Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Children with simple obesity (SO) show increased linear growth with normal or high serum insulin-like growth factor-I (IGF-I) levels during prepubertal period, despite low GH secretion. We measured IGF-I, IGFBP-1, GHBP and other factors to clarify the hormonal relation between the nutrition and the linear growth in SO and compared these factors with children with normal short stature (NS). Subjects were 23 SO and 19 NS children, and their height standard deviation (SD) scores were 0.7 +/- 0.2 SD and -3.4 +/- 0.3 SD (mean +/- SEM) (P < 0.01), respectively. Oral glucose tolerance test (OGTT) was performed in all the subjects and GH-releasing factor (GRF) test was also performed in 13 of SO and 17 of NS. The peak levels of GH in the GRF test were significantly lower in SO than in NS (12.8 +/- 1.7 vs. 39.8 +/- 6.9 ng/ml) and showed a significantly positive correlation with sigma IGFBP-1 (r = 0.63, P < 0.01). Serum GHBP level and IGF-I level were significantly higher in SO than in NS on pubertal stage matching. There was a positive correlation between GHBP and sigma insulin during OGTT (r = 0.75, P < 0.01). When the sum of the values during OGTT was expressed as sigma, sigma insulin, sigma C-peptide and sigma glucose were significantly higher in SO than in NS on pubertal stage matching. Basal and sigma IGFBP-1 were significantly lower in SO than in NS, but IGFBP-3 levels showed no significant difference between the two groups either in prepuberty or midpuberty. In conclusion, it can be hypothesized that the overnutrition causes hyperinsulinemia which increases GH receptor and IGF-I secretion despite low GH secretion. Hyperinsulinemia also may increase free IGF-I by lowering IGFBP-1. These two mechanism are supposed to be the nutrition related hormonal changes in SO and can explain the growth of SO. In addition, the increased free IGF-I may contribute the decreased GH secretion due to negative feedback in SO.
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PMID:Nutrition related hormonal changes in obese children. 970 Apr 75

We here investigate the potential rescue of the relative hyposomatotropism of aging and obesity by 3-day pulsatile GHRH infusions (i.v. bolus 0.33 microg/kg every 90 min) in 19 healthy men of varying ages (18 to 66 years) and body compositions (12 to 37% total body fat). Baseline (control) and GHRH-driven pulsatile GH secretion (in randomly ordered sessions) were quantitated by deconvolution analysis of 24-h (10-min sampling) serum GH concentration profiles measured in an ultrasensitive (threshold 0.005 microg/l) chemiluminescence assay. GHRH infusion significantly increased the mean (24-h) serum GH concentration (0.3 +/- 0.1 basal vs 2.4 +/- 0.4 microg/l treatment; P = 0.0001), total daily pulsatile GH production rate (21 +/- 9.5 vs 97 +/- 17 microg/l/day; P = 0.01), GH secretory burst frequency (11 +/- 0.5 vs 17 +/- 0.3 events/day; P = <0.01), and mass of GH released per burst (1.1 +/- 0.4 vs 5.9 1 microg/l; P < 0.01), as well as serum IGF-I (261 +/- 33 vs 436 +/- 37 microg/l; P = 0.005), insulin (45 +/- 13 vs 79 +/- 17 mU/l; P = 0.0002), and IGF binding protein (IGFBP)-3 (3320 +/- 107 vs 4320 +/- 114 microg/l; P = 0.001) concentrations, while decreasing IGFBP-1 levels (16 +/- 1.2 vs 14 +/- 0.09 microg/l; P = 0.02). Serum total testosterone and estradiol concentrations did not change. GHRH treatment also reduced the half-duration of GH secretory bursts, and increased the GH half-life. GHRH-stimulated 24-h serum GH concentrations and the mass of GH secreted per burst were correlated negatively with age (R[value]:P[value] = -0.67:0.002 and -0.58:0.009 respectively), and percentage body fat (R:P = -0.80:0.0001 and -0.65:0.0005 respectively), but positively with serum testosterone concentrations (R:P = +0.55:0.016 and +0.53:0.019 respectively). GHRH-stimulated plasma IGF-I increments correlated negatively with age and body mass index, and positively with serum testosterone, but not with percentage body fat. Cosinor analysis disclosed persistent nyctohemeral rhythmicity of GH secretory burst mass (with significantly increased 24-h amplitude and mesor values) but unchanged acrophase during fixed pulsatile GHRH infusions, which suggests that both GHRH- and non-GHRH-dependent mechanisms can modulate the magnitude (but only non-GHRH mechanisms can modulate the timing) of somatotrope secretory activity differentially over a 24-h period. In summary, diminished GHRH action and/or non-GHRH-dependent mechanisms (e.g. somatostatin excess, putative endogenous growth hormone-releasing peptide deficiency etc.) probably underlie the hyposomatotropism of aging, (relative) obesity, and/or hypoandrogenemia. Preserved or increased tissue IGF-I responses to GHRH-stimulated GH secretion (albeit absolutely reduced, suggesting GHRH insensitivity in obesity) may distinguish the pathophysiology of adiposity-associated hyposomatotropism from that of healthy aging.
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PMID:Unequal impact of age, percentage body fat, and serum testosterone concentrations on the somatotrophic, IGF-I, and IGF-binding protein responses to a three-day intravenous growth hormone-releasing hormone pulsatile infusion in men. 970 80

