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Sports Medicine (Auckland, N.Z.) Jun 2022Ageing is accompanied by decreases in physical capacity and physiological regulatory mechanisms including altered hormonal regulation compared with age-matched sedentary...
BACKGROUND
Ageing is accompanied by decreases in physical capacity and physiological regulatory mechanisms including altered hormonal regulation compared with age-matched sedentary people. The potential benefits of exercise in restoring such altered hormone production and secretion compared to age-matched physically inactive individuals who are ageing remains unclear.
OBJECTIVES
The aim of this systematic review was to summarise the findings of exercise training in modulating levels of ostensibly anabolic and catabolic hormones in adults aged > 40 years.
METHODS
We searched the following electronic databases (to July 2021) without a period limit: Cochrane Library, PubMed, Science Direct, Scopus, SPORTDiscus and Web of Science. Additionally, a manual search for published studies in Google Scholar was conducted for analysis of the 'grey literature' (information produced outside of traditional commercial or academic publishing and distribution channels). The initial search used the terms 'ageing' OR 'advanced age' OR 'old people' OR 'older' OR elderly' AND 'anabolic hormones' OR 'catabolic hormones' OR 'steroid hormones' OR 'sex hormones' OR 'testosterone' OR 'cortisol' OR 'insulin' OR 'insulin-like growth factor-1' OR 'IGF-1' OR 'sex hormone-binding globulin' OR 'SHBG' OR 'growth hormone' OR 'hGH' OR 'dehydroepiandrosterone' OR 'DHEA' OR 'dehydroepiandrosterone sulfate (DHEA-S)' AND 'exercise training' OR 'endurance training' OR 'resistance training' OR ' strength training' OR 'weight-lifting' OR 'high-intensity interval training' OR 'high-intensity interval exercise' OR 'high-intensity intermittent training' OR 'high-intensity intermittent exercise' OR 'interval aerobic training' OR 'interval aerobic exercise' OR 'intermittent aerobic training' OR 'intermittent aerobic exercise' OR 'high-intensity training' OR 'high-intensity exercise' OR 'sprint interval training' OR 'sprint interval exercise' OR 'combined exercise training' OR 'anaerobic training'. Only eligible full texts in English or French were considered for analysis.
RESULTS
Our search identified 484 records, which led to 33 studies for inclusion in the analysis. Different exercise training programs were used with nine studies using endurance training programs, ten studies examining the effects of high-intensity interval training, and 14 studies investigating the effects of resistance training. Most training programs lasted ≥ 2 weeks. Studies, regardless of the design, duration or intensity of exercise training, reported increases in testosterone, sex hormone-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), human growth hormone (hGH) or dehydroepiandrosterone (DHEA) (effect size: 0.19 < d < 3.37, small to very large) in both older males and females. However, there was no consensus on the effects of exercise on changes in cortisol and insulin in older adults.
CONCLUSION
In conclusion, findings from this systematic review suggest that exercise training increases basal levels of testosterone, IGF-1, SHBG, hGH and DHEA in both male and females over 40 years of age. The increases in blood levels of these hormones were independent of the mode, duration and intensity of the training programs. However, the effects of long-term exercise training on cortisol and insulin levels in elderly people are less clear.
Topics: Adult; Aged; Aging; Dehydroepiandrosterone; Exercise; Female; Hormones; Humans; Hydrocortisone; Insulin-Like Growth Factor I; Insulins; Male; Middle Aged; Sex Hormone-Binding Globulin; Testosterone
PubMed: 34936049
DOI: 10.1007/s40279-021-01612-9 -
Frontiers in Endocrinology 2023To analyze and determine the safety and efficacy of growth hormone (GH) treatment in Down syndrome (DS) pediatric patients and to weigh ethical aspects involved. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To analyze and determine the safety and efficacy of growth hormone (GH) treatment in Down syndrome (DS) pediatric patients and to weigh ethical aspects involved.
DESIGN
Systematic review and mini meta-analysis of the literature.
METHODS
A search was performed in PubMed, Embase, Scopus, and PsycINFO through August 2022. Eligible studies included those who answered at least one of the following two questions: 1) What is the effect of growth hormone treatment in children with Down syndrome? 2) What are the ethical arguments in favor and against growth hormone treatment for children with Down syndrome? Multiple reviewers independently screened each article for eligibility.
RESULTS
In total sixteen reports detailed medical effects of GH treatment in pediatric DS patients and eight studies dealt with ethical aspects of GH treatment. Treatment with GH resulted in significantly higher growth velocity in patients with DS. The ethical complexity is great but does not present insurmountable difficulties to the therapeutic option.
CONCLUSIONS
As GH treatment is safe and effective for short-term height growth, GH therapy should be considered in long-term treatment of DS children.
