Background The independent and joint association of metformin and testosterone replacement therapy (TTh) with the incidence of prostate, colorectal, and male breast cancers remain poorly understood, including the investigation of the risk of these cancers combined (HRCs, hormone‐associated cancers) among men of different racial and ethnic background. Methods In 143,035 men (≥ 65 yrs old) of SEER‐Medicare 2007–2015, we identified White (N = 110,430), Black (N = 13,520) and Other Race (N = 19,085) men diagnosed with incident HRC. Pre‐diagnostic prescription of metformin and TTh was ascertained for this analysis. Weighted multivariable‐adjusted conditional logistic and Cox proportional hazards models were conducted. Results We found independent and joint associations of metformin and TTh with incident prostate (odds ratio [OR]joint = 0.44, 95% confidence interval [CI]: 0.36–0.54) and colorectal cancers (ORjoint = 0.47, 95% CI: 0.34–0.64), but not with male breast cancer. There were also inversed joint associations of metformin and TTh with HRCs (ORjoint = 0.45, 95% CI: 0.38–0.54). Similar reduced associations with HRCs were identified among White, Black, and Other Race men. Conclusion Pre‐diagnostic use of metformin and TTh were, independently and jointly, inversely associated with incident prostate and colorectal cancers. The risk of HRCs was also reduced among White, Black and Other Race men. Greatest reduced associations of prostate and colorectal cancers and HRCs were mainly observed in combination of metformin and TTh. Larger studies are needed to confirm the independent and joint association of metformin plus TTh with these cancers in understudied and underserved populations.

IntroductionSevere burn injury initiates a prolonged stress response which results in hypermetabolism and increased resting energy expenditure. While adequate nutritional provision is imperative to mitigate losses in weight and lean mass following burn trauma, typically total energy expenditure (TEE) and caloric requirements are indirectly estimated from resting energy expenditure (REE). The doubly labelled water (DLW) method allows the direct quantification of TEE in free‐living individuals. The aim of this study was to use DLW to calculate the TEE of severely burned children during their acute hospitalization and outpatient rehabilitation.MethodsFifteen children aged 6–15 years with at least 30% of total body surface area (TBSA) burned admitted to Shriners Hospital for Children – Galveston were recruited. Eight children were studied during their acute hospitalization. Seven children were measured after hospital discharge during their outpatient rehabilitation program. TEE was determined following a 1.5g– 3g/kg dose of 2H218O water (DLW). Urine was collected before DLW administration and then daily for a period of 5–7 days for the acute patients and 14 days for the outpatient group. The elimination of 2H and 18O from body water was used to determine whole body combustion (CO2 production) from which TEE was calculated. Resting energy expenditure was also measured by indirect calorimetry during the study period.ResultsOf the 15 total patients, there were 3 females in the acute and 2 in the exercise group. Mean age was 10 ± 3 years (range, 6–15), mean weight on first study day was 37.3 ± 13.2 kg (range, 20.6–55.3) and mean burn size was 51% ± 17% (range, 30%–83%) of TBSA. For the acute group, study started on average on 22 ± 6 days post burn and for the outpatient group on 52 ± 29 days. Acute patients had a daily TEE that was 1.46 ± 0.27 times greater than measured REE (range, 1.12–1.87). This amounted to an energy requirement of 61 ± 16 kcal/kg/day (range, 42–90). Acute patients with full thickness burns >60% of TBSA had a TEE 1.8 times greater than measured REE. Outpatients had average daily TEE measured as 1.32 ± 0.12 times REE (range, 1.12–1.53), equating to an energy requirement of 53 ± 11 kcal/kg/day (range, 45–74).ConclusionsAcutely injured burn patients have a TEE that is 40–50% greater than REE, despite being largely immobilized. Patients with very large burns (>60% TBSA) have a TEE that is up to 80% greater than REE during their acute hospitalization. Following hospital discharge, TEE is around 30% greater than REE in burned children despite the fact that these patients are now ambulated, suggesting resolution of burn induced hypermetabolism. These preliminary data may be useful in forming guidelines for nutritional therapy in patients with severe burns.Support or Funding InformationThis work was funded by NIH (P50 GM060338 and R01 GM056687) and SHC (84080 and 80490)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

BackgroundStable isotope methods are currently the most accurate in vivo approach to estimate protein kinetics. Tracers are molecules where atoms on their structure have been exchanged with heavier isotopes. The determination of substrate kinetics is possible through the administration of a tracer molecule and subsequent measurement of enrichment (ratio of tracer‐to‐tracee, TTR) over time. The attachment of heavier atoms on molecules results in a shift in the tracer's mass distribution therefore, mass spectrometry readings should be processed to obtain the true TTR. Usually, the correction is done by applying the “skew” correction factor. While improvement is achieved, differences remain between theoretical estimations and actual experimental results. We hypothesize that accounting for tracer's isotopic purity would further improve TTR estimation.MethodsThe L‐[ring‐13C6] Phenylalanine (Cambridge Isotope Laboratories, Andover, MA, USA) with nominal isotopic purity of 99% was used. The TBDMS derivative was prepared and signal intensities at mass spectra 340, 341, 342, 343 (M4, M5, M6, M7) (corresponding to the fragment C17H30N1Si2) were measured using GC‐MS (model 5973, Hewlett‐Packard Co., Palo Alto, CA). Using the binomial and multinomial distributions the most likely value of isotopic purity of the tracer was estimated. Subsequently, three mixtures of unlabeled phenylalanine with varying amounts of tracer were prepared yielding samples with TTR of 0.5%, 4% and 20% respectively. The samples were processed as described above and intensities at mass spectra 336 (M0), 341 (M5) and 342 (M6) were measured. Having established the tracer's isotopic purity, intensities at M0, M5 and M6 were modeled as linear combination of tracer and tracee masses using least squares method and TTR was estimated as the ratio of the two regression coefficients. TTR was also estimated with the traditional method by applying the “skew” correction factor to the signal intensities ratio M6/M0.ResultsThe tracer's isotopic purity was estimated at 99.1%, corresponding to 71% and 4.7% of relative mass at mass numbers 342 (M6) and 341 (M5) respectively. The estimated TTR of the samples with known TTR of 0.5%, 4% and 20% using the traditional method were 0.46%, 3.75% and 19.1% (error of 8%, 6.25% and 4.5%) respectively. With the new method estimated TTR were 0.52%, 3.97%, 20.2% (errors of 4%, 0.7%, 1%) respectively.ConclusionsOur preliminary data suggest mild improvement in TTR estimation. We expect the new method to significantly improve TTR estimates in samples containing multiple tracers with overlapping spectra and more accurate determination of muscle protein kinetics calculated through complicated formulas and rely on exponential decay modeling.Support or Funding InformationThis work was supported by grants from NIH (P50 GM060338, R01 GM056687, T32 GM008256, R01 HD049471, K01 HL070451), NIDILRR (90DP00430100), Shriners of North America (SHC 84080, SHC 84090)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.