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Insulin/IGF-1 Signaling Is Downregulated in Barrett's Esophagus Patients Undergoing a Moderate Calorie and Protein Restriction Program: A Randomized 2-Year Trial.
Arcidiacono, D, Zaramella, A, Fabris, F, Sánchez-Rodríguez, R, Nucci, D, Fassan, M, Nardi, M, Benna, C, Cristofori, C, Morbin, T, et al
Nutrients. 2021;(10)
Abstract
Obesity and associated insulin resistance (Ins-R) have been identified as important risk factors for esophageal adenocarcinoma development. Elevated calories and protein consumption are also associated with Ins-R and glucose intolerance. We investigated the effect of a 24-month moderate calorie and protein restriction program on overweight or obese patients affected by Barrett's esophagus (BE), as no similar dietary approach has been attempted to date in this disease context. Anthropometric parameters, levels of serum analytes related to obesity and Ins-R, and the esophageal insulin/IGF-1 signaling pathway were analyzed. This study is registered with ClinicalTrials.gov, number NCT03813381. Insulin, C-peptide, IGF-1, IGF-binding protein 3 (IGFBP3), adipokines, and esophageal expression of the main proteins involved in insulin/IGF-1 signal transduction were quantified using Luminex-XMAP® technology in 46 patients who followed the restriction program (IA) and in 54 controls (CA). Body mass index and waist circumference significantly decreased in 76.1% of IA and 35.2% of CA. IGF-1 levels were reduced in 71.7% of IA and 51.8% of CA. The simultaneous reduction of glycaemia, IGF-1, the IGF-1/IGFBP3 ratio, and the improvement in weight loss-dependent insulin sensitivity, were associated with the downregulation of the insulin/IGF-1 signal on BE tissue. The proposed intervention program was an effective approach to counteract obesity-associated cancer risk factors. The improvement in metabolic condition resulted in a downregulation of the ERK-mediated mitogenic signal in 43.5% of patients, probably affecting the molecular mechanism driving adenocarcinoma development in BE lesions.
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Quercetin Modulates IGF-I and IGF-II Levels After Eccentric Exercise-Induced Muscle-Damage: A Placebo-Controlled Study.
Sgrò, P, Ceci, R, Lista, M, Patrizio, F, Sabatini, S, Felici, F, Sacchetti, M, Bazzucchi, I, Duranti, G, Di Luigi, L
Frontiers in endocrinology. 2021;:745959
Abstract
BACKGROUND Prolonged or unaccustomed eccentric exercise may cause muscle damage and depending from its extent, this event negatively affects physical performance. OBJECTIVES The aim of the present investigation was to evaluate, in humans, the effect of the flavonoid quercetin on circulating levels of the anabolic insulin-like growth factor 1 (IGF-I) and insulin-like growth factor 2 (IGF-II), produced during the recovery period after an eccentric-induced muscle damage (EIMD). METHODS A randomized, double-blind, crossover study has been performed; twelve young men ingested quercetin (1 g/day) or placebo for 14 days and then underwent an eccentric-induced muscle damaging protocol. Blood samples were collected, and cell damage markers [creatine kinase (CK), lactate dehydrogenase (LDH) and myoglobin (Mb)], the inflammatory responsive interleukin 6 (IL-6), IGF-I and IGF-II levels were evaluated before the exercise and at different recovery times from 24 hours to 7 days after EIMD. RESULTS We found that, in placebo treatment the increase in IGF-I (72 h) preceded IGF-II increase (7 d). After Q supplementation there was a more marked increase in IGF-I levels and notably, the IGF-II peak was found earlier, compared to placebo, at the same time of IGF-I (72 h). Quercetin significantly reduced plasma markers of cell damage [CK (p<0.005), LDH (p<0.001) and Mb (p<0.05)] and the interleukin 6 level [IL-6 (p<0.05)] during recovery period following EIMD compared to placebo. CONCLUSIONS Our data are encouraging about the use of quercetin as dietary supplementation strategy to adopt in order to mitigate and promote a faster recovery after eccentric exercise as suggested by the increase in plasma levels of the anabolic factors IGF-I and IGF-II.
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Effects of Behavioral Weight Loss and Metformin on IGFs in Cancer Survivors: A Randomized Trial.
