Contrasting short-term temperature effects on the profiling of metabolic and stress hormones in non-obese healthy adults: A randomized cross-over trial
Introduction
The World Health Organisation recognises the overall health impacts of a changing climate as overwhelmingly negative (World Health Organization, 2017). Seasonal, long-sustained high temperature weather conditions appear to have a direct impact on human health by affecting the body's ability to regulate its internal temperature (Hajat et al., 2017; Hanna and McIver, 2018; Sarofim et al., 2016; Vardoulakis and Heaviside, 2012; Yang et al., 2014). The direct health impacts of exposure to heat are often assessed in terms of mortality risk (Gasparrini et al., 2015), including cardiovascular, respiratory, renal and infectious diseases, and neurological/psychiatric disorders (Basagaña et al., 2011; Xu et al., 2012; Åström et al., 2011; Checkley et al., 2009).
Evidence of community or regional measures to assess heat effects consist primarily of observational studies conducted in the US and Europe (White-Newsome et al., 2014; Lim and Spanger-Seigfried, 2004). Population vulnerability is defined on the basis of three components, namely, the exposure level, the extent of susceptibility and the adaptive capacity (Michelozzi et al., 2014). Groups of elderly people and individuals with impaired health status may be particularly vulnerable to climate change manifestations of higher temperatures, as they have diminished ability to thermo-regulate body core temperature, thus increasing medical co-morbidities or use of medications, while the social position of an individual could modify the extent of behavioural adjustments to sustained high temperatures (Bennett et al., 2014; Ishigami et al., 2008).
Earlier observational studies demonstrated the effect of heat stress on the cognitive function of elderly (mean age of 73 yrs old) using repeated measures of residential air temperature records (Gasparrini et al., 2015; Dai et al., 2016). Apart from clinical effects, excessive heat could adversely influence human performance and work capacity (Kjellstrom et al., 2009, 2016), or performance in exercise/sports (Brotherhood, 2008). Recently, the relationship between indoor environmental conditions, heat exposures, sleep and cognitive function was examined among young adults living in centrally-controlled air conditioned (AC) and non-AC residence halls on a university campus (Cedeño Laurent et al., 2018); authors found that students living in non-AC spaces during a heat wave in Boston experienced significant decrements on cognitive performance tests (reaction time, throughput, 2-digit visual addition/subtraction test) relative to AC residents at baseline (Cedeño Laurent et al., 2018).
There is currently limited evidence about the effect of elevated ambient air temperatures on metabolic outcomes. An experimental study showed that the adapted thermogenesis process was reduced in temperatures within the thermal comfort zone of the human being, while colder air exposures increased thermogenesis from the brown adipose tissue (BAT) and energy expenditure processes, resulting in lower body weight (Turner et al., 2016). Some evidence also exists about the increasing ambient temperature effects on age adjusted type II diabetes incidence rates in the US, however, these were premature results (ecological study) (Lee et al., 2014). Another experimental study conducted under well controlled conditions (n = 5) showed that a small elevation in ambient temperature (reaching 27 °C, for a month duration) increased leptin and decreased adiponectin levels (Blauw et al., 2017).
Therefore, the design and testing of cost-effective and sustainable health interventions for the public against the detrimental manifestations of climate change and hot weather are of paramount importance. We designed a pilot experimental trial (TEMP trial) in real-life conditions that examined changes in metabolic and stress hormonal profiles of healthy, non-obese adults in two study settings with distinctly different climatological characteristics: urban vs. higher in altitude (range: 650–1200 m, mean ± SD: 881 ± 200 m) mountainous setting (being 1-h away driving from main urban centres of Cyprus). In addition, the trial examined the relationship between personal air and skin temperatures and adipokines (leptin and adiponectin) between the urban and rural settings.
Section snippets
Trial oversight
The TEMP trial was a 2 x 2 cross-over pilot trial of healthy, non-obese adults (n = 41). The trial was conducted under real-life conditions (instead of controlled environment) to examine the effect of setting and personal ambient/skin temperature gradient on metabolic hormones levels (Fig. 1). Eligible participants were those who met the following criteria: healthy, non-obese adults between 20 and 60 years old having their permanent primary residence in one of the two largest cities of Cyprus
Participant characteristics
A total of 41 subjects were recruited and agreed to participate; and upon house visit, 2 of them declined participation (Fig. 2). During follow-up, 3 participants were excluded, since they only provided urinary samples in one of the two settings. During analysis, 5 additional participants were excluded, because exclusion criteria applied following questionnaires digitization [obese status (n = 3) and ongoing thyroxin treatment (n = 1)] and because of abnormally high leptin levels in all four
Discussion
Extending the work published in other hyperthermia human studies, and to the best of our knowledge, this is the first, 2 x 2 prospective, randomized, cross-over, non-pharmacological trial that investigated the alterations of metabolic and stress hormones associated with a short-term stay (mean duration of 7 days) in climatologically cooler areas than those observed in geographically adjacent urban settings (~1-h driving distance). A robust significant leptin reduction (p = 0.024) during the
Contributors
KCM conceived, designed and coordinated the trial. AP, CK and KCM conducted the field work and data collection. CK conducted the sample analyses. CK executed the primary data analysis and ABZ the secondary analysis, both with guidance from KCM and CAC. All authors interpreted the results and drafted the manuscript. KCM obtained internal funding. All authors revised the article for important intellectual content. KCM is the principal investigator and guarantor of the study.
Declaration of competing interest
No competing interests: All authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Transparency declaration
The manuscript's guarantor affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned (and, if relevant, registered) have been explained.
Financial disclosure - role of the funding source
Internal funds of the principal investigator (KC Makris) were used for this study. No external funding was obtained for this study. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Data sharing
The authors commit to making the relevant anonymized patient level data available via open access.
Acknowledgments
We sincerely thank all TEMP trial participants for their willingness to participate in the study. We greatly acknowledge Mrs. Chrystalla Oikonomidou for the field work collecting the data in the field. We also thank Dr. Pantelis Charisiadis for the cortisol analyses.
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