Overt and subclinical hypothyroidism had significant impacts on metabolic components in women. BMI, waist circumference, TGs, SBP and DBP in the subclinical and overt hypothyroidism groups were significantly higher than the euthyroid group in women.

The relative risk of abdominal obesity and hypertriglyceridemia was increased in women with hypothyroidism. Thyroid dysfunction had different effects on metabolic syndrome and its components before and after menopause. Conclusion: Thyroid function had important effects on the prevalence of metabolic syndrome.

Women with hypothyroidism, especially post-menopausal women, had a higher risk of metabolic syndrome than men. Metabolic syndrome comprises a group of interrelated metabolic abnormalities that are characterized by central obesity, high triglycerides TGs , low high-density lipoprotein cholesterol HDL-C , hypertension and hyperglycaemia.

Patients with metabolic syndrome have an increased risk of cardiovascular disease, type 2 diabetes, and all-cause mortality. After adjusting for potential risk factors and each component of metabolic syndrome as a continuous variable, metabolic syndrome was associated with an increased year risk of coronary heart disease 1.

With the development of the social economy in recent decades, the incidence rates of nutritional metabolic diseases, such as obesity, hypertension and diabetes, have significantly increased 3.

A survey from China showed that the prevalence of metabolic syndrome among Chinese adults increased in recent years, and it has become a major public health problem 4 — 7.

The incidence of metabolic syndrome in urban areas is higher than rural areas, and the overall prevalence tends to increase with age. Sex heterogeneity exists in the relationship between risk factors and the prevalence of metabolic syndrome 7 , 8.

Economic development, urbanization, improvements in living standards, changes in lifestyle, dietary modifications and a reduction in physical activities all play key roles in this process 4.

The thyroid plays an important role in metabolic regulation. Thyroid hormones have multiple effects on glucose and lipid metabolism, blood pressure regulation, and energy consumption. Recent studies found that patients with hypothyroidism and subclinical hypothyroidism had an increased risk of metabolic syndrome 9 , Previous studies showed that subjects with thyroid stimulating hormone TSH levels at the upper limit of the normal range 2.

Other reports did not show a significant association between high TSH levels and metabolic syndrome 13 , Obesity also affects thyroid function. This relationship requires further investigation in a representative large-sample population.

There is increasing evidence that thyroid dysfunction affects lipid and glucose metabolism, blood pressure, and body weight, which are associated with various metabolic parameters and may lead to the development or aggravation of components of metabolic syndrome The present cross-sectional study investigated the association between thyroid dysfunction and metabolic syndrome in a Chinese population.

The data were obtained from the Thyroid Disease, Iodine Nutrition and Diabetes Epidemiology TIDE study, which included urban and rural areas, and were obtained via four-stage random sampling The following inclusion criteria for adult respondents were used: aged 18 years or older, living in a target community for at least 5 years, no exposure to iodine or contrast agent in the previous three months, and not pregnant.

The Ethics Committee of China Medical University approved the research plan. After a detailed explanation of the protocol, all respondents signed informed consent forms.

The questionnaire collected data on demographics, personal and family histories of thyroid disease, smoking status, family income, education level and household salt consumption. Fasting blood and urine were collected from each subject, and blood samples were collected from subjects without diagnosed diabetes after the 2-h oral glucose tolerance test OGTT.

The collected serum and urine samples were stored at °C. After investigation and specimen collection, all samples were transported to the central laboratory and adhered to cold chain requirements for the unified testing of thyroid indexes and urinary iodine concentration UIC. Metabolic indexes were detected immediately on site.

Fasting blood glucose FBG , 2-hour blood glucose OGTT 2-hPG , serum TG, total cholesterol TC , low-density lipoprotein cholesterol LDL-C and HDL-C levels were measured using an automatic biochemical analyser BS analyzer, Mindray, Shenzhen, China.