Yeh, HC, Maruthur, NM, Wang, NY, Jerome, GJ, Dalcin, AT, Tseng, E, White, K, Miller, ER, Juraschek, SP, Mueller, NT, et al
The Journal of clinical endocrinology and metabolism. 2021;(10):e4179-e4191
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CONTEXT Higher levels of insulin-like growth factor-1 (IGF-1) are associated with increased risk of cancers and higher mortality. Therapies that reduce IGF-1 have considerable appeal as means to prevent recurrence. DESIGN Randomized, 3-parallel-arm controlled clinical trial. INTERVENTIONS AND OUTCOMES Cancer survivors with overweight or obesity were randomized to (1) self-directed weight loss (comparison), (2) coach-directed weight loss, or (3) metformin treatment. Main outcomes were changes in IGF-1 and IGF-1:IGFBP3 molar ratio at 6 months. The trial duration was 12 months. RESULTS Of the 121 randomized participants, 79% were women, 46% were African Americans, and the mean age was 60 years. At baseline, the average body mass index was 35 kg/m2; mean IGF-1 was 72.9 (SD, 21.7) ng/mL; and mean IGF1:IGFBP3 molar ratio was 0.17 (SD, 0.05). At 6 months, weight changes were -1.0% (P = 0.07), -4.2% (P < 0.0001), and -2.8% (P < 0.0001) in self-directed, coach-directed, and metformin groups, respectively. Compared with the self-directed group, participants in metformin had significant decreases on IGF-1 (mean difference in change: -5.50 ng/mL, P = 0.02) and IGF1:IGFBP3 molar ratio (mean difference in change: -0.0119, P = 0.011) at 3 months. The significant decrease of IGF-1 remained in participants with obesity at 6 months (mean difference in change: -7.2 ng/mL; 95% CI: -13.3 to -1.1), but not in participants with overweight (P for interaction = 0.045). There were no significant differences in changes between the coach-directed and self-directed groups. There were no differences in outcomes at 12 months. CONCLUSIONS In cancer survivors with obesity, metformin may have a short-term effect on IGF-1 reduction that wanes over time.
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Effect of Transdermal Estradiol and Insulin-like Growth Factor-1 on Bone Endpoints of Young Women With Anorexia Nervosa.
Singhal, V, Bose, A, Slattery, M, Haines, MS, Goldstein, MA, Gupta, N, Brigham, KS, Ebrahimi, S, Javaras, KN, Bouxsein, ML, et al
The Journal of clinical endocrinology and metabolism. 2021;(7):2021-2035
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CONTEXT Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency. OBJECTIVE To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes. DESIGN Double-blind, randomized, placebo-controlled 12-month longitudinal study. PARTICIPANTS Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study. INTERVENTION Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range. MAIN OUTCOME MEASURES Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates. RESULTS Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups. CONCLUSIONS We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.
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Influence of Resistance Training Exercise Order on Muscle Strength, Hypertrophy, and Anabolic Hormones in Older Women: A Randomized Controlled Trial.
Tomeleri, CM, Ribeiro, AS, Nunes, JP, Schoenfeld, BJ, Souza, MF, Schiavoni, D, Junior, PS, Cavaglieri, CR, Cunha, PM, Venturini, D, et al
Journal of strength and conditioning research. 2020;(11):3103-3109
Abstract
Tomeleri, CM, Ribeiro, AS, Nunes, JP, Schoenfeld, BJ, Souza, MF, Schiavoni, D, Junior, PS, Cavaglieri, CR, Cunha, PM, Venturini, D, Barbosa, DS, and Cyrino, ES. Influence of resistance training exercise order on muscle strength, hypertrophy, and anabolic hormones in older women: a randomized controlled trial. J Strength Cond Res 34(11): 3103-3109, 2020-The purpose of this study was to analyze the effects of resistance training (RT) exercise order on muscle strength, hypertrophy, and anabolic hormones in older women. Forty-four older women were randomly assigned to 1 of 3 groups: a nonexercise control group (CON, n = 15) and two RT groups that performed a 12-week RT program in a multijoint to single-joint order (MJ-SJ, n = 14), or in a single-joint to multijoint order (SJ-MJ, n = 15). The RT protocol (3×/week) encompassed 8 exercises, with 3 sets of 10-15 repetitions performed per exercise. One repetition maximum tests were used to evaluate muscle strength; dual-energy X-ray absorptiometry was used to estimate lean soft tissue. Both training groups showed significant and similar increases in muscle strength (MJ-SJ = 16.4%; SJ-MJ = 12.7%) and mass (MJ-SJ = 7.5%; SJ-MJ = 6.1%), whereas there were no significant changes in testosterone and insulin-like growth factor 1. The results suggest that both approaches are similarly effective in eliciting morphofunctional improvements in older women.
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Effects of vitamin D3 supplementation for 12 weeks on serum levels of anabolic hormones, anaerobic power, and aerobic performance in active male subjects: A randomized, double-blind, placebo-controlled trial.
