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Clinical Nutrition (Edinburgh, Scotland) Oct 2023The potential effects of resistance training on sarcopenia in patients with intestinal failure (IF) are not fully elucidated. This study aimed to explore the efficacy of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The potential effects of resistance training on sarcopenia in patients with intestinal failure (IF) are not fully elucidated. This study aimed to explore the efficacy of a resistance training program on appendicular skeletal muscle index (ASMI), physical performance, body composition, biochemical parameters, and health-related quality of life (HRQOL) in patients with IF exhibiting sarcopenia.
METHODS
A single-center randomized controlled trial was conducted in a Chinese tertiary teaching hospital. Patients with IF exhibiting sarcopenia were randomly assigned to the exercise group or control group. Participants in the exercise group incorporated four sets of resistance training involving the limbs and abdominal and lower back muscles, six times weekly for 4 weeks. The control group received no specific intervention. The primary outcome was the between-group difference in ASMI 4 weeks after intervention. Secondary outcomes included handgrip strength, 6-m gait speed, body composition, biochemical parameters, and HRQOL.
RESULTS
A total of 60 participants (control group 30, age 51.2 ± 12.9 years, women 43.3%; exercise group 30, age 53.9 ± 14.5 years, women 56.7%) completed the 4-week intervention trial. For the primary outcome, significant intervention effects were found in ASMI between the exercise group and the control group (mean difference 0.72, 95% CI, 0.56-0.89, P < 0.001). There were notable differences in handgrip strength (mean difference 2.7, 95% CI, 1.7-3.6, P < 0.001), 6-m gait speed (mean difference 0.08, 95% CI, 0.01-0.35, P = 0.034), body composition (including total cell mass, bone mineral content, skeletal muscle mass, lean mass, visceral fat area, total body water, intracellular water, extracellular water, and segmental water-legs), and biochemical parameters (including IGF-1, prealbumin, and hemoglobin) between the two groups (P < 0.05). No significant intervention benefits were observed for other secondary outcomes, including biochemical parameters (including albumin, total bilirubin, etc.) and HRQOL (P > 0.05).
CONCLUSIONS
In this randomized clinical trial, we observed that 4 weeks of resistance training was associated with improved ASMI, physical performance, biochemical parameters (including IGF-1, prealbumin, and hemoglobin), and body composition in IF patients with sarcopenia. Resistance training can be recommended as a simple and effective method to improve sarcopenia in patients with IF.
CLINICAL TRIAL REGISTRATION
www.chictr.org.cn, identifier: ChiCTR2100051727.
Topics: Humans; Female; Adult; Middle Aged; Aged; Sarcopenia; Muscle Strength; Insulin-Like Growth Factor I; Prealbumin; Hand Strength; Resistance Training; Quality of Life; Intestinal Failure; Muscle, Skeletal
PubMed: 37625319
DOI: 10.1016/j.clnu.2023.07.013 -
International Journal of Molecular... Jul 2023Pulmonary fibrosis (PF) associated with systemic sclerosis (SSc) results in significant morbidity and mortality. We previously reported that insulin-like growth...
Pulmonary fibrosis (PF) associated with systemic sclerosis (SSc) results in significant morbidity and mortality. We previously reported that insulin-like growth factor-II (IGF-II) is overexpressed in lung tissues and fibroblasts from SSc patients, and IGF-II fosters fibrosis by upregulating collagen type I, fibronectin, and TGFβ. We now show that IGF-II augments mRNA levels of profibrotic signaling molecules ( ≤ 0.01) and ( ≤ 0.05), collagen type III ( ≤ 0.01), and the collagen posttranslational modification enzymes ( ≤ 0.05), ( ≤ 0.05), ( 0.065), ( ≤ 0.05), ( ≤ 0.05) in primary human lung fibroblasts. IGF-II increases protein levels of TGFβ2 ( ≤ 0.01), as well as COL3A1, P4HA2, P4Hβ, and LOXL4 ( 0.05). In contrast, IGF-II decreases mRNA levels of the collagen degradation enzymes cathepsin (CTS) K, , and and protein levels of CTSK ( ≤ 0.05). The SRY-box transcription factor 9 (SOX9) is overexpressed in SSc lung tissues at the mRNA ( ≤ 0.05) and protein ( ≤ 0.01) levels compared to healthy controls. IGF-II induces SOX9 in lung fibroblasts ( 0.05) via the IGF1R/IR hybrid receptor, and SOX9 regulates TGFβ2 ( ≤ 0.05), TGFβ3 ( ≤ 0.05), COL3A1 ( ≤ 0.01), and P4HA2 ( ≤ 0.001) downstream of IGF-II. Our results identify a novel IGF-II signaling axis and downstream targets that are regulated in a SOX9-dependent and -independent manner. Our findings provide novel insights on the role of IGF-II in promoting pulmonary fibrosis.
