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Background: Obstructive sleep apnea hypopnea syndrome OSAHS is a common disease that has serious cardiovascular and metabolic effects. Two researchers analyzed the studies for quality according to the Newcastle-Ottawa Scale. The acquired data were analyzed using Stata The effect size was estimated and calculated using standard mean differences and correlation coefficients. Moreover, a combined analysis was conducted using either a random- or fixed-effects model. Results: Ultimately, 34 studies met our inclusion criteria. Subgroup analyses were performed according to OSAHS severity, ethnicity, age, body mass index, specimen testing method, and study design. The characteristic features of obstructive sleep apnea-hypopnea syndrome OSAHS include periodic, intermittent reductions in airflow hypopnea or no airflow apnea owing to complete or partial collapse of the upper respiratory tract during sleep 1. The respiratory physiological reactions to OSAHS include major alterations in intrathoracic pressure, intermittent hypoxemia, sleep fragmentation, and nocturnal awakening 2. Sleep patterns can change as a result of repeated awakenings, with reduced slow-wave sleep SWS , rapid eye movement sleep, and enhanced light sleep 3. OSAHS is more prevalent in men than women, and its incidence increases sharply with increasing body weight and age 4 , 5. OSAHS causes excessive daytime sleepiness, poor quality of life, poor job performance, and a higher risk of traffic accidents at a societal level 6. More importantly, OSAHS results in increased morbidity and mortality of comorbid conditions, such as coronary heart disease and cardiac failure, creating serious health risks for affected individuals 7. Hypertension, hyperlipidemia, insulin resistance, and metabolic syndrome are all risk factors for early cardiovascular disease, and the incidence of these diseases in patients with OSAHS is much higher than that in subjects matched by sex and body mass index BMI 8 , 9. In addition, OSAHS reportedly affects some hormonal systems, including catecholamines and the hypothalamic-pituitary axis. Sleep fragmentation related to awakening reportedly activates the sympathetic nervous system, which stimulates the release of nocturnal catecholamines 10 , Growth hormone GH secretion is closely associated with different sleep stages. GH is usually released in the form of pulses; two-thirds of GH secretion occurs during the first few hours of sleep, and the onset of pulses is linked to the stages of SWS GH directly effects numerous tissues; however, many of its functions are achieved by increasing the levels of the second messenger, insulin-like growth factor-1 IGF-1 The synergistic effect of GH and IGF-1 is important for the development of bones in children and helps maintain normal metabolism in adults Furthermore, most studies included comparatively small sample sizes. To the best of our knowledge, the present analysis includes the most accessible literature. Case-control, cohort, or cross-sectional study. The exclusion criteria were as follows:. Editorials, reviews, letters, other types of literature reviews, or case report. Unable to extract enough information from the original article or contact the corresponding author for more information. Studies that were not conducted in humans. Studies including patients with OSAHS with a history of chronic airway disease, cerebrovascular disease, chronic cardiac failure, endocrine disease, and malignancies. Studies lacking a control group. Overlapping studies and overlapping data from studies by the same authors. Based on the aforementioned data retrieval methods, two authors separately searched the databases, and the titles and abstracts of relevant articles were reviewed. We made a preliminary list of all eligible full-text papers. Subsequently, we re-evaluated the publications that met the inclusion criteria by carefully reading and reviewing the full text. Upon disagreement between the two authors regarding article eligibility, a third expert researcher was consulted to resolve the dispute by consensus. We created some special tables to extract the following information from each eligible study as follows:. Disease severity. Literature quality scores. The Newcastle-Ottawa Scale 24 was used to assess the quality of the selected papers as follows: study population four items, total score 4 , exposure or outcome three items, total score 3 , and comparability one item, total score 2. Total scores of 7—9, 4—6, and 0—3 were considered high-, medium-, and low-quality studies, respectively. R version 3. Therefore, the Fisher transformation was used to compare each COR, and an investigation was subsequently conducted with the transformed values as the input before converting them back to CORs. In the case of zero heterogeneity among studies, we employed fixed- and random-effects models if heterogeneity was not noted among studies. Descriptive analysis, subgroup analysis, and meta-regression were used to explore the source of heterogeneity. For subgroup analyses, the overall population was categorized according to disease severity, ethnicity, method of specimen testing, study design, age, and BMI. One study at a time was removed for the sensitivity analysis, which was conducted to explore how each study impacted the combined effect size. A total of related papers were collected from the databases. Duplicated