Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults

Funding for open access charge: Universidad de Granada/CBUA. This study was funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01393), by the Retos de la Sociedad program (DEP2016-79512-R), European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU13/04365), the Fundacion Iberoamericana de Nutricion (FINUT), the Redes Tematicas de Investigacion Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)-and Plan Propio de Investigacion 2018-the Programa Contratos-Puente and Contratos Perfeccionamiento de Doctores, the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF; ref. SOMM17/6107/UGR), and the Fundacion Alfonso Martin Escudero (grant awarded to GSD).Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 ± 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P ≤ 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129.Universidad de Granada/CBUASpanish Government PI13/01393Retos de la Sociedad program DEP2016-79512-REuropean CommissionSpanish Government FPU13/04365Fundacion Iberoamericana de Nutricion (FINUT)Redes Tematicas de Investigacion Cooperativa RETIC Red SAMID RD16/0022AstraZenecaUniversity of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Plan Propio de Investigacion 2018-the Programa Contratos-PuenteContratos Perfeccionamiento de DoctoresJunta de AndaluciaConsejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGRFundacion Alfonso Martin Escuder

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.</p

The Mediating Role of Brown Fat and Skeletal Muscle Measured by 18F-Fluorodeoxyglucose in the Thermoregulatory System in Young Adults

The authors would like to thank all the participants who took part in this investigation. This study is part of a PhD thesis conducted in the Biomedicine Doctoral Studies of the University of Granada, Spain. We are grateful to Alberto Quesada-Aranda for helping with the development of the Temperatus software (free trial at http://profith.ugr.es/ temperatus?lang=en). We are grateful to Ms Carmen Sainz-Quinn for assistance with English-language editingObjective: This study aimed to examine whether brown adipose tissue (BAT) or skeletal muscle activity mediates the relationship between personal level of environmental temperature (Personal-ET) and wrist skin temperature (WT). Moreover, we examined whether BAT and skeletal muscle have a mediating role between Personal-ET and WT (as a proxy of peripheral vasoconstriction/vasodilation). Methods: The levels of BAT were quantified by cold-induced 18F-fluorodeoxyglucose–positron emission tomography/computed tomography scan and measured the Personal-ET and WT by using iButtons (Maxim Integrated, Dallas, Texas) in 75 participants (74.6% women). Results: The study found that BAT volume and metabolic activity played a positive and significant role (up to 25.4%) in the association between Personal-ET and WT. In addition, at the coldest temperatures, the participants with lower levels of WT (inducing higher peripheral vasoconstriction) had higher levels of BAT outcomes, whereas in warm temperatures, participants with higher levels of WT (inducing higher peripheral vasodilation) had lower levels of BAT outcomes. The study did not find any mediating role of skeletal muscle activity. Conclusions: BAT volume and metabolic activity play a role in the relationship between Personal-ET and WT. Moreover, the data suggest that there are two distinct phenotypes: individuals who respond better to the cold, both through nonshivering thermogenesis and peripheral vasoconstriction, and individuals who respond better to the heat.This study was supported by the Spanish Ministry of Economy and Competitiveness, Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), Retos de la Sociedad (DEP2016‐79512‐R), and Fondos Estructurales de la Unión Europea (FEDER); by the Spanish Ministry of Education (FPU 13/04365); by the Fundación Iberoamericana de Nutrición; by the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022); by AstraZeneca HealthCare Foundation; by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES); and by the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR, Programa Contratos‐Puente. MAR is supported by a predoctoral research grant from University Jaume I (PREDOC/2015/13). AMN was supported by the Ministry of Economy and Competitiveness, the Instituto de Salud Carlos III through the Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CB16/10/00239), and grant 19899/GERM/15 (cofinanced by FEDER)

Relationship between the Daily Rhythm of Distal Skin Temperature and Brown Adipose Tissue 18F-FDG Uptake in Young Sedentary Adults

