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Page 2 of 22 Mantovani et al. Hepatoma Res 2020;6:78 I http://dx.doi.org/10.20517/2394-5079.2020.75

INTRODUCTION
In the last decades, it became clearly evident that nonalcoholic fatty liver disease (NAFLD) is associated
with insulin resistance, abdominal obesity and type 2 diabetes mellitus(T2DM) [1-5] . Specifically, the
[1-5]
association between NAFLD and T2DM is intricate, and of note, it appears to be even bidirectional . In
fact, convincing data now indicate that abdominal obesity, T2DM and metabolic syndrome (MetS) can
[6,7]
synergistically play a part in the development of NAFLD and its advanced forms . Despite that, NAFLD
is linked to a higher risk of T2DM and MetS, as well as to a poorer glycemic control in diabetic patients .
[6]
Based on these data, it is therefore unsurprising that patients with T2DM have an increased prevalence of
NAFLD, when compared to those without T2DM, as well as a higher risk of developing serious liver-related
[including nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma] and extrahepatic
complications, such as cardiovascular and renal diseases [Figure 1] [2,4,8] .

Since NAFLD, obesity, insulin resistance and T2DM are strictly linked, some researchers in this field have
proposed and recommended a change in nomenclature from NAFLD to MAFLD, i.e., metabolic associated
fatty liver disease [9-11] . This specific issue has not yet reached a consensus and is discussed in another article
published in this journal.

In this review, we will discuss the prevalence and incidence of NAFLD (as detected by imaging techniques
or liver biopsy) in patients with T2DM with particular regard to hepatic and extrahepatic complications.

Search strategy and selection criteria
In the PubMed-Medline database, we used the following terms: “fatty liver” or “NAFLD” or “NASH” and
“diabetes mellitus” or “type 2 diabetes” (concluding research on the 30th July 2020). We did not apply any
publication date or language restrictions. Finally, we used specific references of reviews to identify other
relevant articles.

Prevalence of NAFLD in patients with diabetes mellitus
As reported in Table 1, in the last five years, several population-based studies and hospital-based studies
have reported that in adult patients with T2DM the prevalence of NAFLD, as detected by imaging
techniques or liver biopsy, ranged from 30% to 70% and from 50% to 70%, respectively [12-75] . These data
strongly support the assertion that NAFLD is much more frequent in patients with T2DM, when compared
[1-4]
to the general population or other patient groups . In particular, regarding the observational studies
using liver ultrasound for the diagnosis of NAFLD, which is the recommended first-line imaging method
[76]
for detecting hepatic steatosis in clinical practice , the prevalence of NAFLD was approximately 70%-
75% in patients with T2DM, with however some exceptions. For instance, in a large cohort study involving
[58]
nearly 5,500 South Korean patients with T2DM, Choe et al. documented that the prevalence of NAFLD
was 46%. In another population-based study of 8,571 Chinese hospitalized patients with T2DM, Guo et al.
[24]
showed that the prevalence of NAFLD was approximately 51%. Contrariwise, in a cross-sectional study
including 222 Italian outpatients with T2DM, who were regularly seen at a specific diabetes clinic,
[45]
Mantovani et al. reported that the prevalence of NAFLD was more than 70%. In addition, in a small study
of 106 Australian patients with T2DM belonging a tertiary diabetes center, Williams et al. documented
[22]
that the prevalence of NAFLD was even higher (84%). Interestingly, in a recent cross-sectional study
enrolling 137 patients with non-insulin-treated T2DM who underwent liver ultrasound and liver stiffness
[65]
measurement (LSM) using vibration-controlled transient elastography (FibroScan®), Mantovani et al.
showed that the proportion of T2DM patients with hepatic steatosis (on ultrasound) was 74% and that the
proportion of individuals with significant liver fibrosis was approximately 18% with an LSM cut-off ≥ 7 kPa
and nearly 10% with an LSM cut-off ≥ 8.7 kPa.

The severity of NAFLD on ultrasound is usually graded using a 4-point scoring system: normal, mild,
moderate and severe. In the literature, information regarding the prevalence of different grades of liver