From the Guidelines
Elevated ammonia levels in patients with chronic cirrhosis can potentially affect blood glucose regulation and contribute to hyperglycemia, and thus, it is crucial to manage both conditions simultaneously to prevent further complications. Cirrhosis often leads to hepatic insulin resistance and impaired glucose metabolism, which can worsen hyperglycemia, as noted in the 2023 standards of care in diabetes 1. The liver plays a crucial role in both ammonia detoxification and glucose homeostasis, so when liver function is compromised in cirrhosis, both processes become dysregulated. Hyperammonemia can further impair insulin signaling pathways and may contribute to peripheral insulin resistance.
Some key points to consider in the management of hyperglycemia in patients with chronic cirrhosis include:
- The use of glucose-lowering agents, with insulin being the preferred agent for the treatment of hyperglycemia in adults with type 2 diabetes with decompensated cirrhosis, due to the lack of robust evidence about the safety and efficacy of oral agents and noninsulin injectables 1
- The importance of careful glucose monitoring and ammonia-lowering strategies, such as lactulose, rifaximin, or branched-chain amino acids, to address both conditions simultaneously
- The need to balance protein restriction, which may help manage ammonia levels, against nutritional needs, as protein is essential for maintaining muscle mass and preventing sarcopenia, a common complication in cirrhotic patients 1
- The potential benefits of metabolic surgery in improving NASH and cardiometabolic health, although it should be used with caution in individuals with compensated cirrhosis and is not recommended in those with decompensated cirrhosis 1
Overall, the management of hyperglycemia in patients with chronic cirrhosis requires a comprehensive approach that takes into account the complex metabolic derangements associated with liver disease, and prioritizes the prevention of further complications and the improvement of quality of life.
From the Research
Effect of Elevated Ammonia on Hyperglycemia in Cirrhosis
- There is no direct evidence in the provided studies that elevated ammonia secondary to chronic cirrhosis has an effect on hyperglycemia.
- However, studies have shown that metformin, a common treatment for hyperglycemia, can have a protective effect against hepatic encephalopathy in diabetic cirrhotic patients by inhibiting glutaminase activity and reducing ammonia production 2.
- Additionally, continuation of metformin after cirrhosis diagnosis has been shown to improve survival in patients with diabetes, suggesting that metformin may have benefits beyond just controlling hyperglycemia 3.
- Elevated ammonia levels have been linked to various complications in cirrhosis, including hepatic encephalopathy, sarcopenia, and immune dysfunction 4, 5.
- The relationship between ammonia levels and hyperglycemia is not well established, and further research is needed to understand the potential interactions between these two conditions.