Effects of Medications on Heat Loss Capacity in Chronic Disease Patients: Health Implications Amidst Global Warming.

Pharmacological agents used to treat or manage diseases can modify the level of heat strain experienced by chronically ill and elderly patients via different mechanistic pathways. Human thermoregulation is a crucial homeostatic process that maintains body temperature within a narrow range during heat stress through dry (i.e., increasing skin blood flow) and evaporative (i.e., sweating) heat loss, as well as active inhibition of thermogenesis, which is crucial to avoid overheating. Medications can independently and synergistically interact with aging and chronic disease to alter homeostatic responses to rising body temperature during heat stress. This review focuses on the physiologic changes, with specific emphasis on thermolytic processes, associated with medication use during heat stress. The review begins by providing readers with a background of the global chronic disease burden. Human thermoregulation and aging effects are then summarized to give an understanding of the unique physiologic changes faced by older adults. The effects of common chronic diseases on temperature regulation are outlined in the main sections. Physiologic impacts of common medications used to treat these diseases are reviewed in detail, with emphasis on the mechanisms by which these medications alter thermolysis during heat stress. The review concludes by providing perspectives on the need to understand the effects of medication use in hot environments, as well as a summary table of all clinical considerations and research needs of the medications included in this review. SIGNIFICANCE STATEMENT: Long-term medications modulate thermoregulatory function, resulting in excess physiological strain and predisposing patients to adverse health outcomes during prolonged exposures to extreme heat during rest and physical work (e.g., exercise). Understanding the medication-specific mechanisms of altered thermoregulation has importance in both clinical and research settings, paving the way for work toward refining current medication prescription recommendations and formulating mitigation strategies for adverse drug effects in the heat in chronically ill patients.

Climate change and population health in Singapore: a systematic review.

Gaseous emissions have contributed to global warming, an increase in the frequency of extreme weather events and poorer air quality. The associated health impacts have been well reported in temperate regions. In Singapore, key climate change adaptation measures and activities include coastal and flood protection, and mitigating heat impacts. We systematically reviewed studies examining climate variability and air quality with population health in Singapore, a tropical city-state in South-East Asia (SEA), with the aim to identify evidence gaps for policymakers. We included 14 studies with respiratory illnesses, cardiovascular outcomes, foodborne disease and dengue. Absolute humidity (3 studies) and rainfall (2 studies) were positively associated with adverse health. Extreme heat (2 studies) was inversely associated with adverse health. The effects of mean ambient temperature and relative humidity on adverse health were inconsistent. Nitrogen dioxide and ozone were positively associated with adverse health. Climate variability and air quality may have disease-specific, differing directions of effect in Singapore. Additional high quality studies are required to strengthen the evidence for policymaking. Research on effective climate action advocacy and adaptation measures for community activities should be strengthened. Funding: There was no funding source for this study.

Diet, Physical Activity and Adiposity as Determinants of Circulating Amino Acid Levels in a Multiethnic Asian Population.

Profiles of circulating amino acids have been associated with cardiometabolic diseases. We investigated the associations between dietary protein intake, physical activity and adiposity and serum amino acid profiles in an Asian population. We used data from 3009 male and female participants from the Singapore Prospective Study Program cohort. Dietary and physical activity data were obtained from validated questionnaires; anthropometric measurements were collected during a health examination; and fasting concentrations of 16 amino acids were measured using targeted LC-MS. The association between lifestyle factors and amino acid levels was modeled using multiple linear regression with adjustment for other sociodemographic and lifestyle factors and correction for multiple testing. We observed significant associations between seafood intake (ß-coefficient 0.132, 95% CI 0.006, 0.257 for a 100% increment), physical activity (ß-coefficient -0.096, 95% CI -0.183, -0.008 in the highest versus lowest quartile) and adiposity (BMI ß-coefficient 0.062, 95% CI 0.054, 0.070 per kg/m2; waist circumference ß-coefficient 0.034, 95% CI 0.031, 0.037 per cm) and branched-chain amino acid levels (expressed per-SD). We also observed significant interactions with sex for the association between meat and seafood and total intakes and BCAA levels (P for interaction 0.007), which were stronger in females than in males. Our findings suggest novel associations between modifiable lifestyle factors and amino acid levels in Asian populations.