Topics: Humans; Cells, Cultured; Collagen; Fibroblasts; Insulin-Like Growth Factor II; Lung; Protein-Lysine 6-Oxidase; Pulmonary Fibrosis; RNA, Messenger; Scleroderma, Systemic; SOX9 Transcription Factor
PubMed: 37510994
DOI: 10.3390/ijms241411234 -
International Journal of Molecular... Jul 2023Insulin resistance as a hallmark of type 2 DM (T2DM) plays a role in dementia by promoting pathological lesions or enhancing the vulnerability of the brain. Numerous... (Review)
Review
Insulin resistance as a hallmark of type 2 DM (T2DM) plays a role in dementia by promoting pathological lesions or enhancing the vulnerability of the brain. Numerous studies related to insulin/insulin-like growth factor 1 (IGF-1) signaling are linked with various types of dementia. Brain insulin resistance in dementia is linked to disturbances in Aβ production and clearance, Tau hyperphosphorylation, microglial activation causing increased neuroinflammation, and the breakdown of tight junctions in the blood-brain barrier (BBB). These mechanisms have been studied primarily in Alzheimer's disease (AD), but research on other forms of dementia like vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) has also explored overlapping mechanisms. Researchers are currently trying to repurpose anti-diabetic drugs to treat dementia, which are dominated by insulin sensitizers and insulin substrates. Although it seems promising and feasible, none of the trials have succeeded in ameliorating cognitive decline in late-onset dementia. We highlight the possibility of repositioning anti-diabetic drugs as a strategy for dementia therapy by reflecting on current and previous clinical trials. We also describe the molecular perspectives of various types of dementia through the insulin/IGF-1 signaling pathway.
Topics: Humans; Insulin-Like Growth Factor I; Insulin Resistance; Drug Repositioning; Alzheimer Disease; Insulins
PubMed: 37511207
DOI: 10.3390/ijms241411450 -
Best Practice & Research. Clinical... Dec 2023The gut microbiome has been implicated in a variety of neuropathologies with recent data suggesting direct effects of the microbiome on host metabolism, hormonal... (Review)
Review
The gut microbiome has been implicated in a variety of neuropathologies with recent data suggesting direct effects of the microbiome on host metabolism, hormonal regulation, and pathophysiology. Studies have shown that gut bacteria impact host growth, partially mediated through the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, no study to date has examined the specific role of GH on the fecal microbiome (FMB) or the changes in this relationship following a traumatic brain injury (TBI). Current literature has demonstrated that TBI can lead to either temporary or sustained abnormal GH secretion (aGHS). More recent literature has suggested that gut dysbiosis may contribute to aGHS leading to long-term sequelae now known as brain injury associated fatigue and cognition (BIAFAC). The aGHS observed in some TBI patients presents with a symptom complex including profound fatigue and cognitive dysfunction that improves significantly with exogenous recombinant human GH treatment. Notably, GH treatment is not curative as fatigue and cognitive decline typically recur upon treatment cessation, indicating the need for additional studies to address the underlying mechanistic cause.
