Low Response to Aerobic Training in Metabolic Disease: Role of Skeletal Muscle.

Aerobic exercise is established to increase cardiorespiratory fitness (CRF), which is linked to reduced morbidity and mortality. However, people with metabolic diseases such as type 1 and type 2 diabetes may be more likely to display blunted improvements in CRF with training. Here, we present evidence supporting the hypothesis that altered skeletal muscle signaling and remodeling may contribute to low CRF with metabolic disease.

Cardiorespiratory fitness, body composition, diabetes, and longevity: a two-sample Mendelian randomization study.

CONTEXT: Cardiorespiratory fitness, commonly assessed as maximal volume of oxygen consumption (VO2max), has emerged as an important predictor of morbidity and mortality. OBJECTIVE: We investigated the causality and directionality of the associations of VO2max with body composition, physical activity, diabetes, performance enhancers, and longevity. METHODS: Using publicly available summary statistics from the largest genome-wide association studies publicly available, we conducted a bidirectional two-sample Mendelian randomization (MR) study. Bidirectional MR tested directionality, and estimated the total causal effects, whereas multivariable MR (MVMR) estimated independent causal effects. Cardiorespiratory fitness (VO2max) was estimated from a submaximal cycle ramp test (N≈90,000) and scaled to total body weight, and in additional analyses to fat-free mass (mL/min/kg). RESULTS: Genetically predicted higher (per one standard deviation increase) body fat percentage was associated with lower VO2max (ß=-0.36 [95% CI: -0.40, -0.32], p=6E-77). Meanwhile, genetically predicted higher appendicular lean mass (0.10 [0.08,0.13] p=3E-16), physical activity (0.29 [0.07,0.52]), and performance enhancers (fasting insulin, hematocrit, and free testosterone in men) were all positively associated with VO2max (p<0.01). Genetic predisposition to diabetes had no effect on VO2max. MVMR showed independent causal effects of body fat percentage, appendicular lean mass, physical activity, and hematocrit on VO2max, as well as of body fat percentage and type 2 diabetes (T2D) on longevity. Genetically predicted VO2max showed no associations. CONCLUSION: Cardiorespiratory fitness can be improved by favorable body composition, physical activity, and performance enhancers. Despite being a strong predictor of mortality, VO2max is not causally associated with T2D or longevity.

Cardiorespiratory Fitness Is Impaired in Type 1 and Type 2 Diabetes: A Systematic Review, Meta-Analysis, and Meta-Regression.

INTRODUCTION: Low cardiorespiratory fitness (CRF) increases the risk of cardiovascular disease by up to eightfold and is one of the strongest predictors of mortality. Some studies demonstrate impaired CRF in people living with type 1 and type 2 diabetes compared with those without diabetes, whereas others demonstrate no diabetes-associated impairment in CRF. PURPOSE: We aimed to determine whether diabetes can influence CRF and, if so, identify clinical associations underlying diabetes-associated exercise impairments. METHODS: Sixty-eight studies were included in the quantitative analysis. Standardized mean difference (SMD) was calculated and meta-analyses and meta-regressions were performed by using a random-effects model. RESULTS: Diabetes is associated with a large negative effect on CRF (SMD = -0.80, P < 0.001)-an effect that is partially mitigated, but still significant, in those with high physical activity levels (SMD = -0.50, P = 0.007). A sedentary lifestyle (SMD = -0.83, P = 0.007) and the presence of clinical complications related to diabetes (SMD = -1.66, P < 0.001) predict a greater magnitude of CRF reduction in people with diabetes compared with controls without diabetes. Both type 1 diabetes and type 2 diabetes are independently associated with impaired CRF compared with controls without diabetes; however, the effect is significantly greater in those type 2 diabetes (SMD = -0.97, P < 0.001). Meta-regression analysis demonstrates the effects of diabetes on CRF are primarily associated with HbA1c levels for type 1 diabetes ( B = -0.07, P < 0.001) and body mass index for type 2 diabetes ( B = -0.17, P = 0.005). CONCLUSIONS: These data demonstrate a negative influence of diabetes on the key risk factor of low CRF and provide critical insight into specific clinical markers of low CRF associated with diabetes.

Enhancing Sepsis Outcomes: A 7-Year Multidisciplinary Endeavor.

Regulatory bodies in the United States have implemented quality metrics aimed at improving outcomes for patients with severe sepsis and septic shock. The current study was a quality improvement (QI) project in a community-based academic center aimed at improving adherence to sepsis quality metrics, time to antibiotic administration, and patient outcomes. Electronic health record systems were utilized to capture sepsis-related data. Regular audits and feedback sessions were conducted to identify areas for improvement, with a focus on the timely administration of antibiotics. Interventions included improving access to antibiotics, transitioning from intravenous piggyback to intravenous push formulations, and providing continuous staff education and training. This multidisciplinary QI initiative led to significant improvements in the mortality index, length of stay index, and direct cost index for patients with sepsis. Targeted multidisciplinary QI interventions resulted in improved quality metrics and patient outcomes.