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

The growth hormone (GH)/insulin-like growth factor-I (IGF-I) system and leptin both play an important role in the regulation of body composition. Although the regulation of these two hormonal systems by insulin has been under intense investigation, the physiologic interactions between leptin and the GH/IGF-I system remain unknown. In this study, we examined the relationships among circulating leptin and key elements of the IGF-I system in 60 subjects (27 nondiabetic lean, 21 nondiabetic obese, and 12 type 1 diabetic subjects) with a wide range of insulin secretory capacity. Leptin, glucose, insulin, free IGF-I, total IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured in the basal state after an overnight fast, and the acute insulin response to glucose (AIRG) was determined after intravenous glucose injection. AIRG was significantly higher (P < .01) in the obese (3,365+/-562 pmol/L x min) versus lean subjects (1,624+/-155 pmol/L x min). In simple regression analysis, the serum leptin concentration was positively correlated with the body mass index ([BMI] men, r = .51, P = .005; women, r = .71, P < .001), IGFBP-3 (men, r = .20, P = nonsignificant; women, r = .41, P < .025), and AIRG (men, r = .73, P < .001; women, r = .62, P < .01). There was a nonlinear correlation between leptin and IGFBP-1, but there was no correlation between leptin and free or total IGF-I. In multiple regression analysis with leptin as the dependent variable, gender, BMI, and IGFBP-3 entered the equations at a statistically significant level. The correlation of leptin with IGFBP-3 was independent of obesity and persisted after correction for AIRG, suggesting a link between leptin and GH action.
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PMID:Relationship between serum leptin and the insulin-like growth factor-I system in humans. 1042 Dec 22

Patients with myelomeningocele show an increased incidence of endocrinological disorders during their childhood. These disorders can ulteriorly affect the adult height of these patients who are already extremely short. In the present study we determined the final height in 21 patients (11 females aged 20.55 +/- 3.54 years; 10 males aged 20.99 +/- 2.94 years) with myelomeningocele. The endocrinological implications were investigated by clinical and laboratory assessment at control and an accurate retrospective evaluation of individual clinical history. Auxological data indicated that in male patients mean final height was significantly less (P < 0.05) than target height, but in females the difference between final height and target height was even more marked (P < 0.001). Comparison of SDS for adult height between males (-2.04 +/- 1.89) and females (-4.36 +/- 2.24) evidenced a statistically significant difference (P < 0.05). The analysis of endocrinological data showed that 7 females had had precocious puberty not treated; no case of precocious puberty was evidenced in males. In 4 females we observed plasmatic IGF-1 and IGFBP-3 concentrations significantly reduced either for chronological age and pubertal stage; this finding emerged in only 1 male. Plasmatic thyroid hormone and adrenal steroid concentrations resulted normal in both groups. Finally, obesity, considered as BMI > 90%, resulted present since childhood in 4 females and 2 males. Our data show that females with myelomeningocele have a statistically greater decrease of their adult stature respect to males. This difference is probably due to a more significant incidence in females of endocrinological diseases. Thus, we believe that a better statural prognosis may be joined in these patients (particularly in girls), through a careful endocrinological follow-up, performed from their births, in order to ensure a prompt identification and treatment of the cases of precocious puberty, impaired GH secretion or obesity.
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PMID:[Precocious puberty, Gh deficiency and obesity can affect final height in patients with myelomeningocele: comparison of males and females]. 1057 Jul 85

We have previously demonstrated that obese hyperandrogenic amenorrheic women are less likely to ovulate after clomiphene citrate (CC) medication. The present study was designed to identify whether additional endocrine screening characteristics, all potentially involved in ovarian dysfunction in 182 normogonadotropic oligoamenorrheic infertile women, are associated with ovarian response, which may improve overall prediction of CC-resistant anovulation. Standardized endocrine screening took place before initiation of CC medication (50 mg/day; increasing doses up to 150 mg/day if required) from cycle days 3-7. Screening included serum assays for fasting insulin and glucose, insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, free IGF-I, inhibin B, leptin, and vascular endothelial growth factor. Forty-two women (22% of the total group) did not ovulate at the end of follow-up (a total number of 325 cycles were analyzed). Fasting serum insulin, insulin/glucose ratio, IGFBP-1, and leptin were all significantly different in univariate analyses (P < or = 0.02), comparing CC responders vs. nonresponders. Forward stepwise multivariate analyses in combination with factors reported earlier for prediction of patients remaining anovulatory after CC revealed a prediction model including 1) free androgen index (FAI = testosterone/sex hormone-binding globulin ratio), 2) cycle history (oligomenorrhea or amenorrhea), 3) leptin level, and 4) mean ovarian volume. These data suggest that decreased insulin sensitivity, hyperandrogenemia, and obesity, all associated with polycystic ovary syndrome, are prominent factors involved in ovarian dysfunction, preventing these ovaries from responding to stimulation by raised endogenous FSH levels due to CC medication. By using leptin instead of body mass index or waist to hip ratio, the previous model for prediction of patients remaining anovulatory after CC medication could be slightly improved (area under the curve from 0.82-0.85). This may indicate that leptin is more directly involved in ovarian dysfunction in these patients. The capability of insulin and IGFBP-1 to predict patients who remain anovulatory after CC disappears when FAI enters into the model due to a significant correlation between FAI and these endocrine parameters. This suggests that markers for insulin sensitivity (e.g. IGFBP-1 and insulin) are associated with abnormal ovarian function through its correlation with androgens, whereas leptin is directly involved in ovarian dysfunction.
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PMID:Free androgen index and leptin are the most prominent endocrine predictors of ovarian response during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. 1069 Aug 75

