Association of metabolic flexibility indexes after an oral glucose tolerance test with cardiometabolic risk factors.

BACKGROUND & AIMS: Metabolic flexibility (MetF) is considered a metabolic health biomarker, as excess body weight is associated with lower MetF. We aimed to identify whether MetF indexes were associated with cardiometabolic risk factors before and after adjustment for body size-related factors (body weight, fat-free mass, and resting metabolic rate). METHODS: We studied 51 participants (55% women; 33.6 ± 8.7 years; 26.3 ± 3.8 kg/m²) who consumed a 75-g glucose load. We measured gas exchange before (fasting) and for 3 h after glucose ingestion. MetF indexes were assessed, including the change after each hour and the 3-hour incremental area under the curve (iAUC) in respiratory exchange ratio (RER). These indexes were then related to cardiometabolic risk factors before and after adjusting for body size-related factors. RESULTS: MetF indexes correlated with each other (r ≥ 0.51; P < 0.001) and related to body weight (adjusted R2 ≥ 0.09; P < 0.03). A similar pattern was noted for fat-free mass and resting metabolic rate. MetF, regardless of the index, was not related to cardiometabolic risk factors except to BMI and high-density lipoprotein-cholesterol (HDL-C). The association between BMI and MetF disappeared after adjusting for body size-related factors. Similar adjustments did not modify the association between HDL-C and MetF, especially when approached by the change in RER after the first hour (adjusted R2 = 0.20-0.22; all P < 0.02). CONCLUSIONS: Inter-individual body size differences fully accounted for the associations between BMI and MetF. However, variability in body size-related factors appeared less relevant in affecting the associations of other cardiometabolic risk factors with MetF.

Impact of methods for data selection on the day-to-day reproducibility of resting metabolic rate assessed with four different metabolic carts.

BACKGROUND AND AIMS: Accomplishing a high day-to-day reproducibility is important to detect changes in resting metabolic rate (RMR) and respiratory exchange ratio (RER) that may be produced after an intervention or for monitoring patients' metabolism over time. We aimed to analyze: (i) the influence of different methods for selecting indirect calorimetry data on RMR and RER assessments; and, (ii) whether these methods influence RMR and RER day-to-day reproducibility. METHODS AND RESULTS: Twenty-eight young adults accomplished 4 consecutive RMR assessments (30-min each), using the Q-NRG (Cosmed, Rome, Italy), the Vyntus CPX (Jaeger-CareFusion, Höchberg, Germany), the Omnical (Maastricht Instruments, Maastricht, The Netherlands), and the Ultima CardiO2 (Medgraphics Corporation, St. Paul, Minnesota, USA) carts, on 2 consecutive mornings. Three types of methods were used: (i) short (periods of 5 consecutive minutes; 6-10, 11-15, 16-20, 21-25, and 26-30 min) and long time intervals (TI) methods (6-25 and 6-30 min); (ii) steady state (SSt methods); and, (iii) methods filtering the data by thresholding from the mean RMR (filtering methods). RMR and RER were similar when using different methods (except RMR for the Vyntus and RER for the Q-NRG). Conversely, using different methods impacted RMR (all P ≤ 0.037) and/or RER (P ≤ 0.009) day-to-day reproducibility in all carts. The 6-25 min and the 6-30 min long TI methods yielded more reproducible measurements for all metabolic carts. CONCLUSION: The 6-25 min and 6-30 min should be the preferred methods for selecting data, as they result in the highest day-to-day reproducibility of RMR and RER assessments.

Validity of four commercially available metabolic carts for assessing resting metabolic rate and respiratory exchange ratio in non-ventilated humans.

