Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The relationship of the anti-oxidant bilirubin with free thyroxine is modified by insulin resistance in euthyroid subjects.

ABSTRACT:

Background

The strong anti-oxidative properties of bilirubin largely explain its cardioprotective effects. Insulin resistance is featured by low circulating bilirubin. Thyroid hormone affects both bilirubin generation and its biliary transport, but it is unknown whether circulating bilirubin is associated with thyroid function in euthyroid subjects. Aim is to determine relationships of bilirubin with TSH, free T4 and free T3 in euthyroid subjects without type 2 diabetes mellitus (T2DM), and to assess whether such a relationship would be modified by the degree of insulin resistance.

Methods

Total bilirubin, TSH, free T4, free T3, glucose, insulin, lipids and transaminases were measured in 1854 fasting euthyroid subjects without T2DM, recruited from the general population (PREVEND cohort). Insulin resistance was assessed by homeostasis model assessment.

Results

Bilirubin was positively related to free T4 (β = 0.116, P<0.001) and free T3 (β = 0.078, P = 0.001), but bilirubin was unrelated to TSH. The relationship of bilirubin with free T4 was modified by insulin resistance with a larger effect in more insulin resistant individuals (adjusted for age and sex: β = 0.043, P = 0.056 for interaction; additionally adjusted for smoking, alcohol intake, transaminases and total cholesterol (β = 0.044, P = 0.044 for interaction). The association of bilirubin with free T4 was also modified by high density lipoprotein cholesterol (age- and sex-adjusted: β = 0.040, P = 0.072).

Conclusions

Low bilirubin relates to low free T4 in euthyroid non-diabetic subjects. Low normal free T4 may particularly confer low bilirubin in more insulin resistant individuals.

SUBMITTER: Deetman PE

PROVIDER: S-EPMC3940953 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Association between Lower Normal Free Thyroxine Concentrations and Obesity Phenotype in Healthy Euthyroid Subjects.

Project description:We investigated whether thyroid function could identify obesity phenotype in euthyroid subjects. A cross-sectional analysis was performed among nondiabetic, euthyroid subjects. We stratified subjects into four groups by BMI and insulin resistance (IR). Of 6241 subjects, 33.8% were overweight or obese (OW/OB) and 66.2% were normal weight (NW). Free thyroxine (FT4) levels were negatively associated with body mass index, waist circumference, triglyceride, c-reactive protein, and HOMA-IR and positively with high-density lipoprotein cholesterol in both genders. In multivariate regression analysis, FT4 level, a continuous measurement, was negatively correlated with HOMA-IR (? = -0.155, P < 0.001 in men; ? = -0.175, P < 0.001 in women). After adjustment for age, sex, metabolic, and life style factors, subjects in the lowest FT4 quartile had an odds ratio (OR) for IR of 1.99 (95% confidence interval 1.61-2.46), as compared to those in the highest quartile. The association between low FT4 and IR remained significant in both NW and OW/OB subgroups. In conclusion, low normal FT4 levels were independently related to IR in NW and OW/OB euthyroid subjects. Further studies are needed to investigate the mechanisms by which low FT4 levels are linked to high IR in euthyroid ranges.

| S-EPMC4024385 | biostudies-literature

Association of free thyroxine with obstructive lung pattern in euthyroid middle-aged subjects: A population-based study.

Project description:BackgroundThe association between thyroid hormone levels and pulmonary function in euthyroid population is still unclear. We aimed to examine the relationship between thyroid function and lung function in a large cohort study of euthyroid subjects.MethodsWe analyzed biochemical and spirometry data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 1,261 middle-aged participants aged 45-65 years with spirometry tests and normal thyroid function were included in this study. The subjects were grouped according to free thyroxine (fT4) (ng/dL) quartiles (Q1, 0.89-1.09; Q2, 1.10-1.19; Q3, 1.20-1.30; Q4, 1.31-1.76). Obstructive lung pattern was defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) <0.7. The probability of obstructive lung patterns according to fT4 quartiles was assessed using logistic regression models, adjusted for potential confounders.ResultsOverall, 10.9% of the subjects had an obstructive lung pattern. The mean fT4 levels were significantly higher in those with obstructive lung pattern than in those with normal lung function (1.26 vs. 1.20 ng/dL, p<0.001). The proportion of participants with obstructive lung pattern increased across the fT4 quartile categories (p<0.001). With the Q1 group as reference, the multivariate-adjusted odds ratios (95% confidence intervals) for obstructive lung pattern in the Q3 and Q4 groups were 2.875 (1.265-6.535) and 2.970 (1.287-6.854), respectively, even after adjusting for confounding variables.ConclusionHigh fT4 levels are an independent predictor of obstructive lung pattern in euthyroid middle-aged subjects. Further prospective studies are needed to confirm these findings.

| S-EPMC9307150 | biostudies-literature

Low-Normal Free Thyroxine Levels in Euthyroid Male Are Associated with Prediabetes.