Topics: Humans; Dysbiosis; Brain Injuries, Traumatic; Brain Injuries; Human Growth Hormone; Growth Hormone; Fatigue; Insulin-Like Growth Factor I
PubMed: 38000973
DOI: 10.1016/j.beem.2023.101841 -
Marine Drugs Aug 2023Fish-derived collagen hydrolysate (CH) has shown promise in improving hair and skin health. Therefore, this study sought to comprehensively assess the effects of CH...
Collagen Hydrolysate from the Scales of Mozambique Tilapia () Improve Hair and Skin Health by Alleviating Oxidative Stress and Inflammation and Promoting Hair Growth and Extracellular Matrix Factors.
Fish-derived collagen hydrolysate (CH) has shown promise in improving hair and skin health. Therefore, this study sought to comprehensively assess the effects of CH extracted from Mozambique tilapia () scales on hair and skin using in vitro and in vivo models. Human dermal papilla cells (hDPCs) were used for antioxidant and gene expression analyses, while C57BL/6 mice were orally administered CH for six weeks to assess hair growth patterns. The mice were divided into four groups: negative control (NC; distilled water), positive control (PC; 1 mg/kg finasteride), CH500 (500 mg/kg BW CH), and CH1000 (1000 mg/kg BW CH). CH mitigated catalase activity reduction in hDPCs, increased IGF-1 and VEGF levels, and decreased TGF-β1, TNF-α, and IL-1β expression. In vivo, CH treatment improved hair growth index, length, diameter, weight, and density. Scanning electron microscopy revealed reduced hair damage. Moreover, CH up-regulated IGF-1, VEGF, Elastin, and HAS2 mRNA expression while down-regulating TNF-α and IL-1β. CH enhanced hair shine, growth, and skin health while alleviating inflammation. These findings demonstrate the potential of CH in alleviating oxidative stress, promoting hair growth, and enhancing skin health, both in vitro and in vivo. Fish-derived CH offers a cost-effective and bioavailable option for improving hair and skin health.
Topics: Humans; Animals; Mice; Mice, Inbred C57BL; Tilapia; Insulin-Like Growth Factor I; Vascular Endothelial Growth Factor A; Tumor Necrosis Factor-alpha; Hair; Collagen; Extracellular Matrix; Oxidative Stress; Inflammation
PubMed: 37755088
DOI: 10.3390/md21090475 -
The Journal of Clinical Endocrinology... Oct 2023Pathologies attributed to perturbations of the GH/IGF-I axis are among the most common referrals received by pediatric endocrinologists. (Review)
Review
CONTEXT
Pathologies attributed to perturbations of the GH/IGF-I axis are among the most common referrals received by pediatric endocrinologists.
AIM
In this article, distinctive cased-based presentations are used to provide a practical and pragmatic approach to the management of pediatric growth hormone deficiency (GHD).
CASES
We present 4 case vignettes based on actual patients that illustrate (1) congenital GHD, (2) childhood GHD presenting as failure to thrive, (3) childhood GHD presenting in adolescence as growth deceleration, and (4) childhood-onset GHD manifesting as metabolic complications in adolescence. We review patient presentation and a management approach that aims to highlight diagnostic considerations for treatment based on current clinical guidelines, with mention of new therapeutic and diagnostic modalities being used in the field.
CONCLUSION
Pediatric GHD is diverse in etiology and clinical presentation. Timely management has the potential not only to improve growth but can also ameliorate or even mitigate adverse metabolic outcomes, which can be directly attributed to a GH deficient state.
Topics: Adolescent; Child; Humans; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism; Insulin-Like Growth Factor I
PubMed: 37246615
DOI: 10.1210/clinem/dgad305 -
Best Practice & Research. Clinical... Dec 2023Growth hormone deficiency (GHD) is a common complication of several pituitary and hypothalamic disorders and dependent on the onset of disease. It may have severe... (Review)
Review
Growth hormone deficiency (GHD) is a common complication of several pituitary and hypothalamic disorders and dependent on the onset of disease. It may have severe clinical implications ranging from growth retardation in childhood-onset, to impaired lipid metabolism and increased cardiovascular risk and mortality in adults. GH effectively modulates lipid metabolism at multiple levels and GHD has been associated with an atherogenic lipid profile, that can be reversed by GH replacement therapy. Despite increasing knowledge on the effects of GH on several key enzymes regulating lipid metabolism and recent breakthroughs in the development and wider availability of recombinant GH preparations, several questions remain regarding the replacement therapy in adults with GHD. This review aims to comprehensively summarize the current knowledge on (i) lipid profile abnormalities in individuals with GHD, (ii) proposed mechanisms of action of GH on lipid and lipoprotein metabolism, and (iii) clinical implications of GH replacement therapy in individuals diagnosed with GHD.
