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Impaired sensitivity to thyroid hormones is associated with increased body fat mass/muscle mass ratio (F/M) in the euthyroid population

Diabetology & Metabolic Syndrome volume 17, Article number: 128 (2025) Cite this article

Abstract

Objective

To explore the relationship between body fat mass/muscle mass ratio (F/M) and thyroid hormone sensitivity in the euthyroid population.

Methods

Body compositions of 845 check-up individuals were determined using bioelectrical impedance analysis (BIA). Biochemical indexes including blood glucose, blood lipids, liver and kidney functions and thyrotropic hormones (THs) were detected. Free triiodothyronine to free thyroxine ratio (FT3/FT4), Thyroid Feedback Quantile-based Index (TFQI), Thyrotropin Thyroxine Resistance Index (TT4RI) and TSH Index (TSHI) were calculated for analysis.

Results

TT4RI and TSHI showed increased trends with statistical difference, while FT3/FT4 and TFQI showed no difference among F/M quartile groups. After adjusting for confounding factors, F/M exhibited no correlation with FT3/FT4, but positive correlations with TFQI, TT4RI and TSHI. Gender subgroup analysis showed that F/M exhibited positive relationship with TFQI in females; exhibited positive correlations with TFQI, TT4RI and TSHI before the inflection points, but no correlations thereafter in males. Age subgroup analysis showed that F/M exhibited positive correlations with TFQI, TT4RI and TSHI, but no correlation with FT3/FT4 in age < 65 years group; exhibited no relationship with thyroid hormone sensitivity in age ≥ 65 years group. BMI subgroup analysis showed that F/M exhibited no relationship with thyroid hormone sensitivity in BMI < 25 kg/m2 group; exhibited positive correlations with TFQI, TT4RI and TSHI before the inflection points, but no correlations thereafter in BMI ≥ 25, < 30 kg/m2 group; exhibited positive correlation with TFQI before the inflection point, but no correlation thereafter in BMI ≥ 30 kg/m2 group; exhibited no correlations with TT4RI and TSHI before the inflection points, but negative correlations with them thereafter in BMI ≥ 30 kg/m2 group.

Conclusion

Impaired central, but not peripheral sensitivity to thyroid hormones was associated with increased body fat mass/muscle mass ratio (F/M), this association was obvious in males, individuals with age < 65 years and BMI ≥ 25 kg/m2, with different inflection points. Maybe F/M independently affects thyroid hormone sensitivity, we need more clinical and basic studies in the future.

Introduction

The World Health Organization (WHO) defines overweight and obesity as an excessive accumulation of fat that has adverse influences on health, quality of life and even life expectancy [1]. Obesity, particularly abdominal obesity, has been regarded as an independent risk factor for metabolic disorders such as diabetes mellitus, hypertension, hyperlipidemia [2, 3], as well as cardiovascular and cerebrovascular diseases [4, 5]. Obesity is also intimately associated with the levels of thyroid hormones, the incidence of hypothyroidism was notably elevated among obese individuals [6], particularly among females [7]. Yet, the specific mechanism remains unclear.

Thyroid hormones regulate appetite and body heat production, as well as glucose and lipid metabolisms [6]. In physiological conditions, TSH and FT4 are negatively correlated due to the negative feedback regulation of the hypothalamic-pituitary-thyroid axis [8]. However, in many cases we observed high levels of TSH co-existing with FT4 [9]. In order to explain this, The Thyroid Feedback Quantile-based Index (TFQI) was proposed as an index of central thyroid hormone sensitivity by Laclaustra et al. They proposed a hypothesis that thyroid hormone resistance occurs in the body under certain circumstances, and thyroid hormone sensitivity decreases [9]. Central thyroid hormone sensitivity indexes also include thyrotropin thyroxine resistance index (TT4RI) and TSH index (TSHI), which are also associated with many metabolic diseases [10, 11]. The FT3/FT4 ratio can be used to evaluate the rate of T4-to-T3 conversion, reflecting the peripheral tissue sensitivities of thyroid hormones, and the relationships with metabolic diseases including hyperglycemia, hyperlipemia and fatty liver have also been studied [12,13,14].

Previous studies have suggested that increased TSH and T3 levels in obese individuals may be a physiological mechanism for increasing energy expenditure to improve weight gain. In obese people with normal thyroid function, there were no correlations between resting energy expenditure and serum TSH and FT3 concentrations, despite increased resting energy expenditure [15]. Moreover, a decline in FT4 could also be observed, which might be associated with increased TSH [16]. Studies have also showed that FT4 was negatively correlated with BMI in obese patients, while TSH was positively correlated with BMI [17]. Conclusions regarding the relationships between thyroid hormones and obesity were also inconsistent, and the specific mechanisms were still under exploration.