Ramezani Ahmadi, A, Mohammadshahi, M, Alizadeh, A, Ahmadi Angali, K, Jahanshahi, A
European journal of sport science. 2020;(10):1355-1367
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Maintenance of the serum 25-hydroxyvitamin D (25-OH-D) concentration at recommended levels is essential due to its role in the regulation of anabolic hormones and athletic performance. However, the results of the clinical experiments in athletes are controversial. The present study aimed to investigate the effect of vitamin D3 supplement on serum levels of anabolic hormones, cortisol, anaerobic and aerobic performance in active males. In this double-blind, randomized controlled trial, 46 active males randomly assigned to vitamin D3 supplement (VDS; 2000 IU/day) or placebo for 12 weeks. The Wingate test, VO2max, and serum levels of 25-OH-D, Parathyroid hormone (PTH), total testosterone, growth hormone (GH), Insulin-like growth factor-1 (IGF-1), and cortisol were assessed. Subjects in the VDS group had a higher serum level of 25-OH-D (p = 0.004), VO2max (p = 0.016), and average power (p = 0.044) compared to the placebo at the end of the study. Also, lower levels of PTH (p = 0.004) and fatigue index (p < 0.001) were observed in VDS group at the end of the study. The serum cortisol levels were reduced significantly only in subjects with vitamin D deficiency in VDS group (p = 0.042). There was a significant reduction in serum testosterone levels in VDS group (p = 0.013). No change was indicated in serum levels of GH and IGF-1 in VDS group compared to the placebo (p > 0.05). The present study showed an improvement in aerobic capacity, anaerobic performance, and vitamin D status following vitamin D3 supplementation. However, more studies are required for the effect of vitamin D3 on serum concentration of anabolic hormones.
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Caloric restriction induces anabolic resistance to resistance exercise.
Murphy, C, Koehler, K
European journal of applied physiology. 2020;(5):1155-1164
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PURPOSE Weight loss can result in the loss of muscle mass and bone mineral density. Resistance exercise is commonly prescribed to attenuate these effects. However, the anabolic endocrine response to resistance exercise during caloric restriction has not been characterized. METHODS Participants underwent 3-day conditions of caloric restriction (15 kcal kg FFM-1) with post-exercise carbohydrate (CRC) and with post-exercise protein (CRP), and an energy balance control (40 kcal kg FFM-1) with post-exercise carbohydrate (CON). Serial blood draws were taken following five sets of five repetitions of the barbell back squat exercise on day 3 of each condition. RESULTS In CRC and CRP, respectively, growth hormone peaked at 2.6 ± 0.4 and 2.5 ± 0.9 times the peak concentrations observed during CON. Despite this, insulin-like growth factor-1 concentrations declined 18.3 ± 3.4% in CRC and 27.2 ± 3.8% in CRP, which was greater than the 7.6 ± 3.6% decline in CON, over the subsequent 24 h. Sclerostin increased over the first 2 days of each intervention by 19.2 ± 5.6% in CRC, 21.8 ± 6.2% in CRP and 13.4 ± 5.9% in CON, but following the resistance exercise bout, these increases were attenuated and no longer significant. CONCLUSION During caloric restriction, there is considerable endocrine anabolic resistance to a single bout of resistance exercise which persists in the presence of post-exercise whey protein supplementation. Alternative strategies to restore the sensitivity of insulin-like growth factor-1 to growth hormone need to be explored.
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Effect of anthelmintic treatment on serum free IGF-1 and IGFBP-3: a cluster-randomized-controlled trial in Indonesia.
Kurniawan, F, Tahapary, DL, de Ruiter, K, Yunir, E, Biermasz, NR, Smit, JWA, Supali, T, Sartono, E, Yazdanbakhsh, M, Soewondo, P
Scientific reports. 2020;(1):19023
Abstract
In children, soil-transmitted helminth infections have been linked to poor nutritional status and growth retardation in association with lower levels of IGF-1. In adults, IGF-1 has an anabolic and metabolic function and is related to nutritional status. Here, we assessed the impact of helminth infection on free IGF-1 and its major binding protein, IGFBP-3, in adults. The levels of IGF-1 and IGFBP3 were measured in 1669 subjects aged ≥ 16 years, before and after receiving four rounds of albendazole 400 mg/day or matching placebo for three consecutive days. Helminth infection status was assessed by microscopy (Kato-Katz) and PCR. Serum free IGF-1 level was significantly lower in helminth-infected subjects [mean difference and 95% CI - 0.068 (- 0.103; - 0.033), P < 0.001 after adjustment for age, sex, body mass index, and fasting insulin level]. There was no difference in IGFBP-3 level between helminth infected versus non-infected subjects. In the whole study population, albendazole treatment significantly increased serum free IGF-1 level [estimate and 95% CI 0.031 (0.004; - 0.057), P = 0.024] whereas no effect was found on the IGFBP-3 level. Our study showed that helminth infection in adults is associated with lower free IGF-1 levels but not with IGFBP-3 and albendazole treatment significantly increases free IGF-1 levels in the study population.Clinical Trial Registration: https://www.isrctn.com/ISRCTN75636394 .
