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

Obesity may be characterized by abnormal sex steroid secretion and reduced sex hormone binding globulin (SHBG) which in turn is related to fat distribution and insulin secretion. Recent in-vitro and in-vivo evidence suggests that insulin is the common mechanism regulating the secretion of SHBG and insulin-like growth factor small binding protein (IGFBP-1). IGFBP-1 appears not only to be a carrier for insulin growth factors (IGFs) but also to play an active role in growth processes, independent of growth hormone secretion. We have examined the possible relationship between fasting insulin, SHBG, testosterone, IGF-1, IGFBP-1 and fat distribution in 25 extremely obese, menstruating women (mean weight 107 +/- 3 kg) with normal glucose tolerance. Fat distribution was assessed from measurements of the waist to hip ratio (W/H). The obese women showed an elevated fasting insulin (mean +/- SEM; 21 +/- 2 mumol/l), a normal IGF-1, but reduced IGFBP-1 (14.6 +/- 2 micrograms/l); in 15 women IGFBP-1 levels were undetectable by the present assay. In addition, SHBG levels were reduced in the obese women (24 +/- 2 nmol/l) but total testosterone values (1.9 +/- 0.1 nmol/l) were normal. The elevated fasting insulin levels were positively correlated with increasing upper segment obesity as expressed by a rising W/H ratio (P less than 0.01, r2 = 0.306) and inversely correlated with SHBG (P less than 0.01, r2 = 0.483). Similarly, reduced SHBG values showed an inverse correlation with increasing W/H ratio (P less than 0.001, r2 = 0.383). No correlation was found between IGFBP-1 and W/H ratio but a strong positive correlation was seen between IGFBP-1 and SHBG (P less than 0.001, r2 = 0.466). Furthermore, an equally significant inverse correlation was found between IGFBP-1 and insulin levels (P less than 0.001, r2 = 0.474).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein (IGFBP-1) in extreme obesity. 170 70

Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GH administration (0.03 mg.kg-1 body wt.day-1) in nine obese women (mean +/- SEM: age 30.4 +/- 2.4 years; body mass index 37.0 +/- 2.8 kg/m2) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (microgram/l) levels were subnormal and increased significantly following GH (117 +/- 16 (placebo) vs 434 +/- 33 (GH) vs 198 +/- 15 (control (p < 0.01)). By contrast, serum IGF-II (microgram/l) levels were in the normal range and remained unchanged (608 +/- 20 (placebo) vs 647 +/- 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and IGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF-II and IGFBP-3 remained unchanged. Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp, IGFBP-1 decreased in the placebo study and remained suppressed during GH. Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 +/- 0.36 (placebo) vs 2.21 +/- 0.25 (GH) vs 0.80 +/- 0.19 (control)).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo-controlled study. 754 82

Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments--water, fat, protein and mineral--are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38-130 micrograms/l) compared with normal lit/+ littermates (range 432-567 micrograms/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat increased in both lit/lit and lit/+ mice, while the per cent body water and mineral declined. In lit/lit but not lit/+ mice, per cent protein also declined with age. The changes in body water and fat are attributable to lack of adequate GH in the genetically GH-deficient lit/lit mouse. On the other hand, the changes in body protein are more likely to be effects of IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4. 767 39

Insulin is a major regulator of circulating insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1), suppressing the hepatic production of IGFBP-1. Postmenopausal age, obesity, hypertension, and impaired glucose tolerance, which are known risk factors for endometrial cancer, are all associated with hyperinsulinemia and insulin resistance. In this study, we investigated the relationship among serum insulin, glucose, insulin-like growth factors (IGF-I and IGF-II), and IGFBP-, -2, and -3 in 32 nondiabetic postmenopausal women with endometrial cancer and in 18 healthy controls. The mean fasting levels of glucose and insulin were higher, whereas the mean basal IGF-I, IGF-II, and IGFBP-3 levels were lower in the endometrial cancer patients than in the healthy control subjects. The mean fasting IGFBP-1 and IGFBP-2 levels did not differ between the groups, and no correlation was found between fasting insulin and IGFBP-1 concentrations or between insulin and IGFBP-2 concentrations in either of the study groups. During an oral glucose tolerance test, the mean glucose levels at 1 and 3 h as well as the mean insulin level at 3 h were significantly higher in the endometrial cancer patients than in the controls, and the area under the glucose curve was larger in the first group. An oral glucose load resulted in a similar fall in serum IGFBP-1 levels in endometrial cancer patients and controls (51% and 55% at 3 h). When the cancer patients were divided into two subgroups according to the body mass index (kilograms per m2), the obese group had higher glucose and insulin indices than the nonobese group. No difference was found by the same measures in healthy controls. The fasting serum IGFBP-1 levels tended to be lower in the obese than in the normal weight subjects, but the difference did not reach statistical significance. In summary, these results provide preliminary evidence that the inverse relation between fasting insulin and IGFBP-1, well established in children and young adults, disappears in elderly women, although short term suppression by insulin still occurs. Further, our data indicate that in addition to carbohydrate metabolism, postmenopausal women with endometrial cancer have alterations in their circulating IGF system compared to controls.
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PMID:Relationship between carbohydrate metabolism and serum insulin-like growth factor system in postmenopausal women: comparison of endometrial cancer patients with healthy controls. 768 14

