1 | INTRODUCTION
Insulin has saved numerous lives since its discovery in the 1920s. It is extremely effective in treating hyperglycemia and can be used when hyperglycemia causes critical conditions, such as ketoacidosis or hyperosmolar hyperglycemic state [1]. By carefully manipulating the dose, insulin is also frequently used in persons with hospitalization, major surgery, sepsis, and acute myocardial infarction [2]. Liver cirrhosis also is the strong indication for insulin treatment in persons with type 2 diabetes mellitus (T2DM) [1,2].
Liver cirrhosis is an advanced liver disease; it also is the late stage of chronic liver injury [3]. It can be attributed to several reasons, such as nonalcoholic fatty liver diseases, chronic alcoholism, hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection [3]. With the development of cirrhosis, owing to reduced insulin extraction of liver and portal systemic shunts, serum insulin levels increase and insulin resistance may occur. Approximately 96% of persons with cirrhosis may be glucose intolerant and 30% of them may develop clinical diabetes [4]. Moreover, diabetes treatment in persons with liver cirrhosis is complex [5]. Diet control for persons with cirrhosis is not feasible because they may have poor appetite. Encouraging them to exercise may not be suitable because they may demonstrate weakness. Medications such as metformin, sulphonylureas, and thiazolidinedione may cause lactic acidosis (especially in those with chronic alcoholism), may lead to the risk of hypoglycemia, and may aggravate fluid retention, respectively. Thus, adequate management of T2DM in persons with liver cirrhosis is unclear.
Careful adjustment of the insulin dose and close monitoring of blood glucose levels may enable the effective and safe use of insulin for treating persons with cirrhosis and T2DM [6]. However, insulin has some deleterious side effects. Hypoglycemia is the most critical side effect of insulin use, as it can increase the risks of mortality and cardiovascular diseases [7]. Insulin was also reported to increase body weight and risks of cardiovascular events [8,9], and insulin use is associated with the risk of hepatocellular carcinoma (HCC) [10]. Therefore, we conducted this retrospective cohort study to investigate the long-term outcomes of insulin use in people with T2DM and compensated liver cirrhosis.