Topics: Humans; Child; Human Growth Hormone; Down Syndrome; Body Height; Insulin-Like Growth Factor I
PubMed: 37152958
DOI: 10.3389/fendo.2023.1135768 -
Pituitary Feb 2023This systematic literature review investigated whether extended dosing intervals (EDIs) of pharmacological acromegaly treatments reduce patient burden and costs compared...
PURPOSE
This systematic literature review investigated whether extended dosing intervals (EDIs) of pharmacological acromegaly treatments reduce patient burden and costs compared with standard dosing, while maintaining effectiveness.
METHODS
MEDLINE/Embase/the Cochrane Library (2001-June 2021) and key congresses (2018-2021) were searched and identified systematic literature review bibliographies reviewed. Included publications reported on efficacy/effectiveness, safety and tolerability, health-related quality of life (HRQoL), and patient-reported and economic outcomes in longitudinal/cross-sectional studies in adults with acromegaly. Interventions included EDIs of pegvisomant, cabergoline, and somatostatin receptor ligands (SRLs): lanreotide autogel/depot (LAN), octreotide long-acting release (OCT), pasireotide long-acting release (PAS), and oral octreotide; no comparator was required.
RESULTS
In total, 35 publications reported on 27 studies: 3 pegvisomant monotherapy, 11 pegvisomant combination therapy with SRLs, 9 LAN, and 4 OCT; no studies reported on cabergoline, PAS, or oral octreotide at EDIs. Maintenance of normal insulin-like growth factor I (IGF-I) was observed in ≥ 70% of patients with LAN (1 study), OCT (1 study), and pegvisomant monotherapy (1 study). Achievement of normal IGF-I was observed in ≥ 70% of patients with LAN (3 studies) and pegvisomant in combination with SRLs (4 studies). Safety profiles were similar across EDI and standard regimens. Patients preferred and were satisfied with EDIs. HRQoL was maintained and cost savings were provided with EDIs versus standard regimens.
CONCLUSIONS
Clinical efficacy/effectiveness, safety, and HRQoL outcomes in adults with acromegaly were similar and costs lower with EDIs versus standard regimens. Physicians may consider acromegaly treatment at EDIs, especially for patients with good disease control.
Topics: Adult; Humans; Acromegaly; Octreotide; Insulin-Like Growth Factor I; Cabergoline; Cross-Sectional Studies; Quality of Life; Peptides, Cyclic; Human Growth Hormone
PubMed: 36447058
DOI: 10.1007/s11102-022-01285-1 -
Acta Obstetricia Et Gynecologica... Sep 2013Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are key regulators of fetal growth. However, the literature is inconsistent. Our objective was to... (Meta-Analysis)
Meta-Analysis Review
Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are key regulators of fetal growth. However, the literature is inconsistent. Our objective was to systematically and objectively evaluate the available literature and to develop a balanced opinion on the relation between maternal and fetal IGF-axes and birthweight. A systematic review and a meta-analysis were conducted according to the published Moose (Meta-analysis of Observational Studies in Epidemiology) guidelines. A robust recognized systematic methodology was used in the literature search and analysis to avoid bias. Weighted mean difference and 95% confidence intervals of cord/maternal IGFs and IGFBP-1 and -3 were calculated. Eleven observational studies were included. Cord IGF-I (p < 0.0001) and IGFBP-3 (p = 0.003) were significantly higher in large-for-gestational age (LGA) than appropriate-for-gestational age (AGA) babies. Cord IGFBP-1 was significantly higher in small-for-gestational age (SGA) than AGA babies (p < 0.0001). LGA and AGA babies had similar IGF-II levels, whereas SGA and AGA babies had comparable IGF-I levels. IGF-I was significantly higher in mothers of AGA than SGA babies (p < 0.0001). The assay methods and background population marginally affect the overall homogeneity and the direction of the primary analysis. Fetal IGFs and their binding proteins play different roles in fetal growth at either end of the growth spectrum. Fetal IGF-I and IGFBP-3 may be influential in LGA. However, fetal IGFBP-1 has a more prominent role in SGA.
Topics: Female; Fetal Development; Humans; Insulin-Like Growth Factor Binding Proteins; Pregnancy; Somatomedins
PubMed: 23745729
DOI: 10.1111/aogs.12192 -
International Journal of Molecular... May 2023Obesity is a growing public health problem worldwide, and GH and IGF-1 have been studied as potential therapeutic targets for managing this condition. This review... (Review)
Review
Obesity is a growing public health problem worldwide, and GH and IGF-1 have been studied as potential therapeutic targets for managing this condition. This review article aims to provide a comprehensive view of the interplay between GH and IGF-1 and metabolism within the context of obesity. We conducted a systematic review of the literature that was published from 1993 to 2023, using MEDLINE, Embase, and Cochrane databases. We included studies that investigated the effects of GH and IGF-1 on adipose tissue metabolism, energy balance, and weight regulation in humans and animals. Our review highlights the physiological functions of GH and IGF-1 in adipose tissue metabolism, including lipolysis and adipogenesis. We also discuss the potential mechanisms underlying the effects of these hormones on energy balance, such as their influence on insulin sensitivity and appetite regulation. Additionally, we summarize the current evidence regarding the efficacy and safety of GH and IGF-1 as therapeutic targets for managing obesity, including in pharmacological interventions and hormone replacement therapy. Finally, we address the challenges and limitations of targeting GH and IGF-1 in obesity management.