Project description:Abnormal thyroid function is associated with impaired glucose homeostasis. This study aimed to determine whether free thyroxine (FT4) influences the prevalence of prediabetes in euthyroid subjects using a cross-sectional survey derived from the Korea National Health and Nutrition Examination Survey, conducted between 2013 and 2015. We studied 2,399 male participants of >20 years of age who were euthyroid and non-diabetic. Prediabetic participants had lower FT4 concentrations than those without prediabetes, but their thyrotropin concentrations were similar. We stratified the population into tertiles according to FT4 concentration. After adjusting for multiple confounding factors, glycosylated hemoglobin (HbA1c) levels significantly decreased with increasing FT4 tertile, whereas fasting plasma glucose (FPG) levels were not associated with FT4 tertiles (HbA1c, P<0.01 in T3 vs. T1; FPG, P=0.489 in T3 vs. T1). The prevalence of prediabetes was significantly higher in T1 (odds ratio, 1.426; 95% confidence interval, 1.126 to 1.806; P<0.01) than in T3. In conclusion, subjects with low-normal serum FT4 had high HbA1c and were more likely to have prediabetes. These results suggest that low FT4 concentration is a risk factor for prediabetes in male, even when thyroid function is within the normal range.

| S-EPMC6834837 | biostudies-literature

Association between Serum Free Thyroxine and Anemia in Euthyroid Adults: A Nationwide Study.

Project description:BACKGROUND:Studies on the relationship between thyroid function and anemia in the euthyroid range are scarce. We aimed to evaluate the association between anemia and serum free thyroxine (fT4) and thyrotropin (TSH) in euthyroid adults. METHODS:Data on 5,352 participants aged ?19 years were obtained from the Korea National Health and Nutrition Examination Survey VI (2013 to 2015). Anemia was defined as hemoglobin (Hb) <13 and <12 g/dL for men and women, respectively. RESULTS:Overall, 6.1% of participants had anemia, and more women (9.9%) had anemia than men (2.8%, P<0.001). In multivariate analysis, serum fT4 levels, but not TSH, were positively associated with serum Hb levels in both sexes (P<0.001, each). Serum Hb levels linearly reduced across decreasing serum fT4 quartile groups in both sexes (P<0.001, each). After adjusting for potential confounding factors, participants with low-normal fT4 had 4.4 (P=0.003) and 2.8 times (P<0.001) higher risk for anemia than those with high-normal fT4 among men and women, respectively. When participants were divided into two groups at 50 years of age, in younger participants, men and women with the first quartile were at higher risk of anemia than men with the second quartile (odds ratio [OR], 3.3; P=0.029) and women with the forth quartile (OR, 3.2; P<0.001), respectively. This association was not observed in older participants. CONCLUSION:These results suggest that a low-normal level of serum fT4 was associated with a lower serum Hb level and a higher risk of anemia in euthyroid adults, especially in younger participants.

| S-EPMC7090294 | biostudies-literature

Free Thyroxine Levels are Associated with Cold Induced Thermogenesis in Healthy Euthyroid Individuals.

Project description:Thyroid hormone (TH) is an important regulator of mammalian metabolism and facilitates cold induced thermogenesis (CIT) in brown adipose tissue (BAT). Profound hypothyroidism or hyperthyroidism lead to alterations in BAT function and CIT. In euthyroid humans the inter-individual variation of thyroid hormones is relatively large. Therefore, we investigated whether levels of free thyroxine (T4) or free triiodothyronine (T3) are positively associated with CIT in euthyroid individuals. We performed an observational study in 79 healthy, euthyroid volunteers (mean age 25.6 years, mean BMI 23.0 kg · m-2). Resting energy expenditure (REE) was measured by indirect calorimetry during warm conditions (EEwarm) and after a mild cold stimulus of two hours (EEcold). CIT was calculated as the difference between EEcold and EEwarm. BAT activity was assessed by 18F-FDG-PET after a mild cold stimulus in a subset of 26 participants. EEcold and CIT were significantly related to levels of free T4 (R2 = 0.11, p=0.0025 and R2 = 0.13, p=0.0011, respectively) but not to free T3 and TSH. Cold induced BAT activity was also associated with levels of free T4 (R2 = 0.21, p=0.018). CIT was approximately fourfold higher in participants in the highest tertile of free T4 as compared to the lowest tertile. Additionally, free T4 was weakly, albeit significantly associated with outdoor temperature seven days prior to the respective study visit (R2 = 0.06, p=0.037). These finding suggests that variations in thyroid hormone levels within the euthyroid range are related to the capability to adapt to cool temperatures and affect energy balance.