studies were excluded by filtering the abstracts and titles; articles were omitted from the study, leaving 48 articles. We downloaded these 48 articles and thoroughly reviewed the complete text; 14 papers were discarded following review of the inclusion and exclusion criteria. Articles were excluded for the following reasons: four publications were reviews, two were letters to the editor, four did not include a control group of healthy people, two lacked relevant data, and two were animal experiments. We selected 2 cohort studies, 10 cross-sectional studies, and 22 case-control studies were selected, as shown in Table 1. Figure 1 shows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram for selecting and screening articles from the literature. Tables 1 — 3 present the fundamental data of the included studies. Figure 1 Flow diagram indicating the literature selection process and results based on the preferred reporting items for the meta-analysis. We used Newcastle-Ottawa Scale scores to help assess the methodological quality of the studies selected for this analysis. We included 30 high-quality and 4 medium-quality publications. The heterogeneity index I 2 was Therefore, we opted for a random-effects model for data combination. Moreover, we performed a series of sensitivity assessments to determine the reliability of the merged data. Major alterations were not detected in the meta-analysis outcomes after omitting the included studies individually, thereby proving their reliability Figure 3. The correlation between serum IGF-1 concentrations in patients with OSAHS and those of patients in the control group was investigated in our meta-analysis, which included 26 eligible observational studies. A subgroup analysis was performed according to the different detection techniques used in the samples because variations in detection techniques for plasma IGF-1 levels may cause errors in the outcome analysis. In four studies, plasma IGF-1 levels were calculated using an enzyme-linked immunosorbent assay. Table 4 summarizes these findings. The Caucasian and Asian populations were the major subgroups. We conducted a matched subgroup analysis because of the differences in study designs of the included studies, which might alter the heterogeneity of the results. We conducted a subgroup meta-analysis according to BMI in 26 studies. We included 26 reports on Caucasian, Asian, and Latin American populations in this study. The serum IGF-1 concentrations of patients with OSAHS among these three groups were all lower than those of patients in the respective control groups in subgroup analyses based on varying demographics and ethnicities see Table 4. All included studies had an I 2 value of Therefore, we explored the possible sources of heterogeneity using meta-regression. This heterogeneity was not caused by the sample detection method, age, or study design. Table 5 Meta-regression analysis of variables predicting serum and plasma levels of IGF Funnel plots were used to investigate the probability of publication bias in studies investigating the association between IGF-1 concentration and OSAHS, which appeared to be symmetrical. Only three publications showed a correlation between IGF-1 concentration and ODI score; therefore, publication bias analysis was not conducted. Figure 5 Funnel plots were employed to assess the publication bias among the included studies examining the relationship of leptin levels with OSAS. Similarly, serum IGF-1 concentrations in children with OSAHS were considerably reduced compared with those in the control group, similar to the results reported by Williams et al. Bar et al. The variance in the results might be due to the various sample sources and small sample sizes. Notably, only one study by Gozal et al. The authors also pointed out that a significant increase in IGF-1 levels can occur among children who recovered their cognitive function, whereas in children without cognitive deficits, a decreased rather than increased IGF-1 concentration can be expected. This finding may be related to the inclusion of some particularity for the population resulting in a difference in their study. Cognitive function may affect plasma IGF-1 levels; however, the relationship between IGF-1 level and neurocognitive outcomes in children requires further investigation. GH levels are higher in young people than those in adults, and GH and IGF-1 are important modulators of energy metabolism in children The results indicated that IGF-1 concentration had a moderate negative correlation with AHI score, a negative correlation with ODI score, and a moderate positive correlation with minimum oxygen saturation. Understanding the mechanism by which IGF-1 levels fluctuate in patients with OSAHS is critical because studies have shown that lower IGF-1 levels increase the risk of cardiovascular events following ischemic stroke and coronary intervention 50 , Tsai et al. OSAHS is associated with high cardiovascular and cerebrovascular disease rates as well as malignancies 53 — Furthermore, this research has crucial clinical consequences, as the outcomes suggest that the metabolic levels of children and adults with OSAHS should be evaluated in addition to sleeping indicators assessed by PSG. IGF-1 is a polypeptide protein that depends on GH effects to regulate insulin resistance Patients with obesity and low IGF-1 concentrations have considerably more visceral obesity than patients