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Association of plasma hormones, nutritional status, and stressful life events in anorexia nervosa patients.
Śmiarowska, M, Safranow, K, Dziedziejko, V, Bialecka, M, Koziołek, M, Samochowiec, J
Postepy higieny i medycyny doswiadczalnej (Online). 2014;:162-71
Abstract
OBJECTIVE The aim of the current study was to analyze the relationships between plasma hormones, body weight parameters and stressful life events in anorexia nervosa (AN). MATERIAL AND METHODS 72 females in the active phase of AN were evaluated. 52 healthy women constituted the control group. RIA kits were used to measure plasma hormone levels. RESULTS The concentrations of leptin, insulin, IGF-1, triiodothyronine, LH, FSH, estradiol, and testosterone were significantly lower and those of cortisol and growth hormone significantly higher in the AN than the control group. No hormonal differences between restrictive and binge-purging AN subtypes were found. Leptin, IGF-1, gonadotropins, and sex steroids correlated significantly negatively and growth hormone positively with total reduction of body weight or the degree of undernutrition. Associations were also found between lower insulin concentration and family violence, lower cortisol and psychiatric diseases in the family, higher testosterone and patient's alcohol or drug abuse. DISCUSSION The changed activity of the somatotropin-somatomedin, gonadal, and corticotrophin axes corresponds to the clinical stage of AN. Plasma IGF-1 seems to be the most sensitive and useful independent hormonal marker of cachexia.
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Vitamin D increases circulating IGF1 in adults: potential implication for the treatment of GH deficiency.
Ameri, P, Giusti, A, Boschetti, M, Bovio, M, Teti, C, Leoncini, G, Ferone, D, Murialdo, G, Minuto, F
European journal of endocrinology. 2013;(6):767-72
Abstract
OBJECTIVES Previous studies suggested that vitamin D modulates circulating IGF1. We investigated this effect in adults and its clinical relevance in the management of GH deficiency (GHD). DESIGN AND METHODS IGF1 levels were prospectively measured before and after 12 weeks of treatment with oral vitamin D3 (5000 or 7000 IU/week) vs no intervention in 39 subjects 61.9±7.9 years old. The frequency of IGF1 values ≥50th age- and sex-specific percentile in relation to vitamin D status, as determined by the concentration of 25-hydroxyvitamin D (25(OH)D), was retrospectively assessed in 69 GHD patients (57.4±16.6 years) on stable hormone replacement and with 25(OH)D and IGF1 concurrently measured. RESULTS Treatment with 5000 and 7000 IU vitamin D3/week significantly raised 25(OH)D by 12.7±8.4 and 13.1±6.5 ng/ml respectively (both P<0.001 vs baseline). In the 7000 IU group, IGF1 levels also significantly increased by 31.3±36.7 ng/ml (P=0.01). Neither 25(OH)D nor IGF1 significantly varied in controls. IGF1 was ≥50th percentile more frequently in GHD patients with 25(OH)D levels ≥15 than <15 ng/ml (65.9 vs 40.0%, P<0.05). Logistic regression with adjustment for recombinant human GH (rhGH) dose, vitamin D supplements, gender, use of thyroid hormones, corticosteroids or estrogen/testosterone, and season revealed a significant positive association between ≥15 ng/ml 25(OH)D and IGF1 ≥50th percentile (OR 4.4, 95% CI 1.0-18.8, P<0.05). A significant negative correlation between 25(OH)D concentrations and rhGH dose was found after correcting for age and IGF1 (β -0.042, P<0.01), but not after further adjusting for sex, thyroid, adrenal or gonadal replacement, and season (β -0.037, P=0.06). CONCLUSIONS Vitamin D increases circulating IGF1 in adults. As a result, a better vitamin D status may ease the achievement of normal IGF1 values in GHD.
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Increased energy intake in hip fracture patients affects nutritional biochemical markers.
