**1. Introduction**

Non-alcoholic fatty liver disease (NAFLD) represents the most common liver disease worldwide affecting approximatively 20–30% of the general population [1]. The histopathological and clinical abnormalities of NAFLD spectrum ranges from the accumulation of triglycerides in the liver, i.e., non-alcoholic fatty liver (NAFL), to the inflammation and cellular damage of the hepatocytes, i.e., non-alcoholic steatohepatitis (NASH), that may progress to liver fibrosis and advanced cirrhosis [2]. The most serious clinical manifestations of NAFLD, i.e., NASH and cirrhosis, have very recently become the fastest growing indications for liver transplantation in western countries, heavily impacting on patient health, economic aspects and quality of life [3].

Interestingly, NAFLD is strictly associated with the features of metabolic syndrome such as obesity, type 2 diabetes (T2D), dyslipidaemia and hypertension [4]. In particular, the

**Citation:** Vitale, M.; Della Pepa, G.; Costabile, G.; Bozzetto, L.; Cipriano, P.; Signorini, S.; Leoni, V.; Riccardi, G.; Vaccaro, O.; Masulli, M. Association between Diet Quality and Index of Non-Alcoholic Steatohepatitis in a Large Population of People with Type 2 Diabetes: Data from the TOSCA.IT Study. *Nutrients* **2022**, *14*, 5339. https://doi.org/ 10.3390/nu14245339

Academic Editor: Henry J. Thompson

Received: 22 November 2022 Accepted: 12 December 2022 Published: 15 December 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

association between NAFL/NASH and T2D is well established and there appears to exist an intricate interrelationship whereby the existence of one drives progression to the other. T2D seems to be the most important risk factor for NAFLD and the most important clinical predictor of the advanced forms of NAFLD [5,6]. On the other hand, NAFLD is associated with a worse metabolic profile [7,8] and a higher prevalence of microvascular and macrovascular complications of diabetes, independently of other known risk factors [9–11]. From an epidemiological point of view, it is not surprising that there is a high prevalence of NAFL and NASH in T2D, estimated at 55–70% and 20–40%, respectively [12], and higher in T2D with obesity [13].

Although liver biopsy represents the gold standard for the diagnosis of NASH, it is not feasible in large epidemiological studies. Several indices, based on non-invasive measures easily performed in clinical practice, have been proposed for the diagnosis of NASH [14], although none of these has been validated in people with diabetes. Among others, we used the Index Of NASH (ION), an algorithm constructed from the combination of triglycerides, visceral obesity, alanine aminotransferase (ALT) and Homeostatic Model Assessment (HOMA-IR), and validated against liver biopsy in an obese population sharing several metabolic and clinical features with T2D (i.e., obesity, excess of visceral fat, insulin resistance and high prevalence of NASH) [15]; in this population, the ION has shown a good diagnostic accuracy (AUC = 0.88 [95%CI 0.82–0.95]), with a sensitivity of 92% and a specificity of 60% [15].

No pharmaceutical approaches for NAFLD have been approved to date, and the cornerstone in the prevention and treatment of NAFLD and its severe forms is represented by lifestyle modifications, including diet-related factors [14,16]. Some attempts have been made to clarify the association between dietary components and NAFLD in the general population. Outside the context of clinical trials, epidemiological studies show that high glycaemic index foods and intake in saturated fats and simple sugars—fructose in particular—are associated with a higher prevalence in NAFLD [17–21]; whereas the intake of *n*-3 and *n*-6 polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), and fibre [22] appears to be associated with a lower prevalence of NAFLD [18,21,22]. Among micronutrients, intake of vitamins [23] and polyphenols is associated with a lower prevalence of NAFLD and might beneficially impact on the progression from NAFL to NASH [24].

In individuals with coexisting T2D and NAFL/NASH, hypocaloric diets promoting a weight loss of 7–10% are effective in improving metabolic parameters of both diseases [14], but they are not feasible in the long term and the optimal dietary model for people with T2D and NASH, not subjected to caloric restriction, remains ill-defined [25,26]. Nutritional guidelines for the treatment of diabetes recommend 45–60% of carbohydrates, selecting those with a low glycaemic index and high in fibre, 25–35% of fats, preferring MUFA and PUFA, 15–20% of proteins, and limiting/avoiding the intake of free sugars, sugar-sweetened beverages and added fructose [26,27]. These recommendations are designed with the main focus on correction of hyper-glycaemia; furthermore, the patient's compliance is generally low/very low. Indications based on food consumption, rather than on nutrients, may improve adherence, but evidence regarding the possible association between habitual food consumption and NASH in T2D is lacking.

The aim of this study is to investigate in a large population of patients with T2D the association of habitual diet (i.e., diet composition and food consumption) with NASH, in order to expand knowledge on the potential for dietary components in the prevention/treatment of NASH in people with T2D.