| S-EPMC8236885 | biostudies-literature

Predictive Value of Free Triiodothyronine to Free Thyroxine Ratio in Euthyroid Patients With Myocardial Infarction With Nonobstructive Coronary Arteries.

Project description:BackgroundThyroid function is closely involved in cardiovascular diseases. The free triiodothyronine (fT3) to free thyroxine (fT4) ratio has been reported as a risk factor for coronary artery disease, but its prognostic value in euthyroid patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) remains unclear.MethodsA total of 1162 euthyroid patients with MINOCA were enrolled and divided according to decreased tertiles of fT3/fT4 ratio. The study endpoint was major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier, Cox regression, and receiver-operating characteristic analyses were performed.ResultsPatients with lower fT3/fT4 tertile levels had a significantly higher incidence of MACE (10.0%, 13.9%, 18.2%; p=0.005) over the median follow-up of 41.7 months. The risk of MACE increased with the decreasing fT3/fT4 tertiles even after multivariate adjustment (tertile1 as reference, tertile2: HR 1.58, 95% CI: 1.05-2.39, p=0.030; tertile3: HR 2.06, 95% CI: 1.17-3.11, p=0.006). Lower level of fT3/fT4 ratio remained a robust predictor of MACE in overall (HR 1.64, 95% CI: 1.18-2.29, p=0.003) and in subgroups. When adding fT3/fT4 ratio [area under the curve (AUC) 0.61] into the thrombolysis in myocardial infarction (TIMI) risk score (AUC 0.69), the combined model (AUC 0.74) yielded a significant improvement in discrimination for MACE (ΔAUC 0.05, p=0.023).ConclusionsLow level of fT3/fT4 ratio was strongly associated with a poor prognosis in euthyroid patients with MINOCA. Routine assessment of fT3/fT4 ratio may facilitate risk stratification in this specific population.

| S-EPMC8356082 | biostudies-literature

Alteration of Serum Proteome in Levo-Thyroxine-Euthyroid Thyroidectomized Patients.

Project description:The monotherapy with levo-thyroxine (LT4) is the treatment of choice for patients with hypothyroidism after thyroidectomy. However, many athyreotic LT4-treated patients with thyroid hormones in the physiological range experience hypothyroid-like symptoms, showing post-operative, statistically significant lower FT3 levels with respect to that before total thyroidectomy. Since we hypothesized that the lower plasmatic FT3 levels observed in this subgroup could be associated with tissue hypothyroidism, here we compared, by a preliminary proteomic analysis, eight sera of patients with reduced post-surgical FT3 to eight sera from patients with FT3 levels similar to pre-surgery levels, and six healthy controls. Proteomic analysis highlights a different serum protein profile among the considered conditions. By enrichment analysis, differential proteins are involved in coagulation processes (PLMN-1.61, -1.98 in reduced vs. stable FT3, p < 0.02; A1AT fragmentation), complement system activation (CFAH + 1.83, CFAB + 1.5, C1Qb + 1.6, C1S + 7.79 in reduced vs. stable FT3, p < 0.01) and in lipoprotein particles remodeling (APOAI fragmentation; APOAIV + 2.13, p < 0.003), potentially leading to a pro-inflammatory response. This study suggests that LT4 replacement therapy might restore biochemical euthyroid conditions in thyroidectomized patients, but in some cases without re-establishing body tissue euthyroidism. Since our results, this condition is reflected by the serum protein profile.

| S-EPMC8951767 | biostudies-literature

The Extent of Intracellular Accumulation of Bilirubin Determines Its Anti- or Pro-Oxidant Effect.

