Biological Variation Data in Triathletes for Metabolism and Growth-Related Biomarkers Included in the Athlete Biological Passport.

BACKGROUND: When using biological variation (BV) data, BV estimates need to be robust and representative. High-endurance athletes represent a population under special physiological conditions, which could influence BV estimates. Our study aimed to estimate BV in athletes for metabolism and growth-related biomarkers involved in the Athlete Biological Passport (ABP), by 2 different statistical models. METHODS: Thirty triathletes were sampled monthly for 11 months. The samples were analyzed for human growth hormone (hGH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), insulin, and N-terminal propeptide of type III procollagen (P-III-NP) by immunoassay. Bayesian and ANOVA methods were applied to estimate within-subject (CVI) and between-subject BV. RESULTS: CVI estimates ranged from 7.8% for IGFBP-3 to 27.0% for insulin, when derived by the Bayesian method. The 2 models gave similar results, except for P-III-NP. Data were heterogeneously distributed for P-III-NP for the overall population and in females for IGF-1 and IGFBP-3. BV components were not estimated for hGH due to lack of steady state. The index of individuality was below 0.6 for all measurands, except for insulin. CONCLUSIONS: In an athlete population, to apply a common CVI for insulin would be appropriate, but for IGF-1 and IGFBP-3 gender-specific estimates should be applied. P-III-NP data were heterogeneously distributed and using a mean CVI may not be representative for the population. The high degree of individuality for IGF-1, IGFBP-3, and P-III-NP makes them good candidates to be interpreted through reference change values and the ABP.

Changes of GH-IGFs and its relationship with growth retardation in children with bronchial asthma.

OBJECTIVE: To explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma. METHODS: 112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation. RESULTS: GH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 µg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma. CONCLUSION: GH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.

Minipuberty period of children with atopic dermatitis compared to healthy children.

Background/aim: Atopic dermatitis (AD) is an inflammatory, pruritic, noncontagious, chronic relapsing skin disease. Skin barrier abnormalities, excessive T helper 2 activity, and immune dysregulation are held responsible. Androgens have a negative effect on the integrity of the epidermal skin barrier, while estrogen has a positive effect. We aimed to investigate whether hormones make a difference between healthy children and children with AD during minipuberty. Materials and methods: A total of 96 infants (postnatal 4-13 weeks), 48 diagnosed with AD and 48 controls, were included. Each group consisted of 23 girls (47.9%) and 25 boys (52.1%). Anthropometric examinations and hormone measurements were compared. Results: The two groups, having similar age, sex, body mass index, and weight-for-length standard deviation scores, were compared. Serum free thyroxine (FT4) levels were found to be lower and insulin-like growth factor binding protein-3 (IGFBP3) levels were found to be higher in children with AD (p < 0.001 and p = 0.038, respectively). In girls with AD, estradiol, FT4, and insulin-like growth factor-1 (IGF-1) levels were found to be lower, but thyroid-stimulating hormone (TSH) levels were found to be higher (p = 0.023, p < 0.001, p = 0.038, and p = 0.034, respectively). In boys with AD, the FT4 level was found to be lower (p = 0.023). Serum FT4 and TSH levels were within normal reference ranges in all comparisons. Conclusion: Especially in girls with AD, decreased estradiol and IGF-1 levels were observed compared to the controls during minipuberty. In the logistic regression model, decreased levels of serum estradiol, dehydroepiandrosterone sulfate, FT4, and IGF-1, and increased levels of IGFBP3 were associated with an increased likelihood of exhibiting atopic dermatitis.

Association of lncRNA MEG3 rs941576 polymorphism, expression profile, and its related targets with the risk of obesity-related colorectal cancer: potential clinical insights.