Serum acylcarnitines and amino acids and risk of type 2 diabetes in a multiethnic Asian population.

INTRODUCTION: We evaluated whether concentrations of serum acylcarnitines and amino acids are associated with risk of type 2 diabetes and can improve predictive diabetes models in an Asian population. RESEARCH DESIGN AND METHODS: We used data from 3313 male and female participants from the Singapore Prospective Study Program cohort who were diabetes-free at baseline. The average age at baseline was 48.0 years (SD: 11.9 years), and participants were of Chinese, Malay, and Indian ethnicity. Diabetes cases were identified through self-reported physician diagnosis, fasting glucose and glycated hemoglobin concentrations, and linkage to national disease registries. We measured fasting serum concentrations of 45 acylcarnitines and 14 amino acids. The association between metabolites and incident diabetes was modeled using Cox proportional hazards regression with adjustment for age, sex, ethnicity, height, and parental history of diabetes, and correction for multiple testing. Metabolites were added to the Atherosclerosis Risk in Communities (ARIC) predictive diabetes risk model to assess whether they could increase the area under the receiver operating characteristic curve (AUC). RESULTS: Participants were followed up for an average of 8.4 years (SD: 2.1 years), during which time 314 developed diabetes. Branched-chain amino acids (HR: 1.477 per SD; 95% CI 1.325 to 1.647) and the alanine to glycine ratio (HR: 1.572; 95% CI 1.426 to 1.733) were most strongly associated with diabetes risk. Additionally, the acylcarnitines C4 and C16-OH, and the amino acids alanine, combined glutamate/glutamine, ornithine, phenylalanine, proline, and tyrosine were significantly associated with higher diabetes risk, and the acylcarnitine C8-DC and amino acids glycine and serine with lower risk. Adding selected metabolites to the ARIC model resulted in a significant increase in AUC from 0.836 to 0.846. CONCLUSIONS: We identified acylcarnitines and amino acids associated with risk of type 2 diabetes in an Asian population. A subset of these modestly improved the prediction of diabetes when added to an established diabetes risk model.

Coffee, Black Tea, and Green Tea Consumption in Relation to Plasma Metabolites in an Asian Population.

SCOPE: Coffee and tea are among the most popular beverages in the world. However, the association between habitual coffee, green tea, and black tea consumption with metabolomics profiles in Asian populations remain largely unknown. METHODS AND RESULTS: 158 metabolites (14 amino acids, 45 acylcarnitines, and 99 sphingolipids) in the blood plasma of participants are measured from the population-based Singapore Prospective Study Program cohort using mass spectrometry (MS). Linear regression models are used to obtain the estimates for the association between coffee and tea consumption with metabolite levels, adjusted for potential confounders and false discovery rate (FDR). Coffee consumption is significantly associated with higher levels of 63 sphingolipids (29 sphingomyelins, 32 ceramides, a sphingosine-1-phosphate, and a sphingosine) and lower levels of 13 acylcarnitines and alanine. Black tea consumption is significantly associated with higher levels of eight sphingolipids, and lower levels of an amino acid, whereas green tea is significantly inversely associated with four metabolites (C8:1-OH acylcarnitine, ganglioside GM3 d18:1/16:0, sphingomyelins d18:2/18:0 and d18:1/14:0). CONCLUSIONS: Coffee, black tea, and green tea consumption are associated with plasma levels of certain classes of sphingolipids and acylcarnitines in an Asian population, particularly sphingomyelins, which may mediate the health benefits of these beverages.