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

Abstract

Purpose The aim of this study was to investigate the association between high-normal thyrotropin (TSH) levels and the prevalence of non-alcoholic fatty liver disease (NAFLD) in euthyroid patients with T2DM. Methods A total of 2289 euthyroid adults with T2DM were included in this cross-sectional study conducted at the Third Affiliated Hospital of Sun Yat-sen University from January 2016 to December 2018. NAFLD was diagnosed by abdominal ultrasound. Thyroid function parameters, including the levels of TSH, free triiodothyronine (FT3) and free thyroxine (FT4), were analyzed. The patients were stratified by quartiles (Q1-4) of TSH levels. Multivariate logistic regression models were used to evaluate the association between the quartiles of TSH levels and the risk of NAFLD in euthyroid adults with T2DM. Results There were 940 (41.1%) euthyroid adults with T2DM who were diagnosed with NAFLD. The subjects were divided according to the thyroid function parameter quartiles. The prevalence of NAFLD increased with increasing TSH level quartiles (Q1 to Q4: 34.8%, 37.5%, 44.9% and 47.0%, P <0.01) but not with increasing FT3 or FT4 level quartiles. In the multivariate logistic regression model, compared with the lowest TSH level quartile (Q1), the highest TSH level quartile (Q4) (OR=1.610, 95% CI=1.131–2.289, P =0.008) was independently associated with an increased risk of NAFLD in euthyroid adults with T2DM after adjusting for multiple confounders. After additional stratification by the level of glycosylated haemoglobin (HbA1c) and body mass index (BMI), the highest TSH level quartile was still independently associated with an increased risk of NAFLD in euthyroid patients with T2DM who had an HbA1c level≥7% or a BMI<28 kg/m 2 . Conclusion High-normal serum TSH levels are significantly associated with the presence of NAFLD in T2DM patients with euthyroid function, which provide novel insight for treating NAFLD.

Lack of Faecalibacterium prausnitzii and Bifidobacterium is associated with a higher risk of metabolic associated fatty liver disease in young-onset type 2 diabetes

“…A cross-sectional study showed that in a T2DM population with HbA1c ≥ 7%, elevated levels of TSH were associated not only with the prevalence of MAFLD but also with the degree of MAFLD steatosis. [31] Existing research has shown the following mechanism: TSH acts on hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) to promote adipocyte differentiation and thus inhibit adipose tissue breakdown. In addition, TSH increases triglyceride synthesis by regulating the expression activity of sterol regulatory element-binding protein-1c (SREBP-1c) in hepatocytes.…”

Investigation Roles of Erythropoietin, Testosterone, and Thyroid Hormones in Patients with Chronic Liver Disease

“…Previous study showed the high-normal serum TSH levels are significantly associated with the presence of liver diseases in T2DM patients with euthyroid function, which provide novel insight for treating these diseases [33].…”

Targeting Thyroid Hormone/Thyroid Hormone Receptor Axis: An Attractive Therapy Strategy in Liver Diseases

“… Martínez-Escudé A et al (2021) reported that TSH, regarded as a risk factor of MAFLD, is involved in obesity, atherogenic dyslipidemia, metabolic syndrome (MetS), hypertransaminasemia, and altered cholesterol and triglycerides levels. Then, a recent research hint that TSH is a MAFLD risk factor but excludes the FT3 and FT4 levels ( Tan et al, 2021 ). Intriguingly, the result in a middle-aged and elderly euthyroid subjects showed that high-normal FT3 and low-normal TSH independently predict the high incidence of MAFLD ( Gu et al, 2021 ).…”