The present study examines whether the daily rhythm of distal skin temperature (DST) is associated with brown adipose tissue (BAT) metabolism as determined by 18F-fluorodeoxyglucose (18F-FDG) uptake in young adults. Using a wireless thermometer (iButton) worn on the nondominant wrist, DST was measured in 77 subjects (26% male; age 22 ± 2 years; body mass index 25.2 ± 4.8 kg/m2) for 7 consecutive days. The temperatures to which they were habitually exposed over the day were also recorded. The interday stability of DST was calculated from the collected data, along with the intraday variability and relative amplitude; the mean temperature of the 5 and 10 consecutive hours with the maximum and minimum DST values, respectively; and when these hours occurred. Following exposure to cold, BAT volume and mean and peak standardized 18F-FDG uptake (SUVmean and SUVpeak) were determined for each subject via static 18F-FDG positron emission tomography/computed tomography scanning. Relative amplitude and the time at which the 10 consecutive hours of minimum DST values occurred were positively associated with BAT volume, SUVmean, and SUVpeak (p ≤ 0.02), whereas the mean DST of that period was inversely associated with the latter BAT variables (p ≤ 0.01). The interday stability and intraday variability of the DST were also associated (directly and inversely, respectively) with BAT SUVpeak (p ≤ 0.02 for both). All of these associations disappeared, however, when the analyses were adjusted for the ambient temperature to which the subjects were habitually exposed. Thus, the relationship between the daily rhythm of DST and BAT activity estimated by 18F-FDG uptake is masked by environmental and likely behavioral factors. Of note is that those participants exposed to the lowest ambient temperature showed 3 to 5 times more BAT volume and activity compared with subjects who were exposed to a warmer ambient temperature

Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults

Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 +/- 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P <= 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129

A larger brown fat volume and lower radiodensity are related to a greater cardiometabolic risk, especially in young men

Objectives: Brown adipose tissue (BAT) is important in the maintenance of cardiometabolic health in rodents. Recent reports appear to suggest the same in humans, although if this is true remains elusive partly because of the methodological bias that affected previous research. This cross-sectional work reports the relationships of cold-induced BAT volume, activity (peak standardized uptake, SUVpeak), and mean radiodensity (an inverse proxy of the triacylglycerols content) with the cardiometabolic and inflammatory profile of 131 young adults, and how these relationships are influenced by sex and body weight.Design: This is a cross-sectional study.Methods: Subjects underwent personalized cold exposure for 2 h to activate BAT, followed by static F-18-fluorodeoxyglucose PET-CT scanning to determine BAT variables. Information on cardiometabolic risk (CMR) and inflammatory markers was gathered, and a CMR score and fatty liver index (FLI) were calculated.Results: In men, BAT volume was positively related to homocysteine and liver damage markers concentrations (independently of BMI and seasonality) and the FLI (all P 0.05).Conclusions: A larger BAT volume and a lower BAT mean radiodensity are related to a higher CMR, especially in young men, which may support that BAT acts as a compensatory organ in states of metabolic disruption.</p

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Italienne et ouvrière chez Suchard: une historie sociale

« Nous devons une profonde gratitude à Philippe Suchard, à Carl Russ-Suchard et surtout à la multitude de collaborateurs qui ont consacré une grande partie de leur vie à cette entreprise. Grâce à eux, Suchard est aujourd’hui l’une des plus importantes entreprises suisses du secteur ». En mai 1976, l’éditorial du magazine de l’entreprise Suchard Nous et notre travail, publié dans un numéro spécial à l’occasion du 150e anniversaire de la fondation de l’usine de Serrières, remercie la multitude de travailleurs et travailleuses de diverses nationalités. Nous nous trouvons à la fin des Trente Glorieuses2 et ce texte semble anticiper ce que va traverser une entreprise ayant connu nombre de moments difficiles

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

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. 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. 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). 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

Association of wrist and ambient temperature with cold-induced brown adipose tissue and skeletal muscle [18F]FDG uptake in young adults.

Brown adipose tissue (BAT) activity is influenced by the outdoor temperature variation. However, people spend most of their time indoors, especially in colder regions and during cold seasons. Therefore, outdoor temperature is probably not an accurate tool to quantify the exposure of the participants before BAT quantification. We studied the association of wrist and personal environmental temperatures with cold-induced BAT and skeletal muscle [18F]fluorodeoxyglucose ([18F]FDG) uptake in adults. A total of 74 participants wore two iButtons during 7 days to measure wrist temperature (WT) and personal level of environmental temperature (Personal-ET). Thereafter, we performed a 2-h personalized cooling protocol before performing an [18F]FDG-PET/CT scan. WT was negatively associated with BAT volume ( R2 = 0.122; P = 0.002) and BAT activity [standardized uptake value (SUV)peak, R2 = 0.083; P = 0.012]. Moreover, Personal-ET was negatively associated with BAT volume ( R2 = 0.164;