Edited by: Greg Smith, University of New South Wales, Australia
Reviewed by: Denis P. Blondin, Université de Sherbrooke, Canada; Susanna Iossa, University of Naples Federico II, Italy
Specialty section: This article was submitted to Obesity, a section of the journal Frontiers in Endocrinology
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There is increasing interest in the use of pill-sized ingestible capsule telemetric sensors for assessing core body temperature (Tc) as a potential indicator of variability in metabolic efficiency and thrifty metabolic traits. The aim of this study was to investigate the feasibility and accuracy of measuring Tc using the CorTemp® system.
Tc was measured over an average of 20 h in 27 human subjects, with measurements of energy expenditure made in the overnight fasted state at rest, during standardized low-intensity physical activity and after a 600 kcal mixed meal. Validation of accuracy of the capsule sensors was made
The circadian Tc profile classically reported in free-living humans was confirmed. Significant increases in Tc (+0.2°C) were found in response to low-power cycling at 40–50 W (~3–4 METs), but no changes in Tc were detectable during low-level isometric leg press exercise (<2 METs) or during the peak postprandial thermogenesis induced by the 600 kcal meal. Issues of particular interest include fast “turbo” gut transit with expulsion time of <15 h after capsule ingestion in one out of every five subjects and sudden erratic readings in teletransmission of Tc. Furthermore,
Since Tc is regulated within a very narrow range in the healthy homeotherm’s body (within 1°C), physiological investigations of Tc require great accuracy and precision (better than 0.1°C). Although ingestible capsule methodology appears of great interest for non-invasively monitoring the transit gut temperature, new technology requires a reduction in the inherent error of measurement and elimination of temperature drift and warrants more interlaboratory investigation on the above factors.
During the past decades, there has been considerable debate about the potential role of a low resting energy expenditure (EE) as a “thrifty” metabolic trait in the development of obesity (
To date, however, Tc comparisons between lean and obese subjects have yielded conflicting results (
The aim of this study, therefore, was twofold: (i) to assess the feasibility of measuring Tc using the CorTemp® system in a group of individuals of varying body weight and adiposity under free-living conditions, as well as under standardized laboratory conditions with concomitant EE measurements and (ii) to determine the accuracy of Tc capsules of the CorTemp® system compared with gold standard mercury (Hg) thermometers.
A total of 27 subjects (9 men and 18 women), aged (mean ± SD) 25 ± 6 years, were recruited from university advertisements (
Core body temperature was monitored using ingestible capsules (CorTemp®, HQ Inc., Palmetto, FL, USA): weight 2.75 g, length 23 mm, and diameter 10.25 mm. As the capsule transits through the GI tract, it transmits the temperature measurement values every 20 s
An outline of the entire study protocol is illustrated in Figure
Study design. Capsules were ingested prior to 18:00 the night before the experiment. Subjects were instructed to take their evening meal no later than 12 h before their scheduled test the following morning to ensure all subjects were fasted for ~12 h. Subjects were given instructions on when to go to bed and to wake up the next morning and were advised to take motorized/public transport to the laboratory. Following a rest period, baseline resting energy expenditure (REE) measurements were taken for 30 min, followed by a series of low-intensity exercise tests, and followed by a 600 kcal mixed meal.
The ingestible capsule temperature sensors were validated for accuracy against two Hg thermometers (range 34–42°C; VWR, Dietikon, Switzerland). These two thermometers were compared against a third Hg thermometer with a larger temperature range (0–100°C), which was calibrated using ice (0°C) before reading. Each ingestible capsule was fixed in place in a digital water bath (2.6 L; VWR, Dietikon, Switzerland) directly adjacent to the two Hg thermometers, as well as two electronic EBI310 thermometers with TPX220 probes (EBRO, Ingolstadt, Germany). All equipment were placed in the water bath prior to stepwise heating and during the gradual increase in temperature from room temperature to a starting temperature of 35°C. Based on previous papers reporting submersion times in the range of 4–5 min with multiple submersion temperatures (
Temperature values for both studies were downloaded from the CorTemp® recording device. For the
Data on changes in EE or Tc across time in response to exercise or meal were assessed by ANOVA with repeated measures. For the
The time for the capsules to pass through the GI tract was found to be 31 h on average (range 13–82 h), with evacuation time of ≤15 h in five subjects (24%; Figure
Expulsion times of capsules after ingestion. Complete data available for 21 (out of 24) subjects. Bar chart illustrates the percentage of subjects who expelled the Tc capsule over a period of 13–82 h. Beyond the experimental time period in the laboratory, the precise time of capsule evacuation was unknown for obese subjects (
A decline in night time Tc was observed for all subjects in the current study; a typical sleep pattern for one subject is shown in Figure
Nocturnal changes in core body temperature in one subject. A typical Tc profile for one subject shows the nycthemeral and nocturnal decline in Tc. A, B, and C correspond the following time periods:
Core body temperature (°C) in bed before (A) and during (B) sleep, and after arousal (C).