It has occasionally been suggested that GH directly suppresses circulating IGFBP-1 levels, although it is generally believed that such an effect is secondary to a GH-induced increase in insulin levels. We present data from several experiments in which the effects of GH on IGFBP-1 could be studied more extensively. In normal subjects (n = 36), an i.v. GH bolus caused a small but significant decrease in plasma IGFBP-1 concentrations without changes in insulin [IGFBP-1 (microgram/l): 2.6 +/- 0.3 (GH) vs 3.2 +/- 0.4 (placebo), P < 0.05]. Conversely, a 28-h somatostatin infusion with and without GH administration during fasting in normal subjects yielded higher IGFBP-1 levels in the non-GH substituted study [50.5 +/- 5.3 (GH-suppression) vs 22.6 +/- 5.6 (GH-substitution), P < 0.01], comparable with an increased concentration of IGFBP-1 during fasting in GH-deficient patients without usual GH substitution [23.4 +/- 7.6 (GH pause) vs 14.1 +/- 4.9 (GH substitution), P < 0.01]. In both fasting studies insulin levels remained stable. During a hypocaloric diet, long-term GH treatment in obesity lead to a significant decline in IGFBP-1 level (2.3 +/- 0.6 vs 1.2 +/- 0.2, P < 0.01), while no changes were found in the placebo group. Again, insulin levels remained equally low in both studies. Finally, a significant rebound increase in IGFBP-1 level in response to insulin induced hypoglycemia was only observed among GH-deficient patients, but not in control subjects, the latter of whom responded to hypoglycemia with a significant increase in serum GH levels [23.2 +/- 7.2 (GHDA) vs 2.5 +/- 0.3 (controls), P < 0.01]. In conclusion, a suppressive effect of GH on IGFBP-1 appears to be unmasked in the presence of low or suppressed insulin levels, making GH a potential regulator of IGF-1 bioactivity in a hitherto unrecognized way.
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PMID:Evidence supporting a direct suppressive effect of growth hormone on serum IGFBP-1 levels. Experimental studies in normal, obese and GH-deficient adults. 1020 8

In simple obesity, spontaneous and stimulated growth hormone (GH) secretions are diminished. However, this diminished GH secretion does not result in decreased somatic growth in obese children. Although the increased insulin level, low insulin-like growth factor binding protein (IGFBP)-1 and the resulting increase of bioavailability of insulin-like growth factor I (IGF-I) have been suggested as being involved, the exact mechanism has not yet been established. We investigated serum IGF-I, free IGF-I, IGFBP-1, IGFBP-3 and insulin levels in 36 obese and 39 non-obese healthy children. Insulin and IGFBP-3 were significantly higher in the obese group than in the control group (p < 0.05, p = 0.001, respectively). IGF-I, free IGF-I, free IGF-I/IGF-I and IGFBP-1 levels in the obese children were not significantly different from those in the control group. A positive correlation was found between body mass index (BMI) and IGF-I in the obese children (r = 0.30, p = 0.05). IGFBP-3 levels correlated positively with IGF-I (r = 0.44, p < 0.005), and free IGF-I levels (r = 0.37, p = 0.05) in the obese children. A negative correlation was found between IGFBP-1 and insulin levels (r = -0.30, p = 0.05) in the obese children. We concluded that normal growth in obese children might be maintained through normal IGF-I and increased IGFBP-3 levels, which are stimulated by increased insulin levels or nutritional factors or by increased responsiveness to GH.
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PMID:Serum levels of insulin-like growth factor (IGF)-I, free IGF-I, IGF binding protein (IGFBP)-1, IGFBP-3 and insulin in obese children. 1039 59

