Fatty liver disease is the most common cause of chronic liver disease in North America and is becoming one of the top reasons for liver transplantation. Fatty liver causes inflammation that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. The physiologic relationship between type 2 diabetes mellitus and fatty liver disease is complex and multifactorial. A recent study in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM) found that individuals with fatty liver were five times more likely to develop type 2 diabetes than those without fatty liver. However, researchers are only beginning to unravel the mysteries surrounding the relationship between type 2 diabetes and fatty liver as it applies to large patient populations. In the meantime, clinicians are left to treat individuals with type 2 diabetes and/or fatty liver disease in light of existing evidence.
Already we know that lifestyle modifications that improve fatty liver, including diet, exercise, and weight management, are also beneficial for type 2 diabetes and should be encouraged for all patients. As clinicians individualize therapy for patients with type 2 diabetes, moreover, they should consider fatty liver disease.
Consider the following patient scenario: A 50-year-old male with type 2 diabetes presents for a follow-up visit. The diabetes is currently managed with diet and metformin 1000 milligrams BID. On exam, his BMI is noted to be 33. Laboratory evaluation reveals liver enzymes roughly two times normal and an HbA1C of 8%. Evaluation of the elevated liver enzymes leads to an abdominal ultrasound that establishes the presence of fatty liver disease. Lifestyle modification is strongly encouraged, including diet, exercise, and weight loss.
To improve diabetes control, a second medication is indicated, but which one? Thiazolidinediones are insulin sensitizers, and have been shown to reduce fat in the liver; however, they are associated with weight gain and have been under increased scrutiny with new warnings from the FDA regarding Avandia™. Sulfonylureas are associated with weight gain and are metabolized by the liver and therefore need to be used cautiously in the setting of obesity and fatty liver disease. A GLP-1 receptor agonist (exenatide and liraglutide being the only current FDA approved medications) could be added, but requires daily injections. A DPP-4 inhibitor may be a good choice as a second agent, and we will hopefully have more evidence in the future to evaluate efficacy for this particular patient population. Until then, clinicians will continue to do what they do best–treat patients with type 2 diabetes and fatty liver on an individual basis utilizing the limited evidence that exists for these populations. Sharing observations and experiences from our practices can be helpful, too, so please feel free to share them on this blog.