Gunnarsson, AK, Akerfeldt, T, Larsson, S, Gunningberg, L
Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. 2012;(3):204-10
Abstract
BACKGROUND AND AIMS We have previously shown that nutritional guidelines decreased the incidence of pressure ulcers in hip fracture patients. In the present study, we evaluate whether the nutritional biochemical markers S-IGF-1 (Insulin-like Growth Factor 1), S-Transthyretin and S-Albumin are affected by patients' energy intake, and whether the markers are useful as predictors of postoperative complications. MATERIAL AND METHODS Quasi-experimental design, with one intervention and one control group, as well as pre- and post-study measurements. Eighty-eight hip fracture patients were included: 42 in the control group and 46 in the intervention group. The control group received regular nutritional support pre- and postoperatively, while the intervention group received nutritional support that followed new, improved clinical guidelines from admission to five days postoperatively. S-Albumin, S-Transthyretin, C-Reactive Protein (S-CRP) and S-IGF-1 were analysed at admission and five days postoperatively as well as complications like pressure ulcer and infection. RESULTS The intervention group had a significantly higher energy intake; for example, 1636 kcal versus 852 kcal postoperative day 1. S-IGF-1 levels decreased significantly in the control group, while no decrease in the intervention group. S-Albumin and S-Transthyretin decreased and S-CRP increased significantly in both groups, indicating that those markers were not affected short-term by a high-energy intake. There was no correlation between short-term post-operative complications and S-IGF-1, S-Transthyretin or S-Albumin at admission. CONCLUSION The results of our study showed that S-IGF-1 can be used as a short-term nutritional biochemical marker, as it was affected by a five-day high-energy regimen. However, neither S-IGF-1, S-Transthyretin or S-Albumin were useful in predicting postoperative complications within five days postoperatively.
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Polysomnographic sleep, growth hormone insulin-like growth factor-I axis, leptin, and weight loss.
Rasmussen, MH, Wildschiødtz, G, Juul, A, Hilsted, J
Obesity (Silver Spring, Md.). 2008;(7):1516-21
Abstract
Short sleep appears to be strongly associated with obesity and altered metabolic function, and sleep and growth hormone (GH) secretion seems interlinked. In obesity, both the GH-insulin-like-growth-factor-I (GH-IGF-I) axis and sleep have been reported to be abnormal, however, no studies have investigated sleep in relation to the GH-IGF-I axis and weight loss in obese subjects. In this study polygraphic sleep recordings, 24-h GH release, 24-h leptin levels, free-IGF-I, total-IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), cortisol and insulin sensitivity were determined in six severely obese subjects (BMI: 41+/-1 kg/m(2), 32+/-2 years of age), cross-sectional at baseline, and longitudinal after a dramatically diet-induced weight loss (36+/-7 kg). Ten age- and gender-matched nonobese subjects served as controls. Sleep duration (360+/-17 vs. 448+/-15 min/night; P<0.01), 24-h GH (55+/-9 vs. 344+/-55 mU/l.24 h; P<0.01), free-IGF-I (2.3+/-0.42 vs. 5.7+/-1.2 microg/l; P<0.01), and total-IGF-I (186+/-21 vs. 301+/-18 microg/l; P<0.01) were significantly decreased and 24-h leptin levels were increased (35+/-5 vs. 12+/-3 microg/l; P<0.01) in obese subjects at pre-weight loss compared with nonobese subjects After diet-induced weight loss the differences in GH, free IGF-I, and leptin were no longer present between previously obese and nonobese subjects, whereas a significant difference in sleep duration and total IGF-I levels persisted. Rapid eye movement (REM) sleep, non-REM sleep, IGFBP-3, ALS, and cortisol levels were similar in obese and nonobese subjects. Sleep duration, 24-h GH, and IGF-I levels were decreased and 24-h leptin levels were increased in obese subjects. We conclude that hyposomatotropism and hyperleptinemia in obesity are transient phenomena reversible with weight loss, whereas short sleep seems to persist after weight has been reduced dramatically.
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Administration of recombinant human growth hormone normalizes GH-IGF1 axis and improves malnutrition-related disorders in patients with anorexia nervosa.
Hashizume, K, Suzuki, S, Komatsu, A, Hiramatsu, K, Mori, J, Yamazaki, M, Takeda, T, Kakizawa, T, Miyamoto, T, Koizumi, Y, et al
Endocrine journal. 2007;(2):319-27
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Abstract
High serum level of GH in the presence of low plasma level of insulin-like growth factor-I (IGF-I) is one of the endocrinological features of anorexia nervosa (AN). Whether the amount of endogenous GH is not enough to increase IGF-I is not certain. We studied the effect of recombinant human growth hormone (rhGH) on the GH-IGF-I axis and on malnutrition-related disorders in this syndrome. Twenty patients with AN were divided into two groups; one (N = 13) was given rhGH (0.33 mg/day), and the other (N = 7) was given placebo for 6 or 12 months, respectively. During each treatment, levels of serum GH, plasma IGF-I, serum thyroid hormones, serum cholesterol, fasting plasma glucose and cardiac function were monitored. Changes in body mass index (BMI) and calorie taken were also evaluated. Plasma IGF-I level increased from 74.4 +/- 41.9 to 269.0 +/- 31.2 microg/L (P<0.001) during administration of rhGH, which associated with a decrease in serum GH level from 17.0 +/- 15.0 to 1.6 +/- 0.8 microg/L (P<0.001). Administration of rhGH increased BMI, body temperature, fasting plasma glucose level, and food intake. Serum level of triiodothyronine, but not thyroxine, increased during treatment with rhGH. The treatment decreased serum levels of both total and HDL-cholesterol. Studies with echocardiography showed an increase in cardiac output during the treatment with rhGH. These improvements were not observed in patients treated with placebo. Administration of rhGH is recommended as one of the methods of managing the patients with AN.