Subject# | Gender | Body mass index (kg/m2) | A (before sleep) | B (during sleep) | C (after arousal) | B − A | B − C | C − A |
---|---|---|---|---|---|---|---|---|
1 | F | 17.9 | 37.2 | 36.5 | 36.8 | −0.7 | −0.4 | −0.4 |
2 | M | 25.9 | 36.8 | 36.2 | 36.9 | −0.5 | −0.6 | 0.1 |
3 | F | 21.8 | 37.2 | 37.0 | 37.0 | −0.2 | 0.0 | −0.2 |
4 | M | 23.6 | 36.7 | 36.2 | 36.7 | −0.5 | −0.5 | 0.0 |
5 | F | 20.0 | 37.3 | 37.1 | 37.5 | −0.1 | −0.3 | 0.2 |
6 | F | 18.8 | 37.3 | 36.8 | 37.2 | −0.4 | −0.4 | −0.1 |
7 | F | 17.6 | 37.3 | 36.9 | 37.0 | −0.4 | −0.1 | −0.3 |
8 | F | 20.9 | 37.4 | 37.0 | 37.2 | −0.3 | −0.2 | −0.1 |
9 | M | 24.5 | 36.8 | 36.5 | 36.7 | −0.3 | −0.2 | −0.1 |
10 | F | 18.1 | 37.0 | 36.4 | 36.9 | −0.6 | −0.5 | −0.1 |
11 | M | 19.8 | 37.1 | 36.5 | 36.6 | −0.7 | −0.1 | −0.6 |
12 | M | 20.1 | 37.1 | 36.3 | 36.4 | −0.8 | 0.0 | −0.7 |
13 | M | 23.8 | 37.2 | 36.4 | 36.6 | −0.7 | −0.2 | −0.5 |
14 | M | 21.4 | 36.7 | 36.2 | 36.4 | −0.4 | −0.1 | −0.3 |
15 | F | 30.0 | 36.8 | 36.4 | 36.7 | −0.4 | −0.3 | −0.1 |
16 | M | 37.5 | 36.4 | 36.0 | 37.3 | −0.5 | −1.4 | 0.9 |
17 | F | 33.0 | 37.1 | 36.5 | 37.7 | −0.6 | −1.3 | 0.6 |
18 | F | 29.0 | 37.1 | 36.4 | 36.6 | −0.6 | −0.2 | −0.4 |
19 | F | 23.2 | 37.6 | 36.1 | 36.5 | −1.5 | −0.3 | −1.2 |
20 | F | 36.9 | 37.5 | 37.1 | 37.6 | −0.5 | −0.5 | 0.0 |
21 | F | 22.2 | 37.0 | 35.9 | 36.7 | −1.1 | −0.8 | −0.3 |
22 | F | 30.8 | 37.7 | 36.9 | 37.0 | −0.8 | −0.1 | −0.7 |
23 | F | 30.0 | 37.7 | 36.9 | 37.3 | −0.9 | −0.4 | −0.4 |
24 | F | 39.6 | 37.0 | 36.5 | 37.2 | −0.5 | −0.7 | 0.2 |
Mean changes in Tc and EE in response to the exercise tests and to ingestion of a mixed meal (600 kcal) are shown in Table
Low-level structured exercise and meal-induced changes in energy expenditure (EE) and core body temperature (Tc).