Controversial effects of weight reduction on gonadotropin secretion in obesity have been reported. As a result of pulsatility, single serum samples or frequent sampling studies are somewhat limited with regard to monitoring LH and FSH concentrations. We studied follicular phase nocturnal urinary (nu) LH and FSH secretion and glucose metabolism (150-min euglycemic hyperinsulinemic clamp) during 1 menstrual cycle/30-day period before and after weight reduction in 10 severely overweight infertility patients (age, 29 +/- 3.1 yr; body mass index, 37.1 +/- 3.3 kg/m2; +/-SEM). A 6-week very low calorie diet was followed by a 4-week normocaloric period. The urinary LH and FSH results reported represent samples taken 12 to 2 days before the LH surge, or 10 consecutive samples in the case of amenorrhea. We observed a decrease of 8% (P < 0.001) in percent body fat mass and a 5% (P < 0.005) reduction in waist to hip ratio. Mean nu-LH decreased by 45% [6.06 +/- 1.05 (+/-SEM) to 3.22 +/- 0.71 IU/L], whereas mean nu-FSH remained unchanged. Insulin-stimulated glucose uptake increased by 41% (P < 0.01), which was accounted for by a significant increase in nonoxidative glucose disposal (P = 0.003). Serum sex hormone-binding globulin concentrations increased by 39% (P < 0.01), and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) levels increased by 46% (P < 0.05). Fasting serum insulin concentrations decreased by 38%, those of leptin by 37%, those of androstenedione by 32%, those of testosterone by 20% (all P < 0.01), and those of dehydroepiandrosterone sulfate by 13% (P < 0.05). The percent change in nu-LH correlated negatively with glucose uptake (r = -0.76; P < 0.01) and the increase in serum sex hormone-binding globulin (r = -0.85; P < 0.005) and positively with the percent change in waist to hip ratio (r = 0.79; P < 0.01). The absolute nu-LH levels after weight reduction correlated significantly with fasting insulin concentrations (r = 0.88; P < 0.001) and negatively with glucose uptake (r = -0.67; P < 0.05). No significant relationships were found between absolute levels or changes in nu-LH concentrations and leptin, IGF-I, IGFBP-3, or IGFBP-1 concentrations. Our findings suggest that weight reduction with a very low calorie diet results in a decrease in nu-LH concentrations, a reduction in the LH/FSH ratio, and FSH predominance favoring folliculogenesis. The decrease in LH concentrations is inversely related to the severity of insulin resistance. It is possible that the decrease in LH secretion with weight reduction is more dependent on the absolute levels of insulin sensitivity than on the degree of general adiposity.
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PMID:The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women. 1099 21