The identification of novel screening tools is imperative to empower the early detection of colorectal cancer (CRC). The influence of the long non-coding RNA maternally expressed gene 3 (MEG3) rs941576 single nucleotide polymorphism on CRC susceptibility remains uninvestigated. This research appraised MEG3 rs941576 association with the risk and clinical features of CRC and obesity-related CRC and its impact on serum MEG3 expression and its targets miR-27a/insulin-like growth factor 1 (IGF1)/IGF binding protein 3 (IGFBP3) and miR-181a/sirtuin 1 (SIRT1), along with the potential of these markers in obesity-related CRC diagnosis. 130 CRC patients (60 non-obese and 70 obese) and 120 cancer-free controls (64 non-obese and 56 obese) were enrolled. MEG3 targets were selected using bioinformatics analysis. MEG3 rs941576 was associated with magnified CRC risk in overall (OR (95% CI) 4.69(1.51-14.57), P = 0.0018) and stratified age and gender groups, but not with obesity-related CRC risk or MEG3/downstream targets' expression. Escalated miR-27a and IGFBP3 and reduced IGF1 serum levels were concomitant with MEG3 downregulation in overall CRC patients versus controls and obese versus non-obese CRC patients. Serum miR-181a and SIRT1 were upregulated in CRC patients versus controls but weren't altered in the obese versus non-obese comparison. Serum miR-181a and miR-27a were superior in overall and obesity-related CRC diagnosis, respectively; meanwhile, IGF1 was superior in distinguishing obese from non-obese CRC patients. Only serum miR-27a was associated with obesity-related CRC risk in multivariate logistic analysis. Among overall CRC patients, MEG3 rs941576 was associated with lymph node (LN) metastasis and tumor stage, serum MEG3 was negatively correlated with tumor stage, while SIRT1 was correlated with the anatomical site. Significant correlations were recorded between MEG3 and anatomical site, SIRT1 and tumor stage, and miR-27a/IGFBP3 and LN metastasis among obese CRC patients, while IGF1 was correlated with tumor stage and LN metastasis among non-obese CRC patients. Conclusively, this study advocates MEG3 rs941576 as a novel genetic marker of CRC susceptibility and prognosis. Our findings accentuate circulating MEG3/miR-27a/IGF1/IGFBP3, especially miR-27a as valuable markers for the early detection of obesity-related CRC. This axis along with SIRT1 could benefit obesity-related CRC prognosis.

Biphasic Kinetics of IGF-I and IGFBP-3 in Response to Military Field Training in Brazilian Air Force Recruits.

INTRODUCTION: Insulin-like growth factor type I (IGF-I) has gained considerable notoriety in military training, primarily because it is responsible for energy deficits and sensitive to an inadequate protein intake, which are situations that are commonly experienced in specific military operations. Therefore, this study aimed to assess the kinetics of IGF-I and insulin-like growth factor binding protein type 3 (IGFBP-3) in a 4-day military field training exercise. MATERIALS AND METHODS: The sample comprised 12 male soldiers (21.71 ± 1.64 years). Changes were assessed at 3 times: time 1-basal (control week); time 2-after specific military field training; and time 3-1 week after the specific training (control week). Changes in body composition and serum levels of IGF-I and IGFBP-3 were observed. RESULTS: The main finding of this study was it verified the biphasic kinetics of both IGF-I and IGFBP-3 at the 3 times observed, that is, a significant drop from time 1 (basal-IGF-I: 189 ng/mL and IGFBP-3: 4.71 mg/L) to time 2 (immediately after military training-IGF-I: 162 ng/mL and IGFBP-3: 4.08 mg/L) and a subsequent recovery of these markers, with a significant increase from time 2 (immediately after military training) to time 3 (a week after military training-IGF-I: 199 ng/mL and IGFBP-3: 4.96 mg/L). CONCLUSIONS: It can be concluded that IGF-I and IGFBP-3 levels respond quickly to the stimuli caused by military training, especially after specific field training. However, the same markers quickly return to their basal values after this type of training finishes, simply by following the daily routine of the battalion in the control weeks, with no specific intervention being necessary.

Effects of natural extract interventions in prostate cancer: A systematic review and network meta-analysis.

BACKGROUND: Over years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer. OBJECTIVE: Our study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer. METHODS: Researchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes. RESULTS: Following screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE. CONCLUSION: The NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.

Is bovine somatotropin an alternative strategy to overcome the detrimental effects of high-gain diets on prepubertal Holstein × Gyr heifers?