HbA1c in venous blood samples was measured using high-performance liquid chromatography HPLC BioRad VARIANT II haemoglobin analyser. Thyroid stimulating hormone TSH , thyroid peroxidase antibody TPOAb and thyroglobulin antibody TgAb were measured using electrochemical luminescence immunoassays Cobasc analyser, Roche Diagnostic, Switzerland.

When the TSH level exceeded the upper limit of the reference range 0. FT4 and free triiodothyronine FT3 were measured when TSH levels were lower than the lower limit of the reference range.

UIC was measured using inductively coupled plasma mass spectrometry ICP-MS Agilent x, Agilent Technologies, USA. All statistical analyses were performed using SPSS Corresponding participants was randomly selected from a normal thyroid function population as the control group to eliminate the influence of quantity differences.

Normally distributed data are expressed as means ± standard deviations. Two independent samples t-tests were used to compare differences in metabolic indicators. Two types of risk factor adjustment models were constructed. A P-value less than 0.

A total of 80, participants were enrolled after excluding participants who met the exclusion criteria, and 62, participants were ultimately included in the analyses. The flow chart of participant inclusion is shown in Figure 1. A total of 52, participants In particular, there are 7 patients with central hypothyroidism among the patients with low TSH.

To eliminate the influence of differences in group sizes, 9, participants were randomly selected from the normal group as the euthyroid control group. The general characteristics of participants with different thyroid function statuses are shown in Table 1. Table 1 General characteristics of participants with different thyroid functional statuses.

The metabolic indicators are related to sex. Therefore, we compared differences in metabolic indicators in different thyroid functional statuses in men and women. As shown in Table 2 , SBP and HDL-C were increased in men in the subclinical hyperthyroidism group compared to men the euthyroid group, and the TG level was reduced.

BMI, waist circumference, and TG levels were significantly reduced in the overt hyperthyroidism group. BMI, waist circumference, SBP and TG level were increased in the subclinical hypothyroidism group, and SBP and HDL-C were increased in the overt hypothyroidism group.

BMI, waist circumference, SBP, DBP, and TG levels in the subclinical and overt hypothyroidism groups were significantly increased in the subclinical hypothyroidism group compared to women in the euthyroid group, and HDL-C was significantly decreased.

HbA1c was significantly increased in the overt hypothyroidism group. The prevalence of metabolic syndrome was significantly higher in men than women The prevalence of metabolic syndrome and each of its component in the different thyroid function status groups are shown in Figure 2.

Among the different thyroid function groups, the prevalence of hypertension in men was consistently higher than women, the prevalence of low HDL-C was consistently significantly higher in women than men, and the prevalence of hyperglycaemia was similar between men and women.

The prevalence of metabolic syndrome, abdominal obesity and hypertriglyceridemia in men with overt hypothyroidism, subclinical hyperthyroidism, euthyroid, and subclinical hypothyroidism were higher than the corresponding groups of women. However, differences were not observed in the overt hypothyroidism group.

Figure 2 The prevalence of metabolic syndrome and each of its component in different thyroid function status groups by sex. A Prevalence of metabolic syndrome grouped by sex.

B Prevalence of abdominal obesity grouped by sex. C Prevalence of hypertriglyceridemia grouped by sex. D Prevalence of low HDL-C grouped by sex. E Prevalence of hypertension grouped by sex.

F Prevalence of hyperglycaemia grouped by sex. The associations of thyroid function with metabolic syndrome and its components were analyzed using binary logistic regression according to sex and thyroid function status Table 3. Model 1 was constructed using univariate analysis, and Model 2 was adjusted for the effects of age, ethnicity, education, occupation, annual income, smoking history, and other metabolic factors.

Table 3 Risk of metabolic syndrome associated with thyroid function in men and women. Subclinical hyperthyroidism in men was a risk factor for hypertension. Overt hyperthyroidism was a risk factor for hypertension and hyperglycaemia. Subclinical hypothyroidism was a risk factor for hypertriglyceridemia and low HDL-C.

Overt hypothyroidism had no effect on metabolic syndrome or its components. Overt hyperthyroidism in women was a risk factor for hypertension and hyperglycaemia. Subclinical hypothyroidism was a risk factor for abdominal obesity, hypertriglyceridemia, low HDL-C, hypertension and metabolic syndrome.

