Expert Blog

T2DM and Fatty Liver Disease: Is What’s Good for the Gander Good for the Goose?

Kim C. Dixon, MD
General Internist

Fatty liver disease is the most common cause of chronic liver disease in North America[1] 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.[2] 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.
 
 

Comments

Submitted by Doron Schneider on

Thank you for this thoughtful blog. As you indicate - this all too common scenario requires a patient centered approach to decision making. In the absence of high quality data a review of risks and benefits for each agent should be discussed with the patient. These attributes (including the likelihood to positively impact on NAFLD) are summarized elegantly in the recent ACE gylcemic control algorithm. Readers should stay tuned given the rapidly evolving literature in this area. Separately, given the prevalence of Hepatitis C in the US I would ensure testing for this was part of the workup of his liver

Submitted by Kim Dixon on

Yes - excellent point, Doron! I rather reflexively order Hepatitis B and C studies on patients with elevated liver enzymes, unless previously documented. In the setting of elevated enzymes, I also frequently order ferritin/iron studies (Hemochromatosis screen) and consider getting ceruloplasmin levels (Wilson's disease screen) and/or alpha-1 antitrypsin although these are found much less frequently than Hepatitis B and C!

Submitted by John Leahy, MD on

Fatty liver (NASH) has become a huge health problem. I just finished the endocrine session with our first year medical students - it's grouped with GI diseases - and I was fascinated to see our students had had drilled into them that fatty liver is the number one cause of chronic liver disease/cirrhosis. Your blog points out the dilemma of therapy. TZDs have been shown to be beneficial in high profile papers, but most clinicians are wary of those drugs these days, and things revert fairly quickly when the TZD is stopped. Also metformin is probably helpful, but your patient (and many of the patients in general doctors' practices) are already on that drug. Incretin drugs - not sure. So we are left to recommend lifestyle and maybe insulin for better control - doesn't feel too high tech for such an important health issue.

I was interested that your patient had doubled transaminases. Unfortunately that is not always true. We are taught to look for fatty liver by LFT screening, but many patients have normal or only minimally elevated values. What is your experience in whom and how to screen?

Submitted by Kim Dixon on

Ah yes, whom and how to screen for fatty liver - a great question! Certainly patients with elevated liver enzymes warrant screening. For "at-risk" patients with normal liver enzymes there are no clear guidelines I am aware of and I usually defer to a golden rule I learned in residency - only order the test when the result will change management. Probably the best screening mechanism currently is ultrasound, as it is non-invasive, doesn't require contast or radiation exposure and is relatively inexpensive.

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