Feeding high-gain diets and an inadequate energy and protein ratio during pre-puberty may lead to impaired growth and mammary gland development of heifers. Thus, frequent application of bovine somatotropin (bST) may prevent future losses in productivity, improve mammary development and animal performance. We aimed to evaluate the effects of bST on digestibility, performance, blood metabolites, mammary gland development, and carcass composition of high-performance prepubertal Holstein × Gyr heifers. Thirty-four Holstein × Gyr heifers with an average initial body weight of 218 ± 49 kg and 14 ± 4 months of age were submitted to an 84-day trial evaluating the effects of no bST or bST injections. Treatments were randomly assigned to each animal within one of the tree blocks. The bST did not influence digestibility or performance parameters. Regarding blood results, IGF1 concentration presented an interaction between treatment and day, where bST heifers had the highest IGF1 concentration. Heifers receiving bST also showed increased ribeye area; however, only an experimental day effect for backfat thickness was observed, with greater accumulation of carcass fat on day 84. Heifers receiving bST had lower pixels/mm² on parenchyma, characteristic of greater parenchymal tissue. Moreover, heifers on bST treatment also had reduced pixels/mm2, characteristic of reduced fat pad tissue. Lastly, bST injections did not influence liver and muscle gene expression, nor most genes evaluated in mammary gland tissue, except for IGFBP3 expression, which was greater for bST heifers. In summary, we confirm the efficacy of bST injections to overcome the detrimental effects of high-gain diets on mammary gland growth and to improve lean carcass gain of prepubertal Holstein × Gyr heifers.

The Prostate Cancer Active Lifestyle Study (PALS): A randomized controlled trial of diet and exercise in overweight and obese men on active surveillance.

BACKGROUND: Active surveillance (AS) is increasingly used to monitor patients with lower risk prostate cancer (PCa). The Prostate Cancer Active Lifestyle Study (PALS) was a randomized controlled trial to determine whether weight loss improves obesity biomarkers on the causal pathway to progression in patients with PCa on AS. METHODS: Overweight/obese men (body mass index >25 kg/m2) diagnosed with PCa who elected AS were recruited. The intervention was a 6-month, individually delivered, structured diet and exercise program adapted from the Diabetes Prevention Program with a 7% weight loss goal from baseline. Control participants attended one session reviewing the US Dietary and Physical Activity Guidelines. The primary outcome was change in glucose regulation from baseline to the end of the 6-month intervention, which was measured by fasting plasma glucose, C-peptide, insulin, insulin-like growth factor 1, insulin-like growth factor binding protein-3, adiponectin, and homeostatic model assessment for insulin resistance. RESULTS: Among 117 men who were randomized, 100 completed the trial. The mean percentage weight loss was 7.1% and 1.8% in the intervention and control arms, respectively (adjusted between-group mean difference, -6.0 kg; 95% confidence interval, -8.0, -4.0). Mean percentage changes from baseline for insulin, C-peptide, and homeostatic model assessment for insulin resistance in the intervention arm were -23%, -16%, and -25%, respectively, compared with +6.9%, +7.5%, and +6.4%, respectively, in the control arm (all p for intervention effects ≤ .003). No significant between-arm differences were detected for the other biomarkers. CONCLUSIONS: Overweight/obese men with PCa undergoing AS who participated in a lifestyle-based weight loss intervention successfully met weight loss goals with this reproducible lifestyle intervention and experienced improvements in glucose-regulation biomarkers associated with PCa progression.

The Effect and Potential Mechanism Analysis of Growth Hormone-Secreting Pituitary Adenomas on Thyroid Function.

OBJECTIVE: Current studies on the effect of high growth hormone (GH)/insulin-like growth factor (IGF)-1 on thyroid function are inconsistent. The aim was to explore the effect and potential mechanism of high GH/IGF-1 on thyroid function by analyzing the changes of thyroid function in patients with growth hormone-secreting pituitary adenoma (GHPA). METHODS: This was a retrospective cross-sectional study. Demographic and clinical data of 351 patients with GHPA who were first admitted to Beijing Tiantan Hospital, Capital Medical University, from 2015 to 2022 were collected to analyze the relationship between high GH/IGF-1 levels and thyroid function. RESULTS: GH was negatively correlated with total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH). IGF-1 was positively correlated with total triiodothyronine (TT3), free triiodothyronine (FT3), and FT4 and negatively correlated with TSH. Insulin-like growth factor-binding protein (IGFBP)-3 was positively correlated with TT3, FT3, and FT3:FT4 ratio. The FT3, TT3, TSH, and FT3:FT4 ratio of patients with GHPA and diabetes mellitus (DM) were significantly lower than those with GHPA but without DM. With the increase of tumor volume, thyroid function gradually decreased. GH and IGF-1 were correlated negatively with age in patients with GHPA. CONCLUSION: The study emphasized the complex interaction between the GH and the thyroid axes in patients with GHPA and highlighted the potential effect of glycemic status and tumor volume on thyroid function.