Overt hypothyroidism was a risk factor for abdominal obesity, hypertriglyceridemia, low HDL-C, hypertension and metabolic syndrome. In general, subclinical hypothyroidism and overt hypothyroidism were risk factors for metabolic syndrome. However, subclinical hyperthyroidism had no effect on metabolic syndrome or its components.

TSH levels were divided into quartiles in the euthyroid control group, and the association between TSH levels and components of the metabolic syndrome were analyzed Table 4. The risk of metabolic syndrome in men increased with TSH levels at the lower limit of the normal range 0.

The risk of abdominal obesity in women increased significantly with TSH levels at the upper limit of the normal range 3. Table 4 Risk of metabolic syndrome associated with TSH levels in the euthyroid group. The female population was further divided into pre- and post-menopausal groups, and binary logistic regression was used to investigate the effects of changes in thyroid function on the risk of metabolic syndrome before and after menopause Table 5.

After adjusting for age, ethnicity, education, occupation, annual income, smoking history, and other metabolic factors, overt hyperthyroidism was a risk factor for hypertension and hyperglycaemia in women before menopause.

However, the effect of overt hyperthyroidism disappeared after menopause. Subclinical hypothyroidism increased the risk of abdominal obesity, hypertension, hypertriglyceridemia, low HDL-C and metabolic syndrome before menopause, but these effects were not observed after menopause.

Subclinical hypothyroidism was associated with hypertension before and after menopause. Overt hypothyroidism was significantly associated with abdominal obesity, hypertriglyceridemia and metabolic syndrome before menopause, and these effects persisted after menopause.

Table 5 Risk of metabolic syndrome associated with thyroid function in women before and after menopause. The prevalence of cardiovascular events and stroke and the risk of death in Chinese patients with metabolic syndrome are 2 ~ 3 times higher than Chinese people without metabolic syndrome. Non-diabetic patients with metabolic syndrome have a five-fold increased risk of developing type 2 diabetes compared to nondiabetic patients without metabolic syndrome.

Early intervention and diagnosis of metabolic syndrome are key in the prevention of diabetes and cardiovascular and cerebrovascular diseases. iii Moulin de Moraes CM, Mancini MC, de Melo ME, Figueiredo DA, Villares SM, Rascovski A, Zilberstein B, Halpern A. Prevalence of subclinical hypothyroidism in a morbidly obese population and improvement after weight loss induced by Roux-en-Y gastric bypass.

Obes Surg. iv Bastemir M, Akin F, Alkis E, Kaptanoglu B. Obesity is associated with increased serum TSH level, independent of thyroid function.

Swiss Med Wkly ;— v Marina A. Michalaki, Apostolos G. Vagenakis, Aggeliki S. Leonardou, Marianna N. Argentou, Ioannis G. Habeos, Maria G. Makri, Agathoklis I. Psyrogiannis, Fotis E.

Kalfarentzos, Venetsana E. January 1, , 16 1 : vi Rezzonico J, Rezzonico M, Pusiol E, Pitoia F, Niepomniszcze H. Introducing the thyroid gland as another victim of the insulin resistance syndrome. Help the OAC to raise awareness, advocate for improved access, provide evidence-based education, fight to eliminate weight bias and discrimination and elevate the conversation of weight and its impact on health.

Donate Now. by Rachel Engelhart, RD; Kelly Donahue, PhD; and Renu Mansukhani, MD Summer Welcome to the first…. by Sarah Bramblette, MSHL Summer In the final months of , I experienced both the worst…. Comprehensive obesity care requires teaming up with a qualified and compassionate medical professional.

Find the right healthcare provider to talk about your weight and health at ObesityCareProviders. Click Here. Sort By:.

Default Order Date - Old to New Date - New to Old. Articles Brochures Guides 4. Videos Additional Categories. Fact Sheets. For more information about PLOS Subject Areas, click here.

