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

Simple obesity is characterized by a normal or increased growth rate with an acceleration of bone age maturation. When longitudinal growth slows down in the presence of obesity, a hormonal disturbance should be sought. Despite normal growth, simple obesity is characterized by a reduced GH secretion evaluated by standard provocative tests, the administration of GH-releasing hormone or spontaneous 24-hour secretion. In obese children GH secretion may be as low as in poorly growing children with classical GH deficiency. The endocrine abnormalities along the GH axis seem to involve complex mechanisms at the hypothalamic, pituitary and peripheral level. Recent data suggest that simple obesity is associated with an increase in GH clearance and a decrease in GH synthesis and secretion. It is also associated with high insulin and insulin-like growth factor I levels which may interfere in the complex endocrine interactions. In conclusion, simple obesity is characterized by normal growth in the presence of 'hyposomatotropism'.
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PMID:The effect of simple obesity on growth and growth hormone. 830 46

This review describes the recent developments in the diagnosis and treatment of states of resistance to growth hormone based mainly on the studies performed on patients with an inborn molecular defect of the growth hormone receptor, ie, Laron syndrome. Use of the polymerase chain reaction technique has facilitated the study of the defect, which in the large majority of patients resides in the extracellular domain of the growth hormone receptor. This recessively transmitted hereditary disease, characterized clinically by dwarfism and obesity and biochemically by high levels of serum human growth hormone accompanied by low serum concentrations of insulin-like growth factor I, is diagnosed mainly in inbred societies of Asian Jews, Arabs, Iranians, Italians, and Spaniards or their descendants. Isolated mutations have been found in many countries all around the world. The recent biosynthesis of insulin-like growth factor I has enabled the successful treatment of these patients, accelerating their growth, reducing their obesity, and normalizing their metabolic abnormalities resultant from the insulin-like growth factor I deficiency. The Pygmies are an inbred population in Africa, Asia, and Oceania who seemingly also have a defect in the growth hormone receptor. Acquired states of growth hormone resistance are also discussed.
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PMID:Disorders of growth hormone resistance in childhood. 837 76

The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 +/- 9.8 kg) or placebo (mean body weight 90.7 +/- 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecystokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 +/- 3.5 kg in the Orlistat group versus 3.0 +/- 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric emptying after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.
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PMID:Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects. 865 34

The basic tenet of this investigation was that obesity is not a prerequisite in the development of polycystic ovary syndrome (PCOS), as indicated by the fact that 50% of PCOS women are not obese. Further, obesity itself is a disease entity with the common manifestation of insulin resistance/hyperinsulinemia with PCOS. Given recent evidence that insulin and GH may have gonadotropin-augmenting effects, we have determined the common and distinguishing features of neuroendocrine-metabolic dysfunctions of lean [body mass index (BMI), < 23 kg/m2] and obese (BMI, > 30 kg/m2) women with the classical form of PCOS. Insulin sensitivity, as determined by rapid i.v. glucose tolerance testing; 24-h dynamics of insulin/glucose levels, somatotropic [GH/GH-binding protein/insulin-like growth factor I (IGF-I)/IGF-binding proteins (IGFBP)], and LH axes; and their downstream effects on ovarian steroids were simultaneously assessed in eight lean PCOS and eight obese PCOS patients and an equal number of BMI-matched normal cycling controls. Our results show that insulin sensitivity was reduced 50% (P < 0.01) in lean PCOS from that in lean controls. There was a further decrease in obese controls (P < 0.01) and a 2-fold greater reduction (P < 0.001) in obese PCOS than in obese controls, suggesting that insulin resistance (IR) is a common lesion in PCOS, and that obesity contributes an additional component to IR in obese PCOS. Consistent with the degree of IR, the manifestation of compensatory hyperinsulinemia in lean PCOS was incipient, being evident only in response to meals (P < 0.05), and became overt during the 24-h fasting/feeding phases of the day in obese control (P < 0.001) with a 2- to 3-fold greater elevation (P < 0.001) in obese PCOS. An enhanced early insulin response to glucose occurs equally in obese control (P < 0.01) and obese PCOS (P < 0.05), but not in their lean counterparts. Considering the more profound IR and the associated hyperglycemia in obese PCOS, the magnitude of the early insulin release is inadequate, suggesting that beta-cell dysfunction exists in obese PCOS. Remarkable differences in the somatotropic axis were also observed; although 24-h GH pulse frequency and levels of IGF-I and IGFBP-3 were unaltered by either PCOS or obesity, the 24-h mean GH pulse amplitude was increased by 30% (P < 0.01) in lean PCOS in the presence of normal levels of high affinity GHBP and normal GH response to GHRH. In distinct contrast, the somatotropic axis in both obese control and obese PCOS was profoundly modified, with attenuation of GH pulse amplitude (P < 0.001) and GH response to GHRH (P < 0.001), resulting in a state of hyposomatotropinism with a more than 50% reduction (P < 0.001) of 24-h mean GH levels. In addition, GHBP levels were elevated 2-fold and were correlated inversely with GH (r = -0.81) and positively with insulin (r = 0.75) concentrations. IGFBP-I levels were suppressed in both obese groups, with a 4-fold greater reduction in obese PCOS than that in obese controls. Thus, the downstream effects of hyperinsulinemia on the somatotropic axis may include up-regulation of hepatic production of GHBP, suppression of IGFBP-1 (r = 0.82) and sex hormone-binding globulin (r = -0.69) levels, and a more than 3-fold increase in ratios of IGF-I/IGFBP-1 and estradiol-testosterone/sex hormone-binding globulin, thereby increasing their bioavailabilities. In contrast, LH pulsatility was unaffected by obesity alone. An accelerated LH pulse frequency was evident in both lean and obese PCOS (P < 0.001), whereas the mean 24-h LH pulse amplitude was increased in lean (P < 0.001), but not obese, PCOS patients. These events resulted in a 3-fold increase in 24-h mean LH levels in lean PCOS and a 2-fold increase in obese PCOS. Thus, increased LH pulse frequency and augmented LH response to GnRH are characteristic of PCOS, independent of obesity, and the presence of obesity in PCOS is associated with an attenuated LH pulse amplitude, not accounted f
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PMID:Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features. 876 42

