Concurrent nonalcoholic fatty liver disease and type 2 diabetes: diagnostic and therapeutic considerations

ABSTRACT

Introduction: The relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) is complex and bidirectional. NAFLD increases the risk of incident diabetes and is very prevalent in T2DM patients and T2DM is an aggravating factor for NAFLD. Timely T2DM diagnosis and treatment in subjects with NAFLD and diagnosis, staging and treatment of NAFLD in those with T2DM are critical issues.

Areas covered: PubMed/MEDLINE was searched for articles related to concomitant occurrence of NAFLD and T2DM between January 2013 and May 2019. Areas covered included epidemiological, diagnostic and therapeutic aspects.

Expert opinion: there is a need for increased awareness on NAFLD adding liver disease as an end-organ complication of T2DM. Emphasis on use of simple non-invasive tools to triage patients with potentially severe liver disease should be made. Management of patients with NAFLD and T2DM relies on lifestyle optimization to achieve significant weight loss. Currently, there is no drug approved for treatment of NAFLD in patients with T2DM although Vitamin E and pioglitazone might be used in selected patients. Approved diabetic medications hold promise for NAFLD treatment and several liver-specific drugs are in evaluation clinical trials. A combination approach will likely represent the future of NAFLD therapeutics.

KEYWORDS:

• Nonalcoholic fatty liver disease
• fatty liver disease
• hepatology
• diabetes
• insulin resistance

Article highlights

• Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are conditions of increasing clinical relevance worldwide that frequently coexist in clinical practice

• The relationship between NAFLD and T2DM is complex and bidirectional and occurs in the context of a wider association between NAFLD and metabolic syndrome with intertwined and difficult to dissect underlying pathophysiological mechanisms

• T2DM patients are at high risk of developing severe forms of NAFLD but underappreciation of the prevalence and clinical spectrum of NAFLD and its assessment in T2DM among non-specialists has been documented. Thus, targeted educational activities to increase awareness and knowledge on NAFLD among primary care physicians and non-specialists are needed.

• Screening of T2DM patients for both NASH and liver fibrosis should be implemented in clinical practice using available noninvasive tools.

• Therapeutic approaches to NAFLD/NASH in T2DM patients are mainly based on implementation of lifestyle optimization strategies aiming to achieve significant weight loss, which ideally should be planned in the setting of multidisciplinary teams with the goal of improving both liver and cardiovascular outcomes.

• Optimal pharmacotherapy remains ill-defined since there are no drugs approved for treatment of NAFLD/NASH. A combination approach with multiple drug, including new antidiabetic agents, targeting different pathways will likely represent the future of NASH therapeutics but more robust evidence for this approach is needed.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article was partially supported by grants from the Fondo Nacional de Desarrollo Científico yTecnológico (FONDECYT), grants 1119145 (to M.Arrese) and 1191183 (to F. Barrera) and from the Comisión Nacional de Investigación Científica y Tecnológica, grant CONICYT PIA/Basal PFB12, Basal Centre for Excellence in Science and Technology toM.Arrese.