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.