Metabolic changes such as obesity and fasting modulate pulsatile growth hormone (GH) release in man, but the underlying mechanisms are still elusive. We studied the temporal pattern of pulsatile GH release in five normal-weight men (mean +/- SD: age, 29.8 +/- 4.9 years; body mass index [BMI], 24.3 +/- 1.8 kg/m2) and five obese men (age, 27.8 +/- 4.8 years; BMI, 38.9 +/- 4.8 kg/m2) during their regular energy consumption and the last 24 hours of a 96-hour fasting period. GH plasma levels were determined at 10-minute intervals and glucose level was measured every 20 minutes. GH pulse analysis was performed with three different algorithms. Insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding proteins (IGFBP-1, -2, and -3), and IGF-binding capacity (IGF-BC) were evaluated in samples collected at 7:00 AM, 3:00 PM, and 11:00 PM. Twenty-four-hour mean GH was basally higher in normal subjects (1.1 +/- 0.6 mU/L) than in overweight subjects (0.4 +/- 0.2, P < .01 v normal). The significant fasting-induced GH increase in normal-weight men (to 5.6 +/- 2.2 mU/L, P < .05 v basal) was inversely related to BMI (r = -.86, P = .0006). GH pulse amplitudes but not frequencies were different for both groups and were increased by fasting in normal subjects but not in obese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulsatile growth hormone secretion in normal-weight and obese men: differential metabolic regulation during energy restriction. 775 8

We recently reported the frequent occurrence of polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy, especially when the medication was started before the age of 20 years. In the present study we evaluated the association of obesity and hyperinsulinemia with valproate-related polycystic ovaries and hyperandrogenism in women with epilepsy. Sixty-five women participated in the study. Twenty-two received valproate monotherapy and 43 received carbamazepine monotherapy. In addition to clinical examination, vaginal ultrasonography was performed to determine ovarian size, and the concentrations of serum sex hormones, insulin, insulin-like growth factor 1, and the insulin-like growth factor-binding proteins 1 and 3 (IGFBP-1 and IGFBP-3) were measured. Fifty-nine percent of the women on valproate were obese, and in a retrospective analysis an indisputable weight gain (mean, 21 kg; range, 8-49 kg) was found in 50% of the women taking valproate. Fourteen (64%) of the women on valproate had polycystic ovaries, hyperandrogenism, or both. These women were obese, and in addition to elevated serum androgen levels, they had high concentrations of fasting serum insulin and low levels of serum insulin-like growth factor-binding protein 1. Valproate therapy for epilepsy is associated with weight gain during treatment in approximately 50% of women patients. The weight gain can be progressive, and is associated with hyperinsulinemia and low serum levels of insulin-like growth factor-binding protein 1, which may lead to hyperandrogenism and polycystic ovaries.
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PMID:Obesity and endocrine disorders in women taking valproate for epilepsy. 861 39

Obese Zucker rats maintain normal rates of linear growth and circulating concentrations of insulin-like growth factor-I (IGF-I) and of IGF-binding protein-3 (IGFBP-3) in spite of low GH secretion. The mechanisms underlying this GH-independent growth in obesity are unknown. To assess whether the liver expression of the GH receptor (GHR) messenger RNA (mRNA) is increased and/or if the liver expression of IGFBP-3 mRNA is maintained in the obese, Zucker rats of both genders and phenotypes (four groups, n = 6/group) were studied at 12 weeks of age. By Northern analysis, mRNA levels for GHR and GHBP were not increased in obese rats compared to their sex-matched lean littermates; the expression of these two transcripts was sexually dimorphic and the changes in GHBP mRNA/GHR mRNA ratios associated with obesity were sex-specific. In both genders, IGFBP-1 and IGFBP-3 mRNAs were decreased in the obese. We concluded that the GH-independent growth of obese Zucker rats is not due to increased GHR mRNA or to maintained IGFBP-3 mRNA levels in the liver.
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PMID:The growth hormone (GH)-independent growth of the obese Zucker rat is not due to increased levels of GH receptor messenger RNA in the liver. 867 29