The response of fat tissue to GH or insulin-like growth factor I (IGF-I) differs between humans with hypopituitarism and those with exogenous obesity; the effects of combined GH and IGF-I administration have not been compared in these two situations. In GH-deficient dwarf rats (who have a primary GH deficiency), the excessive fat deposition induced by a high fat diet is completely reversed by combined infusion of GH and IGF-I. Whether the same phenomenon would be observed in genetically obese Zucker rats (in whom, as in obese humans, the decrease in GH secretion is secondary to the obese state) remained to be determined. Growing (6-week-old) female obese Zucker rats received a continuous sc infusion of vehicle, recombinant human GH, recombinant human IGF-I, or GH plus IGF-I for 14 days (3 mg/kg x day for both GH and IGF-I). Combined GH and IGF-I stimulated body weight gain and in naso-anal length to the same extent as IGF-I alone, whereas GH alone was less potent. Because all treatments stimulated weight linear growth proportionately, the progression of obesity was similar in treated and control animals. However, GH plus IGF-I (but not either agent alone) induced a 25% decrease in the relative weight of inguinal fat. GH and IGF-I exerted distinct effects on the relative weights of liver, kidney, and spleen and on the circulating levels of IGF-I and IGF-binding protein-3. Circulating glucose and insulin levels did not change in any group. In summary, GH plus IGF-I infusions decrease the relative weight of inguinal fat in Zucker rats as in obese GH-deficient dwarf rats; however, this effect is of more modest magnitude despite the use of a 2- to 3-fold higher dose and is limited to the inguinal site. Thus, GH plus IGF-I infusions did not influence the obesity index in Zucker rats. Inasmuch as Zucker rats are a better model of childhood-onset obesity than dwarf rats fed a high fat diet, the present results do not appear promising for extrapolation to clinical studies in children. The mechanisms by which the primary vs. secondary nature of the decreased GH secretion influences the effect of GH plus IGF-I on obesity remain to be determined.
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PMID:Effects of 14-day infusions of growth hormone and/or insulin-like growth factor I on the obesity of growing Zucker rats. 877 Sep