Cycling |
Leg press |
Mixed meal |
|||||||
---|---|---|---|---|---|---|---|---|---|
Rest | 50 W | Δ | Rest | 25 kg | Δ | Pre | Post | Δ | |
EE (kcal/min) | 1.17 ± 0.22 | 4.78 ± 0.99 | 3.61 ± 0.94*** | 1.10 ± 0.26 | 1.65 ± 0.36 | 0.55 ± 0.17** | 1.12 ± 0.22 | 1.23 ± 0.22 | 0.11 ± 0.14** |
Tc (°C) | 37.1 ± 0.23 | 37.3 ± 0.23 | 0.17 ± 0.12*** | 37.2 ± 0.27 | 37.1 ± 0.27 | −0.08 ± 0.18 |
37.3 ± 0.30 | 37.2 ± 0.23 | −0.05 ± 0.22 |
Temperature change in response to dynamic (cycling) and isometric (leg press) exercises in one subject. Following a 30-min baseline measurement period, energy expenditure (EE) and core body temperature (Tc) were measured simultaneously during an isometric leg press exercise (5–25 kg) followed by low power cycling (0–50 W) on an ergometer bicycle. Note the sudden drop in EE during “Recovery” periods, which contrasts with the continuous increase in Tc, probably due to thermal lag time between total heat production and total heat loss (
A stability test was first carried out to determine the time required for the capsule temperature to equilibrate following a step-change in water bath temperature. Consecutive 60 s changes in temperature in the range 35–40°C were plotted over 8 min periods (Figure
Time to reach temperature stability in
Prior to validating the capsule temperature against the two Hg thermometers, a blinded test was carried out between two independent investigators I and II to determine the potential influence of investigator (parallax) error in reading the temperature from the Hg thermometer in the range of 35–40°C. The mean interinvestigator bias was 0.041°C (limits of agreement: −0.06 to 0.14°C) for the Hg thermometer 1 (Figures
Interinvestigator-associated bias for each Hg thermometer readings. Top panels show plots comparing readings from both investigators (I vs. II) for Hg thermometer 1
Mercury thermometer bias as measured by each investigator on separate occasions. The top panels compare the temperature readings from the Hg thermometers 1 and 2 (Thermo 1 vs. Thermo 2) across the range of 35–40°C by investigator I
Ingestible capsule temperature was compared with the mean of the two Hg thermometers in the range of 35–40°C at time points within 2 or 3 days. Examination of the initial mean bias between capsules vs. Hg thermometer indicates that ~50% of capsules yielded temperature readings that were well outside the limits of the investigator’s reading (parallax) error (within ±0.1°C) assessed above; the initial bias for these capsules exceeded ±0.5°C, as shown at time point 0 in Figure
Capsule vs. Hg thermometer bias. Mean bias for temperature reading of each capsule vs. Hg thermometer at different time points over 24 h
Assessing potential temperature drift over 24 h observed in two capsules measured simultaneously
Validation of the two identical electronic thermometers (EBRO1; EBRO2) against the Hg thermometers across 35–40°C (concomitant to validation of capsules) showed a mean bias of −0.41°C for electronic thermometer 1 and −0.42°C for electronic thermometer 2. There was no drift in electronic temperature readings vs. Hg thermometer over time (Figure
Temperature bias of electronic thermometers vs. Hg thermometers. The mean difference between Hg thermometers and EBRO1 measured over 24 h
In an additional
Date | # capsules | EBRO1 | EBRO2 | EBRO1 | EBRO2 |
---|---|---|---|---|---|
0–24 h bias | 24–48 h bias | ||||
29.10.2015 | 1 | 0.4 | – | 0.4 | – |
05.11.2015 | 1 | 0.4 | – | 0.4 | – |
23.11.2015 | 1 | 0.2 | 0 | 0.2 | 0.0 |
27.11.2015 | 1 | 0.3 | 0.5 | – | – |
04.12.2015 | 1 | 0.2 | – | 0 | – |
2 | 0.2 | – | 0 | – | |
15.12.2015 | 1 | 0.1 | 0.3 | – | – |
17.12.2015 | 1 | −0.1 | – | – | |
18.12.2015 | 1 | 0.2 | 0.4 | 0.2 | 0.1 |
2 | −0.2 | 0 | 0.1 | 0 | |
23.12.2015 | 1 | − |
−0.1 | −0.3 | 0 |
2 | 0.4 | 0.2 | 0.5 | ||
10.02.2016 | 1 | 0.3 | 0.1 | – | – |
2 | 0.2 | 0 | – | – | |
14.03.2016 | 1 | 0.2 | – | – | |
2 | 0 | – | – | ||
30.05.2016 | 1 | − |
−0.1 | – | – |
07.06.2016 | 1 | 0.2 | 0.2 | – | – |
2 | 0.2 | −0.5 | – | – | |
13.06.2016 | 1 | – | – | ||
2 | − |
– | 0.4 | – |
The aims of this study were to investigate the feasibility of measuring Tc using the CorTemp® system in a group of healthy subjects across a wide range of BMI and to validate the accuracy of these temperature capsules
The interest in Tc as a potential thrifty metabolic trait stems from a few studies, which have shown a relationship between Tc and BMI or fat mass (
Homeotherms conserve energy by lowering body temperature; an example of this can be seen at night when body temperature declines during sleep, part of which is explained by the progressive disappearance of the residual postprandial thermogenesis of the evening meal which often lasts 5–7 h. As expected, a decrease in Tc was observed among all subjects in the current study, which confirms previous reports of the general population (
