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Purpose: Circulating IGF-1 concentrations have been associated with higher cancer risk, particularly prostate, breast and colorectal cancer. There is evidence from observational and intervention studies that milk and dairy products intake is associated with higher IGF-1 concentrations, but results were not always consistent. The purpose of this study was to examine the relationship between dairy intake and circulating IGF-1 concentrations in participants of the Second Bavarian Food Consumption Survey, thereby providing data for a German population for the first time. Methods: In this cross-sectional study of 526 men and women aged 18–80 years, in contrast to most previous investigations, dietary intake was assessed with a more detailed instrument than food frequency questionnaires (FFQs), i.e., by three 24-h dietary recalls conducted on random days close in time to the blood collection. Circulating IGF-1 concentrations were measured in blood samples. Multivariable linear regression models were used to examine the association of dairy intake with IGF-1 concentrations. Results: Each 400 g increment in daily dairy intake was associated with 16.8 µg/L (95% CI 6.9, 26.7) higher IGF-1 concentrations. Each 200 g increment in milk per day was associated with 10.0 µg/L (95% CI 4.2, 15.8) higher IGF-1. In contrast, we observed no association between cheese or yogurt intake and IGF-1 concentrations. Conclusions: Our findings are in line with most previous investigations and support the hypothesis that dairy and milk intake are associated with higher IGF-1 concentrations. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) is widely used in sports medicine. Available PRP preparations differ in white blood cell, platelet, and growth factor concentrations, making standardized research and clinical application challenging. Purpose: To characterize a newly standardized procedure for pooled PRP that provides defined growth factor concentrations. Study Design: Controlled laboratory study. Methods: A standardized growth factor preparation (lyophilized PRP powder) was prepared using 12 pooled platelet concentrates (PCs) derived from different donors via apheresis. Blood samples and commercially available PRP (SmartPrep-2) served as controls (n = 5). Baseline blood counts were analyzed. Additionally, single PCs (n = 5) were produced by standard platelet apheresis. The concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor AB (PDGF-AB), transforming growth factor β1 (TGF-β1), insulin-like growth factor 1 (IGF-1), interleukin (IL)–1α, IL-1β, and IL-1 receptor agonist (IL-1RA) were analyzed by enzyme-linked immunosorbent assay, and statistical analyses were performed using descriptive statistics, mean differences, 95% CIs, and P values (analysis of variance). Results: All growth factor preparation methods showed elevated concentrations of the growth factors VEGF, bFGF, PDGF-AB, and TGF-β1 compared with those of whole blood. Large interindividual differences were found in VEGF and bFGF concentrations. Respective values (mean ± SD in pg/mL) for whole blood, SmartPrep-2, PC, and PRP powder were as follows: VEGF (574 ± 147, 528 ± 233, 1087 ± 535, and 1722), bFGF (198 ± 164, 410 ± 259, 151 ± 99, and 542), PDGF-AB (2394 ± 451, 17,846 ± 3087, 18,461 ± 4455, and 23,023), and TGF-β1 (14,356 ± 4527, 77,533 ± 13,918, 68,582 ± 7388, and 87,495). IGF-1 was found in SmartPrep-2 (1539 ± 348 pg/mL). For PC (2266 ± 485 pg/mL), IGF-1 was measured at the same levels of whole blood (2317 ± 711 pg/mL) but was not detectable in PRP powder. IL-1α was detectable in whole blood (111 ± 35 pg/mL) and SmartPrep-2 (119 ± 44 pg/mL). Conclusion: Problems with PRP such as absent standardization, lack of consistency among studies, and black box dosage could be solved by using characterized PRP powder made by pooling and lyophilizing multiple PCs. The new PRP powder opens up new possibilities for PRP research as well as for the treatment of patients. Clinical Relevance: The preparation of pooled PRP by means of lyophilization may allow physicians to apply a defined amount of growth factors by using a defined amount of PRP powder. Moreover, PRP powder as a dry substance with no need for centrifugation could become ubiquitously available, thus saving time and staff resources in clinical practice. However, before transferring the results of this basic science study to clinical application, regulatory issues have to be cleared. [ABSTRACT FROM AUTHOR]