Thyroid hormones TH are known to stimulate in vitro oxygen consumption of tissues in mammals and birds. Hence, in many laboratory studies a positive relationship between TH concentrations and basal metabolic rate BMR has been demonstrated whereas evidence from species in the wild is scarce.

Even though basal and field metabolic rates FMR are often thought to be intrinsically linked it is still unknown whether a relationship between TH and FMR exists.

Here we determine the relationship between the primary thyroid hormone triiodothyronine T3 with both BMR and FMR in a wild bird species, the black-legged kittiwake Rissa tridactyla.

As predicted we found a strong and positive relationship between plasma concentrations of T3 and both BMR and mass-independent BMR with coefficients of determination ranging from 0. In accordance with in vitro studies our data suggests that TH play an important role in modulating BMR and may serve as a proxy for basal metabolism in wild birds.

However, the lack of a relationship between TH and FMR indicates that levels of physical activity in kittiwakes are largely independent of TH concentrations and support recent studies that cast doubt on a direct linkage between BMR and FMR.

Citation: Welcker J, Chastel O, Gabrielsen GW, Guillaumin J, Kitaysky AS, Speakman JR, et al. PLoS ONE 8 2 : e Received: October 3, ; Accepted: January 7, ; Published: February 20, Copyright: © Welcker et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The study was financially supported by the French Polar Institute IPEV Program to O.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist. It has long been known that plasma concentrations of thyroid hormones TH affect the basal metabolic rate BMR of mammals including humans and birds [1] , [2] , [3].

Although evidence from wild animals is still scarce, studies of laboratory animal models have shown stimulating effects of thyroid hormones on tissue oxygen consumption with corresponding effects on BMR [4] , [5] , [6].

Much less is known about the relationship between thyroid hormones and the field metabolic rate FMR. However, a strong link between BMR and FMR has often been proposed, particularly during periods of peak energy expenditure such as reproduction [7] , [8] , [9] , leading to the expectation of a positive association between TH and FMR.

Yet, the impact of thyroid hormones on FMR of animals remains virtually unknown. In the present study we determined the relationship between the thyroid hormone triiodothyronine T3 and the basal and field metabolic rates of a free-ranging bird species, the black-legged kittiwake Rissa tridactyla , hereafter called kittiwake.

BMR, which can be seen as the minimal energetic cost of living, is defined as the metabolic rate of a resting, normothermic and post-absorptive adult animal within its thermoneutral zone [10] and has long been proposed to be closely related to concentrations of thyroid hormones in endotherms [4] , [11].

In fact, before the advent of radioimmunoassays made it possible to measure plasma concentrations of thyroid hormones directly, BMR was used as a proxy for thyroid status in humans [1] , [2]. Today blood concentrations of the two main thyroid hormones, thyroxine T4 and triiodothyronine T3 are readily assessed.

Although in birds T4 may have high potency for several hormone-triggered responses [12] it is usually regarded as a precursor of the physiologically more active T3. The vast majority of circulating thyroid hormones is bound to plasma proteins and it is the free fraction that is often assumed as physiologically relevant [13].

Although the detailed pathways of how thyroid hormones affect energy metabolism are still debated it is clear that it involves the stimulation of many individual processes in different body tissues [see 4 for a review].

In general, most body tissues have been shown to be thyroid hormone sensitive, and in vitro oxygen consumption of a range of tissues is known to differ according to their thyroid status [3] , [14] , [15]. Hence, many studies on humans and laboratory animals have demonstrated a strong link between thyroid hormones and BMR [4] , [6].

In the chicken, the correlation coefficient between T3 and BMR was as high as 0. However, for animals under natural conditions much less information is available with respect to the relationship between thyroid hormones and BMR, and results are ambiguous [19] , [20] , [21] , [22].

Similarly, there is a paucity of data with which to evaluate the existence of a link between thyroid hormones and FMR. Even though thyroid hormones have occasionally been used as a proxy for FMR [23] , to our knowledge a positive association of thyroid hormones with FMR or daily energy expenditure has so far only been demonstrated in humans under controlled conditions [24].

