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Implications of the variation in biological 18 O natural abundance in body water to inform use of Bayesian methods for modelling total energy expenditure when using doubly labelled water.
RATIONALE: Variation in 18 O natural abundance can lead to errors in the calculation of total energy expenditure (TEE) when using the doubly labelled water (DLW) method. The use of Bayesian statistics allows a distribution to be assigned to 18 O natural abundance, thus allowing a best-fit value to be used in the calculation. The aim of this study was to calculate within-subject variation in 18 O natural abundance and apply this to our original working model for TEE calculation. METHODS: Urine samples from a cohort of 99 women, dosed with 50 g of 20% 2 H2 O, undertaking a 14-day breast milk intake protocol, were analysed for 18 O. The within-subject variance was calculated and applied to a Bayesian model for the calculation of TEE in a separate cohort of 36 women. This cohort of 36 women had taken part in a DLW study and had been dosed with 80 mg/kg body weight 2 H2 O and 150 mg/kg body weight H2 18 O. RESULTS: The average change in the δ18 O value from the 99 women was 1.14‰ (0.77) [0.99, 1.29], with the average within-subject 18 O natural abundance variance being 0.13‰2 (0.25) [0.08, 0.18]. There were no significant differences in TEE (9745 (1414), 9804 (1460) and 9789 (1455) kJ/day, non-Bayesian, Bluck Bayesian and modified Bayesian models, respectively) between methods. CONCLUSIONS: Our findings demonstrate that using a reduced natural variation in 18 O as calculated from a population does not impact significantly on the calculation of TEE in our model. It may therefore be more conservative to allow a larger variance to account for individual extremes
Insulin administration and rate of glucose appearance in people with type 1 diabetes.
OBJECTIVE: To assess whether prandial insulin, in addition to basal insulin, has an effect on the rate of glucose appearance from a meal in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: The rate of glucose appearance from a mixed meal (Ra(meal)) was investigated in six adult (aged 24 +/- 2 years), lean (BMI 23.6 +/- 1.5 kg/m(2)) subjects with well-controlled type 1 diabetes (duration 7.9 +/- 6.9 years, A1C 7.6 +/- 0.9%) with/without prandial insulin. Actrapid was infused to maintain euglycemia before meals were consumed. Subjects consumed two identical meals on separate occasions, and Ra(meal) was measured using a dual isotope method. [6,6-(2)H(2)]glucose was incorporated into the meal (0.081 g/kg body wt), and a primed constant/variable rate infusion of [1,2,3,4,5,6,6-(2)H(2)]glucose was administered. In the tests with prandial insulin, an additional bolus dose of Actrapid was given 20 min before the meal at 0.1 units/kg body wt. RESULTS: Insulin concentration with prandial insulin was significantly higher than during basal insulin studies (119 +/- 16 vs. 66 +/- 15 pmol/l, P = 0.03 by paired t test). Despite differences in insulin concentration, there were no differences in total glucose appearance (3,398 +/- 197 vs. 3,307 +/- 343 micromol/kg) or time taken for 25% (33.1 +/- 3.3 vs. 31.7 +/- 3.5 min), 50% (54.6 +/- 3.5 vs. 54.1 +/- 4.7 min), and 75% (82.9 +/- 7.1 vs. 82.8 +/- 5.8 min) of total glucose appearance. The fraction of the glucose dose appearing in the circulation was the same for basal (73 +/- 8%) and prandial (75 +/- 4%) study days. CONCLUSIONS: These results suggest that meal glucose appearance is independent of prandial insulin concentration in people with type 1 diabetes