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

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

A segregating F(2) pedigree based on two mouse lines (DU6i and DBA/2) with extremely different growth characteristics was generated to search for loci affecting serum levels of insulin-like growth factor (IGF) binding proteins (IGFBPs) and to estimate their effects on growth and body composition. DU6i is characterized by high body mass and obesity associated with hyperinsulinemia, hyperleptinemia, and elevated serum IGF-I concentrations. Furthermore, significantly elevated serum levels of IGFBP-2, IGFBP-3, and IGFBP-4 were found in DU6i vs. DBA/2 mice. Linkage analysis identified loci with major effects on the serum level of IGFBP-3 on Chromosome 5 at 58 cM (Igfbp3q1; F = 9.9) and on Chromosome 10 at 46 cM (Igfbp3q2; F = 33.8). A locus significantly influencing serum IGFBP-2 levels in males was found on Chromosome 7. Additional linkage was detected in males and females for IGFBP-2 on Chromosomes 8, 11, 14, 17, and X, and for IGFBP-4 on Chromosome 4. Additional loci affecting IGFBPs acted in a sex-specific manner. The identified loci coincide in part with chromosomal regions controlling growth and obesity. Thus, multiple genes or pleiotropic gene effects may be assumed for these chromosomal regions. The identification of quantitative trait loci for IGFBPs as subcomponents of growth regulation and differentiation will further improve the understanding of complex trait regulation.
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PMID:Genome-wide search for loci controlling serum IGF binding protein levels of mice. 1129 58

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 aim of this study was to correlate lesions of the pituitary gland with hormonal dysregulation. The hormonal status of 63 children was correlated with MRI findings of the pituitary gland. Two radiologists judged the MRI examinations without knowledge of the hormonal situation. The reliability of the diagnosis "adenoma" was evaluated in five steps from 0-100% for each sequence. A microadenoma was found in six of 14 children with hyperprolactinemia and in six of eight patients with increased IGF-I/IGFBP-3. However, microadenomas were also detected in eight of 28 children without hormonal dysfunction (clinical feature: obesity). The adenomas were seen best in a dynamic sequence after gadolinium administration. An expansive growing macroadenoma was found in one of 13 patients with hypopituitarism. We found a relatively high number of microadenomas even in children without any hormonal dysfunction. Taking into account the reported autopsy results (6.1-27% occult microadenomas), we suggest that the MRI diagnosis "microadenoma" is made too frequently if usual MRI criteria are used. Patients with increased levels of IGF-I/IGFBP-3 had a high incidence of microadenoma (up to 87.5%). Hyperprolactinemia was associated with microadenomas in about 43% (-57%) of patients (nearly on the same level as children without hormonal dysfunction). Therefore unspecific stimulation of the pituitary gland with consecutive increased volume seems to be responsible for hyperprolactinemia in many of these patients.
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PMID:Microadenomas of the pituitary gland in children with and without hypophyseal dysfunction in magnetic resonance imaging. 1187 80

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

Fasting or caloric restriction causes substantial reductions in serum IGF-I in normal weight humans and animals, and reductions of liver IGF-I and IGFBP-3 mRNAs in animals. Obese humans, however, have attenuated and delayed decrements in IGF-I in serum when subjected to caloric restriction. Obese Zucker rats show a clear tendency to preserve body protein during fasting. To determine whether obesity opposes the effects of fasting on IGF-I and IGFBP-3, and thereby contributes to preservation of lean tissue, we have examined the effect of 72 h of fasting on IGF-I and IGFBP-3 in lean and obese Zucker rats. We observe that between lean and obese animals, fasting for 72 h produces similar decrements in body weight, serum IGF-I, liver IGF-I mRNA, serum IGFBP-3 and liver IGFBP-3 mRNA. Our finding that the reduction of IGF-I and IGFBP-3 in liver that results from 72 h of fasting is not attenuated in obese Zucker rats raises the possibility that conservation of lean tissue in these animals during fasting is not related to the hepatic production of IGF-I and IGFBP-3.
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PMID:Hepatic reduction of insulin-like growth factor (IGF)-I and IGF binding protein-3 that results from fasting is not attenuated in genetically obese rats. 1255 63


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