Electronic ArticleHypoglycemia is associated with increased mortality in patients with acute decompensated liver cirrhosis☆,☆☆,★,★★
Introduction
Generally, the liver plays an important role in glucose metabolism, in terms of glucolysis and gluconeogenesis [1]. The liver functions as a reserve for carbohydrates, storing glycogen from glucose in postprandial periods and releasing glucose during fasting periods [2]. In patients with liver cirrhosis, the capacity of the liver to preserve carbohydrates is impaired [2].
The pathogenesis of hepatogenous diabetes is complex and not jet fully understood [1], [3]. It is characterized by elevated by postprandial hyperglycemia and insulin resistance [2]. Hyperinsulinemia in the cirrhotic patient is caused by decreased hepatic extraction and portosystemic shunts [1], [4], [5]. This results in increased insulin resistance in muscular and adipose tissue [1]. Elevated insulin levels also stimulate hepatic proinflammatory cells and reduce anti-inflammatory mechanisms, thus facilitating cirrhotic changes by activating hepatic stellate cells. These then induce the production of collagen, resulting in progressive hepatic fibrosis [4].
All of these changes may lead to hepatogenous diabetes, a common complication of liver cirrhosis [3]. There is little association with common diabetes type 2 risk such as age, obesity, or family history [6].
The incidence of impaired glucose tolerance varies between 30% and 96% of all patients with liver cirrhosis [1], [3], [4], [5], [6], and diabetes is prevalent in between 18% and 71% of all cases [3], [5]. Despite the high incidence of diabetes caused by liver disease, it is not recognized as a separate entity by the World Health Organisation [3]. Several studies have shown that glucose disturbances, in particular hyperglycemia, in patients with liver cirrhosis are associated with progression of the liver disease and increased mortality [1], [2], [3], [4], [6]. Hypoglycemia in patients with liver cirrhosis is caused by impaired gluconeogenesis in these patients [3], [5].
A few studies have examined the association between glucose disturbance and outcome in patients with compensated liver cirrhosis [1], [3], [4], [5], [6]. All of these focused on hyperglycemia. Studies targeting the role of glucose disturbances in patients with acute decompensated liver cirrhosis are scarce. To the best of our knowledge, there is only one study focusing on 30-day survival in patients with abnormal glucose tolerance and elevated glucose levels [3]. No study has ever targeted hypoglycemia. The aim of this study was therefore to assess the characteristics of patients presenting with acute decompensated liver cirrhosis and glucose disturbances to the emergency department (ED).
Section snippets
Setting
The study was conducted at the Department of Emergency Medicine of the Inselspital, Bern University Hospital. Decompensated liver cirrhosis was diagnosed and treated according to common guidelines.
Data collection and retrospective survey
Our retrospective data analysis comprised adult (≥ 16 years) patients admitted to our ED between January 1, 2002, and December 31, 2012, with the primary diagnosis of decompensated liver cirrhosis. Patients were identified using the appropriate search string in the diagnosis or medical history field of
Results
A total of 312 patients were eligible for study inclusion. For an overview of patient characteristics, see Table 1. Two hundred thirty-one (231; 74.0%) patients were male, and 81 (26.0%) were female. The median age was 57 years (range, 51-65 years). The most common etiology of liver cirrhosis was alcohol (159; 51.0%). Child-Pugh C liver cirrhosis was the most common stage of liver cirrhosis (174; 55.8%). The most common sign of decompensated liver cirrhosis was ascites (174; 55.8%). Two hundred
Discussion
Our study showed that almost 30% of our study population had an acute glucose disturbance in the ED. Hypoglycemia was the most common type of glucose disturbance and significantly associated with increased mortality and decreased survival in patients with acutely decompensated liver cirrhosis.
To the best of your knowledge, this is the first study targeting glucose disturbances in acute decompensated liver cirrhosis. A study by Hagel et al [3] focused on abnormal glucose tolerance as a predictor
Conclusion
Hypoglycemia is associated with increased mortality and decreased survival in patients with acute decompensated liver cirrhosis. It is not yet understood whether hypoglycemia is jointly responsible for the increased short-term mortality in patients with acute decompensated liver cirrhosis or is only a consequence of disease severity or complications. Hypoglycemia may be linked to acute hepatic failure. Nevertheless, ED and intensive care personnel should be aware of the increased mortality in
Acknowledgments
The authors thank Mrs Sabina Utiger and Mr Stephan Fuhrimann for their administrative help.