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

We have studied the GH-insulin-like growth factor (IGF) axis in prepubertal children with exogenous obesity at the time of clinical diagnosis and at two time points during weight reduction on a calorie-restricted diet. Spontaneous GH secretion, IGF-I, free IGF-I (fIGF-I), IGF-II, their binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3), and GH-binding protein (GHBP) values at the time of clinical diagnosis (n = 65), after a 25% decrease in the body mass index (BMI) expressed as the SD score (BMI SD score; n = 29), and after a diminution of at least 50% of the initial BMI SD score (n = 9) are reported. GH secretion was significantly reduced at diagnosis, and after a decrease of at least 25% in the initial BMI SD score, it returned to normal in all patients. Total IGF-I levels were not significantly different from those in controls at any point. In contrast, fIGF-1 and IGF-II levels were significantly increased, both at diagnosis and after BMI SD score reduction. Obese patients were hyperinsulinemic at diagnosis and remained so even after a 50% reduction of their BMI SD score. Serum IGFBP-1 and IGFBP-2 levels were significantly decreased at diagnosis and at the two points studied during weight reduction. Serum IGFBP-3 and GHBP levels were increased significantly at diagnosis and returned to normal levels after a reduction in the BMI SD score. A positive correlation between serum GHBP levels and BMI was found in both controls and obese patients. Serum IGFBP-3 levels correlated positively with IGF-I, fIGF-I, and IGF-II in all groups, but these correlations were weaker in the obese patients at diagnosis. IGFBP-2 correlated significantly with IGF-II only in the obese group at diagnosis (r = -0.760; P < 0.0001), but with fIGF-I in all groups. IGFBP-1 was negatively correlated with IGF-I and fIGF-I in all groups. In conclusion, the GH-IGF axis is dramatically altered in patients with exogenous obesity. However, most changes in the peripheral IGF system appear to be independent of the modifications in GH secretion. In addition, in contrast to current thought, not all of the observed abnormalities are reversed with a significant reduction in the BMI SD score.
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PMID:Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in prepubertal children with exogenous obesity: effect of short- and long-term weight reduction. 921 75

Although low GH levels are commonly seen in obese adults and children, the effects of obesity on the insulin-like growth factor (IGF)/IGF-binding protein (IGFBP) system have not been established. As GH and IGF-I normally increase during adolescence, we investigated the effects of obesity on circulating total and free IGF-I levels and IGFBP-1, -2, and -3 in 19 obese adolescents [14 +/- 1 yr old; body mass index (BMI), 34 +/- 3], 20 lean adolescents (14 +/- 1 yr old; BMI, 23 +/- 0.5), and 10 lean adults (22 +/- 0.7 yr; BMI, 22 +/- 0.7). Fasting plasma insulin levels were significantly greater in obese adolescents than in either lean group, whereas circulating IGFBP-1 levels were suppressed in an inverse relationship to basal insulin (r = -0.49; P < 0.01). Low IGFBP-1 levels were associated with normal to increased free IGF-I levels in obese adolescents, even though total IGF-I values were lower than those in lean adolescents. Basal GH and IGFBP-3 levels were also lower in obese vs. lean adolescents. Basal IGFBP-1 levels were markedly reduced in obese adolescents (14 +/- 3 ng/mL) vs. those in adolescents and adults. No further suppression of IGFBP-1 levels was observed in the obese group during a two-step 8 and 40 mU/m2 insulin clamp. In contrast, IGFBP-1 levels were promptly lowered in lean adults. Basal IGFBP-2 levels were significantly lower in both groups of adolescents vs. lean adults (P < 0.05), and IGFBP-2 levels did not change during euglycemic hyperinsulinemia. These data suggest that the compensatory hyperinsulinemia that characterizes adolescent obesity chronically suppresses levels of IGFBP-1, and low IGFBP-1 concentrations may serve to increase the bioavailability of free IGF-I, which may, in turn, contribute to lower circulating GH, total IGF-I, and IGFBP-3 concentrations.
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PMID:The metabolic syndrome and insulin-like growth factor I regulation in adolescent obesity. 958 40


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