Liver and cardiovascular disease outcomes in metabolic syndrome and diabetic populations: Bi-directional opportunities to multiply preventive strategies.

The incidence and prevalence of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are rising globally. MetS and T2DM are associated with significant morbidity and mortality, which is partly related to liver and cardiovascular disease. Insulin resistance is central to MetS and T2DM pathophysiology, and drives ectopic fat deposition in the liver, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). MetS and T2DM are not only risk factors for developing MASLD but are also independently associated with disease progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In addition to the risk of liver disease, MetS and T2DM are independent risk factors for cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF). Importantly, there is a bidirectional relationship between liver and CVD due to shared disease pathophysiology in patients with MetS and T2DM. In this review, we have described studies exploring the relationship of MetS and T2DM with MASLD and CVD, independently. Following this we discuss studies evaluating the interplay between liver and cardiovascular risk as well as pragmatic risk mitigation strategies in this patient population.

Antimicrobial Resistance Linked to Septic System Contamination in the Indiana Lake Michigan Watershed.

Extended-spectrum ß-lactamases confer resistance to a variety of ß-lactam antimicrobials, and the genes for these enzymes are often found on plasmids that include additional antimicrobial resistance genes (ARG). We surveyed aquatic environments in the Indiana Lake Michigan watershed in proximity to areas with high densities of residential septic systems to determine if human fecal contamination from septic effluent correlated with the presence of antimicrobial resistance genes and phenotypically resistant bacteria. Of the 269 E. coli isolated from environmental samples and one septic source, 97 isolates were resistant to cefotaxime, a third-generation cephalosporin. A subset of those isolates showed phenotypic resistance to other ß-lactams, fluoroquinolones, sulfonamides, and tetracyclines. Quantitative PCR was used to quantify human-associated Bacteroides dorei gene copies (Human Bacteroides) from water samples and to identify the presence of ARG harbored on plasmids from E. coli isolates or in environmental DNA. We found a strong correlation between the presence of ARG and human fecal concentrations, which supports our hypothesis that septic effluent is a source of ARG and resistant organisms. The observed plasmid-based resistance adds an additional level of risk, as human-associated bacteria from septic systems may expand the environmental resistome by acting as a reservoir of transmissible resistance genes.