Project description:Severe hyperbilirubinemia can cause permanent neurological damage in particular in neonates, whereas mildly elevated serum bilirubin protects from various oxidative stress-mediated diseases. The present work aimed to establish the intracellular unconjugated bilirubin concentrations (iUCB) thresholds differentiating between anti- and pro-oxidant effects. Hepatic (HepG2), heart endothelial (H5V), kidney tubular (HK2) and neuronal (SH-SY5Y) cell lines were exposed to increasing concentration of bilirubin. iUCB, cytotoxicity, intracellular reactive oxygen species (ROS) concentrations, and antioxidant capacity (50% efficacy concentration (EC50)) were determined. Exposure of SH-SY5Y to UCB concentration > 3.6 µM (iUCB of 25 ng/mg) and >15 µM in H5V and HK2 cells (iUCB of 40 ng/mg) increased intracellular ROS production (p < 0.05). EC50 of the antioxidant activity was 21 µM (iUCB between 5.4 and 21 ng/mg) in HepG2 cells, 0.68 µM (iUCB between 3.3 and 7.5 ng/mg) in SH-SY5Y cells, 2.4 µM (iUCB between 3 and 6.7 ng/mg) in HK2 cells, and 4 µM (iUCB between 4.7 and 7.5 ng/mg) in H5V cells. In all the cell lines studied, iUCB of around 7 ng/mg protein had antioxidant activities, while iUCB > 25 ng/mg protein resulted in a prooxidant and cytotoxic effects. UCB metabolism was found to be cell-specific resulting in different iUCB.

| S-EPMC7663266 | biostudies-literature

Higher Muscle Mass Implies Increased Free-Thyroxine to Free-Triiodothyronine Ratio in Subjects With Overweight and Obesity.

Project description:Thyroid hormones control both metabolic pathways and body composition, whereas little knowledge is available about the possible influence of skeletal muscle mass (MM) on thyroid hormone metabolism and circulating levels. This was a cross-sectional study conducted at the Population Health Unit of the National Institute of Gastroenterology IRCCS "S. de Bellis" (Italy) and investigating the extent to which skeletal MM affects thyroid function in obesity. Two hundred twenty-seven consecutive healthy volunteers (155 women and 72 men) with overweight and obesity (BMI ? 25 kg/m2) and taking no medication or supplement were assessed for hormone, metabolic and routine laboratory parameters. Body composition parameters were collected by using bioelectrical impedance analysis (BIA). MM was directly related to the body mass index (BMI), waist circumference (WC), insulin, triglycerides, uric acid and free-triiodothyronine (FT3) serum levels, FT3 to the free-thyroxine (FT4) ratio, and insulin-resistance (HOMA-IR), and inversely related to age, total, and HDL-cholesterol serum levels. Multiple regression models confirmed the relationship between MM and the FT3 to FT4 ratio, independently of age, BMI, TSH, triglycerides, and insulin serum levels. The same analyses run by gender showed that this relationship maintained significance only in men. Increased skeletal MM in obesity results in improved thyroid activity mediated by increased T4 conversion to T3, and higher FT3 circulating levels, particularly in men. In conclusion, preserving a greater skeletal MM in obesity helps to enhance thyroid activity. Clinical Trial Registration:ClinicalTrials.gov, identifier NCT04327375.

| S-EPMC7553046 | biostudies-literature

Advances in applied homeostatic modelling of the relationship between thyrotropin and free thyroxine.

Project description:INTRODUCTION:The relationship between pituitary TSH and thyroid hormones is central to our understanding of thyroid physiology and thyroid function testing. Here, we generated distribution patterns by using validated tools of thyroid modelling. METHODS:We simulated patterns of individual set points under various conditions, based on a homeostatic model of thyroid feedback control. These were compared with observed data points derived from clinical trials. RESULTS:A random mix of individual set points was reconstructed by simulative modelling with defined structural parameters. The pattern displayed by the cluster of hypothetical points resembled that observed in a natural control group. Moderate variation of the TSH-FT4 gradient over the functional range introduced further flexibility, implementing a scenario of adaptive set points. Such a scenario may be a realistic possibility for instance in treatment where relationships and equilibria between thyroid parameters are altered by various influences such as LT4 dose and conversion efficiency. CONCLUSIONS:We validated a physiologically based homeostatic model that permits simulative reconstruction of individual set points. This produced a pattern resembling the observed data under various conditions. Applied modelling, although still experimental at this stage, shows a potential to aid our physiological understanding of the interplay between TSH and thyroid hormones. It should eventually benefit personalised clinical decision making.

| S-EPMC5695809 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data