It has recently been reported that impaired central sensitivity to thyroid hormones were significantly associated with the reductions of visceral fat area (VFA) and subcutaneous fat area (SFA) [18]. Given that body fat areas are affected by individual differences in height, and also thyroid hormones are critical regulators of muscle metabolism in both healthy and unhealthy conditions [19], in our study, we used body fat mass/muscle mass ratio (F/M) to evaluate the relationships between body compositions and thyroid hormone sensitivity. We examined the relationships between F/M and thyroid hormone sensitivity indices (TFQI, TT4RI, TSHI and FT3/FT4) in the physical examination population to investigate the impact of F/M on central and peripheral thyroid hormone sensitivity. Considering the differences in the impacts of agender, age and BMI on thyroid hormone, the corresponding subgroup analyses were conducted.

Materials and methods

In the Physical examination Center of Hefei First People's Hospital from January 2024 to June 2024, 29,909 individuals underwent health examinations. Among them, there were 1192 individuals completed the determinations of body compositions using bioelectrical impedance analysis. After excluding people who did not meet the criteria, we eventually included 845 eligible people (Fig. 1). Sample size calculation was performed using Power Analysis and Sample Size software 15, and the sample size we have calculated was 689.

Fig. 1
figure 1

Studied objects screening flow chart

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Inclusion criteria: 1. Age 18–90 years old; 2. BMI > 18.5 kg/m2.

Exclusion criteria: 1. Incomplete data; 2. History of hyperthyroidism and hypothyroidism; 3. Patients with abnormal thyroid function; 4. Severe liver and kidney insufficiency.

Body composition including height, weight, body fat mass (kg) and muscle mass(kg) were determined by fasting state in the morning by bioelectrical impedance analysis (BIA, DONGHUAYUAN MEDICAL, Beijing city). Subjects taked off excess clothing and jewelry, shoes and socks, stood on the metal base, held the handles with both hands, with arms naturally straight and slightly stretched to the sides of the body, legs do not touch each other. BMI was calculated as weight(kg)/height2(m2). Medical histories including hypertension, diabetes, hyperuricemia and hyperlipidemia were recorded. Thyroid hormones were determined by blood serum samples (chemiluminescence method. Abbott 12000SR), including thyrotropic hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4). The biochemical indexes of fasting blood-glucose (GLU), albumin (ALB), alanine transaminase (ALT), aspartic transaminase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBIL), serum creatinine (SCr), uric acid (SUA), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were all measured by well-trained technicians utilizing standardized laboratory methods (Roche automatic biochemical analyzer. combas 8000).

Index of Peripheral thyroid hormone sensitivity was calculated as FT3/FT4;

Three different indices of central thyroid hormone sensitivity were calculated [20, 21]:

$${\text{TFQI }} = \, \left( {{\text{cdf}}} \right){\text{ FT4}}{-}\left( {{1}{-}\left( {{\text{cdf}}} \right){\text{ TSH}}} \right);$$
$${\text{TT4RI}} = {\text{FT4 }}\left( {{\text{pmol}}/{\text{L}}} \right) \times {\text{TSH }}\left( {{\text{mIU}}/{\text{L}}} \right);$$
$${\text{TSHI }} = {\text{ Ln TSH }}\left( {{\text{mIU}}/{\text{L}}} \right) + 0.{1345} \times {\text{FT4 }}\left( {{\text{pmol}}/{\text{L}}} \right).$$

Definition of hypertension [22]: ① History of hypertension, ② Systolic blood pressure ≥ 140 mmHg, ③ Diastolic blood pressure ≥ 90 mmHg, meet any of the diagnostic criteria.

Definitions of diabetes [23]: ① a history of diabetes, ② Fasting blood glucose ≥ 7.0 mmol/l, ③ Hemoglobin A1C ≥ 6.5%, meet any of the diagnostic criteria.

Definitions of hyperuricemia [24]: ① a history of hyperuricemia, ② Blood uric acid ≥ 420umol/l, meet any of the diagnostic criteria.

Definitions of hyperlipidemia [25]: ① a history of hyperlipidemia, ② TC ≥ 5.2 mmol/l, TG ≥ 1.7 mmol/l, LDL-C ≥ 3.4 mmol/l, HDL-C < 1.0 mmol/l, meet any of the diagnostic criteria.

Statistical analysis

We utilized GraphPad Prism 10.0.3 and Empower(R) (www.empowerstats.com, X&Y Solutions, Inc.) (Boston, MA) and R (http://www.r-project.org) for data analysis. The normality of the data was assessed using the Shapiro–Wilk test and Q-Q plot. Variables with a normal distribution were presented as mean ± standard deviation (SD), while skewed variables were expressed as median (25th percentile, 75th percentile). We conduct sample size calculation using Power Analysis and Sample Size software 15. Differences in continuous variables in the F/M quartile groups were compared using One-Way ANOVA, and we used Bonferroni correction multiple hypothesis testing. Smoothing function and threshold effect analysis were employed to determine the relationships of F/M with TFQI, TT4RI, TSHI and FT3/FT4. Log-likelihood ratio tests were conducted on both single-line linear regression model and two-stage linear regression model. The same analysis was performed for gender, age and BMI subgroups. Statistical significance was considered if P < 0.05.

