DOI: https://doi.org/10.21203/rs.3.rs-2274259/v1
Objective: To investigate the prevalence and risk factors of subclinical hypothyroidism (SCH) in obese people.
Patients and Methods: A survey was conducted on adult Han Chinese residents in Gansu Province, Northwest China, and the subjects' examination data were recorded. χ2 test was used to analyze the prevalence of SCH in the obese people, and Pearson correlation analysis of TSH levels in the overweight and obese people was conducted. Logistic regression analysis model was used to analyze the risk factors for SCH in the obese people.
Results: A total of 2849 individuals (1456 males and 1393 females) were included in this study, including 352 obese patients and 694 patients with SCH (294 males and 400 females).The prevalence of SCH was lower in men than in women in the obese people (23.48% vs 35.25%, P=0.019).The overall trend of SCH prevalence in overweight and obese people increases with age.TSH levels in overweight and obese people were positively correlated with age, systolic blood pressure (SBP), body mass index (BMI), serum total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and blood phosphorus.Logistic regression analysis concluded increased age, high fasting glucose (FPG), high TPOAb, high SBP, high AST, and high blood phosphorus as risk factors for SCH in overweight and obese people, and male, uric acid (UA) as protective factors.
Conclusions: The prevalence of SCH in overweight and obese people is relatively high, and effective control of BMI may have a role in reducing the prevalence of SCH; the prevalence of SCH in overweight and obese people is higher in women than in men, and attention should be paid to its screening and prevention.
Obesity is a chronic metabolic disease caused by multiple factors and has been included in the list of diseases by the World Health Organization.In recent years, there has been a surge in the number of obese people due to changes in lifestyle and diet structure and the prevalence of high-sugar and high-fat diets [1].Some studies have shown that the rate of overweight and obesity in urban and rural residents of all age groups has continued to rise in recent years, and by 2020 more than half of adult residents was already overweight or obese [2].Subclinical hypothyroidism (SCH) is a common endocrine disorder in which serum thyroid stimulating hormone (TSH) levels are elevated and free thyroid hormone levels are normal [3].Relevant studies have shown that the prevalence of SCH in China is 16.7%, and there is an increasing trend [4-5].Studies have found a correlation between BMI and the development of thyroid-related diseases.Therefore, this study aims to investigate the correlation between BMI level and SCH prevalence through a random survey of residents in Gansu Province, aiming to provide reference ideas for clinical prevention and treatment of SCH.
1.1 Investigation object
Selection method: A total of 2849 adult Han Chinese residents who had lived in Lanzhou, Longnan, Dingxi, Baiyin, and Linxia areas for more than 5 years were selected in Gansu Province using a multi-stage stratified whole-group random sampling method.Subjects were aged 18-87 years with a mean of (42.88±15.02) years.The following conditions must be excluded for enrollment:(i)People with major liver, kidney, cardiovascular and cerebrovascular diseases;(ii)Abnormal thyroid function:people with hyperthyroidism, clinical hypothyroidism, inflammatory thyroid conditions, etc;(iii)People who have taken medication that interferes with blood lipids and thyroid function within the last 3 months, and those who have been exposed to radioactive substances;(iv)Pregnant and breastfeeding people.
1.2 Methods
1.2.1 Basic information
Records were collected: gender, age, height, weight, waist circumference, systolic blood pressure (SP), diastolic blood pressure (DP), heart rate, calculated body mass index (BMI), and past medical history.
1.2.2 Biochemical tests
(i)Lipid-related indexes: total cholesterol (TC), triglyceride (TG) using kits and biochemical assay (BS-180), high density lipoprotein cholesterol (HDL-C ), low density lipoprotein cholesterol (LDL-C); (ii)Glucose related indexes: fasting plasma glucose (FPG), oral glucose tolerance test , blood glucose 2 hours after OGTT (2h PG) was monitored by glucose oxidase (Beckman 5 800 automatic biochemical analyzer); (iii)Thyroid function tests: thyroid-stimulating hormone (TSH) using kits and testers (Roche Cobase 601 electrochemiluminescence immunoassay), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb); (iv)Other tests: uric acid (UA), blood phosphorus,aspartate aminotransferase (AST),alanine aminotransferase (ALT) using kits and a biochemical assay (BS-180 from Myriad).
1.2.3 Diagnostic criteria and reference range
According to the Chinese Guidelines for Prevention and Control of Overweight and Obesity in Adults (Abridged) [2], the diagnostic criteria are as follows:(i)low body mass group: BMI < 18.5 kg/m2;(ii)normal group:18.5 ≤ BMI ≤ 23.9 kg/m2;(iii)overweight group: 24.0 ≤ BMI ≤ 27.9 kg/m2;(iv)obese group: BMI ≥ 28.0 kg/m2.
The diagnosis of SCH refers to the criteria of the "Guidelines for the diagnosis and management of adult hypothyroidism" [6]: (i)normal group: 0.27 ≤ TSH ≤ 4.2mIU/L; (ii)subclinical hypothyroidism group: TSH > 4.2mIU/L.