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Pregnancy supplementation of Gambian mothers with calcium carbonate alters mid-childhood IGF1 in a sex-specific manner.
Prentice, A, Ward, KA, Nigdikar, S, Hawkesworth, S, Moore, SE
Bone. 2019;:314-320
Abstract
CONTEXT Sex-specific effects of pregnancy calcium carbonate supplementation have been reported in 8-12 year old Gambian children, indicating faster growth in boys but slower growth in girls born to calcium-supplemented mothers. OBJECTIVE To determine whether the pregnancy supplement resulted in sex-specific effects on offspring IGF1 and other growth-related indices in mid-childhood. DESIGN Analysis of archived data obtained in mid-childhood from the children of rural Gambian mothers who had been randomised to 1500 mgCa/d (Ca) or placebo (P) from 20 weeks pregnancy to delivery (ISRCTN96502494). PARTICIPANTS AND METHODS Of the 526 children born and followed in infancy, 290 had early-morning, fasting plasma assayed for IGF1, IGFBP3, leptin, insulin and calcium-related indices and had anthropometry performed at age 7.5 (SD1.2) years (N/group: Males(M)-Ca = 64, Females(F)-Ca = 77; M-P = 76, F-P = 73). Sex-specific effects of maternal supplementation were considered using regression with sexes separated and together to test for sex ∗ supplement interactions. RESULTS Boys had lower IGF1, IGFBP3, leptin and insulin than girls (P ≤ 0.004). IGF1 was higher in M-Ca than M-P (+14.2 (SE7.7)%, P = 0.05) but lower in F-Ca than F-P (-17.8 (SE7.4)%, P = 0.01); sex ∗ supplement interaction P = 0.001. IGF1 concentrations (ng/ml, geometric mean [-1SE,+1SE]) were M-Ca = 78.1[4.3,4.5], M-P = 67.8[3.4,3.6]; F-Ca = 99.5[4.8,5.1], F-P = 118.9[6.4,6.8]. Similar sex ∗ supplement interactions were seen for IGFBP3 and IGF1-adjusted-for-IGFBP3 but group differences were smaller. There were no significant supplement effects on the other biochemical indices. CONCLUSIONS Calcium carbonate supplementation of pregnant Gambian mothers resulted in higher IGF1 in boys and lower IGF1 in girls during mid-childhood, consistent with the reported maternal supplement effects on growth of the offspring in later childhood.
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Modifications of Own Mothers' Milk Fortification Protocol Affect Early Plasma IGF-I and Ghrelin Levels in Preterm Infants. A Randomized Clinical Trial.
Agakidou, E, Karagiozoglou-Lampoudi, T, Parlapani, E, Fletouris, DJ, Sarafidis, K, Tzimouli, V, Diamanti, E, Agakidis, C
Nutrients. 2019;(12)
Abstract
The aim was to investigate the effect of two own mother's milk (OMM) fortification protocols on (a) IGF-I and ghrelin plasma levels at 35 post-conceptional weeks (PCW, T2) and whether this effect is maintained after elimination of the differences in OMM fortification, and (b) growth until 12 months corrected age. Forty-eight OMM-fed preterm infants (GA 24-32 weeks) were randomly allocated to the fixed-fortification (FF) group (n = 23) and the protein-targeting fortification (PTF) group (n = 25) targeting the recommended daily protein intake (PI). Plasma IGF-I and ghrelin were assessed at 35 (T2) and 40 (T3) PCW while growth was longitudinally assessed until 12 months corrected age. PTF group had lower IGF-I and higher ghrelin than FF group at T2, while receiving lower daily protein and energy amounts. PI correlated positively to T2-IGF-I and inversely to T3-ghrelin while energy intake (EI) correlated inversely to T2- and T3-ghrelin. Group and PI were independent predictors of adjusted T2-IGF-I, while group and EI were predictors of adjusted and T2-ghrelin. Growth parameter z-scores were comparable between groups up to 12 months corrected age. Modifications of OMM fortification have a transient effect on early plasma IGF-I and ghrelin levels in preterm infants in a way consistent with the previously recognized protein-energy/endocrine balance, indicating a potential programming effect.