Impact of obesity on day-night differences in cardiac metabolism

An intrinsic property of the heart is an ability to rapidly and coordinately adjust flux through metabolic pathways in response to physiologic stimuli (termed metabolic flexibility). Cardiac metabolism also fluctuates across the 24-hours day, in association with diurnal sleep-wake and fasting-feeding cycles. Although loss of metabolic flexibility has been proposed to play a causal role in the pathogenesis of cardiac disease, it is currently unknown whether day-night variations in cardiac metabolism are altered during disease states. Here, we tested the hypothesis that diet-induced obesity disrupts cardiac diurnal metabolic flexibility , which is normalized by time-of-day-restricted feeding. Chronic high fat feeding (20-wk)-induced obesity in mice, abolished diurnal rhythms in whole body metabolic flexibility, and increased markers of adverse cardiac remodeling (hypertrophy, fibrosis, and steatosis). RNAseq analysis revealed that 24-hours rhythms in the cardiac transcriptome were dramatically altered during obesity; only 22% of rhythmic transcripts in control hearts were unaffected by obesity. However, day-night differences in cardiac substrate oxidation were essentially identical in control and high fat fed mice. In contrast, day-night differences in both cardiac triglyceride synthesis and lipidome were abolished during obesity. Next, a subset of obese mice (induced by 18-wks ad libitum high fat feeding) were allowed access to the high fat diet only during the 12-hours dark (active) phase, for a 2-wk period. Dark phase restricted feeding partially restored whole body metabolic flexibility, as well as day-night differences in cardiac triglyceride synthesis and lipidome. Moreover, this intervention partially reversed adverse cardiac remodeling in obese mice. Collectively, these studies reveal diurnal metabolic inflexibility of the heart during obesity specifically for nonoxidative lipid metabolism (but not for substrate oxidation), and that restricting food intake to the active period partially reverses obesity-induced cardiac lipid metabolism abnormalities and adverse remodeling of the heart

Diabetes-Related Cardiac Dysfunction

The proposal that diabetes plays a role in the development of heart failure is supported by the increased risk associated with this disease, even after correcting for all other known risk factors. However, the precise mechanisms contributing to the condition referred to as diabetic cardiomyopathy have remained elusive, as does defining the disease itself. Decades of study have defined numerous potential factors that each contribute to disease susceptibility, progression, and severity. Many recent detailed reviews have been published on mechanisms involving insulin resistance, dysregulation of microRNAs, and increased reactive oxygen species, as well as causes including both modifiable and non-modifiable risk factors. As such, the focus of the current review is to highlight aspects of each of these topics and to provide specific examples of recent advances in each area

Effect of elevated HbA1c on outcomes in on-pump versus off-pump coronary artery bypass grafting

Abstract Background Diabetic patients are at an increased risk of cardiovascular morbidities. We aimed to examine if elevated pre-operative glycosylated hemoglobin (HbA1c) levels are associated with higher likelihood of experiencing adverse events in on-pump (ONCAB) versus off-pump (OPCAB) coronary artery bypass graft (CABG) procedures. We examined characteristics of patients undergoing CABG using our institutional STS Adult Cardiac Surgery Database (ACSD) from 2014 to 2020. Descriptive statistics and univariate analyses were used to compare postoperative outcomes between ONCAB and OPCAB based on preoperative HbA1c levels: (1) HbA1c ≤ 6.0%, (2) 6.0% 8.5%. Multivariable models were built to assess risk factors associated with adverse events. Primary outcomes were operative mortality and stroke. Results For ONCAB, statistically significant associations were found between increasing HbA1c and new post-operative dialysis (p=0.01), rates of readmission (p=0.003) and greater lengths of stay (p=0.002). For OPCAB, statistically significant associations were found between increasing HbA1c and rates of operative mortality (p=0.04), post-operative renal failure (p=0.0001), new post-operative dialysis (p=0.0001), sternal wound infection (p=0.01), and greater lengths of stay (p=0.03). No significant relationship was noted between HbA1c and stroke, reoperation due to bleeding, or post-operative transfusion. Conclusions Increasing HbA1c positively correlated with numerous adverse patient outcomes in both ONCAB and OPCAB, and differences were noted in which outcomes were most impacted between the two techniques. Pre-operative medical optimization from a diabetes standpoint is paramount to improve CABG outcomes in both on-pump or off-pump techniques