The potential for utilising in-hospital glucose measurements to detect individuals at high risk of previously undiagnosed diabetes: retrospective cohort study

Background Many people with undiagnosed diabetes have hyperglycaemia when admitted to hospital. Inpatient hyperglycaemia can be an indication of diabetes mellitus but can also indicate a stress response. This study reports the extent to which an in-hospital maximum observed random glucose measurement is an indicator of the need for in-hospital (or subsequent) HbA1c measurement to look for undiagnosed diabetes. Methods Blood glucose, HbA1c, age and sex were collected for all adults following admission to a UK NHS trust hospital from 1 January 2019 to 31 December 2020. We restricted the analysis to those participants who were registered with a GP practice that uses the trust laboratory and who had at least some tests requested by those practices since 2008. We stratified individuals according to their maximum in-hospital glucose measurement and report the number of these with HbA1c measurement ≥48 mmol/mol (6.5%) prior to the index admission, and during and after admission. We calculated an estimated proportion of individuals in each blood glucose stratum without a follow-up HbA1c who could have undiagnosed diabetes. Results In toal, 764,241 glucose measurements were recorded for 81,763 individuals who were admitted to the Oxford University Hospitals Trust. The median (Q1, Q3) age was 70 (56, 81) years, and 53% were males. Of the population, 70.7% of individuals declared themselves to be of White ethnicity, 3.1% of Asian background, and 1.1% of Black background, with 23.1% unstated. Of those individuals, 22,375 (27.4%) had no previous HbA1c measurement recorded. A total of 1689 individuals had a diabetes-range HbA1c during or after their hospital admission (2.5%) while we estimate an additional 1496 (2.2%) may have undiagnosed diabetes, with the greatest proportion of these having an in-hospital glucose of ≥15 mmol/L. We estimate that the number needed to detect a possible new case of diabetes falls from 16 (in-hospital glucose 8 mmol/L to <9 mmol/L) to 4 (14 mmol/L to <15 mmol/L). Conclusion The number of people who need to be tested to identify an individual who may have diabetes decreases as a testing threshold based on maximum in-hospital glucose concentration increases. Among those with hyperglycaemia and no previous HbA1c measurement in the diabetes range, there appears to be a lack of subsequent HbA1c measurement. This work identifies the potential for integrating the testing and follow-up of people, with apparently unrecognised hospital hyperglycaemia across primary and secondary care

Statistical methodology for age-adjustment of the GH-2000 score detecting growth hormone misuse

Background: 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 (GH) sensitive markers, insulin-like growth factor-I (IGF-I) and the amino-terminal pro-peptide of type III collagen (P-III-NP). With the collection and establishment of an increasingly large database it has become apparent that the score shows a positive age effect in the male athlete population, which could potentially place older male athletes at a disadvantage.Methods: We have used results from residual analysis of the general linear model to show that the residual of the GH-2000 score when regressed on the mean-age centred age is an appropriate way to proceed to correct this bias. As six GH-2000 scores are possible depending on the assays used for determining IGF-I and P-III-NP, methodology had to be explored for including six different age effects into a unique residual. Meta-analytic techniques have been utilized to find a summary age effect.Results: The age-adjusted GH-2000 score, a form of residual, has similar mean and variance as the original GH-2000 score and, hence, the developed decision limits show negligible change when compared to the decision limits based on the original score. We also show that any further scale-transformation will not change the adjusted score. Hence the suggested adjustment is optimal for the given data. The summary age effect is homogeneous across the six scores, and so the generic adjustment of the GH-2000 score formula is justified.Conclusions: A final revised GH-2000 score formula is provided which is independent of the age of the athlete under consideration.<br/

The effects of recombinant human insulin-like growth factor-I/Insulin-like growth factor binding protein-3 administration on body composition and physical fitness in recreational athletes

Context:Insulin-like growth factor-I (IGF-I) is thought to mediate many of the anabolic actions of growth hormone (GH) and there are anecdotal reports that IGF-I is misused by elite athletes. There is no published evidence regarding the effects of IGF-I administration on athletic performance.Objective:To investigate the effects of IGF-I administration on body composition and physical fitness in recreational athletes.Design and Setting:Randomised, double-blind, placebo-controlled rhIGF-I/rhIGFBP-3 administration study at Southampton General Hospital, UK.Participants:56 recreational athletes (30 men, 26 women)Intervention:Participants were randomly assigned to receive placebo, low dose rhIGF-I/rhIGFBP-3 (30 mg/day) or high dose rhIGF-I/rhIGFBP-3 (60 mg/day) for 28 days. Body composition (assessed by Dual Energy X-ray Absorptiometry) and cardiorespiratory fitness (assessed by incremental treadmill test), were measured before and immediately after treatment. Within-individual changes after treatment were analysed using paired t-tests.Results:There were no significant changes in body fat mass or lean body mass in women or men after administration of rhIGF-I/rhIGFBP-3 complex. There was a significant increase in maximal oxygen consumption (VO2 max) after treatment. When women and men and low and high dose treatment groups were combined, mean VO2 max increased by approximately 7% (P = 0.001). No significant change in VO2 max was observed in the placebo group.Conclusions:rhIGF-I/rhIGFBP-3 administration for 28 days improves aerobic performance in recreational athletes but there are no effects on body composition.<br/

