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Comorbidities and Nonalcoholic Fatty Liver Disease: The Chicken, the Egg, or Both?

Improvement in NAFLD may lead to improvement of metabolic syndrome, cardiovascular disease, and malignancy and vice versa.
Federal Practitioner. 2019 February;36(2)a:64-71
February 12, 2019|Federal Practitioner
Lisa M. Glass, MD;Christine M. Hunt, MD;Michael Fuchs, MD, PhD;Grace L. Su, MD
Author and Disclosure Information

Lisa Glass is a Staff Physician, and Grace Su is Chief of Gastroenterology and Associate Chief of Medicine, both at VA Ann Arbor Healthcare System. Christine Hunt is a Physician Affiliate and Director of the Cooperative Studies Program Epidemiology Centers at Durham VAMC in North Carolina. Michael Fuchs is Chief of Hepatology and Liver Transplantation at Hunter Holmes McGuire VAMC. Christine Hunt is an Adjunct Associate Professor of Medicine at Duke University Medical Center in Durham. Lisa Glass is an Assistant Professor and Grace Su is a Professor of Medicine, both at the University of Michigan Medical School in Ann Arbor. Michael Fuchs is Professor of Medicine at Virginia Commonwealth University in Richmond. Correspondence: Lisa Glass (lisaglas@med.umich.edu)

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Metabolic Syndrome

Hepatic fat deposition can be associated with or precede MetS. MetS is defined as having at least 3 of the following characteristics: abdominal obesity, elevated triglycerides (TGs) (≥ 150 mg/dL), reduced high-density lipoprotein cholesterol (< 40 mg/dL in men or < 50 mg/dL in women), elevated blood pressure (BP) (systolic BP ≥ 130 mm Hg or diastolic BP ≥ 85 mm Hg), or elevated fasting glucose (≥ 110 mg/dL). Population studies have found that 50% of patients with MetS have NAFLD, and liver fat content is strongly correlated with the number of MetS features present in an individual.5,7 In addition to this association, NAFLD also promotes the development of MetS. Increased energy intake relative to energy expenditure will facilitate ectopic fat accumulation in the liver, which then increases hepatic gluconeogenesis and drives the pathogenesis of insulin resistance.8 Therefore, the presence of NAFLD is both a marker and a promotor of insulin resistance and its complications.

Related: 

 

Type 2 Diabetes Mellitus

At 70% to 75%, the prevalence of NAFLD in patients with T2DM is more than twice as high as that in the general US adult population. Conversely, about 23% of patients with NAFLD also have T2DM.9

Influence of NAFLD on T2DM

Patients with ultrasound-based evidence of NAFLD are 2 to 5 times more likely to develop T2DM after adjusting for lifestyle and metabolic risk factors in multiple epidemiologic studies.10,11 The severity of hepaticfat content measured by ultrasound also is associated with an increasing risk of T2DM incidence over the next 5 years (normal,7%; mild, 9.8%; moderate-severe, 17.8%; P < .001).12 In another study, 58% of patientswith biopsy-proven NAFLD developed T2DM after a mean follow-up of 13.7 years.13 Those who were found to have NASH had a 3-fold higher risk of developing T2DM than did those with simple steatosis. This finding was confirmed in another study where T2DM incidence was 2 times higher in patients predicted to have advanced fibrosis compared with those who did not.14

Because liver steatosis interferes with insulin-induced glycogen production and suppression of gluconeogenesis, hepatic fat content predicts the insulin dose required for adequate glucose control in patients with diabetes mellitus (DM) and NAFLD.15 Higher levels of insulin are required in patients with DM and NAFLD compared with those without NAFLD.5 

Furthermore, patients with DM and NAFLD have increased complications, including both retinopathy and CKD.5 It is thus not surprising that a population-based study of more than 330 patients with T2DM found that the presence of NAFLD was associated with a 2-fold increase in all-cause mortality over a mean follow-up period of 11 years.16

Additionally, a 10-year cohort study found that resolution of ultrasound-based NAFLD in patients without baseline T2DM, was associated with a reduced T2DM incidence (multivariate odds ratio [OR] 0.27, 95% CI, 0.12-0.61) after controlling for factors such as age, BMI, and impaired fasting glucose.11,17

Given this close relationship between T2DM and NAFLD, both the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of Liver Diseases (EASL) guidelines recommend that patients found to have NAFLD should be screened for the presence of impaired fasting glucose/T2DM by testing hemoglobin A1c or fasting glucose levels.18,19 Recognizing the role that NAFLD can play in patients with DM also is important, as improving hepatic steatosis may also improve DM.

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