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Treatment of iodine deficiency in school-age children increases insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations and improves somatic growth.
Zimmermann, MB, Jooste, PL, Mabapa, NS, Mbhenyane, X, Schoeman, S, Biebinger, R, Chaouki, N, Bozo, M, Grimci, L, Bridson, J
The Journal of clinical endocrinology and metabolism. 2007;(2):437-42
Abstract
CONTEXT Iodine deficiency in utero impairs fetal growth, but the relationship between iodine deficiency and postnatal growth is less clear. OBJECTIVE The objective of the study was to determine whether iodine repletion improves somatic growth in iodine-deficient children and investigate the role of IGF-I and IGF binding protein (IGFBP)-3 in this effect. DESIGN, PARTICIPANTS, AND INTERVENTIONS Three prospective, double-blind intervention studies were done: 1) in a 10-month study, severely iodine-deficient, 7- to 10-yr-old Moroccan children (n = 71) were provided iodized salt and compared with children not using iodized salt; 2) in a 6-month study, moderately iodine-deficient, 10- to 12-yr-old Albanian children (n = 310) were given 400 mg iodine as oral iodized oil or placebo; 3) in a 6-month study, mildly iodine-deficient 5- to 14-yr-old South African children (n = 188) were given two doses of 200 mg iodine as oral iodized oil or placebo. At baseline and follow-up, height, weight, urinary iodine (UI), total T4 (TT4), TSH, and IGF-I were measured; in Albania and South Africa, IGFBP-3 was also measured. RESULTS In all three studies, iodine treatment increased median UI to more than 100 microg/liter, whereas median UI in the controls remained unchanged. In South Africa, iodine repletion modestly increased IGF-I but did not have a significant effect on IGFBP-3, TT4, or growth. In Albania and Morocco, iodine repletion significantly increased TT4, IGF-I, IGFBP-3, weight-for-age z scores, and height-for-age z scores. CONCLUSION This is the first controlled study to clearly demonstrate that iodine repletion in school-age children increases IGF-I and IGFBP-3 concentrations and improves somatic growth.
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Effect of nucleotide intake and nutritional recovery on insulin-like growth factor I and other hormonal biomarkers in severely malnourished children.
Vásquez-Garibay, E, Stein, K, Kratzsch, J, Romero-Velarde, E, Jahreis, G
The British journal of nutrition. 2006;(4):683-90
Abstract
The objective of the present study is to demonstrate the effect of nucleotide intake and intensive nutritional support on the concentration of insulin-like growth factor I (IGF-I) and other hormonal biomarkers in severely malnourished children. Twenty-six severely malnourished children < 48 months of age received formula without lactose via enteral feeding for 2 weeks and ad libitum for an additional 2 weeks. Anthropometrical measurements were performed and serum concentrations of IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3), leptin, soluble leptin receptor (sOB-R), as well as the estimated molar excess of sOB-R over leptin were obtained. Two groups were formed. One group received formula with nucleotides (NT+; n 13) and the other without nucleotides (NT-; n 13). A control group was included (n 13). Parametric and non-parametric tests as well as ANOVA models were used. Nutritional recovery, nucleotides intake, type of malnutrition, age and the interaction between gender and malnutrition influenced the concentration of IGF-I (P < 0.001). Nutritional recovery, nucleotides intake, gender and type of malnutrition had an effect on IGFBP-3 (P < 0.001). Nutritional recovery had a significant effect on serum leptin (P = 0.001). Age and nutritional recovery had an effect on sOB-R (P < 0.001); all variables included affected the molar excess of sOB-R over leptin (P < 0.001). In conclusion, nucleotide intake and nutritional recovery had a notable effect on IGF-I, IGFBP-3 and other hormonal biomarkers. This outcome could stimulate the catch-up growth of severely malnourished infants and toddlers during the nutritional recovery period.
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Is IGF-1 involved in the regulatory modifications of cholesterolemia following the administration of embryonary peptides?
