Elsevier

Endocrine Practice

Volume 26, Issue 4, April 2020, Pages 444-453
Endocrine Practice

Original Articles
Impact of Type 2 Diabetes on Nonalcoholic Steatohepatitis and Advanced Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

https://doi.org/10.4158/EP-2019-0342Get rights and content

ABSTRACT

Objective: Type 2 diabetes mellitus (T2DM) is a risk factor for nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the effect of T2DM on nonalcoholic steatohepatitis (NASH) and advanced fibrosis.

Methods: A total of 221 NAFLD patients who had undergone a liver biopsy were included in this study. Subjects were divided into a non-T2DM group and a T2DM group based on glycemic control. NASH was diagnosed by the joint presence of steatosis, ballooning, and lobular inflammation. The steatosis, activity, and fibrosis (SAF) score and NAFLD activity score (NAS) were used to evaluate the severity of NAFLD. The severity of liver fibrosis was evaluated based on the fibrosis stage.

Results: The total percentages of NASH and advanced fibrosis in this study were 95.0% and 50.2%, respectively. The percentages of NASH and advanced fibrosis in NAFLD patients with T2DM were 96.1% and 56.5%, respectively, which were higher than those in the non-T2DM group. SAF score (especially activity and fibrosis stage) and NAS (especially ballooning) were higher in NAFLD patients with T2DM than in NAFLD patients without T2DM. Glycemic control and insulin resistance were positively associated with SAF, NAS, and fibrosis stage. Additionally, T2DM elevated the risk of a high NAS and advanced fibrosis.

Conclusion: T2DM increases the risk of serious NASH and advanced fibrosis in patients with NAFLD. Liver biopsy can be performed in NAFLD patients with T2DM to confirm the stage of NAFLD. Screening of NASH and advanced fibrosis in NAFLD patients with T2DM is needed.

Abbreviations: ALT = alanine aminotransferase; APO = apolipoprotein; AST = aspartate aminotransferase; BMI = body mass index; CI = confidence interval; FPG = fasting plasma glucose; GGT = gamma-glutamyl transferase; HbA1c = hemoglobin A1c; HDL-c = high-density-lipoprotein cholesterol; 1H-MRS = proton magnetic resonance spectroscopy; HOMA-IR = homeostasis model assessment of insulin resistance; 2hPG = postprandial plasma glucose at 2 hours; LDL-c = low-density-lipoprotein cholesterol; LFC = liver fat content; NAFLD = nonalcoholic fatty liver disease; NAS = NAFLD activity score; NASH = nonalcoholic steatohepatitis; OGTT = oral glucose tolerance test; OR = odds ratio; T2DM = type 2 diabetes mellitus; TC = total cholesterol; TG = triglyceride; SAF = steatosis, activity, and fibrosis; US-FLI = ultrasonographic fatty liver indicator

Section snippets

INTRODUCTION

The global prevalence of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing. Indeed, it has been established that the global prevalence of NAFLD reaches 25%, which makes it one of the most common causes of chronic liver disease in many parts of the world (1,2).

Studies show that type 2 diabetes mellitus (T2DM) is a risk factor for NAFLD, including nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even hepatic carcinoma, and is related to a worse prognosis for NAFLD (3,4).

Patients

The participants were from the fatty liver clinic of Zhongshan Hospital, Fudan University. Patients diagnosed with fatty liver by ultrasonography who had indications of liver biopsy, such as diabetes, obesity, or an elevated level of liver enzymes, were suggested to undergo liver biopsy according to the EASL–EASD–EASO clinical practice guidelines (13); only some of the patients agreed to the procedure. Among all patients, 221 (117 men and 104 women, 11 with simple steatosis and 210 with NASH,

Clinical Characteristics of Subjects

A total of 221 patients with biopsy-proven NAFLD (mean age 44 ± 15 years, female/male 104/117) were enrolled in this study. The BMI and LFC (1H-MRS) of this population were 29.0 ± 4.6 kg/m2 and 42.4% (25th to 75th percentiles, 22.3 to 54.9%), respectively (Table 1). The percentage of T2DM in this population was 69.7%.

To investigate the percentage of NASH and advanced fibrosis in patients with T2DM, we next divided subjects into two groups, non-T2DM and T2DM, based on glycometabolism status. The

DISCUSSION

In this study, SAF score and NAS were used to evaluate the severity of liver histology in NAFLD patients with or without T2DM. The major findings are as follows: (1) the total percentages of NASH and advanced fibrosis in this cohort were 95.0% and 50.2%, respectively; (2) the percentage of advanced fibrosis in the T2DM group was much higher than that in the non-T2DM group (56.5% versus 35.8%); (3) NAS and SAF score in patients with T2DM were higher than in patients without T2DM; (4) glycemic

CONCLUSION

In conclusion, the percentages of NASH and advanced fibrosis in this population were 95.0% and 50.2%, respectively. The percentages of NASH and advanced fibrosis in the NAFLD patients with T2DM were 96.1% and 56.5%, respectively. Based on two methods, SAF score and NAS, we found that the severity of liver disease based on histology in the patients with T2DM was much more serious than that in individuals without T2DM. Moreover, glycemic control and insulin resistance indicators, such as FPG,

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    DISCLOSURE

    The authors have no multiplicity of interest to disclose.

    *

    These authors contributed equally

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