Search

Objective: Previous studies suggested that recombinant human IGF‐1 (rhIGF‐1) administration affects carbohydrate and lipid metabolism in healthy people and in people with diabetes. This study aimed to determine the effects of rhIGF‐1/rhIGF binding protein‐3 (rhIGFBP‐3) administration on glucose homeostasis and lipid metabolism in healthy recreational athletes. Design and Setting: Randomized, double‐blind, placebo‐controlled rhIGF‐1/rhIGFBP‐3 administration study at Southampton General Hospital, UK. Participants: 56 recreational athletes (30 men, 26 women). Methods: Participants were randomly assigned to receive placebo, low‐dose rhIGF‐1/rhIGFBP‐3 (30 mg/day) or high‐dose rhIGF‐1/rhIGFBP‐3 (60 mg/day) for 28 days. The following variables were measured before and immediately after the treatment period: fasting lipids, glucose, insulin, C‐peptide and glycated haemoglobin. The homeostatic model assessment (HOMA‐IR) was used to estimate insulin sensitivity and indirect calorimetry to assess substrate oxidation rates. The general linear model approach was used to compare treatment group changes with the placebo group. Results: Compared with the placebo group, there was a significant reduction in fasting triglycerides in participants treated with high‐dose rhIGF‐1/rhIGFBP‐3 (p =.030), but not in the low‐dose group (p =.390). In women, but not in men, there were significant increases in total cholesterol (p =.003), HDL cholesterol (p =.001) and LDL cholesterol (p =.008). These lipid changes were associated with reduced fasting insulin (p =.010), C‐peptide (p =.001) and HOMA‐IR (p =.018) in women and reduced C‐peptide (p =.046) in men. Conclusions: rhIGF‐1/rhIGFBP‐3 administration for 28 days reduced insulin concentration, improved insulin sensitivity and had significant effects on lipid profile including decreased fasting triglycerides. [ABSTRACT FROM AUTHOR]

This paper is motivated by the GH‐2000 biomarker test, though the discussion is applicable to other diagnostic tests. The GH‐2000 biomarker test has been developed as a powerful technique to detect growth hormone misuse by athletes, based on the GH‐2000 score. Decision limits on the GH‐2000 score have been developed and incorporated into the guidelines of the World Anti‐Doping Agency (WADA). These decision limits are constructed, however, under the assumption that the GH‐2000 score follows a normal distribution. As it is difficult to affirm the normality of a distribution based on a finite sample, nonparametric decision limits, readily available in the statistical literature, are viable alternatives. In this paper, we compare the normal distribution–based and nonparametric decision limits. We show that the decision limit based on the normal distribution may deviate significantly from the nominal confidence level 1−α or nominal FPR γ when the distribution of the GH‐2000 score departs only slightly from the normal distribution. While a nonparametric decision limit does not assume any specific distribution of the GH‐2000 score and always guarantees the nominal confidence level and FPR, it requires a much larger sample size than the normal distribution–based decision limit. Due to the stringent FPR of the GH‐2000 biomarker test used by WADA, the sample sizes currently available are much too small, and it will take many years of testing to have the minimum sample size required, in order to use the nonparametric decision limits. Large sample theory about the normal distribution–based and nonparametric decision limits is also developed in this paper to help understanding their behaviours when the sample size is large. [ABSTRACT FROM AUTHOR]

The GH-2000 score has been developed as a powerful and unique technique for the detection of growth hormone misuse by sportsmen and women. The score depends upon the measurement of two growth hormone sensitive markers, insulin-like growth factor-I and the amino-terminal pro-peptide of type III collagen. It also includes a term to adjust for the age of the athlete. Decision limits for the GH-2000 score have been developed and are incorporated into the guidelines of the World Anti-Doping Agency. These decision limits are derived by setting a 1 in 10,000 false-positive rate rule. As these decision limits are estimated from samples of GH-2000 scores, they carry uncertainty. In previous work, this uncertainty has been addressed by establishing an upper 95% confidence interval for the true decision limits based on a normal approximation which has been shown to be appropriate if sample sizes are large (such as 1000 and above). Here, we show that these approximations, whether reasonable or not, can be entirely avoided by developing an upper 95% confidence interval for the true decision limits using an approach based upon the t-distribution. While there are considerable differences for smaller sample sizes, these become negligible when the sample size is large such as 1000 and above. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-I (IGF-I) is abused by elite athletes for its metabolic and anabolic effects. We have previously shown that it is possible to detect IGF-I misuse by measuring serum IGF-I and procollagen type III amino-terminal propeptide (P-III-NP) but a pilot study suggested measuring IGF-II, IGF binding protein-2 (IGFBP-2) and acid-labile subunit (ALS) may improve the detection of IGF-I administration. The aim of the study was to assess this in a randomized controlled trial. Twenty-six female and 30 male recreational athletes were randomized to 28 days' treatment with placebo or recombinant human (rh)IGF-I/rhIGF binding protein-3 (IGFBP-3) complex (30 mg/day or 60 mg/day), followed by 56 days' washout. IGF-II, IGFBP-2 and ALS (women only) were measured using commercial immunoassays. IGFBP-2 increased and IGF-II decreased in response to both low and high dose rhIGF-I/rhIGFBP-3 in both women and men while ALS decreased in women in response to high dose rhIGF-I/rhIGFBP-3. Two days after discontinuing treatment, significant differences remained between the three treatment groups in IGFBP-2 and IGF-II, but not ALS. Thereafter there were no significant differences between the three treatment groups in any of the markers. Combining IGF-I with IGF-II and/or IGFBP-2 improved the performance of the test to detect rhIGF-I/rhIGFBP-3 administration in both women and men. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]