The objective of this study was to determine whether obese patients with polycystic ovary syndrome (PCOS) show different ovarian and uterine blood flow patterns in comparison with lean patients. Sixteen obese (body mass index: BMI = 31.4 +/- 3.6 kg/m2) and 22 lean (BMI = 21.1 +/- 1.3 kg/m2) PCOS patients underwent, in the early follicular phase if oligomenorrheic or randomly if amenorrheic, ultrasonographic evaluation of ovarian volume, echodensity and follicle number; transvaginal color Doppler evaluation of uterine and intraovarian blood flow; and radioimmunological assay of luteinizing hormone, follicle stimulating hormone, growth hormone, estradiol, progesterone, testosterone, androstenedione, insulin, insulin-like growth factor I, and other hormonal parameters. Hematocrit, plasma glucose, total cholesterol, high density lipoprotein and triglycerides were also evaluated. Insulin levels were significantly higher in the obese group, whereas levels of growth hormone were significantly lower. Moreover, a more adverse lipid profile was observed in overweight patients. This was associated with higher hematocrit values. At Doppler analysis, a significantly higher mean uterine artery pulsatility index (PI) was observed in the obese group. Furthermore, the PI was inversely correlated with high density lipoprotein values (r = -0.4820; p < 0.05). In both groups, androstenedione was correlated with the uterine PI. The above findings may, in part, explain the increased risk in women with PCOS of developing cardiovascular diseases, and emphasize that obesity may further increase the risk.
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PMID:Color Doppler analysis in lean and obese women with polycystic ovary syndrome. 877 99

Pubertal development is associated with a rise in plasma insulin-like growth factor I (IGF-I) levels that is related both to the increase in sex steroids and/or to the sex steroid-induced augmentation in endogenous growth hormone (GH) secretion. In order to investigate the relationship between IGF-I, GH and testosterone, we examined 42 male subjects with various clinical conditions (classical GH deficiency (CGHD, N = 5), non-classical GH deficiency (NCGHD, N = 7), short idiopathic stature (N = 6), nutritional obesity (N = 8), GH-treated CGHD (N = 4), GH-treated NCGHD (N = 5) and normal stature (N = 7)) in which , for evaluation of hypogonadism (i.e. the absence of one or both testes from the scrotal sac), human chorionic gonadotropin (hCG) tests were performed. We measured IGF-I, total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) by radioimmunoassays before and 48 and 96 h after the start of the test. The values of IGF-I were lower (0.001 < p < 0.005) in CGHD and NCGHD than in the other groups. In comparison to basal levels, IGF-I values increased (0.005 < p < 0.05) both 48 and 96 h after the start of the hCG test in short idiopathic and normal stature children and in GH-treated subjects with NCGHD, but only 96 h in subjects with untreated NCGHD and GH-treated CGHD. No difference was demonstrated in basal values of total testosterone among any of the groups, while basal free testosterone levels were higher (0.001 < p < 0.05) in GH-treated subjects with NCGHD than in all the other groups except nutritional obesity; furthermore, free testosterone was higher (p < 0.05) in nutritional obesity than in CGHD. The values of total and free testosterone obtained both 48 and 96 h after the start of the hCG test were higher (0.001 < p < 0.05) than basal values in all groups. The DHEAS values did not show any significant change during the hCG test. Basal values were higher (0.01 < p < 0.05) in nutritional obesity than in the other groups. Considering all groups, chronological age, bone age and bone age/chronological age ratio were correlated with basal free testosterone, IGF-I and DHEAS levels (0.001 < p < 0.05), while basal free testosterone and IGF-I values were correlated with DHEAS levels (p < 0.005 and < 0.01, respectively). In conclusion, our study during the hCG test in boys with various clinical conditions demonstrated an increase in IGF-I concentrations only in those boys with sufficient GH secretion or GH replacement therapy. These findings indicate that both sex steroids and GH are necessary to allow for the pubertal increase in IGF-I levels.
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PMID:Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone. 881 Jul 35