BACKGROUND & AIMS: The validity of most commercially available metabolic cart is mostly unknown. Thus, we aimed to determine the accuracy, precision, within-subject reproducibility, and concordance of RMR and RER measured by four commercially available metabolic carts [Cosmed Q-NRG, Vyaire Vyntus CPX, Maastricht Instruments Omnical, and Medgraphics Ultima CardiO2]. Further, we studied whether a previously proposed simulation-based post-calorimetric calibration of cart readouts [individual calibration control evaluation (ICcE)] modify the RMR and RER reproducibility and concordance. METHODS: Three experiments simulating different RMR and RER by controlled pure gas (N2 and CO2) infusions were conducted on 5 non-consecutive days. Moreover, 30-min methanol burns were performed on 3 non-consecutive days. Lastly, the RMR and RER of 29 young non-ventilated adults (11 women; 25 ± 4 years-old; BMI: 24.1 ± 3.2 kg/m2) were assessed twice using each instrument, 24 hours apart, under standardized conditions. RESULTS: The Omnical presented the lowest measurement error for RER (Omnical = 1.7 ± 0.9%; Vyntus = 4.5 ± 2.0%; Q-NRG = 6.6 ± 1.9%; Ultima = 6.8 ± 6.5%) and EE (Omnical = 1.5 ± 0.5%; Q-NRG = 2.5 ± 1.3%; Ultima = 10.7 ± 11.0%; Vyntus = 13.8 ± 5.0%) in all in vitro experiments (controlled pure gas infusions and methanol burns). In humans, the 4 metabolic carts provided discordant RMR and RER estimations (all P < 0.001). No differences were detected in RMR within-subject reproducibility (P = 0.058; Q-NRG inter-day coefficient of variance = 3.6 ± 2.5%; Omnical = 4.8 ± 3.5%; Vyntus = 5.0 ± 5.6%; Ultima = 5.7 ± 4.6%), although the Ultima CardiO2 provided larger RER inter-day differences (4.6 ± 3.5%) than the others carts (P = 0.001; Omnical = 1.9 ± 1.7%; Vyntus = 2.1 ± 1.3%; Q-NRG = 2.4 ± 2.1%). The ICcE procedure did not modify the RMR or RER concordance and did not reduce the inter-day differences in any of the carts. CONCLUSIONS: The 4 metabolic carts provided discordant measurements of RMR and RER. Overall, the Omnical provides more accurate and precise estimations of RMR and RER than the Q-NRG, Vyntus and Ultima CardiO2, and might be considered the best for assessing RMR and RER in non-ventilated humans. Finally, our results do not support the use of an ICcE procedure.

Diurnal variations of cold-induced thermogenesis in young, healthy adults: A randomized crossover trial.

BACKGROUND: Harnessing cold-induced thermogenesis (CIT) and brown adipose tissue (BAT) activity has been proposed as a means of counteracting a positive energy balance, and thus of combating obesity and its related comorbidities. However, it has remained unclear whether CIT and BAT activity show diurnal variation in humans - knowledge that might allow treatments based on these factors to be time-optimized. METHODS: A randomized crossover experiment was designed to examine whether CIT shows morning/evening variation in young, healthy adults (n = 14, 5 women). On the first experimental day, subjects' shivering thresholds were determined following a cooling protocol. After ≈96 h had elapsed, the subjects then returned on two further days (approx. 48 h apart) at 08:00 h or 18:00 in random order. On both the latter days, the resting energy expenditure (REE) was measured before the subjects underwent personalized cold exposure (i.e., according to their shivering threshold). CIT was then assessed for 60 min by indirect calorimetry. In an independent cross-sectional study (n = 133, 88 women), subjects came to the laboratory between 8:00 and 18:00 h and their BAT 18F-fluordeoxyglucose (18F-FDG) uptake was assessed after personalized cold stimulation. RESULTS: Both the REE and CIT were similar in the morning and evening (all P > 0.05). Indeed, 60 min of personalized-mild cold exposure in the morning or evening elicited a similar change in energy expenditure (16.8 ± 12.8 vs. 15.7 ± 15.1% increase above REE, P = 0.72). BAT 18F-FDG uptake was also similar in the morning, evening and afternoon (all P > 0.05). CONCLUSION: CIT does not appear to show morning/evening variation in young healthy adults, with the current study design and methodology. BAT 18F-FDG uptake appears not to change across the day either, although experiments with a within-subject study design are needed to confirm these findings. Registered under ClinicalTrials.gov Identifier no. NCT02365129.

Cardiovascular Risk Factors and Heart Rate Variability: Impact of the Level of the Threshold-Based Artefact Correction Used to Process the Heart Rate Variability Signal.