Results

Analyses of thyroid hormones Sensitivity indexes in groups of F/M ratio quartile using One-Way ANOVA

We divided the studied population into four groups according to F/M quartile: F/MQ1: F/M ranged 0.0563 to 0.3397, F/MQ2: F/M ranged 0.3397 to 0.4320, F/MQ3: F/M ranged 0.4320 to 0.537, F/MQ4: F/M ranged 0.537 to 1.19. With increased trends of F/M ratio, TT4RI (P<0.001) and TSHI (P=0.002) exhibited increased trends with significant statistical difference (P<0.001), while FT3/FT4 (P=0.658) and TFQI (P=0.312) showed no statistical difference among F/M quartile groups. There were significant differences of age, BMI and gender among F/M quartile groups, so three subgroup analyses were performed below, by adjusting for multiple confounding factors (Table 1, Figure 2).

Table 1 Baseline characteristics of total participants among F/M quartile groups
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Fig. 2
figure 2

The comparisons of indexes of thyroid hormones among four groups divided by F/M ratio using inter-quartile range

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Smoothing function and threshold effect analysis of the correlation between F/M and thyroid hormone sensitivity

After adjusting for confounding factors including age, agender, BMI, GLU, HbA1c, LDL-C, TC, HDL-C and SUA, we found that F/M exhibited no correlation with FT3/FT4 (β (95%CI): − 0.03 ( − 0.06, 0.00), P = 0.0504), but positive correlations with TFQI (β (95%CI): 0.52 (0.26, 0.79), P < 0.0001), TT4RI (β (95%CI): 9.07 (1.11, 17.04), P = 0.0258) and TSHI (β (95%CI): 0.59 (0.24, 0.94), P = 0.0010) (Table 2, Fig. 3).

Table 2 The associations of F/M with thyroid hormone sensitivity
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Fig. 3
figure 3

Smooth curve fitting diagrams of the relationships between F/M and thyroid hormone sensitivity indexes

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Smoothing function and threshold effect analysis of the correlation between F/M and thyroid hormone sensitivity in BMI subgroup

In BMI < 25 kg/m2 group, F/M exhibited no relationships with FT3/FT4 (β (95%CI): 0.01 ( − 0.03, 0.05), P = 0.5131), TFQI (β (95%CI): 0.23 ( − 0.10, 0.57), P = 0.1667), TT4RI (β (95%CI):3.96 ( − 5.67, 13.59), P = 0.4203) and TSHI (β (95%CI):0.31 ( − 0.12, 0.74), P = 0.1539). In BMI ≥ 25, < 30 kg/m2 group, F/M exhibited positive correlations with TFQI (β(95%CI): 1.64 (0.78, 2.49), P = 0.0002, inflection point: F/M = 0.41), TT4RI (β (95%CI): 42.62 (11.79, 73.44), P = 0.0071, inflection point: F/M = 0.39) and TSHI (β (95%CI): 2.06 (0.88, 3.23), P = 0.0007, inflection point: F/M = 0.41) before the inflection points, but no correlations thereafter. In BMI ≥ 30 kg/m2 group, F/M exhibited negative correlation with FT3/FT4 before the inflection point at F/M = 0.42 (β (95%CI): − 2.99 ( − 5.59, − 0.38), P = 0.0296), but no correlation thereafter; exhibited positive correlation with TFQI before the inflection point at F/M = 0.42 (β (95%CI): 24.35 (2.32, 46.37), P = 0.0357), but no correlation thereafter; exhibited no correlations with TT4RI and TSHI before the inflection points, but negative correlations with TT4RI (β (95%CI): − 101.16 ( − 173.14, − 29.19), P = 0.0085, inflection point: F/M = 0.86) and TSHI (β (95%CI): − 3.54 ( − 6.47, -0.60), P = 0.0227, inflection point: F/M = 0.83) thereafter(Table 3, Fig. 4).

Table 3 The associations of F/M with thyroid hormone sensitivity in BMI subgroup
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Fig. 4
figure 4

Smooth curve fitting diagrams of the relationships between F/M and thyroid hormone sensitivity indexes in BMI subgroup

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Smoothing function and threshold effect analysis of the correlation between F/M and thyroid hormone sensitivity in age subgroup

In age < 65 years group, F/M exhibited positive correlations with TFQI (β (95%CI): 0.54 (0.28, 0.81), P < 0.0001), TT4RI (β (95%CI): 8.27 (0.20, 16.33), P = 0.0448) and TSHI (β (95%CI): 0.55 (0.18, 0.91), P = 0.0031), but no correlation with FT3/FT4 (β (95%CI): − 0.03 ( − 0.07, 0.00), P = 0.0523); In age ≥ 65 years group, F/M exhibited no relationships with thyroid hormone sensitivity (Table 4, Fig. 5).