Thermoregulation may be an important driver of FMR, especially in small mammals [25] , Given that thyroid hormones stimulate several processes of metabolic heat production and therefore are thought to be important modulators of both obligatory and facultative thermogenesis [5] , [12] , one may expect a positive relationship of FMR with TH concentrations.

However, for species such as kittiwakes that often operate within their thermoneutral zone [26] this is likely to play only a minor role, and physical activity rather than thermoregulation presumably accounts for most of the difference between BMR and FMR.

Whether TH concentrations have an effect on levels of physical activity largely remains to be demonstrated [27]. Nonetheless, a relationship between thyroid hormones and FMR is expected under the assumption that BMR and FMR are intrinsically linked, i. that the BMR determines the level of FMR an individual can sustain [7] , [28] , [29].

This hypothesis is mainly based on the notion that a high FMR needs to be sustained by high energy intake and therefore requires large internal organs such as the liver, kidneys and alimentary tract.

The size of these organs together with their high metabolic intensities [30] represent an important determinant of BMR and would consequently intrinsically link basal and field metabolic rates [29].

Supporting this hypothesis, a large number of studies have reported a positive association between BMR and FMR both on the inter-specific [9] , [29] , [31] and intra-specific level [32] , [33] , [34]. In the present study we tested the strength of the relationship between thyroid hormones T3 and both BMR and FMR in a free-ranging bird species, the kittiwake during a period of peak energy demands chick-rearing.

We predicted a strong positive relationship between T3 and BMR based on the known contribution of TH to tissue in vitro oxygen consumption. We also expected a positive, albeit weaker, association of T3 with FMR given the proposed link between BMR and FMR.

The study was approved by the Governor of Svalbard and by the Norwegian Animal Research Authority. The breeding season May-September at the study site is characterized by continuous daylight and an average ambient temperature of approx. Kittiwakes are medium sized body mass approx — g , cliff-breeding seabirds that mainly feed on pelagic fish [e.

In Spitsbergen, kittiwakes usually lay two eggs and both partners of a pair share parental duties during incubation and chick-rearing. In , we captured 24 adult kittiwakes 12 males and 12 females to simultaneously measure plasma total T3 concentration and BMR.

Birds were caught during the chick-rearing period when their chicks were between 2 and 21 d old. Only one adult per nest was captured, and data obtained for males and females were considered as statistically independent. Birds were captured at their nests with a noose at the end of a telescopic pole.

Blood samples were stored on ice, centrifuged after max. Morphometric measurements were used to determine the sex of the birds following Moe et al. After capture and blood sampling, birds were kept in an individual opaque cloth bag to be rapidly within 15 min transported by boat to the laboratory to measure BMR by open flow-through respirometry.

Birds were fasting for about six hours before being placed into a metabolic chamber. The metabolic chamber was situated inside a larger walk-in temperature-controlled cabinet.

The ambient temperature T a , measured using a type T thermocouple placed inside the metabolic chamber during the measurements was on average During the experiment, birds were kept in continuous light reflecting natural conditions at the breeding site. Outside air was dried over silica gel and pumped through an approximately 25 L respiratory chamber with a flow rate of approximately 1.

Actual flow rates were measured using a calibrated mass flow-meter Bronkhorst high-tech, type C-FA, Ruurlo, the Netherlands. An aliquot of the effluent air was dried over silica-gel and the oxygen concentration measured using an oxygen analyzer Servomex Xentra , Zoetermeer, the Netherlands.

The oxygen analyzer was calibrated using dry outside air set to The minimum value of oxygen consumption was obtained after an average time of 17 h S. The BMR was calculated from the lowest minute running average [10] of instantaneous oxygen consumption.

Rates of oxygen consumption VO 2 were calculated using formula 3A given by Withers [37] , and corrected for wash-out delay in the system by the method described by Niimi [38].