Combined diagnostic value of insulin-like growth factor-1, insulin-like growth factor binding protein-3, and baseline luteinizing hormone levels for central precocious puberty in girls.

OBJECTIVES: The golden standard test for diagnosing central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test, which has many limitations. This study aimed to investigate the value of insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and basal luteinizing hormone (LH) levels in diagnosing CPP. METHODS: Cross-sectional study of the levels of IGF-1, IGFBP-3, and basal LH in girls with a chief complaint of premature breast development. Seventy-nine girls with CPP and 37 girls with premature thelarche (PT) diagnosed at West China Second University Hospital from January 2016 to October 2018 were recruited. All patients underwent physical examination, laboratory tests, uterine and ovarian ultrasound, and bone age tests, only CPP patients underwent pituitary magnetic resonance imaging (MRI). Statistical analysis was performed using the SPSS software 21.0. A receiver operating characteristic curve was used to determine diagnostic value. RESULTS: The anthropometric data and hormone indicators between CPP and PT were statistically different (p<0.001), except for peak follicle stimulating hormone (FSH) levels (p=0.181). IGF-1, IGFBP-3, and basal LH levels were significantly higher in the subjects with CPP than in those with PT; IGF-1 and basal LH were positively correlated with peak LH and LH/FSH (peak) (p<0.001). The area under the curve (AUC) of IGF-1, IGFBP-3, and basal LH were 0.880, 0.853, and 0.915, respectively. When combined, the AUC reached the highest value of 0.978. CONCLUSIONS: IGF-1, IGFBP-3, and baseline LH levels were useful in diagnosing CPP. The combined analysis improved the diagnostic effectiveness.

Growth Hormone and Thyroid Function in Children With Attention Deficit Hyperactivity Disorder Undergoing Drug Therapy.

CONTEXT: The trends in hormone indices of children with attention deficit hyperactivity disorder (ADHD) who received long-term medication treatment remains controversial. OBJECTIVE: This prospective study aimed to examine the changes in the growth hormone and thyroid hormone systems among children with ADHD undergoing various medication treatments. METHODS: In total, 118 children who were diagnosed with ADHD and were drug-naive were observed naturalistically over 12 months. Of them, 22 did not receive any medication, while 39, 40, and 17 were treated with low doses of short-acting methylphenidate (MPH) (14 ±â€…6.7 mg/day), osmotic-release oral system (OROS) long-acting MPH (32 ±â€…9.6 mg/day), and atomoxetine (29.2 ±â€…9.7 mg/day), respectively. Blood samples were obtained at both the baseline and the endpoint (month 12) to measure serum levels of insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), prolactin, thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and free T4. RESULTS: Trends for IGF-1, IGFBP-3, prolactin, TSH, T3, T4, and free T4 levels were similar among the 4 groups. Changes in serum levels of IGF-1 were positively correlated with changes in height and weight of all the children with ADHD. However, patients who received MPH treatment had less body weight gain than the nonmedicated group. The ratio of MPH doses to body weight was inversely correlated with the increment in height. CONCLUSION: There were no changes in thyroid or growth hormones associated with the low doses of ADHD medications used in this study within 1 year's duration. Nonetheless, patients' growth and the appropriateness of drug dosage should be closely monitored.

BMI and Contraceptives Affect New Age-, Sex-, and Puberty-adjusted IGF-I and IGFBP-3 Reference Ranges Across Life Span.