Table 4 The associations of F/M with thyroid hormone sensitivity in age subgroup
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Fig. 5
figure 5

Smooth curve fitting diagrams of the relationships between F/M and thyroid hormone sensitivity indexes in age subgroup

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Smoothing function and threshold effect analysis of the correlation between F/M and thyroid hormone sensitivity in gender subgroup

In female group, F/M showed positive relationship with TFQI (β (95%CI): 0.51 (0.12, 0.89), P = 0.0101), but no relationships with FT3/FT4 (β (95%CI): − 0.03 ( − 0.07, 0.02), P = 0.2375), TT4RI (β (95%CI): 8.85 ( − 3.15, 20.85), P = 0.1491) and TSHI (β (95%CI): 0.51 ( − 0.01, 1.03), P = 0.0532); In male group, F/M exhibited positive correlations with TFQI (β (95%CI): 0.85 (0.41, 1.29), P = 0.0002, inflection point: F/M = 0.57), TT4RI (β (95%CI): 14.87 (1.92, 27.83), P = 0.0249, inflection point: F/M = 0.58) and TSHI (β (95%CI): 0.92 (0.34, 1.50), P = 0.0019, inflection point: F/M = 0.58) before the inflection points, but no correlations thereafter (Table 5, Fig. 6).

Table 5 The associations of F/M with thyroid hormone sensitivity in gender subgroup
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Fig. 6
figure 6

Smooth curve fitting diagrams of the relationships between F/M and thyroid hormone sensitivity indexes in agender subgroup. 0 = female, 1 = male

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Discussion

The global prevalence of overweight and obesity was steadily increasing recent years [1, 26], especially during the COVID-19 pandemic, with increased related mortalities [27]. It is the same situation in China, the latest national prevalence estimates were 6.8% for overweight and 3.6% for obesity in children younger than 6 years, 11.1% for overweight and 7.9% for obesity in children and adolescents, and 34.3% for overweight and 16.4% for obesity in adults [28]. Not only was obesity prevalent among young individuals, but also among middle-aged and elderly populations, particularly postmenopausal women. This trend may be attributed to the age-related decline in basal metabolic rate and the significant decrease in estrogen levels following menopause [29].

Inadequate oxidation of adipocytes, hypoxia, and oxidative stress resulting from excessive fat accumulation contribute to cellular inflammation and fibrosis, all of which have implications on cardiovascular health and increased mortality [30]. Obese patients with diabetes are at significantly increased risks of developing diabetic nephropathy, as well as cardiovascular and cerebrovascular diseases [31]. Obese individuals defined by body mass index (BMI), waist circumference (WC) or waist to height ratio (WtHR), who concurrent suffered from hypertension and diabetes, were closely associated with the increased risk of mortality related to these conditions [32]. Therefore, the impact of obesity on physical health should not be underestimated.

Previous studies have shown that thyroid hormones play important roles in obesity. In middle-aged individuals, there were positive correlations between FT3 and BMI, WC, triglycerides, blood pressure, blood sugar, and other metabolic indicators [33]. Elevated levels of thyroid hormones were closely associated with higher fat mass and lower muscle mass [34]. Whether in terms of fat percentage (according to the 1998 criteria of the World Health Organization, fat% ≥ 25% for men and ≥ 30% for women) or BMI standard obesity (BMI ≥ 25 kg/m2), FT3 and FT3/FT4 levels were positively correlated with obesity [35]. Additionally, low levels of FT4 in overweight and obese individuals were independently correlated with insulin resistance [36]. Meanwhile, numerous studies have also demonstrated the impacts of obesity on thyroid hormones. In postmenopausal women, the levels of FT4, TSH, and HOMA-IR were significantly increased in the obese group. After adjusting for age and BMI, there was a negative correlation between visceral fat and FT4 level, as well as positive correlations between visceral fat and FT3 and FT3/FT4 levels [37]. In individuals with normal thyroid function, there was a positive correlation between visceral fat area and FT3 [38]. Furthermore, the increased visceral fat content among obese patients served as an independent predictor for TSH level [39]. Obesity was associated with increased thyrotropin, and the changes in thyroid hormone levels were consequences of weight gain rather than the cause of obesity. It has been observed that increases in body weight by 0.6 kg for women and 0.7 kg for men corresponded to a rise in TSH levels by 1 mIU/L [40]. Hypothyroidism was only associated with moderate weight gain, typically attributed to the changes in body compositions. Thyroid hormone replacement therapy generally resulted in mild weight loss (less than 10%), indicating that severe obesity was not commonly a result of hypothyroidism [16]. This theory was further supported by the fact that following weight loss achieved by bariatric surgery [41] or a low-calorie diet [42], there were significant decreases in TSH, FT3, and T3 levels, with subsequent normalization of thyroid function. In conclusion, the relationships between obesity and thyroid hormones were not consistently established and remained in the stage of ongoing research and exploration.