Topics: Adult; Humans; Human Growth Hormone; Hypopituitarism; Dwarfism, Pituitary; Dyslipidemias; Lipids; Growth Hormone; Insulin-Like Growth Factor I
PubMed: 37821339
DOI: 10.1016/j.beem.2023.101821 -
JAMA Network Open Feb 2024Youth-onset type 2 diabetes (T2D) has a more aggressive phenotype than adult-onset T2D, including rapid loss of glycemic control and increased complication risk. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Youth-onset type 2 diabetes (T2D) has a more aggressive phenotype than adult-onset T2D, including rapid loss of glycemic control and increased complication risk.
OBJECTIVE
To identify associations of growth hormone mediators with glycemic failure, beta cell function, and insulin sensitivity in youth-onset T2D.
DESIGN, SETTING, AND PARTICIPANTS
This post hoc secondary analysis of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomized clinical trial, which enrolled participants from July 2004 to February 2009, included 398 participants from 15 university-affiliated medical centers with available plasma samples from baseline and 36 months. Participants were youths aged 10 to 17 years with a duration of T2D of less than 2 years who were randomized to metformin, metformin plus lifestyle intervention, or metformin plus rosiglitazone. Participants were followed up for a mean (SD) of 3.9 (1.5) years during the trial, ending in 2011. Statistical analysis was performed from August 2022 to November 2023.
EXPOSURE
Plasma insulin-like growth factor-1 (IGF-1), growth hormone receptor (GHR), and insulin-like growth factor binding protein 1 (IGFBP-1).
MAIN OUTCOMES AND MEASURES
Main outcomes were (1) loss of glycemic control during the TODAY study, defined as hemoglobin A1c (HbA1c) level of 8% or more for 6 months or inability to wean from insulin therapy, and (2) baseline and 36-month measures of glycemia (fasting glucose, HbA1c), insulin sensitivity (1/fasting C-peptide), high-molecular-weight adiponectin, and beta cell function (C-peptide index, C-peptide oral disposition index).
RESULTS
This analysis included 398 participants (mean [SD] age, 13.9 [2.0] years; 248 girls [62%]; 166 Hispanic participants [42%]; 134 non-Hispanic Black participants [34%], and 84 non-Hispanic White participants [21%]). A greater increase in IGF-1 level between baseline and 36 months was associated with lower odds of glycemic failure (odds ratio [OR], 0.995 [95% CI, 0.991-0.997]; P < .001) and higher C-peptide index per 100-ng/mL increase in IGF-1 (β [SE], 0.015 [0.003]; P < .001). A greater increase in log2 GHR level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.75 [95% CI, 1.05-2.99]; P = .04) and lower C-peptide index (β [SE], -0.02 [0.006]; P < .001). A greater increase in log2 IGFBP-1 level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.37 [95% CI, 1.09-1.74]; P = .007) and higher high-molecular-weight adiponectin (β [SE], 431 [156]; P = .007).
CONCLUSIONS AND RELEVANCE
This study suggests that changes in plasma growth hormone mediators are associated with loss of glycemic control in youth-onset T2D, with IGF-1 associated with lower risk and GHR and IGFBP-1 associated with increased risk.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT00081328.
Topics: Adult; Female; Adolescent; Humans; Growth Hormone; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Diabetes Mellitus, Type 2; Glycemic Control; Adiponectin; C-Peptide; Glycated Hemoglobin; Insulin Resistance; Metformin
PubMed: 38421647
DOI: 10.1001/jamanetworkopen.2024.0447 -
European Journal of Pain (London,... Sep 2023The prevalence of chronic non-cancer pain (CNCP) has increased dramatically the past decades, which combined with indiscriminate use of prescribed opioids has become a...