1.3 Statistical methods
SPSS 26.0 software was used to analyze the data. Normal distribution measures were expressed as (x ± s), two independent samples t-test was used to compare between two groups, count data were described by frequency, and the difference in prevalence between groups was compared using χ2 test. Logistic regression models were used to analyze the risk factors, and the test level was α=0.05.
2.1 Comparison of general information between the SCH and Non-SCH groups
In this study, 2849 subjects were selected, including 694 patients with SCH (294 males, 20.19%; 400 females, 28.72%).The subjects were first stratified according to BMI for comparison, and later divided into the group with SCH (SCH) and the group without SCH (Non-SCH) for analysis.The results showed that age, SBP, DBP, FPG, 2h PG, TG, TC, LDL-C, blood phosphorus, TPOAb and TgAb were higher in the SCH group than in the Non-SCH group and UA was lower than in the Non-SCH group in both normal and overweight obese people, and the differences were statistically significant (all P < 0.05), as detailed in Figure 1.
2.2 Comparison of the prevalence of clinical obesity and its prevalence of SCH
Grouping by different BMI levels, along with gender stratification.The chi-square test was used to compare the differences in the prevalence of SCH at different BMI levels.The results showed that the highest prevalence of SCH (27.56%) was found in the obese population in the total population.The prevalence of SCH was significantly higher among women than men in the overweight and obese population (31.92% vs 19.24%, P < 0.001; 35.25% vs 23.48%, P = 0.019), as detailed in Figure 2.
2.3 Quality of people in different age groups and distribution of SCH patients
Grouping by different age groups, along with BMI stratification.The prevalence of SCH in all four cohorts showed an overall increasing trend with increasing patient age, and the prevalence reached more than 27% when patients were ≥ 61 years old.The differences in the prevalence of SCH between the population with normal body mass and those with overweight and obesity were statistically significant between the age groups (all P < 0.001), as shown in Figure 3.
2.4 Correlation analysis of TSH levels in overweight and obese people
The overweight and obese population was analyzed by gender stratification, and TSH levels were found to be positively correlated with age, TC, SBP, LDL-C, HDL-C, TPOAb, TgAb, and blood phosphorus in the overweight and obese population, and TSH levels were positively correlated with age, SBP, TC, TPOAb, and TgAb in men, and TSH levels were positively correlated with age, BMI, TC, TPOAb, TgAb, LDL-C, and blood phosphorus in women, as detailed in Figure 4.
2.5 Multivariate logistic analysis of factors influencing SCH formation in overweight and obese people
In the overweight and obese population, the dependent variable was the presence or absence of SCH, and the independent variables were screened by univariate analysis, and those with significant significance were substituted into the independent variables before multivariate analysis.It was concluded that increased age, high AST, high blood phosphorus, high SBP, and high TPOAb were risk factors for SCH, and male and UA were protective factors, as detailed in Figure 5.
In recent years, obesity and thyroid disease have become common factors affecting the health of our population.There is a strong association between obesity and the development of SCH.About 14% of obese people with a BMI of 30-40 kg/m2 have combined SCH [7], and the incidence increases to 25% when the BMI is > 40 kg/m2 [8].In the context of rapid socioeconomic development and population aging, the prevention and treatment of obesity and thyroid diseases need to be given high priority.
This study found that the prevalence of SCH in overweight and obese people in Gansu was significantly higher than that in people with normal body mass (24.22% vs. 23.84%, P = 0.003; 27.56% vs. 23.84%, P < 0.001) and higher than that in the southwest (11.32%) [9], which may be related to various factors such as geographical environment and living habits in this region and should be given sufficient attention. This may be related to various factors such as geographical environment and living habits in the region, which should be given sufficient attention.By comparing the general data, it was found that the age of the SCH group was higher than that of the Non-SCH group, and there was an overall increasing trend in the prevalence of SCH with age in both normal body weight and overweight obese people, and the same conclusion as in the present study was found in the study by Qiao Jie et al [10].Logistic regression analysis also found that increasing age was a risk factor for SCH prevalence, suggesting a correlation between age and the prevalence of SCH in overweight and obese people, and therefore for the middle-aged and elderly people, extra attention should be paid to the regulation of BMI levels.Further study found that the prevalence of SCH in obese people was significantly higher in women (35.25%) than in men (23.48%), and Li Jiang et al [11] found that women were more susceptible to SCH than men in high BMI people, similar to the results of this study.Multifactorial logistic regression analysis of SCH prevalence in the overweight and obese people indicated men as protective factors, again suggesting that overweight and obese women are more likely to develop SCH, the reason for which may be related to differences in sex hormone metabolism.The results of this study showed that TPOAb levels were higher in the SCH group than in the Non-SCH group in the overweight obese people (P < 0.001), and high TPOAb was a risk factor for SCH in the overweight obese people, suggesting a close association between BMI and abnormal status of thyroid function and related antibodies.Some studies have shown that obesity is associated with an increased risk of TPOAb positivity [12], possibly because leptin produced by adipocytes regulates the immune system by altering the Th1 cell phenotype and suppressing the function of regulatory T (Treg) cells, promoting TPOAb production and leading to increased thyroid autoimmune damage and increased destruction of the thyroid gland itself, resulting in hypothyroidism [13].It was found that UA levels were lower in the SCH group than in the Non-SCH group in the overweight obese population, and multi-factor logistic regression analysis indicated that UA was a protective factor against SCH in the overweight obese population.A study by Desideri G [14] indicated that the relationship between UA metabolism and thyroid function could be regulated by insulin signaling, with the possible mechanism being obesity-induced insulin resistance [15], a significant increase in URAT1 expression and a decrease in ABCG2 expression by insulin, leading to an increase in UA reabsorption [14] and a moderate increase in UA levels, whose powerful antioxidant effects affect thyroid hormones [16], ultimately resulting in altered TSH levels.General data showed that SBP and blood phosphorus levels were higher in the SCH group than in the Non-SCH group in the overweight obese population.Multi-factor logistic regression analysis indicated that SBP and blood phosphorus were risk factors for SCH in overweight and obese people, suggesting an association between hypertension, serum phosphate levels and thyroid function.A study by Abdel-Gayoum AA [17] indicated a correlation between hypothyroidism and increased blood phosphorus levels, the exact mechanism of which remains to be investigated.