with obesity and normal IGF-1 concentrations OSAHS and obesity have a bidirectional relationship. The small sample sizes had a major impact on the outcomes. Further investigations on plasma IGF-1 concentrations and OSAHS are expected to be conducted in the future with larger sample sizes to confirm our findings. Grijalva-Avila et al. Numerous studies have revealed that IGF-1 enhances insulin sensitivity during glucose metabolism Based on the sources, metabolism, and other influencing factors of IGF-1, several plausible biological explanations are summarized as follows. Respiratory disorders and intermittent hypoxia during nighttime sleep are the major causes of glucose metabolism disorders and insulin resistance, and their pathogenic effects are independent of confounding factors, such as obesity and age. Although OSAHS complicated by type 2 diabetes is clinically common, its detailed mechanism has not yet been elucidated. IGF-1 and insulin have a synergistic effect, possibly indicating the level of insulin resistance in the human body. Clemmons et al. Second, repeated sleep apnea in patients with OSAHS can cause hypoxia, hypercapnia, acidosis, and even lower the affinity of insulin to its receptor. Insulin receptor activity tyrosine kinase also decreases simultaneously, leading to structural or functional defects in various enzymes in the glucose metabolic pathway e. Meanwhile, long-term and repeated nocturnal hypoxic stress responses may increase the antagonistic products of insulin in the body, thereby aggravating insulin resistance 66 , Furthermore, even during the intermittent stages of stressful periods, the catecholamine and cortisol levels in patients with OSAHS are higher than those of individuals in the general population, thereby aggravating insulin resistance and lowering IGF-1 levels Sleep deprivation can directly alter the transcription and post-transcriptional translation levels of IGF-1 mRNA in vivo , thereby lowering IGF-1 concentrations below the normal range and exacerbating insulin resistance. GHs may play a major role in the stimulation of local IGF-1 synthesis According to Han et al. Our subsequent findings revealed that IGF-1 concentration was negatively correlated with AHI and ODI scores and positively correlated with minimum oxygen saturation, demonstrating that sleep hypoxia and sleep structure disorder have a significant impact on IGF-1 concentration. The quality of the included studies, overall characteristics, experimental procedures, and other factors contributed to the heterogeneity of our meta-analysis. Moreover, variations in sleep-disordered breathing examinations can cause heterogeneity, although most of the publications included in this study used standard PSG examinations; therefore, none of the subgroup analyses were based on the type of sleep-disordered breathing examinations. Galerneau et al. Third, this is the most thorough meta-analysis of the relevant literature conducted to date, resulting in reliable information. We included cross-sectional, case-control, and cohort studies to investigate variations in IGF-1 concentrations between patients with OSAHS and controls. Our study included a comparatively larger sample size 2, subjects and more recent studies with medium-to high-quality publications. Finally, the serum and plasma IGF-1 concentrations were examined to eliminate sample origin-related confounding factors. Despite the originality of our findings, this study has some limitations. First, this study may have included confounding variables, such as age, smoking history, lifestyle, alcohol consumption, sex, and diabetes. In particular, diabetes may be a major confounding factor for circulating IGF-1 levels. Moreover, OSA is more common in men, the older, and individuals with obesity compared with the general population 4. We were unable to control for the aforementioned confounding factors because the included articles did not provide data on past medical history, specific lifestyle factors, or analysis by sex, and no studies were conducted only in older patients with OSAHS. To a greater or lesser extent, several potential confounding factors might have influenced the final findings. Further inquiries can be directed to the corresponding author. Data curation: JH and MY. Formal analysis: XL. Methodology: XL and MY. Project administration: XL. Resources: JH. Supervision: XL. Validation: JH. Writing-original draft: XL. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Pei C, Gui S. Effect of arterial blood bicarbonate HCO 3 - concentration on the accuracy of STOP-bang questionnaire screening for obstructive sleep apnea. BMC Pulm Med T Regulatory lymphocytes and endothelial function in pediatric obstructive sleep apnea. PloS One 8:e Knappe SW, Sonnesen L. Mandibular positioning techniques to improve sleep quality in patients with obstructive sleep apnea: Current perspectives. Nat Sci Sleep — Increased prevalence of sleep-disordered breathing in adults. 