Fatty liver disease in type 2 diabetes: Common and often unmanaged

,

Original Research

Fatty liver disease in type 2 diabetes: Common and often unmanaged

J Fam Pract. 2012 March;61(3):E5-E7

By

Eric L. Johnson, MD

This study of patients with type 2 diabetes in a large rural clinic showed that abnormal liver function tests do not usually lead to diagnostic imaging studies.

PDF Download

References

1. Caldwell SH, Oelsner DH, Iezzoni JC, et al. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology. 1999;29:664-669.

2. Pagano G, Pacini G, Musso G, et al. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology. 2002;35:367-372.

3. Tolman KG, Fonseca V, Dalpiaz A, et al. Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease. Diabetes Care. 2007;30:734-743.

4. de Marco R, Locatelli F, Zoppini G, et al. Cause-specific mortality in type 2 diabetes: the Verona Diabetes Study. Diabetes Care. 1999;22:756-761.

5. Koehler E, Watt K, Charlton M. Fatty liver and liver transplantation. Clin Liver Dis. 2009;13:621-630.

6. Saremi A, Allison M, Ditomasso D, et al. Preliminary report: hepatic fat and inflammation in type 2 diabetes mellitus. Metabolism. 2010;59:430-432.

7. Hultcrantz R, Glaumann H, Lindberg G, et al. Liver investigation in 149 asymptomatic patients with moderately elevated activities of serum aminotransferases. Scand J Gastroenterol. 1986;21:109-113.

8. Schreuder TC, Verwer BJ, van Nieuwkerk CM, et al. Nonalcoholic fatty liver disease: an overview of current insights in pathogenesis, diagnosis and treatment. World J Gastroenterol. 2008;14:2474-2486.

9. Chavez-Tapia NC, Tellez-Avila FI, Barrientos-Gutierrez T, et al. Bariatric surgery for non-alcoholic steatohepatitis in obese patients. Cochrane Database Syst Rev. 2010;(1):CD007340.-

10. Medina J, Fernández-Salazar LI, García-Buey L, et al. Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis. Diabetes Care. 2004;27:2057-2066.

11. Khashab M, Chalasani N. Use of insulin sensitizers in NASH. Endocrinol Metab Clin North Am. 2007;36:1067-1087.

12. Ding X, Saxena NK, Lin S, et al. Exendin-4, a glucagon-like protein (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology. 2006;43:173-181.

13. Matafome P, Nunes E, Louro T, et al. A role for atorvastatin and insulin combination in protecting from liver injury in a model of type 2 diabetes with hyperlipidemia. Naunyn Schmiedebergs Arch Pharmacol. 2009;379:241-251.

14. Ratziu V, Bellentani S, Cortez-Pinto H, et al. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol. 2010;53:372-384.

CORRESPONDENCE Eric L. Johnson, MD, 501 N. Columbia Road, Stop 9037, Grand Forks, ND 58202; eric.I.johnson@med.und.edu

ABSTRACT

Purpose The objective of this pilot study was to evaluate the prevalence and management of nonalcoholic fatty liver disease in a rural type 2 diabetes population.

Methods We randomly selected 100 patients with type 2 diabetes from a large rural clinic/hospital system in the upper Midwest and conducted a chart review to determine the prevalence of abnormal results of serum liver function tests and liver imaging (eg, computed tomography, ultrasound, magnetic resonance imaging). We also determined the number of patients who were given a diagnosis of fatty liver disease and who among those were subsequently managed for the condition.

Results Of the 100 subjects, 40 had abnormal serum liver function testing, and half of those individuals underwent imaging. This resulted in a diagnosis of fatty liver disease in 11 (27.5% of the 40 with abnormal liver function). Only 4 patients received specific interventions for fatty liver disease.

Conclusion In this rural population, fatty liver disease was common and untreated, suggesting a possible need for a change in screening and management protocols.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States.¹ In particular, NAFLD and the related inflammatory nonalcoholic steatohepatitis (NASH) often develop in individuals who are obese or who have prediabetes or type 2 diabetes, affecting up to 75% of patients with these conditions.²

In addition to NAFLD and NASH, other liver diseases associated with type 2 diabetes include cirrhosis, hepatocellular carcinoma, liver failure, and hepatitis.^1,3,4 Of patients with type 2 diabetes, more than 600,000 have cirrhosis; 4.4% of diabetes-related deaths have been attributed to cirrhosis.^4,5

NAFLD and NASH share a common pathophysiology in type 2 diabetes with respect to insulin resistance, which results in hyperlipidemias that enhance fatty deposits in the liver.^1,2 Hepatic fat accumulation is also associated with increasing measures of inflammation, including C-reactive protein.⁶

Resultant liver function test abnormalities and characteristic appearance on imaging studies (ultrasound, computed tomography [CT], or magnetic resonance imaging [MRI]) may be similar in NAFLD and NASH.^1-3 Liver biopsy therefore is necessary to distinguish NAFLD from NASH, with NASH showing characteristic inflammatory and fibrotic changes.^1,2 Evaluations of patients with minor liver test abnormalities reveal that up to 98% may have liver disease, most often fatty liver disease.⁷

Weight loss is a strategy for managing NAFLD and NASH, although large randomized controlled trials are lacking.^8-10 Several agents used for diabetes and dyslipidemias, including glucagon-like peptide-1 (GLP-1) mimetics, metformin, thiazolidinediones, and statins, have been studied as possible treatments for NAFLD and NASH.^8-13 Currently, these medications carry cautions or warnings about using them in patients with liver disease and are not indicated as treatments for NAFLD or NASH.

SUBJECTS AND METHODS

One hundred patients were randomly selected from a type 2 diabetes patient database at the Altru Health System (Grand Forks, ND) for cross-sectional analysis. Manual data extraction from “paper charts” was necessary in some cases, limiting the size of the study.

All subjects had a diagnosis of type 2 diabetes confirmed by American Diabetes Association criteria, were between the ages of 18 and 64 years, and had no known liver disease other than that associated with their diabetes. Other criteria included visiting a health care provider regarding diabetes management within the last year and having undergone laboratory blood testing of liver function within the last 5 years. The study population comprised an equal number of men and women.

We collected data about abnormal liver function from blood test results, including levels of aspartate transaminase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP); results of radiologic imaging of the liver (ultrasound, MRI, or CT) and liver biopsy; any interventions (medication changes, lifestyle management, or surgery); and referral to a specialist (gastroenterologist or surgeon).

DATA ANALYSIS

Of the 100 subjects, 40 had at least one abnormal serum liver function test (AST, ALT, or ALP), although we could find no record of tests for one of the 100 subjects. Of the 40 with abnormal test results, 17 (42.5%) were women and 23 (57.5%) were men. None of these patients had highly elevated levels of AST, ALT, or ALP.

FAST TRACK

Of 40 patients with abnormal serum liver function tests, only 10 were specifically referred for imaging studies that might confirm a diagnosis of fatty liver disease.

Of the 40 patients with abnormal serum liver function tests, only 10 (25%) were specifically referred for imaging studies related to a possible diagnosis of fatty liver disease. Four of these 10 patients (1 woman and 3 men) had both ultrasound and CT imaging. Another 10 subjects (25%) had incidental findings of fatty liver disease on imaging performed for another presumed diagnosis or symptom, eg, abdominal pain. Overall, 11 (6 men, 5 women) of the 40 subjects (27.5%) with at least one abnormal liver function test received a diagnosis of fatty liver disease based on imaging findings. None of the subjects had a diagnosis of cirrhosis or other end-stage liver disease.