHR). However, the PR of DHEA was not correlated with WHR. There was no correlation between the IC of either androgen and BMI or WHR. However, partial correlation analysis revealed that correction of the BMI for WHR resulted in a significant negative correlation between BMI and IC of A. We conclude that the MCR and PR of A and DHEA were increased in obese nonhirsute eumenorrheic women; there was a strong correlation between BMI and the MCR and PR of A and DHEA; upper segment obesity, as measured by WHR, was correlated with the MCR and PR of A and the MCR of DHEA, but not with the PR of DHEA; and circulating DHEA and A were maintained at normal levels in the obese eumenorrheic women despite an increase in the MCR, which suggests that a servo-mechanism is operative which registers the body size and adjusts the PR according to the MCR.
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PMID:Maintenance of normal circulating levels of delta 4-androstenedione and dehydroepiandrosterone in simple obesity despite increased metabolic clearance rates: evidence for a servo-control mechanism. 295 65

The MCR of synthetic human GH was studied in eight adult male rhesus monkeys (Macaca mulatta). Four monkeys were lean (less than 20% body fat), and four were obese (greater than 35% body fat). The monkeys were given a single bolus injection of GH (2.5 micrograms/kg BW), followed by a constant infusion of GH (250 micrograms/h) for 2.5 h. Venous blood samples were collected before the infusion and every 10 min during the infusion. In both groups a plateau of the plasma GH concentrations, indicating a steady state, was reached 70 min after the start of the infusion. The MCR of GH was calculated from the ratio of the constant GH infusion rate and the plateau plasma GH concentration in each monkey. The MCR of synthetic GH was 12.7 +/- 1.7 (+/- SD) L/24 h in the lean group and 19.5 +/- 2.9 L/24 h in the obese group (P less than 0.007). However, the MCR/kg ratio in the lean monkeys was the same as that in the obese animals. We conclude that 1) MCR of GH is directly proportional to body weight; and 2) the lower plasma GH levels in obesity may be due to an increase in its MCR not compensated for by an appropriate increase in the rate of GH secretion.
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PMID:Metabolic clearance rates of synthetic human growth hormone in lean and obese male rhesus monkeys. 318 57

Genetically obese Zucker fatty rats require two autosomal recessive genes (fa/fa) to express the obese phenotype. The obese Zucker rat (fa/fa) has decreased total and free serum T3 concentrations, but normal serum T4 concentrations, compared to those in their lean littermates. To elucidate the mechanism of these differences, we measured the MCR and production rate (PR) of T4 and T3 in the three genotypes of 4-month-old male Zucker rats (Fa/Fa, Fa/fa, and fa/fa). In addition, 5'-deiodinase activity in liver, kidney, and brown adipose tissue homogenates was determined. T4 MCRs were equivalent in all three genotypes, but a decreased T3 MCR was seen in Fa/fa and fa/fa rats. An additive effect of the fa gene was noted with respect to the decrease in T3 MCR (Fa/Fa, 42.0 +/- 1.5; Fa/fa, 38.7 +/- 2.4; fa/fa, 34.7 +/- 3.4 ml/h; P less than 0.05). Whole body T4 PRs were equal in all three genotypes, but the T3 PR was decreased in the fa/fa rat by 25% compared to that in the homozygous lean rats (15.7 +/- 2.1 vs. 21.2 +/- 2.4 ng/h; P less than 0.005). Liver and kidney 5'-deiodinase activities were decreased in the fa/fa rat by 34% (P less than 0.005) and 20% (P less than 0.01), respectively. Brown adipose tissue and pituitary 5'-deiodinase activity were similar in all three genotypes. These results show a reduction in T3, but not T4, MCR in obese Zucker rats. Whole body T3 production and type I 5'-deiodinase activity were decreased in the obese (fa/fa) rats. These results suggest that decreased T4 to T3 conversion is responsible for the decreased T3 production rate in the fatty rat and may contribute to its obesity.
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PMID:Altered triiodothyronine metabolism in Zucker fatty rats. 333 15