Topics: Animals; Humans; Insulin-Like Growth Factor I; Growth Hormone; Obesity; Adipose Tissue; Insulin; Human Growth Hormone
PubMed: 37298507
DOI: 10.3390/ijms24119556 -
Reviews in Endocrine & Metabolic... Oct 2022Spinal cord injury (SCI) can lead to dramatic physiological changes which can be a factor in developing secondary health conditions and might be reflected in biomarker... (Meta-Analysis)
Meta-Analysis Review
Spinal cord injury (SCI) can lead to dramatic physiological changes which can be a factor in developing secondary health conditions and might be reflected in biomarker changes in this elevated risk group. We focused specifically on the endocrine and inflammation profile differences between SCI and able-bodied individuals (ABI). Our aim was to determine the differences in inflammatory markers and endocrine profiles between SCI and ABI. We systematically searched 4 electronic databases for relevant studies. Human observational (cross-sectional, cohort, case-control) studies that compared biomarkers of interest between SCI and ABI population were included. Weighted mean difference between SCI and ABI was calculated using random-effects models. Heterogeneity was computed using I statistic and chi-squared test. Study quality was evaluated through the Newcastle-Ottawa Scale. The search strategy yielded a total of 2,603 studies from which 256 articles were selected for full-text assessment. Sixty-two studies were included in the meta-analysis. SCI individuals had higher levels of pro-inflammatory C-reactive protein and IL-6 than ABI. Creatinine and 25-hydroxyvitamin D levels were lower in SCI than ABI. Total testosterone levels and IGF-1 were also found to be lower, while cortisol and leptin levels were higher in SCI when compared to ABI. Accordingly, meta-regression, subgroup analysis, and leave-one-out analysis were performed, however, they were only able to partially explain the high levels of heterogeneity. Individuals with SCI show higher levels of inflammatory markers and present significant endocrinological changes when compared to ABI. Moreover, higher incidence of obesity, diabetes, osteoporosis, and hypogonadism in SCI individuals, together with decreased creatinine levels reflect some of the readily measurable aspects of the phenotype changes in the SCI group. These findings need to be considered in anticipating medically related complications and personalizing SCI medical care.
Topics: Biomarkers; C-Reactive Protein; Creatinine; Cross-Sectional Studies; Humans; Hydrocortisone; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Spinal Cord Injuries; Testosterone
PubMed: 35978214
DOI: 10.1007/s11154-022-09742-9 -
Nutrients Oct 2022A ketogenic diet characterized by high fat and low carbohydrate can drive the body to produce a large number of ketone bodies, altering human metabolism. Unlike normal... (Meta-Analysis)
Meta-Analysis
A ketogenic diet characterized by high fat and low carbohydrate can drive the body to produce a large number of ketone bodies, altering human metabolism. Unlike normal cells, tumor cells have difficulty in consuming ketone bodies. Therefore, the application of ketogenic diets in cancer therapy is gaining attention. However, the effect of ketogenic diets on body parameters of cancer patients is not well established. This meta-analysis aimed to summarize the effects of ketogenic diets on cancer patients in earlier controlled trials. PubMed, Embase, and Cochrane Library were searched for clinical trials that enrolled cancer patients who received ketogenic diets intervention. Ten controlled trials were included in this meta-analysis. Data were extracted and checked by three authors independently. Pooled effect sizes revealed a significant effect of ketogenic diets on body weight (SMD −1.83, 95% CI −2.30 to −1.35; p < 0.00001) and fat mass (SMD −1.52, 95% CI −1.92 to −1.07; p < 0.00001). No significant effect on blood glucose, insulin, or lipid profile except triglycerides was found in the analysis. It had no effect on liver and kidney function except that GGT were decreased a little. There were no significant changes in IGF-1 and TNF-α related to tumor growth. Mental health improvement of cancer patients was supported by several trials. Taken together, findings in this study confirmed that the ketogenic diet was a safe approach for cancer patients reducing body weight and fat mass. In addition, cancer treatment-related indicators changed insignificantly. Ketogenic diets may be beneficial to the quality of life of cancer patients. However, intervention duration in most studies is shorter than 6 months, and the effect of a long-term ketogenic diet is still required further validation. More trials with a larger sample size are necessary to give a more conclusive result; PROSPERO registration number: CRD42021277559.