In this way, we obtained the instantaneous oxygen consumption rates. We assumed a respiratory quotient RQ of 0. Birds usually have uric acid as their main nitrogenous waste product and because of the stoichiometry of uric acid metabolism RQ during both fasting predominantly fat metabolism and during protein metabolism carbohydrates are negligible in the diet of piscivorous seabirds will be essentially equal 0.

The maximal error in calculating VO 2 caused by variation in RQ will consequently be small below 0. BMR W was calculated from the value of oxygen consumption rate using a conversion factor of All birds were later seen back on their nests without any apparent effect of the handling.

In , we captured 49 adult kittiwakes 24 males and 25 females to simultaneously measure plasma T3 concentration total and free fraction and FMR. This included both partners of 23 breeding pairs and three single birds 1 male and 2 females.

Birds were sampled when their chicks were between 18 and 25 d old hatching dates were known through nest content monitoring every two days.

We estimated FMR using the doubly-labeled water DLW method [39] , [40]. Immediately after capture, birds were weighed and intra-peritoneally injected with 1. Birds were marked with an individually numbered steel band and a coded plastic band for easy identification.

Birds were then kept in a cloth bag for 1 h to allow for complete equilibration of isotopes with the body water of the injected animal [40]. Prior to release, birds were weighed again and an initial blood sample was collected from the alar vein.

Blood was stored in several 75 µL glass micro-capillaries which were immediately flame-sealed. Additionally, blood samples were taken from 12 unlabeled adult kittiwakes to determine the mean background level of isotopes [ method C]. To eliminate high day to day variation of DEE [42] , [43] , we aimed to recapture all individuals after approximately three days mean ± SD: Upon recapture, birds were weighed and a final blood sample was taken as described above to estimate FMR and measure plasma concentrations of thyroid hormones.

We were able to recapture all injected individuals. For thyroid hormone analysis, blood c. The sex of birds in was determined by molecular sexing following standard procedures as described in Fridolfsson and Ellegren [44].

Analysis of isotopic enrichment of blood samples was done by isotope ratio mass spectrometry as detailed in Speakman and Krol [45]. In short, water for analysis of 2 H and 18 O was obtained by vacuum distilling blood samples into glass Pasteur pipettes [46].

Isotope ratios were then determined by gas source isotope mass spectrometry IRMS with isotopically characterized gases of H 2 and CO 2 in the reference channels. Hydrogen samples were run on an Isoprime mass spectrometer Isoprime Ltd, Cheadle hulme, UK and oxygen samples were run on a Micromass µG mass spectrometer Micromass ltd, Manchester, UK.

In both cases the samples were ordered according to their expected enrichment and run from high to low enrichment.

The samples were preceded by three characterized working standards whose enrichments had been previously established by reference to the international IAEA standards SMOW and SLAP.

These three working standards were run at the start and end of each batch of samples. In the initial standard set the order was low to high, this was followed by the samples running high to low, and then the final batch of standards was also run low to high.

This ordering minimized large isotope changes between samples to minimize memory effects. The measured enrichments of the standards were compared to their established enrichments to generate a correction at the start and end of each run.

This allowed us to correct for machine drift throughout the measurements of each batch of samples. A typical run would include 30—40 samples 15 to 20 duplicates bracketed between the standards which were run in quintuplicate.

Enrichment of the injectate was estimated by a dilution series with tap water and mass spectrometric analysis of 5 subsamples of each solution [45]. We calculated rates of CO 2 -production using a single pool model as recommended for this size of animal [40] , [48].

Initial body water was determined from the 18 O dilution space which was calculated by the plateau method [40]. Final body water was inferred from final body mass and assuming a similar fraction of body water throughout the measurement period.

The rate of CO 2 -production was converted into estimates of FMR W using a caloric equivalent of This represents the mean conversion factor derived from year-specific factors based on dietary information and estimated over 5 study years for kittiwakes at the same colony [51].

Variation among year-specific conversion factors was negligible [CV: 0. In , we determined both tT3 and unbound free T3 fT3 concentrations at the Institute of Arctic Biology, Fairbanks, by radioimmunoassay based on a commercially available kit MP Biomedicals optimized for our study species.