HIV-lipodystrophy (HIV-LD) is characterized by the loss of body fat from the limbs and face, an increase in truncal fat, insulin resistance, and hyperlipidemia, factors placing affected patients at increased risk for vascular disease. This study evaluated insulin sensitivity and inflammatory status associated with HIV-LD and provides suggestions about its etiology. Insulin sensitivity and immune activation markers were assessed in 12 control subjects and 2 HIV-positive groups, 14 without and 15 with LD syndrome. Peripheral insulin sensitivity (mostly skeletal muscle) was determined with the hyperinsulinemic-euglycemic clamp. Circulating insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) and free fatty acid (FFA) levels, and their response to insulin infusion were indicative of insulin responsiveness of liver and adipose tissue, respectively. Serum levels of soluble type 2 tumor necrosis factor-alpha (TNF-alpha) receptor (sTNFR2) were used as an indicator of immune activation. HIV-LD study subjects had significantly reduced (twofold) peripheral insulin sensitivity, but normal levels of FFA and reduced levels of IGFBP-1, relative to the nonlipodystrophy groups, indicating that the loss of insulin sensitivity was more pronounced in skeletal muscle than in liver or fat. The significant loss of peripheral fat in the HIV-LD group (34%; p <.05) closely correlated with the reduced peripheral insulin sensitivity (p =. 0001). Levels of sTNFR2 were elevated in all HIV-infected study subjects, but they were significantly higher in those with lipodystrophy than without, and sTNFR2 levels strongly correlated with the reduction in insulin sensitivity (p =.0001). Loss of peripheral fat, normal levels of FFA, and reduced levels of IGFBP-1 indicate that insulin resistance in HIV-LD is distinct from type 2 diabetes and obesity. The relationship between the degree of insulin resistance and sTNFR2 levels suggests an inflammatory stimulus is contributing to the development of HIV-associated lipodystrophy.
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PMID:Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy. 1151 29

Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) is altered in different diseases and might be used as an indication of its severity. The aims of our study were to investigate: (1) the developmental pattern of the serum IGFBP-2 concentration at birth and during childhood and adolescence; (2) whether the serum IGFBP-2 level could be a marker for the diagnosis and evolution of diseases where the growth hormone (GH)-IGF axis is altered, and (3) whether this binding protein shows a relationship with IGF-I, its free fraction, IGFBP-1 and -3. We report reference values for 55 normal full-term newborns and 221 normal children who were divided into 5 groups according to their Tanner stage. Serum levels were higher in newborns when compared with Tanner stages I-V (p < 0.001, ANOVA), with no further changes throughout development. Furthermore, we studied IGFBP-2 levels in 24 children with congenital GH deficiency (GHD), 26 with acute lymphoblastic leukemia (ALL), 75 obese children, and 60 girls with anorexia nervosa (AN) at diagnosis and during a follow-up period. IGFBP-2 at diagnosis was increased in GHD, ALL and AN, and decreased in obesity (p < 0.05, ANOVA). During the follow-up, IGFBP-2 concentrations tended to normalize. IGFBP-2 correlated positively with IGFBP-1 and negatively with IGF-I and IGFBP-3 in normal subjects and at diagnosis of the pathologies studied. Although IGFBP-2 functions are not well understood, these results suggest a possible role for this protein in diseases where the GH-IGF axis is altered.
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PMID:Insulin-like growth factor-binding protein-2 levels in pediatric patients with growth hormone deficiency, eating disorders and acute lymphoblastic leukemia. 1115 Aug 83

Several recent epidemiological studies have shown an increase in breast cancer risk among women who have elevated plasma levels of testosterone, reduced levels of sex hormone-binding globulin (SHBG), and hence elevated levels of bioavailable androgens and estrogens not bound to SHBG. This endocrine profile is generally associated with obesity and chronic hyperinsulinemia, of which it is most likely a result. Lack of physical activity, obesity, and a diet rich in rapidly digestible carbohydrates and poor in fibre favour the development of insulin resistance and hyperinsulinemia. The elevated insulin levels, in turn are related to decreases in plasma and tissue levels of IGFBP-1 and IGFBP-2 (insulin-like growth factor-binding proteins), and this may increase the availability of insulin-like growth factor-I (IGF-I) to its receptors. Like insulin, IGF-I also inhibits the hepatic synthesis of SHBG, whereas both hormones stimulate the ovarian synthesis of sex steroids. Moreover, insulin and IGF-I can both enhance the development of breast tumours, through their cognate receptors within the mammary tissue. Taken together, these observations lead to the hypothesis that breast cancer risk may be increased in women with elevated plasma insulin levels, and/or with elevated levels of bioactive IGF-I. Hyperinsulinemia and an increased IGF-I bioactivity could thus be an important physiological link between a western lifestyle, overnutrition, a hyperandrogenic sex steroid profile, and increased breast cancer risk. Prospective cohort studies will be needed to test this hypothesis, and to study in greater detail the possible relationships of breast cancer risk with plasma levels of IGF-I and IGFBPs. Confirmation of a relationship of breast cancer risk with plasma insulin levels, on the one hand, or with total plasma IGF-I, on the other hand, could open up new perspectives for breast cancer prevention, either by changes in dietary intake patterns and physical activity, or by the use of certain chemopreventive drugs.
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PMID:[Plasma insulin, IGF-I and breast cancer]. 1130 43