The associations between cardiovascular disease (CVD) risk factors and heart rate variability (HRV) have shown some inconsistencies. To examine the impact of the different Kubios threshold-based artefact correction levels on the associations between different CVD risk factors and a heart rate variability (HRV) score in three independent human cohorts. A total of 107 children with overweight/obesity, 132 young adults, and 73 middle-aged adults were included in the present study. Waist circumference and the HRV score were negatively associated using the medium and the strong Kubios filters in children (ß = -0.22 and - 0.24, P = 0.03 and 0.02 respectively) and the very strong Kubios filter in middle-aged adults (ß = -0.39, P = 0.01). HDL-C was positively associated with the HRV score across Kubios filters (ß ranged from 0.21 to 0.31, all P ≤ 0.04), while triglycerides were negatively associated with the HRV score using the very strong Kubios filter in young adults (ß = -0.22, P = 0.02). Glucose metabolism markers (glucose, insulin, and HOMA index) were inversely associated with the HRV score across Kubios filters in young adults (ß ranged from -0.29 to -0.22; all P ≤ 0.03). Importantly, most of these associations disappeared after including HR as a covariate, especially in children and young adults. It should be mandatory to report the Kubios filter used and to include the HR (as a confounder factor) to allow the comparability of the results across different studies.

Inter- and intra-researcher reproducibility of heart rate variability parameters in three human cohorts.

Heart rate variability (HRV) is a valid and non-invasive indicator of cardiac autonomic nervous system functioning. Short-term HRV recordings (e.g., 10 min long) produce data that usually is manually processed. Researcher subjective decision-making on data processing could produce inter- or intra-researcher differences whose magnitude has not been previously quantified in three independent human cohorts. This study examines the inter- and intra-researcher reproducibility of HRV parameters (i.e., the influence of R-R interval selection by different researchers and by the same researcher in different moments on the quantification of HRV parameters, respectively) derived from short-term recordings in a cohort of children with overweight/obesity, young adults and middle-age adults. Participants were recruited from 3 different studies: 107 children (10.03 ± 1.13 years, 58% male), 132 young adults (22.22 ± 2.20 years, 33% males) and 73 middle-aged adults (53.62 ± 5.18 years, 48% males). HRV was measured using a Polar RS800CX heart rate monitor. The intraclass correlation coefficient (ICC) ranged from 0.703 to 0.989 and from 0.950 to 0.998 for inter-and intra-researcher reproducibility, respectively. Limits of agreement for HRV parameters were higher for the inter-researcher processing compared with the intra-researcher processing. On average, the intra-researcher differences were 31%, 62%, and 80% smaller than the inter-researchers differences based on Coefficient of Variation in children, young and middle-aged adults, respectively. Our study provides the quantification of the inter-researcher and intra-researcher differences in three independent human cohorts, which could elicit some clinical relevant differences for HRV parameters. Based on our findings, we recommend the HRV data signal processing to be performed always by the same trained researcher and we postulate a development of algorithms for an automatic ECG selection.

Congruent validity and inter-day reliability of two breath by breath metabolic carts to measure resting metabolic rate in young adults.

BACKGROUND & AIMS: Achieving high inter-day reliability is a key factor to analyze the magnitude of change in RMR, for instance after an intervention. The aims of this study were: i) to determine the congruent validity of RMR and respiratory quotient (RQ) with two breath by breath commercially available metabolic carts [CCM Express (CCM) and Ultima CardiO2 (MGU)]; and ii) to analyze the inter-day reliability of RMR and RQ measurements. METHODS & RESULTS: Seventeen young adults participated in the study. RMR measurements were performed during two consecutive 30-min periods, on two consecutive days with both metabolic carts. The 5-min period that met the steady state criteria [Coefficient of variance (CV) < 10% for VO2, VCO2, and VE, and CV<5% for RQ] and with the lowest CV average was included in further analysis. RMR values were higher with the MGU than with the CCM on both days (two-way ANOVA, P = 0.021), however, no differences were found on RQ values obtained by both metabolic carts (P = 0.642). Absolute inter-day RMR differences obtained with the MGU were higher than those obtained with the CCM (219 ± 185 vs. 158 ± 154 kcal/day, respectively, P = 0.002; 18.3 ± 17.2% vs. 13.5 ± 15.3%, respectively, P = 0.046). We observed a significant positive association of absolute inter-day differences in RMR obtained with both metabolic carts (ß = 0.717; R2 = 0.743; P < 0.001). CONCLUSIONS: The CCM metabolic cart provides lower RMR values and seems more reliable than the MGU in our sample of young adults. Our findings also suggest that a great part of inter-day variability is explained by the individuals.