BACKGROUND
The prevalence of chronic non-cancer pain (CNCP) has increased dramatically the past decades, which combined with indiscriminate use of prescribed opioids has become a public health problem. Endocrine dysfunction may be a complication of long-term opioid treatment (L-TOT), but the evidence is limited. This study aimed at investigating the associations between L-TOT and endocrine measures in CNCP patients.
METHODS
Cortisol (spot and after stimulation), thyrotropin (TSH), thyroxin (T4), insulin-like growth factor 1 (IGF-1), prolactin (PRL), 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone (DHEAS), sex hormone-binding globulin (SHBG), total testosterone (TT) and free testosterone (fT) were measured. Group comparisons were done between CNCP patients in L-TOT and controls as well as between patients on high- or low-dose morphine equivalents.
RESULTS
Eighty-two CNCP patients (38 in L-TOT and 44 controls not receiving opioids) were included. Low TT (p = 0.004) and fT concentrations (p < 0.001), high SHBG (p = 0.042), low DEAS (p = 0.017) and low IGF-1 (p = 0.003) in men were found when comparing those in L-TOT to controls and high PRL (p = 0.018), low IGF-1 standard deviation score (SDS) (p = 0.006) along with a lesser, but normal cortisol response to stimulation (p = 0.016; p = 0.012) were found when comparing L-TOT to controls. Finally, a correlation between low IGF-1 levels and high opioid dose was observed (p < 0.001).
CONCLUSIONS
Our study not only supports previous findings but even more interestingly disclosed new associations. We recommend future studies to investigate endocrine effects of opioids in larger, longitudinal studies. In the meanwhile, we recommend monitoring endocrine function in CNCP patients when prescribing L-TOT.
SIGNIFICANCE
This clinical study found associations between L-TOT, androgens, growth hormone and prolactin in patients with CNCP compared to controls. The results support previous studies as well as add new knowledge to the field, including an association between high opioid dose and low growth hormone levels. Compared to existing research this study has strict inclusion/exclusion criteria, a fixed time period for blood sample collection, and adjustments for potential confounders, which has not been done before.
Topics: Male; Humans; Analgesics, Opioid; Insulin-Like Growth Factor I; Hydrocortisone; Prolactin; Chronic Pain; Testosterone; Growth Hormone
PubMed: 37243401
DOI: 10.1002/ejp.2136 -
International Journal of Molecular... Apr 2024The insulin-like growth factor (IGF) system has paracrine and endocrine roles in the central nervous system. There is evidence that IGF signalling pathways have roles in... (Review)
Review
The insulin-like growth factor (IGF) system has paracrine and endocrine roles in the central nervous system. There is evidence that IGF signalling pathways have roles in the pathophysiology of neurodegenerative disease. This review focusses on Alzheimer's disease and Parkinson's disease, the two most common neurodegenerative disorders that are increasing in prevalence globally in relation to the aging population and the increasing prevalence of obesity and type 2 diabetes. Rodent models used in the study of the molecular pathways involved in neurodegeneration are described. However, currently, no animal model fully replicates these diseases. Mice with triple mutations in , and show promise as models for the testing of novel Alzheimer's therapies. While a causal relationship is not proven, the fact that age, obesity and T2D are risk factors in both strengthens the case for the involvement of the IGF system in these disorders. The IGF system is an attractive target for new approaches to management; however, there are gaps in our understanding that first need to be addressed. These include a focus beyond IGF-I on other members of the IGF system, including IGF-II, IGF-binding proteins and the type 2 IGF receptor.
Topics: Humans; Animals; Neurodegenerative Diseases; Alzheimer Disease; Signal Transduction; Insulin-Like Growth Factor I; Somatomedins; Disease Models, Animal; Parkinson Disease; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Peptides
PubMed: 38674097
DOI: 10.3390/ijms25084512