Association between Thyroid Function and Nonalcoholic Fatty Liver Disease in Euthyroid Type 2 Diabetes Patients

Abstract

Thyroid function and type 2 diabetes mellitus (T2DM) are both associated with increased risks of adverse clinical outcomes in nonalcoholic fatty liver disease (NAFLD). Our study is aimed at evaluating the association between thyroid function and NAFLD in T2DM patients with normal thyroid function (euthyroid) and analyzing the potential effects of metformin on the pathological process. Overall, 369 T2DM patients were enrolled between July 2017 and September 2018 and stratified into NAFLD and non-NAFLD groups. Data on age, gender, body mass index (BMI, kg/m2), metformin use, and basal metabolic rate (BMR) were obtained from participants’ records. All patients were tested for biochemical markers, indexes of glucose metabolism, lipid metabolism, bone metabolism, and thyroid function at baseline. Multivariate analyses detected increased odds of NAFLD among individuals with T2DM per unit increase in their BMI and free triiodothyronine (FT3) and thyroid stimulating hormone (TSH); the odds ratios (OR) were 1.25, 3.02, and 1.58, respectively (all p<0.05). Positive correlations were detected between alanine aminotransferase (ALT) and FT3 (r=0.221, p=0.010), and negative correlations were noted between TSH and BMR (r=−0.618, p<0.001) and between BMR and FT3 (r=−0.452, p<0.001) in T2DM subjects with NAFLD. A significant difference in serum FT3 (t=2.468, p=0.0167) and TSH (t=2.658, p=0.010) levels was found between obese individuals with NAFLD who used and did not use metformin. The pathological mechanism of T2DM complicated by NAFLD in euthyroid patients may be associated with insulin resistance and a thyroid hormone resistance-like manifestation, i.e., relevant hypothyroidism. Metformin can potentially decrease the double-resistance situation, especially in obese individuals.

High-Normal Serum Thyrotropin Levels Increased the Risk of Non-Alcoholic Fatty Liver Disease in Euthyroid Subjects with Type 2 Diabetes

“… 11 , 28 Recently, a study with small participant sample showed that NAFLD in euthyroid T2DM patients may be associated with thyroid hormone resistance-like manifestation. 29 Consistently, our study confirmed that a higher-normal TSH level was associated with an increased risk of NAFLD in euthyroid subjects with T2DM.…”

TSH Levels as an Independent Risk Factor for NAFLD and Liver Fibrosis in the General Population

“…Higher TSH levels, lower T4 levels and a higher prevalence of positivity of anti-thyroid peroxidase antibodies were found in patients where T2DM and NAFLD coexist, compared to those without NAFLD [35]. In another similar study, carried out in a diabetic and euthyroid population, it was shown that subjects with higher levels of T3 and TSH had a higher risk of presenting NAFLD, with ORs of 3.02 and 1.58, respectively [36].…”

Associations among FT₄ level, FT₃/FT₄ ratio, and non-alcoholic fatty liver disease in Chinese patients with hypopituitarism

“…A matched casecontrol study reported a two-fold higher risk of hypothyroidism in patients with hepatic steatosis than that in controls [26]. Numerous studies have shown an inverse relationship of serum TH levels with NAFLD since patients with clinical and subclinical hypothyroidism have an increased risk of NAFLD and vice versa [27][28][29]. A study confirmed that independent of insulin resistance, the FT 3 /FT 4 ratio was a predictor of NAFLD in both patients with euthyroidism and hypothyroidism [30].…”