The association between obesity and hypothyroidism is bidirectional.In terms of pathogenesis, the induction of obesity alters the hypothalamic-pituitary-thyroid secretion pattern [18].The rationale for the significant changes in thyroid hormones due to overeating may be the increased caloric intake due to increased food intake and the increased overall processing rate of T3 in plasma.However, it did not change the percentage of T3 metabolized by the type I deiodination pathway [19], and the decrease in T3 levels affects the decrease in the free thyroid hormone index, leading to an increase in TSH levels and ultimately to the development of SCH.Meanwhile TSH controls thermogenesis and is an important determinant of energy expenditure, regulating food intake, energy expenditure and body weight.And the continuous interaction between hormones and cytokines from adipose tissue and central regulatory mechanisms in the brain reflects the amount of energy stores through other related peptides and hormones [18].
In conclusion, this study provides a reference for the prevention and treatment of SCH in less developed areas, including Gansu, by analyzing the close correlation between overweight and obese populations and the occurrence and development of subclinical hypothyroidism.Overweight obesity may be a contributing factor to SCH, and regular thyroid function tests are recommended for overweight and obese people.The prevalence of SCH among Gansu residents is relatively low compared to other regions, and early prevention, early detection and early treatment can be achieved by screening the elderly and overweight and obese population, especially the female group.
SCH subclinical hypothyroidism
SBP systolic blood pressure
BMI body mass indexserum
TC total cholesterol
HDL-C high-density lipoprotein
LDL-C low-density lipoprotein
TPOAb thyroid peroxidase antibody
TgAb thyroglobulin antibody
FPG high fasting glucose
UA uric acid
TSH stimulating hormone
SP systolic blood pressure
DP diastolic blood pressure
TG triglyceride
2h PG blood glucose 2 hours after OGTT
AST aspartate aminotransferase
ALT alanine aminotransferase
Ethical Consideration
We obtained ethical approval and a letter of cooperation from the Medical Ethics Research Committee of the First Affiliated Hospital of China Medical University (AF-SOP-07-1.0-01), and our study was conducted in accordance with the Declaration of Helsinki. All of the study participants provided written informed consent and were informed of the confidentiality, purpose, and importance of their information.
Not applicable
The data that support the findings of this study are available from the corresponding author.
The authors declare that they have no competing interests
Funding
2020 special project for the central government to guide local science and technology development (innovative platform for improving the ability of prevention and control of frequently-occurring diseases in Gansu Province, China) ；Gansu Province Endocrine Disease Clinical Medicine Research Center Construction Plan (20JR10FA667); Natural Science Foundation of Gansu Province (20JR10RA681); Lanzhou Science and Technology Development Guiding Plan Project (2019-ZD-38); National Health and Family Planning Commission Public Welfare Industry Scientific Research Project (201402005); The National Key R and D Program "Prevention and Control Research" 2017YFC1310700,2017YFC1310702;Lanzhou University 2021 College Students Innovation and Entrepreneurship (20220060112).
Author contributions
All authors contributed to the study conception and design.The specific division of labor is as follows:
Songbo Fu: contributed to conception, design, data collection and analysis. Critically revised the manuscript.
Weiqi Che;Qianqian Liu: contributed to the conception, design, data processing, statistical analysis Graphics rendering and drafting the manuscript.
Xulei Tang, Gaojing Jing, Qianglong Niu,Weiping Teng: contributed to participation in data collection. Critically revised the manuscript.
All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Acknowledgments
We would like to thank everyone who participated in this study and helped collect data. And to thank all the anonymous participants for responding to our questions.