Based on the aforementioned findings, an increase in body fat mass/muscle mass (F/M) was found to be associated with a decrease in the sensitivity of central, but not peripheral thyroid hormone. Subgroup analysis based on age indicated that F/M had a more pronounced relationship with central thyroid hormone sensitivity in individuals aged < 65 years, but did not have a significant impact on individuals with age ≥ 65 years. In terms of gender subgroup, F/M exhibited weaken positive correlation with central thyroid hormone sensitivity index of TFQI, but not TT4RI and TSHI in female group. In male group, F/M exhibited significant positive correlation with central thyroid hormone sensitivity before the inflection, but no correlation thereafter. Subgroup analysis based on BMI indicated that F/M had a positive relationship with central thyroid hormone sensitivity in individuals with BMI ≥ 25 kg/m2, but this correlation disappears at a certain level of F/M. Individuals with BMI ≥ 30 kg/m2 showed negative relationship between F/M and central thyroid hormone sensitivity when F/M reached a high level. The possible reason maybe when the proportion of body fat reaches a high level in male and obese people, thyroid function decreases and thyroid hormone resistance decreases significantly, this leads to the disappearance of their positive correlation, or even a negative correlation, but the exact mechanism is unclear (Additional file 1).

Similar to the impact of obesity on insulin resistance, obesity may also lead to a relative resistance to thyroid hormone levels, resulting in a weakened effect of thyroid hormones. This may be an important factor contributing to the decrease in basal metabolic rate (BMR) associated with higher levels of body fat in overweight individuals [43].

The possible mechanisms of thyroid hormone resistance in obesity may be explained as follows: Firstly, there is an interaction between thyroid hormone and leptin in the regulation of body composition. Research has indicated a positive correlation between visceral fat and leptin level, and the same positive correlation existed between leptin and TSH level [44]. Leptin, secreted by adipocytes, regulates the expression of thyrotropin-releasing hormone (TRH gene) in the paraventricular nucleus (PVN) and arcuate nucleus (ARC). TSH binds to leptin receptors in adipocytes, leading to the stimulation of leptin secretion. A complex positive feedback system exists between serum TSH and leptin. Additionally, leptin promotes the intracellular synthesis of T3 by regulating the activity of deiodinase in adipocytes [45, 46]. Secondly, the TSH receptor is expressed in both adipocytes and preadipocytes of animals and humans. Additionally, TSH has the ability to induce the transformation of preadipocytes into adipocytes [47, 48]. In obese patients, the expressions of TSH and TRalpha1 receptors in adipose tissue are reduced, leading to increased levels of TSH and FT3. Additionally, the local action of T3 is impaired due to changes in the expressions of thyroid receptors in adipocytes. However, hormone levels and central thyroid hormone resistance returned to normality after weight-loss surgery [41, 49]. Thirdly, the expressions of 5'-deiodonase (DIO2) in the subcutaneous adipose tissue of obese patients was decreased, leading to a reduction in local T4 to T3 conversion [50].

Limitations

Also, there were several limitations in our study. Firstly, for study design, our study was of a cross-sectional design and lacked longitudinal comparative data, thus the evidence of the relationship between body composition and thyroid hormone sensitivity was not sufficient. Secondly, for missing variables, we failed to include thyroid-related antibodies which may potentially affect thyroid hormones. Thirdly, for sample size, the small number of individuals with BMI ≥ 30 kg/m2 reduced the credibility in studies of this population. In the future, we need to strengthen the study of obese population.

Conclusion

In conclusion, impaired central sensitivity to thyroid hormones is associated with increased body fat mass/muscle mass (F/M). We hypothesized that an increase in the F/M ratio would increase thyroid hormone resistance, but whether F/M independently affects thyroid hormone sensitivity needs to be verified by further clinical and basic studies in the future. We believe that the results could be helpful for obesity management in clinical work.

Data availability

The original data generated and analyzed in this study are included in the supplementary material and can be requested from corresponding author.

References

  1. WHO. Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

  2. Esmaeili F, Karimi K, Akbarpour S, Naderian M, Djalalinia S, Tabatabaei-Malazy O, et al. Patterns of general and abdominal obesity and their association with hypertension control in the iranian hypertensive population: insights from a nationwide study. BMC Public Health. 2025;25(1):241.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Katarzyna WS, Lucyna O, Urszula C, Joanna L, Marta JM, Marcin KH. Estimation of the impact of abdominal adipose tissue (Subcutaneous and Visceral) on the occurrence of carbohydrate and lipid metabolism disorders in patients with obesity-a pilot study. Nutrients. 2024;16(9):1301.