Topics: Blood Glucose; Body Composition; Body Weight; Diet, Ketogenic; Humans; Insulin-Like Growth Factor I; Insulins; Ketone Bodies; Neoplasms; Quality of Life; Triglycerides; Tumor Necrosis Factor-alpha
PubMed: 36235844
DOI: 10.3390/nu14194192 -
Cells Feb 2023Diabetic and obese patients have a high prevalence of non-alcoholic fatty liver disease (NAFLD). This condition groups a spectrum of conditions varying from simple... (Review)
Review
Diabetic and obese patients have a high prevalence of non-alcoholic fatty liver disease (NAFLD). This condition groups a spectrum of conditions varying from simple steatosis to non-alcoholic steatohepatitis (NASH), with or without fibrosis. Multiple factors are involved in the development of NAFLD. However, details about its pathogenesis and factors that promote the progression to NASH are still missing. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) regulate metabolic, immune, and hepatic stellate cell functions. Increasing evidence suggests they may have roles in the progression from NAFLD to NASH. Following the PRISMA reporting guidelines, we conducted a systematic review to evaluate all clinical and experimental studies published in the literature correlating GH and IGF-1 to inflammation and fibrosis in NAFLD and NASH. Our results showed that GH and IGF-1 have a fundamental role in the pathogenesis of NASH, acting in slightly different ways to produce a synergic effect. Indeed, GH may mediate its protective effect in the pathogenesis of NASH by regulating lipogenesis pathways, while IGF-1 has the same effect by regulating cholesterol transport. Therefore, they could be used as therapeutic strategies in preventing NAFLD progression to NASH.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Growth Hormone; Insulin-Like Growth Factor I; Insulin; Liver Cirrhosis; Human Growth Hormone; Insulin, Regular, Human; Hepatitis
PubMed: 36831184
DOI: 10.3390/cells12040517 -
Journal of Cachexia, Sarcopenia and... Jun 2024Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for...
BACKGROUND
Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy.
METHODS
We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-C]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level.
RESULTS
The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-C]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8).
CONCLUSIONS
Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.
Topics: Glucose; Muscle, Skeletal; Animals; Mice; Humans; Hypertrophy; Muscle Fibers, Skeletal; Insulin-Like Growth Factor I; Metabolomics
PubMed: 38742477
DOI: 10.1002/jcsm.13468 -
Frontiers in Endocrinology 2023Cardiovascular (CV) disorders are steadily increasing, making them the world's most prevalent health issue. New research highlights the importance of insulin-like growth...
INTRODUCTION
Cardiovascular (CV) disorders are steadily increasing, making them the world's most prevalent health issue. New research highlights the importance of insulin-like growth factor 1 (IGF-1) for maintaining CV health.
METHODS
We searched PubMed and MEDLINE for English and non-English articles with English abstracts published between 1957 (when the first report on IGF-1 identification was published) and 2022. The top search terms were: IGF-1, cardiovascular disease, IGF-1 receptors, IGF-1 and microRNAs, therapeutic interventions with IGF-1, IGF-1 and diabetes, IGF-1 and cardiovascular disease. The search retrieved original peer-reviewed articles, which were further analyzed, focusing on the role of IGF-1 in pathophysiological conditions. We specifically focused on including the most recent findings published in the past five years.
RESULTS
IGF-1, an anabolic growth factor, regulates cell division, proliferation, and survival. In addition to its well-known growth-promoting and metabolic effects, there is mounting evidence that IGF-1 plays a specialized role in the complex activities that underpin CV function. IGF-1 promotes cardiac development and improves cardiac output, stroke volume, contractility, and ejection fraction. Furthermore, IGF-1 mediates many growth hormones (GH) actions. IGF-1 stimulates contractility and tissue remodeling in humans to improve heart function after myocardial infarction. IGF-1 also improves the lipid profile, lowers insulin levels, increases insulin sensitivity, and promotes glucose metabolism. These findings point to the intriguing medicinal potential of IGF-1. Human studies associate low serum levels of free or total IGF-1 with an increased risk of CV and cerebrovascular illness. Extensive human trials are being conducted to investigate the therapeutic efficacy and outcomes of IGF-1-related therapy.
DISCUSSION
We anticipate the development of novel IGF-1-related therapy with minimal side effects. This review discusses recent findings on the role of IGF-1 in the cardiovascular (CVD) system, including both normal and pathological conditions. We also discuss progress in therapeutic interventions aimed at targeting the IGF axis and provide insights into the epigenetic regulation of IGF-1 mediated by microRNAs.
Topics: Humans; Insulin-Like Growth Factor I; Epigenesis, Genetic; Heart; Myocardial Infarction; MicroRNAs; Cardiac Output
PubMed: 36843588
DOI: 10.3389/fendo.2023.1142644