CONTEXT: Various clinical factors influencing serum levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are not entirely consistently described. OBJECTIVE: We asked whether body mass index (BMI), contraceptive drugs (CDs), and hormone replacement therapy (HRT) have potential effects on data for interpreting new age-, sex-, and puberty-adjusted reference ranges for IGF-I and IGFBP-3 serum levels. DESIGN AND SETTING: Subjects were mainly participants from 2 population-based cohort studies: the LIFE Child study of children and adolescents and the LIFE Adult study. PARTICIPANTS: We investigated 9400 serum samples from more than 7000 healthy and 1278 obese subjects between 3 months and 81 years old. MAIN OUTCOME MEASURES: Associations between IGF-I or IGFBP-3, measured with a new electrochemiluminescence immunoassay, and the predictors BMI and CDs were estimated using hierarchical linear modeling. RESULTS: During infancy, obese children had up to 1 SD score (SDS) higher mean predicted IGF-I values, converging with levels of normal-weight subjects up to 13 years old. Between 20 and 40 years of age, obesity was related to up to -0.5 lower IGF-I SDS values than the predicted values. Obesity had less impact on IGFBP-3. Estrogen- and progestin-based CDs, but not HRT, decreased IGF-I and increased IGFBP-3 (P < 0.01) in adolescents (ß IGF-I = -0.45, ß IGFBP-3  = 0.94) and adults (ß IGF-I = -0.43, ß IGFBP-3  = 1.12). Conversely, progestin-based CDs were significantly positive associated with IGF-I (ß IGF-I  =0.82). CONCLUSIONS: BMI and CDs must be considered when assessing and interpreting the clinical relevance of IGF-I and IGFBP-3 measurements.

Association of significantly elevated plasma levels of NGAL and IGFBP4 in patients with diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a type of progressive kidney disease affecting approximately 40% of patients with diabetes. Current DN diagnostic criteria predominantly rely on albuminuria and serum creatinine (sCr) levels. However, the specificity and reliability of both markers are limited. Hence, reliable biomarkers are required for early diagnosis to effectively manage DN progression. METHODS: In this study, a cohort of 159 individuals were clinically evaluated and the plasma levels of NGAL, IGFBP-1, IGFBP-3, and IGFBP-4 were determined using Multiplexing Assays. Additionally, the association between the plasma levels of NGAL, IGFBP-1, IGFBP-3, and IGFBP-4 in patients with DN were compared to those in patients with T2D without kidney disease and control participants. RESULTS: Circulating level of NGAL were significantly higher in people with DN compared to people with T2D and non-diabetic groups (92.76 ± 7.5, 57.22 ± 8.7, and 52.47 ± 2.9 mg/L, respectively; p <  0.0001). IGFBP-4 showed a similar pattern, where it was highest in people with DN (795.61 ng/ml ±130.7) compared to T2D and non-diabetic people (374.56 ng/ml ±86.8, 273.06 ng/ml ±27.8 respectively, ANOVA p <  0.01). The data from this study shows a significant positive correlation between NGAL and IGFBP-4 in people with DN (ρ = .620, p <  0.005). IGFBP-4 also correlated positively with creatinine level and negatively with eGFR, in people with DN supporting its involvement in DN. CONCLUSION: The data from this study shows a parallel increase in the plasma levels of NGAL and IGFBP-4 in DN. This highlights the potential to use these markers for early diagnosis of DN.

Energy homeostasis genes modify the association between serum concentrations of IGF-1 and IGFBP-3 and breast cancer risk.

Breast cancer is a multifactorial disease in which the interplay among multiple risk factors remains unclear. Energy homeostasis genes play an important role in carcinogenesis and their interactions with the serum concentrations of IGF-1 and IGFBP-3 on the risk of breast cancer have not yet been investigated. The aim of this study was to assess the modifying effect of the genetic variation in some energy homeostasis genes on the association of serum concentrations of IGF-1 and IGFBP-3 with breast cancer risk. We analyzed 78 SNPs from 10 energy homeostasis genes in premenopausal women from the 4-Corner's Breast Cancer Study (61 cases and 155 controls) and the Mexico Breast Cancer Study (204 cases and 282 controls). After data harmonization, 71 SNPs in HWE were included for interaction analysis. Two SNPs in two genes (MBOAT rs13272159 and NPY rs16131) showed an effect modification on the association between IGF-1 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). In addition, five SNPs in three genes (ADIPOQ rs182052, rs822391 and rs7649121, CARTPT rs3846659, and LEPR rs12059300) had an effect modification on the association between IGFBP-3 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). Our findings showed that variants of energy homeostasis genes modified the association between the IGF-1 or IGFBP-3 serum concentration and breast cancer risk in premenopausal women. These findings contribute to a better understanding of this multifactorial pathology.