Insulin-like growth factor-I (IGF-I) misue in athletes and potential methods for detection

To athletes, insulin-like growth factor-I (IGF-I) is an attractive performance-enhancing drug, particularly as an alternative to growth hormone (GH) because IGF-I mediates many of the anabolic actions of GH. IGF-I has beneficial effects on muscle protein synthesis and glycogen storage that could enhance performance in several sporting disciplines. Recombinant human IGF-I (rhIGF-I) is used in clinical practice, but a variety of IGF-I compounds and IGF-I analogues are also advertised on the internet and many have been available on the black market for several years. Although methods for detecting GH misuse are now well established and there have been several cases in which athletes have tested positive for GH, no test is yet in place for detecting IGF-I misuse. The GH-2004 research group has been investigating methods for detection of IGF-I misuse and a test is being developed on the basis of the principles of the successful GH-2000 marker method, in which markers from the IGF axis and markers of collagen and bone turnover are used to detect GH misuse. Commercial immunoassays for these markers have been validated for anti-doping purposes but new methods, including IGF-I measurement by use of mass spectrometry, should improve the performance of the tests and help in the detection of athletes who are doping with these peptide hormones

IGF-I abuse in sport

It is widely believed that growth hormone (GH) is abused by athletes for its anabolic and lipolytic effects. Many of the physiological effects of GH are mediated by the production of insulin-like growth factor-I (IGF-I). Both GH and IGF-I appear on the World Anti-Doping Agency list of prohibited substances. Little is known, however, about the prevalence of abuse with exogenous IGF-I. IGF-I has effects on carbohydrate, lipid and protein metabolism and some of these actions could prove beneficial to competitive athletes. No studies have demonstrated a positive effect of IGF-I on physical performance in healthy individuals but this has not yet been studied in appropriately designed trials. Two pharmaceutical preparations of IGF-I have recently become available for the treatment of growth disorders in children. This availability is likely to increase the prevalence of IGF-I abuse. Combining IGF-I with its binding protein IGFBP-3 in one preparation has the potential to reduce the side-effect profile but the adverse effects of long term IGF-I abuse are currently unknown. Detection of abuse with IGF-I is a major challenge for anti-doping authorities. It is extremely difficult to distinguish the exogenous recombinant form of the hormone from endogenously-produced IGF-I. One approach currently being investigated is based on measuring markers of GH and IGF-I action. This has already proved successful in the fight against GH abuse and, it is hoped, will subsequently lead to a similar test for detection of IGF-I abuse.<br/

Silicon nanowires, carbon nanotubes, and magnetic nanocrystals: synthesis, properties, and applications

textCentral to the practical use of nanoscale materials is the controlled growth in technologically meaningful quantities. Many of the proposed applications of the nanomaterials potentially require inexpensive production of the building blocks. Solution-based synthetic approach offers controllability, high throughput, and scalability, which make the process attractive for the potential scale-up. Growth kinetics could be readily influenced by chemical interactions between the precursor and the solvent. In order to fully utilize its benefits, it is therefore pivotal to understand the decomposition chemistry of the precursors used in the reactions. Supercritical fluids were used as solvent in which high temperature reactions could take place. Silicon nanowires with diameters of 20~30 nm was synthesized in supercritical fluids with metal nanocrystals as seeds for the nanowire growth. To unravel the effect of silicon precursors, several silicon precursors were reacted and the resulting products were investigated. The scalability of the system is discussed based on the experimental data. The nanowires were characterized with various characterization tools, including high-resolution transmission electron microscopy and electron energy loss spectroscopy. The crystallographic signatures were analyzed through the transmission electron microscopic study, and fundamental electrical and optical properties were probed by electron energy loss spectroscopy. Carbon nanotubes were prepared by reacting carbon-containing chemicals in supercritical fluids with organometallic compounds that form metal seed particles in-situ. A batch reaction, in which the temperature control was relatively poor, yielded a mixture of multiwall nanotubes and amorphous carbon nanofilaments with a low selectivity of nanotubes in the product. When reaction parameters were translated into a continuous flow-through reaction, nanotube selectivity as well as the throughput of the total product significantly improved. Magnetic properties of various metal nanocrystals were also studied. Colloidal synthesis enables the growth of FePt and MnPt3 nanocrystals with size uniformity. The as-synthesized nanocrystals, however, had compositionally disordered soft-magnetic phases. To obtain hard magnetic layered phase, the nanocrystals must be annealed at high temperatures, which led to sintering of the inorganic cores. To prevent sintering, the nanocrystals were encapsulated with silica layer prior to annealing. Interparticle magnetic interactions were also explored using particles with varying silica thickness.Chemical Engineerin