Mihăescu, GF, Olinescu, RM, Grigorescu, A
Romanian journal of internal medicine = Revue roumaine de medecine interne. 2006;(4):443-53
Abstract
Significant modifications of IGF-1 and cholesterol (total and LDL) were observed following the administration of an extract of embryonary peptides (EP) to old subjects for 60 days. For most of the subjects, due to the aging process, the initial values of the biochemical parameters were shifted towards pathological range. Following the administration of EP, the serum levels of IGF-1 and cholesterol (total and LDL) were shifted towards the physiological limits for their age. The most significant modifications towards physiological range were observed for subjects with high, initial levels of IGF-1, when the decrease was striking (1-2 orders of magnitude). For these subjects, significant modifications were observed simultaneously for cholesterol. The modifications induced following the administration of EP exhibit a regulatory feature, as they are dependent on the initial levels of these parameters. The action of EP on the levels of IGF-1 and cholesterol was significantly equal for both sexes, but the influence of EP was more clear-cut in men. In conclusion, our results support an implication of IGF-1 in the regulatory mechanisms of cholesterolemia in old subjects following the long-term administration of EP.
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Effects of short-term caloric restriction on circulating free IGF-I, acid-labile subunit, IGF-binding proteins (IGFBPs)-1-4, and IGFBPs-1-3 protease activity in obese subjects.
Rasmussen, MH, Juul, A, Kjems, LL, Hilsted, J
European journal of endocrinology. 2006;(4):575-81
Abstract
OBJECTIVE Decreased levels of GH and total IGF-I have been reported in obesity. It has been hypothesized that increased free (biologically active) IGF-I levels generated from IGF-binding protein (IGFBP) protease activity could be the mechanism for the low GH release in dieting obese subjects. However, no published data exist on free IGF-I levels, acid labile subunit (ALS), or IGFBP protease activity in relation to GH release during a hypocaloric diet. The main purpose of this study was to determine free IGF-I, ALS, IGFBPs-1-4, and IGFBPs-1-3 protease activity in relation to 24-h GH release before and after a short-term very low-calorie diet (VLCD). DESIGN Six obese subjects before weight loss, five after an average weight loss of 36.1 kg, and five age-and sex-matched lean controls underwent a 4-day VLCD. All subjects were studied on two occasions, once during normal basic diet and again during the last day of the VLCD (1.6 MJ). METHODS Free IGF-I was determined by a non-competitive immunoradiometric assay. RESULTS Free IGF-I levels decreased in concert with increased ALS and unchanged blunted GH release after a VLCD in the obese subjects. IGFBPs-1-3 proteolytic activity was found to be unchanged by hypocaloric diet in all groups. CONCLUSIONS We conclude that free IGF-I decreases after a short-term hypocaloric diet in obese subjects with no concomitant change in 24-h GH release. Circulating free IGF-I per se cannot be the main mechanism of the attenuated GH release in dieting obese subjects.
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Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal.
Parkinson, C, Kassem, M, Heickendorff, L, Flyvbjerg, A, Trainer, PJ
The Journal of clinical endocrinology and metabolism. 2003;(12):5650-5
Abstract
Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio, and urinary calcium (24 h collection) were measured (single-batch analysis) at study entry and after IGF-I normalization, along with sera from 32 age- and sex-matched controls. Compared with controls, PIIINP, OC, and CTx were significantly elevated in patients at baseline. Pegvisomant-induced serum IGF-I normalization (699 +/- 76 to 242 +/- 28 micro g/liter, P < 0.001) was associated with a significant decrease in PIIINP, markers of bone formation (type I procollagen amino-terminal propeptide, OC, and bone-related alkaline phosphatase), and resorption (CTx and urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio). 1,25-(OH)(2) vit D decreased and intact PTH increased significantly, but 25-hydroxy vitamin D was unaffected. A significant decline in calculated calcium clearance was observed. The decrease in serum IGF-I correlated positively with the decrease of serum PIIINP (r = 0.7, P < 0.01). After normalization of serum IGF-I, there was no statistical difference between patients and controls for any parameters for which control data were available. In conclusion, GH excess is associated with increased bone and soft tissue turnover. Pegvisomant-induced normalization of serum IGF-I results in a decrease in markers of bone and soft tissue turnover to levels observed in age-matched controls, and these changes are accompanied by an increase in PTH and a decrease in 1,25-(OH)(2) vit D. These data provide further evidence of the effectiveness of pegvisomant in normalizing the altered biological effects of GH hypersecretion.