The hyperinsulinemia of obesity could result from a decrease in the metabolic clearance rate of insulin (MCR-I), an increase in the secretory rate of insulin (SR-I), or a combination of both these processes. Because C-peptide and insulin are secreted in an equimolar ratio, the plasma concentrations of C-peptide (C) and insulin (I) are inversely proportional to their rates of metabolic clearance (C/I = MCR-I/MCR-C). We obtained 24-h integrated concentrations (IC) of insulin (IC-I) and C-peptide (IC-C) in 23 obese and 45 nonobese subjects over a period of normal activity and food intake. The IC-I was 69% higher in the obese subjects (P less than 0.0001). A 13% increase in the IC-C (P = 0.04), with a constant rate of C-peptide clearance, indicates a proportionate increase in SR-I. A 33% decrease in the IC-C/IC-I in the obese group (P less than 0.005) reflects a decrease in MCR-I; hence, 75% of the hyperinsulinemia is due to a decrease in the clearance of insulin. Because peripheral MCR-I (pMCR-I) is similar in obese and nonobese subjects, the decrease in MCR-I may be due to a decrease in the hepatic clearance of insulin. This conclusion was supported by our comparison of 24-h IC-C/IC-I ratios in the obese and nonobese subjects. Whereas the 24-h IC-C/IC-I of the nonobese resembled the fasting state, the 24-h IC-C/IC-I of the obese resembled the postprandial state, when insulin removal by the liver is known to be suppressed. These data are consistent with a decreased 24-h hepatic MCR-I (hMCR-I) as the cause of the hyperinsulinemia of obesity.
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PMID:Hyperinsulinemia of obesity is due to decreased clearance of insulin. 634 80

The 24 hr mean plasma cortisol concentration was measured in 65 healthy women ranging from 21% below to 218% above desirable weight and in 47 healthy men ranging from 5% below to 330% above desirable weight. In the women, there was a clear-cut inverse linear correlation between the plasma cortisol concentration and the percent deviation from desirable weight (y = 7.5 -- 0.3 x; r = -0.49; p less than 0.001); the relation of free to total cortisol concentration was weight-invariant; the MCR of cortisol in the most obese women was much higher than that of nonobese women (340 +/- 76 versus 211 +/- 31 liters/gm urinary creatinine; p less than 0.01). In the men, the plasma cortisol level and MCR were weight-invariant. To account for the finding in women of a linear correlation of the decrement in plasma cortisol level with the percent deviation from desirable weight (which in turn is nearly perfectly correlated with the total body fat content), we postulate that a given weight of adipose tissue in women takes up a constant amount of cortisol; this in turn suggests that their adipose tissue contains a saturable binding system such as corticosteroid receptor. By the same logic, the weight-invariance of plasma cortisol and MCR in men suggests the absence of significant amounts of corticosteroid receptor in their adipose tissue. The finding that the increased cortisol MCR of obese women results in decreased plasma cortisol levels rather than an increase in cortisol production (the latter, corrected for muscle mass, is normal in obesity: Strain et al, Metabolism 29:980, 1980) suggests a defect in their cortisol ACTH feedback system. Such a defect, presumably hypothalamic, is not unexpected in the light of reports of defective hypothalamic control of prolactin and growth hormone secretion in obesity.
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PMID:Sex difference in the influence of obesity on the 24 hr mean plasma concentration of cortisol. 707 9

In normal and obese young males [90--120% and > 160% of ideal body weight (IBW); IBW = 100%], plasma concentrations of testosterone, androstenedione, estrone, and estradiol were measured. Metabolic clearance and production rates of androstenedione and the conversion ratios of androstenedione to testosterone, estrone, and estradiol were determined using the constant infusion technique. In the obese subjects, IBW was inversely correlated (P < 0.001) with plasma concentrations of androstenedione (r = 0.81) and testosterone (r = 0.87), while the levels of estrone (r = 0.92) and estradiol (r = 0.95) increased with IBW (P < 0.001). Thus, when normal and obese subjects were compared as groups, plasma androstenedione decreased form 1.24 +/- 0.13 to 0.93 +/- 0.15 ng/ml (mean +/- SD) and plasma testosterone decreased from 5.89 +/- 0.82 to 3.29 +/- 0.92 ng/ml (P < 0.001), while estrone increased from 28.2 +/- 3.4 to 60.0 +/- 9.4 pg/ml, and estradiol increased from 21.7 +/- 3.5 to 43.9 +/- 5.3 pg/ml. The testosterone to androstenedione and the estradiol to estrone ratios were not different in obesity, but changes in IBW were positively correlated (P < 0.001) with differences in the estrone to androstenedione (r = 0.93) and estradiol to testosterone ratios (r = 0.93), indicating that fat tissue may aromatize androgens, whereas reduction of 17-oxo-steroid appears to be of minor importance. As the MCR of androstenedione increased with IBW (from 2156 to 2636 liters/day P < 0.05) while plasma levels decreased, the apparent production rate of androstenedione was not influenced by the degree of obesity. The conversion of androstenedione to estrone (r = 0.89) and of androstenedione to estradiol (r = 0.82) was enhanced in obese subjects (P < 0.001). We suggest that enhanced aromatization of androstenedione due to an increased adipose tissue mass may account for the high plasma estrogen levels observed in obese men.
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PMID:Enhanced conversion of androstenedione to estrogens in obese males. 741 88

