High Rate of Hospital Admissions Among Patients with Cirrhosis Seeking Care in US Emergency Departments

BACKGROUND AND AIMS: Emergency Departments (ED) can serve as a gateway to specialty care for patients with cirrhosis with limited care access. We described the rates and characteristics of patients with cirrhosis who access United States (US) EDs, and identified factors associated with subsequent hospitalization. METHODS: Using data from the National Hospital Ambulatory Medical Care Survey, cirrhosis-related ED from 2000 to 2009 were identified and compared to all other ED visits. RESULTS: From 2000 to 2009, there were an estimated 1,029,693 cirrhosis and 877 million non-cirrhosis visits. Compared to the general ED population, those with cirrhosis were more frequently male (58 vs. 44 %, p = 0.02), Hispanic (18.6 vs. 10.6 %, p<0.05), seeking care in urban areas (91.6 vs. 73.4 %, p<0.05) and had Medicaid/no insurance (43 vs. 35 %, p < 0.01). Patients with cirrhosis were more frequently triaged immediately or emergently (72.3 vs. 54.2 %, p < 0.01). The majority were admitted or transferred to another hospital (66.8 vs. 17.4 %, p < 0.01). Among patients with cirrhosis, patients with age ≥ 65 - years were more likely to be admitted (adjusted OR 2.49, 95 % CI 1.08–5.73), and Medicaid/uninsured (adjusted OR 0.34; 95 % CI 0.17–0.67) were less likely to be admitted, after adjusting for patient demographics, hospital characteristics, and triage score. CONCLUSIONS: Patient with cirrhosis account for approximately 100,000 US ED visits annually. The higher admission rates among patients with cirrhosis indicate a high acuity of illness. Older age among those admitted may reflect poorer functional status. Finally, high visit but low admission rates among those with Medicaid/no insurance suggest a gap in specialty care

Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo

Metformin, the universal first-line treatment for type 2 diabetes, exerts its therapeutic glucose-lowering effects by inhibiting hepatic gluconeogenesis. However, the primary molecular mechanism of this biguanide remains unclear, though it has been suggested to act, at least partially, by mitochondrial complex I inhibition. Here we show that clinically relevant concentrations of plasma metformin achieved by acute intravenous, acute intraportal or chronic oral administration in awake normal and diabetic rats inhibit gluconeogenesis from lactate and glycerol but not from pyruvate and alanine, implicating an increased cytosolic redox state in mediating metformin’s antihyperglycemic effect. All of these effects occurred independently of complex I inhibition, evidenced by unaltered hepatic energy charge and citrate synthase flux. Normalizing the cytosolic redox state by infusion of methylene blue or substrates that contribute to gluconeogenesis independently of the cytosolic redox state abrogated metformin-mediated inhibition of gluconeogenesis in vivo. Additionally, in mice expressing constitutively active acetyl-CoA carboxylase, metformin acutely decreased hepatic glucose production and increased the hepatic cytosolic redox state without altering hepatic triglyceride content or gluconeogenic enzyme expression. These studies demonstrate that metformin, at clinically relevant plasma concentrations, inhibits hepatic gluconeogenesis in a redox-dependent manner independently of reductions in citrate synthase flux, hepatic nucleotide concentrations, acetyl-CoA carboxylase activity, or gluconeogenic enzyme protein expression