Relation of 24-hour urinary caffeine and caffeine metabolite excretions with self-reported consumption of coffee and other caffeinated beverages in the general population.

Caffeine intake is generally estimated by self-reported consumption, but it remains unclear how well self-report associates with metabolite urinary excretion. We investigated the associations of self-reported consumption of caffeinated drinks with urinary excretion of caffeine and its major metabolites in an adult population. We used data from the population-based Swiss Kidney Project on Genes in Hypertension (SKIPOGH) study. Consumption of caffeinated coffee, decaffeinated coffee and other caffeinated beverages was assessed by self-administered questionnaire. Quantification of caffeine, paraxanthine, theobromine and theophylline was performed by ultra-high performance liquid chromatography tandem mass spectrometry in 24-h urine. Association of reported consumption of caffeinated drinks with urinary caffeine derived metabolites was determined by quantile regression. We then explored the association between urinary metabolite excretion and dichotomized weekly consumption frequency of caffeinated coffee, with Receiver Operator Characteristic (ROC) analysis. In the present analysis, we included 598 individuals (52% women, mean age =46 ± 17 years). Self-reported caffeinated coffee intake was positively associated with 24-h urinary excretions of paraxanthine, theophylline and caffeine (p < 0.001), whereas reported intakes of decaffeinated coffee and other caffeinated beverages showed no association. In ROC analysis, optimal discrimination between individuals consuming less than one caffeinated coffee/week, vs. at least one coffee, was obtained for 24-h urinary paraxanthine (Area Under Curve (AUC) = 0.868, 95% Confidence Interval (CI) [0.830;0.906]), with slightly lower performance for theophylline and caffeine, whereas theobromine did not allow any discrimination. Our results suggest that reported consumption of caffeinated coffee is positively associated with 24-h urinary excretion of caffeine, paraxanthine, and theophylline, and may be used as a marker of caffeine intake for epidemiological studies

Gestational diabetes mellitus and offspring's carotid intima-media thickness at birth: MySweetHeart Cohort study.

Hyperglycaemia during pregnancy is associated with cardiometabolic risks for the mother and the offspring. Mothers with gestational diabetes mellitus (GDM) have signs of subclinical atherosclerosis, including increased carotid intima-media thickness (CIMT). We assessed whether GDM is associated with increased CIMT in the offspring at birth. MySweetHeart Cohort is a prospective cohort study conducted in Switzerland. This work included pregnant women with and without GDM at 24-32 weeks of gestation and their singleton live-born offspring with data on the primary outcome of CIMT. GDM was diagnosed based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. Offspring's CIMT was measured by ultrasonography after birth (range 1-19 days). Data on CIMT were available for 99 offspring of women without GDM and 101 offspring of women with GDM. Maternal age ranged from 18 to 47 years. Some 16% of women with GDM and 6% of women without GDM were obese. Smoking during pregnancy was more frequent among women with GDM (18%) than among those without GDM (4%). Neonatal characteristics were comparable between the two groups. The difference in CIMT between offspring of women with and without GDM was of 0.00 mm (95% CI -0.01 to 0.01; p=0.96) and remained similar on adjustment for potential confounding factors, such as maternal prepregnancy body mass index, maternal education, smoking during pregnancy, family history of diabetes, as well as offspring's sex, age, and body surface area (0.00 mm (95% CI -0.02 to 0.01; p=0.45)). We found no evidence of increased CIMT in neonates exposed to GDM. A longer-term follow-up that includes additional vascular measures, such as endothelial function or arterial stiffness, may shed further light on the cardiovascular health trajectories in children born to mothers with GDM. NCT02872974; Pre-results

Urinary Sex Steroid and Glucocorticoid Hormones Are Associated With Muscle Mass and Strength in Healthy Adults.

Sex steroid hormones exhibit anabolic effects whereas a deficiency engenders sarcopenia. Moreover, supraphysiological levels of glucocorticoids promote skeletal muscle atrophy, whereas physiologic levels of glucocorticoids may improve muscle performance. To study the relationship between both groups of steroid hormones at a physiological range with skeletal muscle mass and function in the general population. Cross-sectional analysis of the associations between urinary excreted androgens, estrogens, glucocorticoids, and steroid hormone metabolite ratios with lean mass and handgrip strength in a population-based cohort. Three centers in Switzerland including 1128 participants. Urinary steroid hormone metabolite excretion by gas chromatography-mass spectrometry, lean mass by bioimpedance analysis, and isometric handgrip strength by dynamometry. For lean mass a strong positive association was found with 11β-OH-androsterone and with most glucocorticoids. Androsterone showed a positive association in middle-aged and older adults. Estriol showed a positive association only in men. For handgrip strength, strong positive associations with androgens were found in middle-aged and older adults, whereas positive associations were found with cortisol metabolites in young to middle-aged adults. Sex steroids and glucocorticoids are strongly positively associated with skeletal muscle mass and strength in the upper limbs. The associations with muscle strength appear to be independent of muscle mass. Steroid hormones exert age-specific anabolic effects on lean mass and handgrip strength. Deficits in physical performance of aged muscles may be attenuated by androgens, whereas glucocorticoids in a physiological range increase skeletal muscle mass at all ages, as well as muscle strength in particular in younger adults

COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19

The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p