Purpose: Maternal diet during pregnancy impacts foetal growth and development. In particular, dietary levels of methylating micronutrients (methionine, folate, choline, vitamins B6, and B12) interfere with the availability and allocation of methyl groups for methylation reactions, thereby influencing normal transcription. However, the currently recommended methylating micronutrient supplementation regimen is haphazard and arbitrary at best. Methods: To investigate the effects of a methylating micronutrient-rich maternal diet, pregnant Pietrain sows were fed either a standard diet (CON) or a diet supplemented with methionine, folate, choline, B6, B12, and zinc (MET). Foetal liver and muscle ( M. longissimus dorsi) tissues were collected at 35, 63, and 91 days post-conception. Transcriptional responses to diet were assessed in foetal liver. Altered insulin-like growth factor (IGF) signalling in transcriptome analyses prompted investigation of IGF-2 and insulin-like growth factor binding proteins (IGFBPs) levels in muscle and liver. Results: Maternal diet enriched with methylating micronutrients was associated with increased foetal weight in late gestation. Hepatic transcriptional patterns also revealed differences in vitamin B6 and folate metabolism between the two diets, suggesting that supplementation was effective. Additionally, shifts in growth-supporting metabolic routes of the lipid and energy metabolism, including IGF signalling, and of cell cycle-related pathways were found to occur in liver tissue in supplemented individuals. Weight differences and modulated IGF pathways were also reflected in the muscle content of IGF-2 (increased in MET) and IGFBP-2 (decreased in MET). Conclusions: Maternal dietary challenges provoke stage-dependent and tissue-specific transcriptomic modulations in the liver pointing to molecular routes contributing to the organismal adaptation. Subtle effects on late foetal growth are associated with changes in the IGF signalling mainly in skeletal muscle tissue that is less resilient to dietary stimuli than liver. [ABSTRACT FROM AUTHOR]

Purpose: Effects of pre- and early postnatal exposure to maternal high-protein diets are not well understood. Transcription profiling was performed in male mouse offspring exposed to maternal high-protein diet during pregnancy and/or lactation to identify affected hepatic molecular pathways. Methods: Dams were fed isoenergetic diets with control (20% w/w) or high protein levels (40%). The hepatic expression profiles were evaluated by differential microarray analysis 3 days (d3) and 3 weeks (d21) after birth. Offspring from three different high-protein dietary groups, HP (d3, high-protein diet during pregnancy), HPHP (d21, high-protein diet during pregnancy and lactation) and CHP (d21, control diet during pregnancy and high-protein diet during lactation), were compared with age-matched offspring from dams fed control diet. Results: Offspring body and liver mass of all high-protein groups were decreased. Prenatal high-protein diet affected hepatic expression of genes mapping to the acute response/complement system and the GH/JAK/STAT/IGF signalling pathways. Maternal exposure to high-protein diet during lactation affected hepatic gene expression of the same pathways but additionally affected genes mapping to protein, fatty acid, hexose and pyruvate metabolism. Conclusions: (1) Genes of the acute response/complement system and GH/JAK/STAT/IGF pathways were down-regulated in offspring of dams exposed to high-protein diets during pregnancy and/or lactation. (2) Genes related to nutrient and energy metabolism, however, were only affected when high-protein diet was administered during lactation. (3) Modulation of the GH/JAK/STAT/IGF pathway might be responsible for reduced body and liver masses by maternal high-protein diet. [ABSTRACT FROM AUTHOR]

Background: Circumscribed cartilage defects are considered as prearthritic lesions and lead to differential intra-articular cytokine expression. Mechanisms of associated pain development and influence of smoking behavior are not yet fully understood in humans.Purpose: This study aimed to reveal relations between synovial cytokine levels in knees with circumscribed cartilage defects and pain sensation.Study Design: Descriptive laboratory study.Methods: In a clinical trial, knee lavage fluids of 42 patients with circumscribed cartilage lesions treated by either microfracturing (n = 19) or by autologous chondrocyte implantation (n = 23) and fluids of 5 healthy control individuals were prospectively collected. Preoperative knee pain was evaluated according to frequency and strength; subjective knee function was assessed using a visual analog scale and the International Knee Documentation Committee (IKDC) score. Synovial concentrations of aggrecan, insulin-like growth factor (IGF)-I, basic fibroblast growth factor (bFGF), interleukin (IL)-1β, bone morphogenetic protein (BMP)-2, and BMP-7 were determined by enzyme-linked immunosorbent assay.Results: Pain strength showed a highly significant association with intra-articular IGF-1 levels (ρ = .48, P < .01), but no correlation with synovial concentrations of aggrecan, bFGF, IL-1β, BMP-2, and BMP-7. Although pain strength and frequency demonstrated a statistically significant relationship, no substantial association between pain frequency and any of the examined cytokine levels was