    Article  Google Scholar 

  4. Christiansen MR, Romero-Lado MJ, Carrasquilla GD, Kilpeläinen TO. The differential impact of abdominal obesity on fasting and non-fasting triglycerides and cardiovascular risk. Eur J Prevent Cardiol. 2025. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/eurjpc/zwaf058.

    Article  Google Scholar 

  5. Karahan Yilmaz S, Eskici G. Association between dynapenic abdominal obesity and cardio-cerebrovascular events in hemodialysis patients. Clin Nutr ESPEN. 2024;63:1201–2.

    Article  Google Scholar 

  6. Yao L, Zhang L, Tai Y, Jiang R, Cui J, Gang X, et al. Visual analysis of obesity and hypothyroidism: a bibliometric analysis. Medicine. 2024;103(1): e36841.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Saqib M, Sadia R, Farhat N, Najma R, Zainab S. Exploring the link between obesity and hypothyroidism. J Ayub Med Coll Abbottabad JAMC. 2023;35(4):608–11.

    Article  Google Scholar 

  8. Mariotti S, Beck-Peccoz P. Physiology of the Hypothalamic-Pituitary-Thyroid Axis. In: Feingold KR, Ahmed SF, Anawalt B, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc. Copyright © 2000–2025, MDText.com, Inc.; 2000.

  9. Wang ZX, Wu MH, Pan T, Zhao XL, Zhang L, Tang FY, et al. Impaired sensitivity to thyroid hormones is associated with albuminuria in the euthyroid population: results from NHANES. Hormones-Int J Endocrinol Metabol. 2024;23(2):245–55.

    Google Scholar 

  10. Zhang XW, Zhang XW, Liu J, Wang Q, Wang Q, Han C, et al. Impaired sensitivity to thyroid hormone is associated with developing non-alcoholic fatty liver disease in euthyroid diabetic subjects. Front Endocrinol. 2024;15:1450049.

    Article  Google Scholar 

  11. Shi CX, Liu XN, Du ZX, Tian LM. Impaired sensitivity to thyroid hormones is associated with the risk of diabetic nephropathy in euthyroid patients with type 1 diabetes mellitus. Diabetes Metabol Syndr Obes. 2024;17:611–8.

    Article  CAS  Google Scholar 

  12. Jin QK, Huang GQ, Tian XQ, Shu YM, Ximisinuer T, Mao YS. Increased serum adipocyte fatty acid-binding protein levels are associated with decreased sensitivity to thyroid hormones in the euthyroid population. Thyroid Off J Am Thyroid Assoc. 2020;30(12):1718–23.

    Article  Google Scholar 

  13. Liu YJ, Ma M, Li L, Liu FF, Li Z, Yu L, et al. Association between sensitivity to thyroid hormones and dyslipidemia in patients with coronary heart disease. Endocrine. 2023;79(3):459–68.

    Article  CAS  PubMed  Google Scholar 

  14. Bi TB. Relationship between thyroid hormone levels and metabolic dysfunction associated steatotic liver disease in patients with type 2 diabetes: a clinical study. Medicine. 2024;103(26): e38643.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wright TG, Dawson B, Jalleh G, Guelfi KJ. Influence of hormonal profile on resting metabolic rate in normal, overweight and obese individuals. Ann Nutr Metab. 2015;66(2–3):162–7.

    Article  CAS  PubMed  Google Scholar 

  16. Santini F, Marzullo P, Rotondi M, Ceccarini G, Pagano L, Ippolito S, et al. Mechanisms in endocrinology: the crosstalk between thyroid gland and adipose tissue: signal integration in health and disease. Eur J Endocrinol. 2014;171(4):137–52.

    Article  Google Scholar 

  17. Song B, Lu C, Teng D, Shan Z, Teng W. Association between different metabolic phenotypes of obesity and thyroid disorders among Chinese adults: a nationwide cross-sectional study. Front Endocrinol. 2023;14:1158013.

    Article  Google Scholar 

  18. Nappi A, Moriello C, Morgante M, Fusco F, Crocetto F, Miro C. Effects of thyroid hormones in skeletal muscle protein turnover. J Basic Clin Physiol Pharmacol. 2024;35(4–5):253–64.

    CAS  PubMed  Google Scholar 

  19. Cao B, Li K, Ke J, Zhao D. Impaired sensitivity to thyroid hormones is associated with the change of abdominal fat in euthyroid type 2 diabetes patients: a retrospective cohort study. J Diabetes Res. 2024;2024:8462987.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Yagi H, Pohlenz J, Hayashi Y, Sakurai A, Refetoff S. Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3,5,3’-triiodothyroinine binding affinity. J Clin Endocrinol Metab. 1997;82(5):1608–1614.

