SUMMARY
Increasing energy expenditure through activation of endogenous brown adipose tissue (BAT) is a potential approach to treat obesity and diabetes. The class of β3-adrenergic receptor (AR) agonists stimulates rodent BAT, but this activity has never been demonstrated in humans. Here we determined the ability of 200 mg oral mirabegron (Myrbetriq, Astellas Pharma, Inc.), a β3-AR agonist currently approved to treat overactive bladder, to stimulate BAT as compared to placebo. Mirabegron led to higher BAT metabolic activity as measured via 18F-fluorodeoxyglucose (18F-FDG) using positron emission tomography (PET) combined with computed tomography (CT) in all twelve healthy male subjects (p = 0.001), and it increased resting metabolic rate (RMR) by 203 ± 40 kcal/day (+13%; p = 0.001). BAT metabolic activity was also a significant predictor of the changes in RMR (p = 0.006). Therefore, a β3-AR agonist can stimulate human BAT thermogenesis and may be a promising treatment for metabolic disease.
Key PointsQuestionHow frequently were mechanical cardiopulmonary resuscitation devices used in the United States by prehospital emergency medical services professionals for patients with out-of-hospital cardiac arrest from 2010 to 2016?FindingsIn this cross-sectional study, the risk-adjusted use of mechanical cardiopulmonary resuscitation devices rose from 1.9% to 8.0% among all out-of-hospital cardiac arrests. This increase was consistent among patients when stratified by demographic characteristics and geographical location.MeaningUse of mechanical cardiopulmonary resuscitation devices has increased more than 4-fold among patients with out-of-hospital cardiac arrest treated by emergency medical services professionals, despite significant costs and minimal evidence that these devices improve clinically meaningful outcomes among patients.
Brown adipose tissue (BAT) has been identified as a potential target in the treatment and prevention of obesity and metabolic disease. The precise kinetics of BAT activation and the duration of stimulus required to recruit metabolically active BAT, and its subsequent deactivation, are not well-understood. In this clinical trial, 19 healthy adults (BMI: 23.7±0.7 kg/m2, Age: 31.2±2.8 y, 12 female) underwent three different cooling procedures to stimulate BAT glucose uptake, and active BAT volume was determined using 18F-Fluorodeoxyglucose (FDG) PET/CT imaging. We found that 20 minutes of pre-injection cooling produces activation similar to the standard 60 minutes (39.9 mL vs. 44.2 mL, p= 0.52), indicating that BAT activity approaches its peak function soon after the initiation of cooling. Furthermore, upon removal of cold exposure, active BAT volume declines (13.6 mL vs. 44.2 mL, p=0.002), but the deactivation process persists even hours following cessation of cooling. Thus, the kinetics of human BAT thermogenesis are characterized by a rapid increase soon after cold stimulation but a more gradual decline after rewarming. These characteristics reinforce the feasibility of developing mild, short-duration cold exposure to activate BAT and treat obesity and metabolic disease.
This cost model estimates the direct healthcare costs of incident diabetes-related complications in a U.S. adult population with diabetes and provides a benchmark for evaluating the cost-effectiveness and potential leakage within a care delivery network.
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