Circulating Insulin-Like Growth Factor 1-Related Biomarkers and Risk of Lethal Prostate Cancer.

Background: Experimental and epidemiologic evidence supports the role of circulating insulin-like growth factor-1 (IGF-1) levels with the risk of prostate cancer. Most circulating IGF-1 is bound to specific binding proteins, and only about 5% circulates in a free form. We explored the relation of free IGF-1 and other components of the IGF system with lethal prostate cancer. Methods: Using prospectively collected samples, we undertook a nested case-only analysis among 434 men with lethal prostate cancer and 524 men with indolent, nonlethal prostate cancer in the Physicians' Health Study and the Health Professionals Follow-up Study. Prediagnostic plasma samples were assayed for free IGF-1 and total IGF-1, acid labile subunit, pregnancy-associated plasma protein A (PAPP-A), and intact and total IGF binding protein 4. We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the associations between IGF-1-related biomarkers and lethal prostate cancer using unconditional logistic regression models adjusted for age, height, and body mass index. Results: Men in the highest quartile of PAPP-A levels had 42% higher odds of lethal prostate cancer (pooled adjusted OR = 1.42, 95% CI = 1.04 to 1.92) compared with men in the lowest 3 quartiles. There were no statistically significant differences in the other plasma analytes. The positive association between PAPP-A and lethal prostate cancer was present among men with intact PTEN but not among those with tumor PTEN loss (2-sided P interaction = .001). Conclusions: Our study provides suggestive evidence that among men who later develop prostate cancer, higher plasma PAPP-A levels measured prior to diagnosis are associated with increased risk of lethal compared with indolent disease.

Myokine Expression and Tumor-Suppressive Effect of Serum after 12 wk of Exercise in Prostate Cancer Patients on ADT.

PURPOSE: Although several mechanisms have been proposed for the tumor-suppressive effect of exercise, little attention has been given to myokines, even though skeletal muscle is heavily recruited during exercise resulting in myokine surges. We measured resting serum myokine levels before and after an exercise-based intervention and the effect of this serum on prostate cancer cell growth. METHODS: Ten prostate cancer patients undertaking androgen deprivation therapy (age, 73.3 ± 5.6 yr) undertook a 12-wk exercise-based intervention including supervised resistance training, self-directed aerobic exercise, and protein supplementation. Body composition was assessed by dual-energy x-ray absorptiometry and muscle strength by the one-repetition maximum method. Fasting blood was collected at baseline and postintervention, and serum levels of myokines-secreted protein acidic and rich in cysteine, oncostatin M (OSM), decorin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 (IGFBP-3)-were measured. The growth of the prostate cancer cell line DU145 with baseline and postintervention serum was measured. RESULTS: Body weight (P = 0.011), fat mass (P = 0.012), and percent body fat (P = 0.033) were reduced, whereas percent lean mass (P = 0.001) increased, as did strength (leg press, P = 0.006; chest press, P = 0.020) across the intervention. Serum OSM levels (P = 0.020) and relative serum OSM levels (P = 0.020) increased compared with baseline. A significant reduction in DU145 Cell Index (P = 0.012) and growth rate (P = 0.012) was observed after applying postintervention serum compared with baseline serum. CONCLUSIONS: This study provides evidence for enhanced myokine expression and tumor-suppressive effects of serum from chronically exercise-trained prostate cancer patients on androgen deprivation therapy.

Dynamic Changes in Serum IGF-I and Growth During Infancy: Associations to Body Fat, Target Height, and PAPPA2 Genotype.