found. Intra-articular IGF-1 concentrations significantly correlated with the area of cartilage damage (ρ = .35, P < .02); the other investigated cytokines failed to show this association. Neither of the determined intra-articular mediators demonstrated statistically significant correlations with subjective knee function or IKDC score. Only intra-articular concentrations of IGF-1 and BMP-2 statistically significantly correlated with age; total protein content was negatively associated with body mass index (P < .05). In smokers, synovial expression of total protein content, IGF-1, and bFGF was significantly diminished compared to nonsmokers (P < .05).Conclusion: Insulin-like growth factor–I is present in knees with circumscribed cartilage lesions in a size-dependent manner. IGF-1 levels correlated with indicators of pain perception; smoking negatively influenced synovial cytokine expression related to cartilage metabolism, but pain perception was not altered. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Previous population-based studies provided conflicting results regarding the association of total serum insulin-like growth factor I (IGF-I) and mortality. The aim of the present study was to assess the relation of IGF-I levels with all-cause mortality in a prospective study. Design: DETECT (Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment) is a large, multistage, and nationally representative study of primary care patients in Germany. The study population included 2463 men and 3603 women. Death rates were recorded by the respective primary care physician. Serum total IGF-I levels were determined by chemiluminescence immunoassays and categorized into three groups (low, moderate, and high) according to the sex- and age-specific 10th and 90th percentiles. Results: Adjusted analyses revealed that men with low [hazard ratio (HR) 1.70 (95% confidence interval [CI] 1.05–2.73), p=0.03] and high [HR 1.76 (95% CI 1.09–2.85), p=0.02] IGF-I levels had higher risk of all-cause mortality compared to men with moderate IGF-I levels. The specificity of low IGF-I and high IGF-I levels increased with lower and higher cut-offs, respectively. No such association became apparent in women. Conclusions: The present study revealed a U-shaped relation between IGF-I and all-cause mortality in male primary care patients. [Copyright &y& Elsevier]

OBJECTIVE: To analyse 12-month response to GH treatment in a single-country cohort of hypopituitary adult patients with GH deficiency (GHD) in regards to health-related quality of life (HRQoL) and insulin-like growth factor-1 (IGF-1) compared with values from general population sample. Moreover, association between the response in HRQoL and the IGF-1 values in patients and in the background population was investigated. DESIGN: HRQoL was assessed by quality of life assessment of GH deficiency in adults (QoL-AGHDA) in 651 patients retrieved from the German KIMS (Pfizer International Metabolic Database) before and after 12 months of GH replacement and in a sample drawn from a cross-sectional study in Germany (n=2734). IGF-1 was measured in KIMS patients and in the population-based study with the same assay technique. RESULTS: In KIMS patients, mean QoL-AGHDA scores before GH replacement were 9.2±6.8 (8.7±6.8) in women (men) and in the general population sample 4.5±5.3 (4.3±5.0) in women (men). Mean differences in QoL-AGHDA scores were statistically significant for all age categories (P<0.05). The mean IGF-1 SDS of KIMS patients before GH replacement was –1.1±1.4 (–0.8±1.4) in women (men). After GH replacement, a significant increase of IGF-1 concentration and a significant decrease of QoL-AGHDA scores near to age- and gender-specific population-based values were observed. CONCLUSIONS: This study confirms an improvement in HRQoL and an increase of IGF-1 SDS in GH-replaced adults, which approximated the values of general population. However, there was no association between IGF-1 values and HRQoL assessment as one of the important treatment outcomes. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the relationships of different insulin-like growth factor-1 (IGF1) measures [5 distinct IGF1 concentrations on particular days, area under the curve (AUC), and linear regression coefficient] in the postpartum period in lactating dairy cows and reproductive performance. A total of 417 healthy multiparous Holstein-Friesian cows were enrolled in the study. Serum samples for the determination of the concentration of IGF1 were collected on d 0, 4, 10, 20, and 40 postpartum (pp). The concentration of total IGF1 in serum was determined by immunometric chemiluminescence immunoassay. All cows were examined for vaginal discharge as a sign of clinical endometritis at 20 d pp by external inspection and rectal palpation. The mean concentration of IGF1 ranged from 57 ± 18.9 ng/mL within the first 12 h pp to 74 ± 19.9 ng/mL at 40 d pp. On d 10 pp, first and all artificial insemination conception