The potential effects of growth hormone (GH) deficiency in adults and the importance of GH secretion in adult life have only been recognized and documented recently. It has been suggested that GH-deficient adults may have premature mortality, abnormalities in body composition and bone density with impaired physical performance and psychological well-being, which are sometimes improved by GH replacement. It is essential, therefore, to establish reliable standards to define GH deficiency in adults. Patients with possible GH deficiency often have primary pituitary or hypothalamic disorders or have undergone surgery or radiotherapy, and thus show evidence of a failure of one of the other pituitary hormones. Several biochemical approaches have been studied to define GH deficiency in the adult and no universal consensus has yet been reached. The most widely established criterion is the peak serum GH concentration achieved during a provocative test, usually the insulin tolerance test (ITT), or following other pharmacological stimuli (e.g. glucagon, arginine, clonidine or GH-releasing factor) but, alternatively, a more physiological stimulus (such as sleep, fasting or exercise) has been used. Spontaneous circulating levels of hormones of the GH axis [24-hour integrated GH concentration, serum insulin-like growth factor I (IGF-I) or IGF-binding protein-3] have been used in the diagnosis of childhood GH deficiency. They have been tested in adults as well but seem to have a more limited role. There are several factors complicating the evaluation of these results. Basal and stimulated GH and IGF-I levels decline with age and with obesity, levels tend to be higher in females and are dependent on nutritional and physical status. The ITT potentially has some risk attached, e.g. in the presence of ischaemic heart disease, but it has proved to be safe in general when used in specialized departments. Other tests are less reliable; releasing hormone tests only assess the readily releasable stores within the pituitary and not the physiological secretory status. The 'cut-off' point for the definition of subnormal responses ideally needs to be set for each provocative test, for each age group, for each degree of obesity and for both sexes. There is considerable variability in GH assays among different laboratories, which makes it difficult to compare hormone levels. The reproducibility of provocative tests can also be variable. An advantage of the hypoglycaemia and glucagon tests is that they allow simultaneous assessment of the adrenocorticotropic hormone reserve.
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PMID:Diagnosis of growth hormone deficiency in adults. 895 Jun 17

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

Both spontaneous and stimulated growth hormone (GH) secretion is reduced in obesity, in which state insensitivity to the inhibitory effect of hyperglycemia also has been reported. To further investigate this point, in eight male obese (OB) patients (27-49 years old; body mass index = 39.5 +/- 1.7 kg/m2) we studied the effect of oral glucose load (100 g) on the GH response to Hexarelin (HEX, 2 micrograms/kg iv), a synthetic hexapeptide belonging to the GH-releasing peptide family, which has been reported to be able to induce a marked GH rise even in obese patients. As a control group, six male age-matched normal subjects (NS) were studied (26-35 years old; body mass index = 22.3 +/- 1.5 kg/m2). In all subjects the GH response to growth hormone-releasing hormone (GHRH, 1 microgram/kg iv) was also studied. Basal GH and insulin-like growth factor I (IGF-I) levels in OB and NS were similar (0.3 +/- 0.1 vs 0.5 +/- 1.0 microgram/l and 166.7 +/- 12.3 vs 145.4 +/- 6.9 micrograms/l, respectively). Hexarelin induced a clear GH rise in OB (peak: 20.0 +/- 2.9 micrograms/l; AUC: 1193.0 +/- 213.7 micrograms.l-1.120 min-1) but this response was clearly lower (p < 0.0002) than that observed in NS (62.6 +/- 7.3 micrograms/l, 4587.5 +/- 614.9 micrograms.l-1.120 min-1). The GHRH-induced GH rise was lower (p < 0.002) in OB (4.4 +/- 1.2 micrograms/l, 331.0 +/- 95.9 micrograms.l-1.120 min-1) than that in NS (20.2 +/- 1.9 micrograms/l, 1281.0 +/- 157.5 micrograms.l-1 .120 min-1) and both were lower (p < 0.05) than those induced by HEX. In NS, glucose significantly blunted the GH response to HEX (38.4 +/- 7.2 micrograms/l, 2236.5 +/- 514.8 micrograms.l-1.120 min-1, p < 0.05) but failed to modify it in OB (19.4 +/- 2.7 micrograms/l, 934.5 +/- 151.3 micrograms.l-1. 120 min-1). Plasma glucose peaks after oral glucose load in OB and NS were similar (164.5 +/- 9.7 vs 145.8 +/- 4.6 mg/dl). In conclusion, the present data demonstrate that, in contrast to normal subjects, in obese patients HEX has a reduced GH-releasing effect that is not inhibited by glucose. In OB patients as well as in normal subjects HEX releases more GH than GHRH. These findings strengthen the evidence that GH secretion in obesity is refractory either to stimulatory inputs or to the inhibitory effect of hyperglycemia.
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PMID:Somatotrope responsiveness to Hexarelin, a synthetic hexapeptide, is refractory to the inhibitory effect of glucose in obesity. 902 12


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