    CAS  PubMed  Google Scholar 

  21. Jostel A, Ryder WD, Shalet SM. The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index. Clin Endocrinol. 2009;71(4):529–34.

    Article  CAS  Google Scholar 

  22. Egan BM, Zhao Y. Different definitions of prevalent hypertension impact: the clinical epidemiology of hypertension and attainment of Healthy People goals. J Clin Hypertens (Greenwich). 2013;15(3):154–61.

    Article  PubMed  Google Scholar 

  23. WHO Guidelines Approved by the Guidelines Review Committee. In: Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation. Geneva: World Health Organization. Copyright © World Health Organization 2011.; 2011.

  24. Critical Metabolism Branch of China National Health Association. China multi-disciplinary expert consensus on diagnosis and treatment of hyperuricemia and related diseases (2023 edition). Chinese J Pract Internal Med. 2023;43:6.

    Google Scholar 

  25. Li JJ, Zhao SP. Chinese guidelines for lipid management (2023). Chin J Cardiol. 2023;51:3.

    Google Scholar 

  26. Schlienger J-L. The burden of obesity: epidemiology and cost. Medecine des Maladies Metaboliques. 2025;19:10–7.

    Google Scholar 

  27. Boutari C, Mantzoros CS. A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabol Clinic Exp. 2022;133:155217.

    Article  CAS  Google Scholar 

  28. Pan XF, Wang L, Pan A. Epidemiology and determinants of obesity in China. Lancet Diabetes Endocrinol. 2021;9(6):373–92.

    Article  PubMed  Google Scholar 

  29. Huang FL, Chen R. Management of weight gain and body composition changes in perimenopausal and early postmenopausal women. Chinese J Endoc Surg. 2024;18(3):330–3.

    Google Scholar 

  30. Cesaro A, De Michele G, Fimiani F, Acerbo V, Scherillo G, Signore G, et al. Visceral adipose tissue and residual cardiovascular risk: a pathological link and new therapeutic options. Front Cardiovas Med. 2023;10:1187735.

    Article  CAS  Google Scholar 

  31. Wan H, Wang Y, Xiang Q, Fang S, Chen Y, Chen C, et al. Associations between abdominal obesity indices and diabetic complications: Chinese visceral adiposity index and neck circumference. Cardiovasc Diabetol. 2020;19(1):118.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Li H, Shi Z, Chen X, Wang J, Ding J, Geng S, et al. Relationship between obesity indicators and hypertension-diabetes comorbidity in an elderly population: a retrospective cohort study. BMC Geriatr. 2023;23(1):789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Roef GL, Rietzschel ER, Van Daele CM, Taes YE, De Buyzere ML, Gillebert TC, et al. Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects. Thyroid Offic J Am Thyroid Assoc. 2014;24(2):223–31.

    Article  CAS  Google Scholar 

  34. Hyunah K, Da YJ, Lee SH, Cho JH, Yim HW, Kim HS. Retrospective cohort analysis comparing changes in blood glucose level and body composition according to changes in thyroid-stimulating hormone level. J Diabetes. 2022;14(9):620–9.

    Article  Google Scholar 

  35. Nie X, Ma X, Xu Y, Shen Y, Wang Y, Bao Y. Characteristics of serum thyroid hormones in different metabolic phenotypes of obesity. Front Endocrinol. 2020;11:68.

    Article  Google Scholar 

  36. Gu LP, Yang JY, Gong YJ, Ma YH, Yan S, Huang YH, et al. Lower free thyroid hormone levels are associated with high blood glucose and insulin resistance; these normalize with metabolic improvement of type 2 diabetes. J Diab. 2021;13(4):318–29.

    Article  CAS  Google Scholar 

  37. Yang Q, Wan YH, Hu S, Cao YH. Associations between the levels of thyroid hormones and abdominal obesity in euthyroid post-menopausal women. Endokrynol Pol. 2020;71(4):299–305.

    CAS  PubMed  Google Scholar 

  38. Nie X, Xu Y, Ma X, Xiao Y, Wang Y, Bao Y. Association between abdominal fat distribution and free triiodothyronine in a euthyroid population. Obes Facts. 2020;13(3):358–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mukherjee S, Deoghoria D, Mukhopadhyay D. Visceral and subcutaneous abdominal fat in relation to thyroid stimulating hormone (TSH) level in eu-thyroid female subjects. Indian J Physiol Pharmacol. 2016;60(5):94–5.