Recent theories propose that a Western lifestyle may increase cancer risk through alterations in the metabolism of insulin and insulin-like growth factors (IGF: McKeown-Eyssen, 1994; Giovannucci, 1995; Kaaks, 19%; Werner & LeRoith, 1996). Insulin regulates energy metabolism, and increases the bioactivity of IGF-I, by enhancing its synthesis. and by decreasing several of its binding proteins (IGFBP; IGFBP-1 and -2). Insulin and IGF-I both stimulate anabolic processes as a function of available energy and elementary substrates (e.g. amino acids). The anabolic signals by insulin or IGF-I can promote tumour development by inhibiting apoptosis, and by stimulating cell proliferation. Furthermore, both insulin and IGF-I stimulate the synthesis of sex steroids, and inhibit the synthesis of sex hormone-binding globulin (SFIBG), a binding protein that regulates the bioavailability of circulating sex steroids to tissues. The present paper reviews epidemiological findings relating the risk of cancers of the colo-rectum, pancreas, breast, endometrium and prostate to body size (obesity, height) and physical activity, and discusses the relationships between obesity and physical activity and plasma levels of insulin, IGF-I and IGFBP. Subsequent sections review epidemiological findings relating cancer risk to indices of chronic hyperinsulinaemia, and to plasma levels of IGF-I and IGFBP. Conclusions are that chronic hyperinsulinaemia may be a cause of cancers of the colon, pancreas and endometrium, and also possibly of the breast. On the other hand, elevated plasma IGF-I, as total concentrations or relative to levels of IGFBP-3, appears to be related to an increased risk of prostate cancer, breast cancer in young women, and possibly cob-rectal cancer. For cancers of the endometrium, breast and prostate, these findings are discussed in the context of relationships between insulin and IGF-I and levels of bioavailable sex steroids.
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PMID:Energy balance and cancer: the role of insulin and insulin-like growth factor-I. 1131 Apr 28

The IGF family of growth factors is believed to play a role in the development and progression of breast cancer. We recently identified an adverse prognostic effect of insulin in breast cancer; we now report prognostic effects of circulating IGFBP's 1 and 3. 512 women with T1-3, N0-1, M0 breast cancer provided fasting blood which was analysed for IGFBP's I and 3. Information on body size, diet and traditional prognostic factors and treatment was obtained; women were followed for recurrence and death. IGFBP-1 levels correlated inversely with insulin levels (Spearman r = -0.60, p < 0.0001), reflecting known inhibition of IGFBP-1 gene expression by insulin. Insulin explained 36% of the variance in IGFBP-1 levels. IGFBP-1 levels were also correlated with obesity and diet. Levels of IGFBP-1 significantly predicted distant recurrence and death, hazard ratio (95% CI) for lower versus upper quartile 2.08 (1.20-3.61) and 3.0 (1.45-6.21), respectively. These effects persisted after adjustment for tumor-related variables and treatment but were not independent of insulin levels. High levels of IGFBP-3 predicted distant recurrence (hazard ratio upper v.s. lower quartile 1.8, 95% CI 1.1-3.0) but not death (hazard ratio 1.0, 95% CI 0.5-1.9). The effect on distant recurrence was restricted to postmenopausal women (hazard ratio 3.8, 95% CI 1.6-9.0) and to those with estrogen receptor positive tumors (p = 0.002). Prognostic effects of IGFBP-1 appear related to the known effect of insulin on IGFBP-1 gene expression. The adverse effect of IGFBP-3 on distant recurrence in postmenopausal women with estrogen receptor positive breast cancer should be further investigated.
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PMID:Insulin-like growth factor binding proteins 1 and 3 and breast cancer outcomes. 1215 Apr 54


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