References (28)
- et al.
Impact of diabetes on the severity of liver disease
Am J Med
(2007) - et al.
Inpatient management of diabetes and hyperglycemia
Clin Ther
(2013) - et al.
Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club
Hepatology
(1996) - et al.
Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management
Lancet Neurol
(2007) - et al.
Liver cirrhosis and diabetes: risk factors, pathophysiology, clinical implications and management
World J Gastroenterol
(2009) - et al.
Oral glucose tolerance test predicts prognosis of patients with liver cirrhosis
Am J Gastroenterol
(2006) - et al.
Abnormal glucose tolerance: a predictor of 30-day mortality in patients with decompensated liver cirrhosis
Z Gastroenterol
(2011) - et al.
Insulin resistance and chronic liver disease
World J Hepatol
(2011) - et al.
Impact of liver diseases on the development of type 2 diabetes mellitus
World J Gastroenterol
(2011) - et al.
Transection of the oesophagus for bleeding oesophageal varices
Br J Surg
(1973)
Glycemic levels in critically ill patients: are normoglycemia and low variability associated with improved outcomes?
J Diabetes Sci Technol
Glucose control in the intensive care unit
Crit Care Med
Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data
CMAJ
Clinical review: Consensus recommendations on measurement of blood glucose and reporting glycemic control in critically ill adults
Crit Care
Cited by (48)
Stress, hypoglycemia, and the autonomic nervous system
2022, Autonomic Neuroscience: Basic and ClinicalCitation Excerpt :Rates of hypoglycemia are much lower among individuals with T2DM, but still occur with advanced disease and polypharmacy (U.K. prospective diabetes study 16, 1995). Hypoglycemia may even occur in the absence of diabetes in numerous disease conditions including Addison's disease, renal failure, sepsis, growth hormone deficiency, ectopic production of insulin-like growth factor, insulinoma, liver failure, and following bariatric surgery (Pfortmueller et al., 2014; Abrahamsson et al., 2015). Individuals can be exposed to numerous hypoglycemic episodes (physiological stress events) over their lifetime, contributing to allostatic load and affirming the importance of studying hypoglycemia and its effects.
Influence of Liver Cirrhosis on Blood Glucose, Insulin Sensitivity and Islet Function in Mice
2021, American Journal of the Medical SciencesCitation Excerpt :Gjorgjieva et al.28 reported hepatic stress associated with pathologies characterized by disturbed glucose production; during fasting periods, glucose is consumed by all organs, resulting in a decrease in glucose levels. Pfortmueller et al.29 reported that decompensated liver cirrhosis was associated with hypoglycemia. However, all these studies observed one time point of liver cirrhosis, and to the best of our knowledge, there have not been studies of glucose levels in different periods of cirrhosis.
Reply
2021, Clinical Gastroenterology and HepatologyImplications of Nonalcoholic Steatohepatitis as the Cause of End-Stage Liver Disease Before and After Liver Transplant
2020, Gastroenterology Clinics of North AmericaCitation Excerpt :Furthermore, because diabetes is a key risk factor for fibrosis progression, the relative prevalence of diabetes and associated complications is considerably higher among patients with NASH cirrhosis compared with other causes of cirrhosis.39 Hypoglycemia in patients with cirrhosis is caused by impaired gluconeogenesis and is associated with increased mortality in patients with acute decompensated liver cirrhosis.40 Several studies have documented the negative impact of diabetes on survival and clinical outcomes in patients with cirrhosis.41–47
Accuracy of pipeline blood glucose monitoring in patients with severe liver injury undergoing artificial liver support system treatment
2019, Hepatobiliary and Pancreatic Diseases International
- ☆
Source of funding: Self-funding.
- ☆☆
Financial disclosure: None reported.
- ★
Conflict of interest: None.
- ★★
Author's contribution. Study design: Pfortmueller, Wiemann, Lindner, and Exadaktylos. Evaluation of data: Wiemann, Pfortmueller, Leichtle, and Fiedler. Analysis of data: Pfortmueller, Funk, and Lindner. Drafting of the manuscript: Pfortmueller, Lindner, and Funk. Revision for important intellectual content: Pfortmueller, Lindner, Funk, Exadaktlyos, Leichtle, and Fiedler.