To evaluate the principal determinants of the MCR and plasma t1/2 of unbound (free) GH in man, we performed steady state infusions of 3 doses of recombinant human GH during pharmacological suppression (iv octreotide) of endogenous GH secretion in 24 healthy adults and 12 patients (6 adults and 6 children) with chronic renal failure (CRF). Free plasma GH was calculated from total plasma GH (measured by immunoradiometric assay) and GH-binding protein activity (radioligand assay). The MCR of free GH was determined from free plasma GH and the rate of recombinant human GH infusion. The t1/2 of free plasma GH, and the concentration and the in vivo dissociation constant (Kd) of GH-binding protein (GHBP) were estimated by dynamic modeling of the postinfusion total plasma GH concentration decay curves. The MCR of free GH decreased and the plasma GH t1/2 increased significantly with increasing plasma GH concentrations. The MCR of free GH over its physiological concentration range was positively correlated with the body mass index as a measure of relative obesity and negatively related to age, but only at supraphysiological GH concentrations. In the adult patients with CRF, the MCR of free GH was decreased at each infusion rate by 25-38%, and the t1/2 was increased by 80-170%. Children with CRF showed a significantly lower MCR and higher t1/2 of plasma free GH than adult patients. Modeling and direct measurements of the off-rate of GH from its high affinity GHBP indicated normal dissociation rate constants but decreased molar concentrations of the GHBP in uremic plasma. We conclude that the rate of elimination of free GH from plasma in man is controlled by 1) plasma total free GH concentrations, 2) relative obesity, and 3) renal function within the physiological GH concentration range, whereas 4) age is a negative predictor of MCR only at supraphysiological GH concentrations.
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PMID:Multifactorial control of the elimination kinetics of unbound (free) growth hormone (GH) in the human: regulation by age, adiposity, renal function, and steady state concentrations of GH in plasma. 855 Jul 55

Cushing's syndrome is characterized by central obesity and muscle wasting. As GH is anabolic, it may be able to counteract the loss of body protein. To evaluate the potential therapeutic use of GH preoperatively, eight patients with Cushing's syndrome received sc injections of recombinant human GH (0.07 U/kg.day) for 7 days. Whole body leucine and glucose turnover were measured after an infusion of [1-13C]leucine and [6,6-2H2]glucose before (day 0) and after 2 and 7 days of GH treatment. Compared with the value on day 0, there was a significant increase on days 2 and 7 in insulin (P < 0.005 and P < 0.001), C peptide (P < 0.01 and P < 0.005), insulin-like growth factor I (P < 0.001), and glucose concentrations (P < 0.01 and P < 0.005) and a decrease in the leucine concentration (P < 0.005). There was no significant change in glucose production rate, glucose MCR, leucine production rate (a measure of protein degradation), or nonoxidative leucine disappearance rate (a measure of protein synthesis). The leucine MCR was increased after 7 days (P < 0.05), and the clearance of leucine into protein (nonoxidative leucine disappearance rate/leucine concentration) was increased (P < 0.05) after 2 and 7 days of GH treatment. This is consistent with GH stimulating the availability of amino acid transporters. GH may, therefore, have a therapeutic role in the preoperative treatment of Cushing's syndrome.
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PMID:The effect of recombinant human growth hormone on glucose and leucine metabolism in Cushing's syndrome. 898 67


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