    Google Scholar 

  40. Bjergved L, Jørgensen T, Perrild H, Laurberg P, Krejbjerg A, Ovesen L, et al. Thyroid function and body weight: a community-based longitudinal study. PLoS ONE. 2014;9(4): e93515.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Tian ZR, Nie YT, Li ZQ, Wang PP, Zhang NR, Hei XF, et al. Total weight loss induces the alteration in thyroid function after bariatric surgery. Front Endocrinol. 2024;15:1333033.

    Article  Google Scholar 

  42. Chapela SP, Simancas-Racines A, Ceriani F, Martinuzzi AL, Russo MP, Zambrano AK, et al. Obesity and obesity-related thyroid dysfunction: any potential role for the very low-calorie ketogenic diet (VLCKD)? Curr Nutr Rep. 2024;13(2):194–213.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Luo X, Cai B, Jin WW. The prevalence rate of adult sarcopenic obesity and correlation of appendicular skeletal muscle mass index with body mass index, percent body fat, waist-hip ratio, basal metabolic rate, and visceral fat area. Metab Syndr Relat Disord. 2023;21(1):48–56.

    Article  CAS  PubMed  Google Scholar 

  44. Witte T, Völzke H, Lerch MM, Hegenscheid K, Friedrich N, Ittermann T, et al. Association between serum thyroid-stimulating hormone levels and visceral adipose tissue: a population-based study in Northeast Germany. Eur Thyroid J. 2017;6(1):12–9.

    Article  CAS  PubMed  Google Scholar 

  45. Duntas LH, Biondi B. The interconnections between obesity, thyroid function, and autoimmunity: the multifold role of leptin. Thyroid Offic J Am Thyroid Assoc. 2013;23(6):646–53.

    Article  CAS  Google Scholar 

  46. Ortega FJ, Jílková ZM, Moreno-Navarrete JM, Pavelka S, Rodriguez-Hermosa JI, Kopeck Ygrave J, et al. Type I iodothyronine 5’-deiodinase mRNA and activity is increased in adipose tissue of obese subjects. Int J Obes. 2012;36(2):320–4.

    Article  CAS  Google Scholar 

  47. Veroniqa L, Agné K, Ingrid D, Claude M. Adipose-specific inactivation of thyroid stimulating hormone receptors in mice modifies body weight, temperature and gene expression in adipocytes. Physiol Rep. 2020;8(16): e14538.

    Google Scholar 

  48. Zhang YJ, Feng L. Thyroid-stimulating hormone inhibits insulin receptor substrate-1 expression and tyrosyl phosphorylation in 3T3-L1 adipocytes by increasing NF-kappa B DNA-binding activity. Dis Markers. 2022;2022:1–9.

    Article  Google Scholar 

  49. Maria S, Marcello A, Sara D, Giuseppe NC, Chiara M, Gloria F, et al. Postoperative biochemical outcomes in metabolic bariatric surgery: results from a high-adherence cohort. J Person Med. 2025;15(1):7.

    Google Scholar 

  50. Marek S, Magdalena S, Agnieszka N, Monika KK. The effect of diet-induced weight-loss on subcutaneous adipose tissue expression of genes associated with thyroid hormone action. Clin Nutr (Edinburgh, Scotland). 2024;43(12):245–50.

    Article  Google Scholar 

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Funding

This work was supported by National Natural Science Foundation of China (82200805) and Scientific Project of Anhui Provincial Health Commission(AHWJ2022a039).

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Authors and Affiliations

  1. Department of Endocrinology, The First People’s Hospital of Hefei, No. 3200, Changsha Road, Binhu New District, Hefei, 230001, Anhui, China

    Ying Li, Qianqian Zhang, Li Chen & Qibao Ye

  2. Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China

    Yue Wang

  3. Laboratory Department, The First People’s Hospital of Hefei, Hefei, 230001, Anhui, China

    Wei Liu

  4. Department of Physical Examination Center, The First People’s Hospital of Hefei, Hefei, 230001, Anhui, China

    Yan Liu

  5. Department of Endocrinology, The First People’s Hospital of Hefei, Hefei, 230001, Anhui, China

    Guojuan Wang

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  1. Ying Li
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Contributions

Ying Li, Guojuan Wang and Qianqian Zhang wrote the main manuscript text, Li Chen, Yue Wang and Qibao Ye prepared figures and tables. All authors reviewed the manuscript.

Corresponding author

Correspondence to Guojuan Wang.

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This study obtained consent from all participants and was approved by the Ethics Committee of Hefei City First People's Hospital in accordance with the Declaration of Helsinki. All participants had signed informed consents [No. 2024–167-01].

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Li, Y., Zhang, Q., Chen, L. et al. Impaired sensitivity to thyroid hormones is associated with increased body fat mass/muscle mass ratio (F/M) in the euthyroid population. Diabetol Metab Syndr 17, 128 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13098-025-01693-w

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Keywords

Diabetology & Metabolic Syndrome

ISSN: 1758-5996

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