CONTEXT: IGF-I is important for postnatal growth and may be of diagnostic value in infants suspected of pituitary disease; however, little is known about the impact of IGF-I and its determinants on infant growth. Importantly, detailed reference ranges for IGF-I and IGF binding protein-3 (IGFBP-3) concentrations during infancy are lacking. OBJECTIVE: To evaluate the rapid changes in weight and length as well as their determinants in healthy infants, and to establish age- and sex-specific reference curves for IGF-I and IGFBP-3 in children aged 0 to 1 years. DESIGN: Prospective longitudinal study. SETTING: Cohort study. PARTICIPANTS: A total of 233 healthy children (114 girls) with repeated blood samples during the first year of life. MAIN OUTCOME MEASURE(S): Serum concentrations of IGF-I and IGFBP-3, length velocity, weight velocity, and PAPPA2 (rs1325598) genotype. RESULTS: Individual trajectories of length and weight velocities were sex specific. We provide detailed reference curves based on longitudinal data for IGF-I and IGFBP-3 during infancy. In both girls and boys, IGF-I decreased during infancy, whereas IGFBP-3 remained stable. IGF-I and IGFBP-3, but not PAPPA2 genotype, were positively associated with weight gain, but not with longitudinal growth. When stratified by sex, the association between weight gain and IGF-I only remained significant in girls. CONCLUSIONS: Interestingly, we found a significant association between IGF-I and infant weight gain in girls, but not with longitudinal growth in the first year of life. Our findings highlight the role of IGF-I as an important anabolic hormone that is not limited to linear growth.

Malnutrition in children associated with low insulin-like growth factor binding protein-3 (IGFBP-3) levels.

OBJECTIVE: This study aimed to compare serum levels of Insulin-like Growth Factor Binding Protein-3 in children with malnutrition and good nutritional status. METHOD: This cross-sectional study included 41 participants consisting of 31 malnourished, 10 well-nourished children aged between 36 and 60 months. Demographic data of participants were obtained utilizing a questionnaire. Nutritional status was determined by calculating the Z-score of body weight for age, height for age, and body weight for height indices using the WHO classification. IGFBP-3 levels were determined by the Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULT: Median serum IGFBP-3 levels in malnourished children were found to be lower i.e. 0.35mcg/mL (minimum-maximum: 0.04-1.52mcg/mL) compared to well-nourished children 1.52ng/mL (minimum-maximum 0.47-3.17mcg/mL). CONCLUSION: Serum IGFBP-3 levels can be used as indicators to assess nutritional status.

GH Responsiveness in Children With Noonan Syndrome Compared to Turner Syndrome.

Background: Despite different genetic background, Noonan syndrome (NS) shares similar phenotype features to Turner syndrome (TS) such as short stature, webbed neck and congenital heart defects. TS is an entity with decreased growth hormone (GH) responsiveness. Whether this is found in NS is debated. Methods: Data were retrieved from combined intervention studies including 25 children diagnosed with NS, 40 diagnosed with TS, and 45 control children (all prepubertal). NS-children and TS-girls were rhGH treated after investigation of the GH/IGFI-axis. GH was measured with poly- and monoclonal antibodies; 24hGH-profile pattern analysed by PULSAR. The NS-children were randomly assigned to Norditropin® 33 or 66 µg/kg/day, and TS-girls were consecutively treated with Genotropin® 33 or 66 µg/kg/day. Results: Higher PULSAR-estimates of 24h-profiles were found in both NS-children and TS-girls compared to controls: Polyclonal GHmax24h-profile (Mean ± SD) was higher in both groups (44 ± 23mU/L, p<0.01 in NS; 51 ± 47, p<0.001 in TS; compared to 30 ± 23 mU/L in controls) as was GH-baseline (1.4 ± 0.6 mU/L in NS; 2.4 ± 2.4 mU/L in TS, p<0.01 for both, compared to 1.1 ± 1.2 mU/L in controls). Pre-treatment IGFISDS was 2.2 lower in NS-children (-1.7 ± 1.3) compared to TS-girls (0.6 ± 1.8, p<0.0001). GHmax, IGFI/IGFBP3-ratioSDS, and chronological age at start of GH accounted for 59% of the variance in first-year growth response in NS. Conclusion: Both prepubertal NS-children and TS-girls had a high GH secretion, but low IGFI/IGFBP3 levels only in NS-children. Both groups presented a broad individual response. NS-children showed higher response in IGFI and growth, pointing to higher responsiveness to GH treatment than TS-girls.