Cirrhosis and insulin resistance: current knowledge, pathophysiological mechanisms, complications and potential treatments.

End-stage chronic liver diseases are often associated with insulin resistance (IR) and diabetes mellitus (DM). Indeed, to quantify insulin sensitivity the euglycemic clamp technique was utilized, allowing the following to be stated: in small groups of patients, an IR in almost all cirrhotic patients can be observed, compared with a control group. Additionally, it has been demonstrated that IR in cirrhosis is linked to a decreased peripheral (muscle) glucose uptake rather than an increased liver glucose production. The homoeostasis model of IR (HOMA-IR) technique, devised only later, was then exploited to assess this same phenomenon in a larger sample population. The research established that even in patients with preserved liver function, cirrhosis is associated with significant alterations in glucose homoeostasis levels. The purpose of the present paper is to present the current research around the affiliation of cirrhosis and IR, discuss potential mechanisms explaining the association between cirrhosis and IR (i.e. endocrine perturbation, liver inflammation, altered muscle mass and composition, altered gut microbiota and permeability), complications that can arise as well as treatment options, through a critical review of the literature surrounding this subject. This research will also be investigating the beneficial impact, if there is any, of identifying and curing IR in patients with cirrhosis.

Patients with chronic liver diseases are at risk for diabetes even before development of cirrhosis.

BACKGROUND AND AIMS: The prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) is higher in patients with cirrhosis, compared to control patients without liver disease. The exact mechanism for this is unknown but could include liver inflammation. In this study we investigate whether cirrhosis is the primum movens of IR or if impaired insulin sensitivity is already present in non-cirrhotic patients with chronic liver diseases. METHODS: Patients were recruited and divided into three groups: control (CTL), chronic liver disease without cirrhosis (CLD) and cirrhosis (CIR). In patients not taking pharmacological treatment for T2DM, IR was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). The proportion of patients with T2DM as well as HOMA-IR levels among different disease etiologies were recorded and compared. RESULTS: 532 patients were included in our study. Median glycemia and insulinemia and therefore HOMA-IR values were significantly different between the three cohorts (p-value <0.001): IR levels in CLD subjects lie between those seen in CTL and CIR subjects. The proportion of diabetic patients in the two case categories also differs (p-value = 0.027): one quarter of CLD subjects and one third of CIR patients suffer from T2DM. Finally, HOMA-IR levels vary according to disease etiology (p-value <0.001): metabolic steatosis and chronic viral hepatitis C are at greater risk than alcohol and other disease causes. CONCLUSION: CLD is already a predisposing factor to T2DM, regardless of the presence of CIR. CIR is a factor which elicits additional increase in insulin levels. Metabolic steatosis and hepatitis C are associated with more severe IR.

Do Non-COVID-19 Patients' Behaviour Towards Emergency Changed During the COVID-19 Outbreak? A Severity-Based Approach.

Objective: During the COVID-19 pandemic, the number of patients presenting to the emergency department (ED) declined. The main goal of this study was to compare and describe the non-COVID-19 patient's disease severity presentation during the pandemic with its pre-pandemic severity. Methods: We conducted a retrospective observational study. We selected two samples of visits: one during the first COVID-19 wave of 2020 (pandemic period, PP) and the other during the same months of 2019 (control period, CP). The primary endpoints were the comparison of severity and distribution of the Emergency Severity Index (ESI). Secondary endpoints were comparisons of specific patient characteristics (age, sex, length of the symptoms before the visits, spontaneous visits or not, return home or not). Results: The mean ESI of the visits during the PP (3.19) was statistically significantly lower (P = 0.001) than it was in the CP (3.43). These changes were more pronounced during the months of March (3.03 versus 3.33, P = 0.037) and April (2.96 versus 3.48, P < 0.001). The change in ESI was mainly due to an increase in the proportion of visits by patients with an ESI score of 3 (42% versus 28%, P < 0.001). There were no differences in the characteristics of patients except a decline in patients whose symptoms had a duration of more than 30 days (2% during PP versus 4% during CP, P = 0.03). Conclusion: The COVID-19 pandemic caused a change in the pattern of non-COVID-19 visits, with proportionally more severe presentations based on the ESI. To our knowledge, this is the first description of changes in behaviour in ED visits by specifically non-COVID-19 patients.