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Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol —5. Association between social support and suicidal ideation in patients with cancer: A systematic review and meta-analysis. Eur J Cancer Care Engl e Association between circulating neuregulin4 levels and diabetes mellitus: A meta-analysis of observational studies. Prevalence of sleep apnea and lung function abnormalities in patients with acromegaly. Lung India — Insulin resistance and daytime sleepiness in patients with sleep apnoea. Thorax — Relationship between sleep parameters, insulin resistance and age-adjusted insulin like growth factor-1 score in non diabetic older patients. Concomitant impairment of growth hormone secretion and peripheral sensitivity in obese patients with obstructive sleep apnea syndrome. J Clin Endocrinol Metab —7. Endocrine — IGF-1 levels are inversely associated with metabolic syndrome in obstructive sleep apnea. J Clin Sleep Med — The effect of CPAP therapy on insulin-like growth factor and cognitive functions in obstructive sleep apnea patients. Clin Respir J — Plasma dehydroepiandrosterone sulphate and insulin-like growth factor I levels in obstructive sleep apnoea syndrome. Clin Endocrinol Oxf — Sleep apnoea-hypopnoea syndrome in the obese and non-obese: Clinical, polysomnographical and clinical characteristics. Pediatr Engl Ed — Metabolic risk factors for vascular disease in obstructive sleep apnea: a matched controlled study. Growth and biochemical markers of growth in children with snoring and obstructive sleep apnea. Pediatrics e Alterations of IGF-1, complement C3 and superoxide dismutase in patients with moderate-to-severe obstructive sleep apnea hypopnea syndrome. Densely granulated adenoma pattern is associated with an increased risk of obstructive sleep apnea in patients with acromegaly. Sleep Breath Expression and significance of serum insulin-like growth factor-1 in patients with obstructIve sleep apnea hypopnea syndrome. Insulin growth factor I levels in adult patients with obstructive sleep apnea syndrome correlated with sleep structural disorders and cognitive dysfunction. Anhui Med J — Association between insulin-like growth factor 1 and its heat pump function in patients with obstructive sleep apnea syndrome. J Clin Pulmon Med — Analysis of the influence factors for serum growth factor in children with obstructIve sleep apnea hypopnea syndrome. Chin J Child Health Care —9. Zhang W, Cai W. Jiangsu Med — IGF-1, the cross road of the nutritional, inflammatory and hormonal pathways to frailty. Nutrients — The effects of adenotonsillectomy on growth in young children. Otolaryngol Head Neck Surg — The effect of adenotonsillectomy on serum insulin-like growth factor-I and growth in children with obstructive sleep apnea syndrome. J Pediatr — Growth hormone improves nerve regeneration, muscle re-innervation, and functional outcomes after chronic denervation injury. Sci Rep Dipeptidyl peptidase-4 inhibitors reduced long-term cardiovascular risk in diabetic patients after percutaneous coronary intervention via insulin-like growth factor-1 axis. Front Aging Neurosci Prognostic significance of circulating insulin growth-like factor 1 and insulin growth-like factor binding protein 3 in renal cell carcinoma patients. Am J Cancer Res — PubMed Abstract Google Scholar. Update on osteosarcoma. Curr Oncol Rep Cancer and OSA: Current evidence from human studies. Chest — Obstructive sleep apnea and cardiovascular disease: A scientific statement from the American heart association. Circulation e56— Reduced environmental stimuli is associated with improved insulin-like growth factor-1 levels and physical growth in very low birth weight premature infants. Exp Ther Med —6. Low circulating levels of insulin-like growth factor binding protein-1 IGFBP-1 are closely associated with the presence of macrovascular disease and hypertension in type 2 diabetes. Impact of BMI on peak growth hormone responses to provocative tests and therapeutic outcome in children with growth hormone deficiency. IGF-1 and its receptor in esophageal cancer: Association with adenocarcinoma and visceral obesity. Am J Gastroenterol — The association between IGF-1 polymorphisms, IGF-1 serum levels, and cognitive functions in healthy adults: The Amsterdam growth and health longitudinal study. Int J Endocrinol Milk intake and IGF-1 rs polymorphism as protective factors to obesity. Int J Food Sci Nutr — The relationship between polymorphism of insulin-like growth factor I gene and susceptibility to type 2 diabetes in uygur population, Xinjiang, China. Genes Genomics — Phenotypic alterations in insulin-deficient mutant mice. Growth factors and adipocytokines in prepubertal children born small for gestational age: relation to insulin resistance. Diabetes Care —9. The combination of insulin-like growth factor I and insulin-like growth factor-binding protein-3 reduces insulin requirements in insulin-dependent type 1 diabetes: Evidence for in vivo biological activity. J Clin Endocrinol Metab — Metabolomic and lipidomic profile in men with obstructive sleep apnoea: Implications for diagnosis and biomarkers of cardiovascular risk. Influence of multiple apolipoprotein a-I and b genetic variations on insulin resistance and metabolic syndrome in obstructive sleep apnea. Nutr Metab Lond Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes. J Appl Physiol — Cui T, Schally AV. Oncotarget — The response of growth hormone and prolactin of rats to hypoxia. Neurosci Lett — Am J Physiol L— The somatotropic axis in the sleep apnea-obesity comorbid duo. Front Endocrinol Lausanne The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office. Translational and Clinical Endocrinology. The exclusion criteria were as follows: 1. Literature quality scores 5. Table 1 Characteristics of included studies.

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