Changes in sex hormone and thyroid hormone levels in patients with type 2 diabetes mellitus complicated by non-alcoholic fatty liver disease and their clinical significance

Abstract

Abstract: Objective To investigate the patterns of sex hormone and thyroid hormone alterations in patients with T2DM complicated by NAFLD, and to examine their associations with metabolic and liver function indicators, thereby providing evidence for clinical assessment in this population. Methods A total of 122 individuals who attended outpatient clinics or underwent health examinations between January 2023 and May 2025 were enrolled in Feidong County Traditional Chinese Medicine Hospital. According to the presence of T2DM and NAFLD, participants were divided into four groups: T2DM with NAFLD (n=42), NAFLD alone (n=24), T2DM alone (n=24), and healthy controls (n=32). General clinical characteristics, metabolic parameters, and levels of sex hormones and thyroid hormones were compared among groups. Spearman correlation analysis was performed to assess the relationships between hormone levels and body mass index (BMI), glycemic control, and liver function indices. Results Compared with the healthy control group, patients in the T2DM with NAFLD group exhibited significantly higher BMI, fasting blood glucose, glycated hemoglobin, transaminase levels, and triglyceride concentrations (P<0.05). Sex hormone analysis revealed that total testosterone and sex hormone-binding globulin (SHBG) levels were significantly lower in the T2DM with NAFLD group than in the other groups (P<0.05), whereas estradiol levels were relatively elevated (P<0.05). With respect to thyroid function, patients with T2DM complicated by NAFLD showed increased thyroid-stimulating hormone (TSH) levels and decreased free triiodothyronine (FT3) levels, while free thyroxine (FT4) levels remained unchanged. Correlation analysis demonstrated that total testosterone, SHBG, and FT3 levels were negatively correlated with BMI, HbA₁c, transaminases, and triglycerides, whereas TSH levels were positively correlated with these parameters. Conclusion Patients with T2DM complicated by NAFLD exhibit marked disturbances in sex hormone and thyroid hormone metabolism, which are closely associated with disordered glucose and lipid metabolism and impaired liver function. Assessment of sex hormone and thyroid hormone levels may help provide a more comprehensive evaluation of metabolic status and offer useful information for the integrated clinical management of these patients.

Key words: Type 2 diabetes mellitus, Non-alcoholic fatty liver disease, Sex hormones, Thyroid hormones

Liu Yuhan, Zhang Jian, Wang Dingyuan, Wang Yong. Changes in sex hormone and thyroid hormone levels in patients with type 2 diabetes mellitus complicated by non-alcoholic fatty liver disease and their clinical significance[J]. Chinese Hepatolgy, 2026, 31(7): 1020-1023.

References

[1] Młynarska E, Czarnik W, Dzieża N, et al. Type 2 diabetes mellitus: new pathogenetic mechanisms, treatment and the most important complications[J]. Int J Mol Sci, 2025, 26(3):1094.
[2] Singh A, Shadangi S, Gupta P K, et al. Type 2 diabetes mellitus: a comprehensive review of pathophysiology, comorbidities, and emerging therapies[J]. Compr Physiol, 2025, 15(1):e70003.
[3] Liu C, Chen H, Ma Y, et al. Clinical metabolomics in type 2 diabetes mellitus: from pathogenesis to biomarkers[J]. Front Endocrinol (Lausanne), 2025, 16:1501305.
[4] Nychas E, Marfil-Sánchez A, Chen X, et al. Discovery of robust and highly specific microbiome signatures of non-alcoholic fatty liver disease[J]. Microbiome, 2025, 13(1):10.
[5] Zheng C, Qi Z, Chen R, et al. The association between the dietary index for gut microbiota and non-alcoholic fatty liver disease and liver fibrosis: evidence from NHANES 2017—2020[J]. BMC Gastroenterol, 2025, 25(1):163.
[6] Cheng Y, Su J, Wang X, et al. Associations between brominated flame retardants exposure and non-alcoholic fatty liver disease: mediation analysis in the NHANES[J]. Ecotoxicol Environ Saf, 2025, 290:117762.
[7] En Li Cho E, Ang C Z, Quek J, et al. Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis[J]. Gut, 2023, 72(11):2138-2148.
[8] Tanase D M, Gosav E M, Costea C F, et al. The intricate relationship between type 2 diabetes mellitus (T2DM), insulin resistance (IR), and nonalcoholic fatty liver disease (NAFLD)[J]. J Diabetes Res, 2020, 2020:3920196.
[9] Song M J, Choi J Y. Androgen dysfunction in non-alcoholic fatty liver disease: role of sex hormone binding globulin[J]. Front Endocrinol (Lausanne), 2022, 13:1053709.
[10] Dong J, Liu C, Lu J, et al. The relationship between sex hormone-binding protein and non-alcoholic fatty liver disease using Mendelian randomisation[J]. Eur J Clin Invest, 2024, 54(1):e14082.
[11] Du J, Chai S, Zhao X, et al. Association between thyroid hormone levels and advanced liver fibrosis in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease[J]. Diabetes Metab Syndr Obes, 2021, 14:2399-2406.
[12] Saatmann N, Schön M, Zaharia O P, et al. Association of thyroid function with non-alcoholic fatty liver disease in recent-onset diabetes[J]. Liver Int, 2024, 44(1):27-38.
[13] Porgere I F, Rocha B M, Escott G M, et al. Association of age and insulin resistance with sex hormone-binding globulin levels in healthy men[J]. Arch Endocrinol Metab, 2025, 69(4):e240360.
[14] Januszewski A S, Rankin W A, O′Neal D N, et al. Sex hormone binging globulin as an indicator of insulin resistance in type 1 diabetes[J]. Diabetes Res Clin Pract, 2025, 229:112935.
[15] van Bree B E, van der Heijden D M B, van Golde R J T, et al. Sex hormone-binding globulin as a biomarker for metabolic risk in European women with polycystic ovary syndrome[J]. Gynecol Endocrinol, 2025, 41(1):2500462.
[16] Mucinski J M, Kelley D E, Winters S J, et al. Effects of weight loss on testosterone, sex hormone-binding globulin, adiposity, and insulin sensitivity in women and men[J]. Obesity (Silver Spring), 2025, 33(5):962-973.
[17] Aydin B, Winters S J. Sex hormone-binding globulin and metabolic syndrome in children and adolescents: a focus on puberty[J]. Metabolites, 2025, 15(8):494.
[18] Xu T, Han T, Zhai J, et al. Association between thyroid hormone sensitivity and non-alcoholic fatty liver disease in individuals with normal thyroid function[J]. Diabetes Metab Syndr Obes, 2025, 18:3575-3588.
[19] Zhang X, Liu J, Wang Q, et al. Impaired sensitivity to thyroid hormone is associated with developing non-alcoholic fatty liver disease in euthyroid diabetic subjects[J]. Front Endocrinol (Lausanne), 2024, 15:1450049.
[20] Bi T. Relationship between thyroid hormone levels and metabolic dysfunction associated steatotic liver disease in patients with type 2 diabetes: a clinical study[J]. Medicine (Baltimore), 2024, 103(26):e38643.