rates were greater in cows with IGF1 concentrations above the median compared with cows with IGF1 concentrations below the median. Cows with greater AUC (second to fourth quartile) conceived earlier (11.4, 16.0, and 18.8 d) than cows in the first IGF1 quartile (117.0 ± 43.6). Proportion of cows pregnant within 200 d pp increased significantly from the first to the third IGF1 quartile of AUC (58.7, 66.7, and 74.0%). The proportion of cows culled decreased from the first to the fourth IGF1 quartile. Correlations between IGF1 measures and days to pregnancy were significant (except for the linear regression coefficients) but low (R² = 0.0009 to 0.025). Differences between single or composite measurements of IGF1 were not significant. We could also demonstrate a statistically significant correlation between the concentration of IGF1 in serum and the average 10-d milk production (31.6 to 44.0 kg). In conclusion, our study indicates that single or multiple measurements of IGF1 concentration in the postpartum period have very limited value to predict individual fertility in dairy cows. [ABSTRACT FROM AUTHOR]

IGFs are important regulators of pancreatic beta-cell development, growth, and maintenance. Mutations in the IGF genes have been found to be associated with type 2 diabetes, myocardial infarction, birth weight, and obesity. These associations could result from changes in insulin secretion. We have analyzed glucose-stimulated insulin secretion using hyperglycemic clamps in carriers of a CA repeat in the IGF-I promoter and an ApaI polymorphism in the IGF-II gene. Normal and impaired glucose-tolerant subjects (n = 237) were independently recruited from three different populations in the Netherlands and Germany to allow independent replication of associations. Both first- and second-phase insulin secretion were not significantly different between the various IGF-I or IGF-II genotypes. Remarkably, noncarriers of the IGF-I CA repeat allele had both a reduced insulin sensitivity index (ISI) and disposition index (DI), suggesting an altered balance between insulin secretion and insulin action. Other diabetes-related parameters were not significantly different for both the IGF-I and IGF-II gene variant. We conclude that gene variants in the IGF-I and IGF-II genes are not associated with detectable variations in glucose-stimulated insulin secretion in these three independent populations. Further studies are needed to examine the exact contributions of the IGF-I CA repeat alleles to variations in ISI and DI. [ABSTRACT FROM AUTHOR]

Age related decrease in muscle mass is a strong predictor of health-related outcomes for older adults. Factors related to these decreases in muscle mass include a reduction in physical activity and a weakened anabolic response to dietary protein. Currently there is significant research that suggests the addition of protein supplementation to a resistance training (RT) program can augment many physiological and neuromuscular adaptations to offset the deleterious effect of reduced muscle mass in the older population. PURPOSE: To assess the efficacy of post-exercise Icelandic yogurt consumption on lean mass, strength, and skeletal muscle regulatory factors in healthy untrained older males. METHODS: Thirty healthy untrained older males were randomly assigned to consume Icelandic yogurt (IR; n =15, age: 67 ± 4 yr., body mass: 61.1 ± 4.1 kg, 18 g of protein) or an iso- energetic placebo (PR; n =15, age: 68 ± 4 yr., body mass: 62 ± 3.5 kg, 0 g protein) immediately following supervised RT sessions (3x/week) for 8 weeks. Before and after training, lean mass, strength, and skeletal muscle regulatory factors (insulin-like growth factor 1 [IGF-1], transforming growth factor-beta 1 [TGF-β1], growth differentiation factor 15 [GDF15], activin A, myostatin [MST], and follistatin [FST]) were assessed. RESULTS: There were group x time interactions (p < 0.05) for body mass, lean mass, strength, and all skeletal muscle regulatory factors. Improvements in body mass ( IR: 1 ± 0.7 vs. PR: 0.7 ± 0.7 kg), lean mass (IR: 1.3 ± 0.5 vs. PR: 0.6 ± 0.7 kg ), bench press (IR: 4 ± 1.8 vs. PR: 2.3 ± 1 kg), leg press (IR: 4.2 ± 1.4 vs. PR: 2.5 ± 0.7 kg), IGF-1 (IR: 0.5 ± 0.1 vs. PR: 0.1 ± 0.1 ng/ml), TGF-β1 (IR: -0.2 ± 0.07 vs. PR: -0.09 ± 0.07 ng/ml), GDF15 (IR: -10.3 ± 5.7 vs. PR: -4.8 ± 7.1 pg/ml), activin A (IR: -9.8 ± 4.4 vs. PR: -2.9 ± 4.6 pg/ml), MST (IR: -0.1 ± 0.05 vs. PR: -0.04 ± 0.03 ng/ml), and FST (IR: 0.1 ± 0.05 vs. PR: 0.03 ± 0.02 ng/ml) concentrations in the IR group were significantly (p < 0.05) greater than those of the PR group. CONCLUSIONS: The addition of Icelandic yogurt consumption to a RT program significantly improved lean mass, strength, and skeletal muscle regulatory factors in healthy untrained older males compared to placebo. These findings support the consumption of yogurt dietary protein following RT to improve skeletal muscle adaptations in older men. [ABSTRACT FROM AUTHOR]