Internal Tc is measured as the telemetric capsule moves through the GI tract. Therefore, the speed of progression of the capsule through the gut will have a significant influence on the time taken for evacuation of the capsule from the body (i.e., expulsion time) and hence on the duration of Tc recording. The average expulsion time in the current study was 31 h, with a large variation among subjects (range: 13–82 h). In those in whom the capsule was evacuated in less than 15 h (
We observed large erratic temperature excursions outside of the physiological range for all subjects, which occurred to a greater frequency in subjects with greater abdominal adiposity (waist circumference > 100 cm). This may relate to noise due to the proximity of the recording device (worn on the waist) to the capsule within the intestine. Greater processing was required for data from these subjects, which reduced the number of data points available. Previous studies have excluded outliers greater than 2SD from the mean (of a particular time period) when the outlier was included in the mean value (
Following these technical difficulties (number and uncertainty of outliers), a validation study was carried out to investigate the accuracy of the capsules measured in the physiological range of 35–40°C, twice per day for 3 days. We identified a substantial bias exceeding ±0.5°C compared to Hg thermometers in half of the capsules, with the bias in some capsules exceeding ±1°C (Figure
While considering the source of bias, it is important to note that there is an inherent investigator error in reading the temperature value (parallax error). In the current study, the degree of investigator-associated bias was assessed before comparing the Tc capsules with Hg thermometers. An investigator-associated bias of <0.05°C was identified, and hence of small magnitude. These inherent errors of random nature were taken into account for all subsequent comparisons between capsule and thermometers and constitute a window of uncertainty that should be an important consideration in studies of Tc where minute differences can have a considerable impact on the final result.
In the current study, repeated accuracy tests of each capsule recording were taken in order to determine whether or not the accuracy of the capsules changed over time (up to 3 days). This information is vital given that Tc studies generally measure subjects for 24 h or more. We were interested in exploring whether the initial bias observed between the capsules and thermometer, as reported previously (
Researchers have sought to remove the bias associated with the Tc capsules by employing an additional calibration step prior to ingestion
The current study has a number of caveats. First, physical activity was not measured in subjects who underwent Tc measurement prior to the standardized laboratory measurements. The use of accelerometry in future studies would provide activity measurements during the non-standardized component of the experiment, as well as during sleep, which could be incorporated into the analysis and determine the extent to which day-to-day movement influences Tc. Second, the meal subjects consumed the night before the experiment was not strictly standardized. This may have accounted for the differences in expulsion time between subjects and the evolution of Tc during the night. Future studies should consider providing a standardized meal, taking into consideration nutritional factors likely to affect GI transit time, e.g., meal size, dietary fiber content, etc., and which in turn may influence the capsule’s expulsion time. Third, in the measurement of Tc with the ingestible capsule, it is assumed that (i) the anatomical location of the capsule in the gut has very little influence on Tc (e.g., heat production as a result of bacterial fermentation by colon microbiota) and (ii) the presence or absence of food in the gut does not influence Tc significantly. In order to offset this effect of fluctuating Tc over time (Figure
This validation study is the first to measure a series of Tc capsules for up to 3 days and to identify a change in bias between the capsules and gold standard Hg thermometers, as well as against electronic thermometers. The feasibility of using Tc capsules has been shown, particularly for detecting rapid changes in Tc associated with low-intensity dynamic exercise, but not in response to food or low-intensity isometric exercise; while noting that during daily life, dynamic and isometric activities are intertwined pertaining to their impact on EE (
The study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human subjects were approved by the Commission Cantonale D’éthique de la Recherche sur L’être Humain (CER-VD), the ethics committee for human research in the Swiss cantons of Vaud, Fribourg, Neuchâtel and Valais. Written informed consent was obtained from all subjects prior to participation in the study.
Conception and design of the work: AD, YS, DD, CM, and JM-C. Data acquisition: CM, JM-C, E-JF, JC, YS, and DD. Data analysis: CM, E-JF, and JC. Interpretation of the data: CM, AD, YS, E-JF, JC, JM-C, J-PM, and DD. Drafted the manuscript: CM and AD. Revised the manuscript: E-JF, JC, JM-C, J-PM, DD, and YS. All the authors approved the final version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.