Although leucine has many positive effects on metabolism in multiple tissues, elevated levels of this amino acid and the other branched-chain amino acids (BCAAs) and their metabolites are implicated in obesity and insulin resistance. While some controversies exist about the direct effect of leucine on insulin action in skeletal muscle, little is known about the direct effect of BCAA metabolites. Here, we first showed that the inhibitory effect of leucine on insulin-stimulated glucose transport in L6 myotubes was dampened when other amino acids were present, due in part to a 140% stimulation of basal glucose transport (P < 0.05). Importantly, we also showed that α-ketoisocaproic acid (KIC), an obligatory metabolite of leucine, stimulated mTORC1 signaling but suppressed insulin-stimulated glucose transport (-34%, P < 0.05) in an mTORC1-dependent manner. The effect of KIC on insulin-stimulated glucose transport was abrogated in cells depleted of branched-chain aminotransferase 2 (BCAT2), the enzyme that catalyzes the reversible transamination of KIC to leucine. We conclude that although KIC can modulate muscle glucose metabolism, this effect is likely a result of its transamination back to leucine. Therefore, limiting the availability of leucine, rather than those of its metabolites, to skeletal muscle may be more critical in the management of insulin resistance and its sequelae.
Background:Cardiac rehabilitation (CR) reach is minimal globally, primarily due to financial factors. This study characterized CR funding sources, cost to patients to participate, cost to programs to serve patients, and the drivers of these costs. Methods:In this cross-sectional study, an online survey was administered to CR programs globally.Cardiac associations and local champions facilitated program identification. Costs in each country were reported using purchasing power parity (PPP). Results were compared by World Bank country income classification using generalized linear mixed models. Results:111/203 (54.68%) countries in the world offer CR, of which data were collected in 93 (83.78% country response rate; N=1082 surveys, 32.0% program response rate). CR was most-often publicly funded (more in high-income countries [HICs]; p<.001), but in 60.20% of countries patients paid some or all of the cost. Funding source impacted capacity (p=.004), number of patients per exercise session (p<.001), personnel (p=.037), and functional capacity testing (p=.039). The median cost to serve 1 patient was $945.91PPP globally. In low and middleincome countries (LMICs), exercise equipment and stress testing were perceived as the most expensive delivery elements, with front-line personnel costs perceived as costlier in HICs (p=.003). Modifiable factors associated with higher costs included CR team composition (p=.001), stress testing (p=.002) and telemetry monitoring in HICs (p=.01), and not offering alternative models in LMICs (p=.02). Conclusions:Too many patients are paying out-of-pocket for CR, and more public funding is needed. Lowercost delivery approaches are imperative, and include walk tests, task-shifting, and intensity monitoring via perceived exertion.
More research is needed regarding the costs to deliver CR in community settings, the cost-effectiveness of CR in most countries, and the economic impact of return-to-work with CR participation. A low-cost model of CR should be standardized and tested for efficacy across multiple healthcare systems.
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Purpose: Despite evidence of the effectiveness of cardiac rehabilitation (CR), there is wide variability in programs, which may impact their quality. The objectives of this review were to (1) evaluate the ways in which we measure CR quality internationally; (2) summarize what we know about CR quality and quality improvement; and (3) recommend potential ways to improve quality. Methods: For this narrative review, the literature was searched for CR quality indicators (QIs) available internationally and experts were also consulted. For the second objective, literature on CR quality was reviewed and data on available QIs were obtained from the Canadian Cardiac Rehabilitation Registry (CCRR). For the last objective, literature on health care quality improvement strategies that might apply in CR settings was reviewed. Results: CR QIs have been developed by American, Canadian, European, Australian, and Japanese CR associations. CR quality has only been audited across the United Kingdom, the Netherlands, and Canada. Twenty-seven QIs are assessed in the CCRR. CR quality was high for the following indicators: promoting physical activity post-program, assessing blood pressure, and communicating with primary care. Areas of low quality included provision of stress management, smoking cessation, incorporating the recommended elements in discharge summaries, and assessment of blood glucose. Recommended approaches to improve quality include patient and provider education, reminder systems, organizational change, and advocacy for improved CR reimbursement. An audit and feedback strategy alone is not successful. Conclusions: Although not a lot is known about CR quality, gaps were identified. The quality improvement initiatives recommended herein require testing to ascertain whether quality can be improved.
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