Associations between sensitivity to thyroid hormones and insulin resistance in euthyroid adults with obesity
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PROVIDER: S-EPMC11338882 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:The aim was to characterise associations between circulating thyroid hormones-free thyroxine (FT4) and thyrotropin (TSH)-and the metabolite profiles in serum samples from participants of the German population-based KORA F4 study. Analyses were based on the metabolite profile of 1463 euthyroid subjects. In serum samples, obtained after overnight fasting (≥8), 151 different metabolites were quantified in a targeted approach including amino acids, acylcarnitines (ACs), and phosphatidylcholines (PCs). Associations between metabolites and thyroid hormone concentrations were analysed using adjusted linear regression models. To draw conclusions on thyroid hormone related pathways, intra-class metabolite ratios were additionally explored. We discovered 154 significant associations (Bonferroni p < 1.75 × 10-04) between FT4 and various metabolites and metabolite ratios belonging to AC and PC groups. Significant associations with TSH were lacking. High FT4 levels were associated with increased concentrations of many ACs and various sums of ACs of different chain length, and the ratio of C2 by C0. The inverse associations observed between FT4 and many serum PCs reflected the general decrease in PC concentrations. Similar results were found in subgroup analyses, e.g., in weight-stable subjects or in obese subjects. Further, results were independent of different parameters for liver or kidney function, or inflammation, which supports the notion of an independent FT4 effect. In fasting euthyroid adults, higher serum FT4 levels are associated with increased serum AC concentrations and an increased ratio of C2 by C0 which is indicative of an overall enhanced fatty acyl mitochondrial transport and β-oxidation of fatty acids.
| S-EPMC4042025 | biostudies-literature
Project description:BackgroundImpaired sensitivity to thyroid hormones is a newly proposed clinical entity associated with hyperuricemia in the subclinical hypothyroid population. However, it is unknown whether the association exists in the euthyroid population. This study aimed to explore the association of impaired sensitivity to thyroid hormones (assessed by the thyroid feedback quantile-based index [TFQI], parametric thyroid feedback quantile-based index [PTFQI], thyrotrophic thyroxine resistance index [TT4RI] and thyroid-stimulating hormone index [TSHI]) with hyperuricemia and quantify the mediating effect of body mass index BMI in the euthyroid population.MethodsThis cross-sectional study enrolled Chinese adults aged ≥ 20 years who participated in the Beijing Health Management Cohort (2008-2019). Adjusted logistic regression models were used to explore the association between indices of sensitivity to thyroid hormones and hyperuricemia. Odds ratios [OR] and absolute risk differences [ARD] were calculated. Mediation analyses were performed to estimate direct and indirect effects through BMI.ResultsOf 30,857 participants, 19,031 (61.7%) were male; the mean (SD) age was 47.3 (13.3) years; and 6,515 (21.1%) had hyperuricemia. After adjusting for confounders, individuals in the highest group of thyroid hormone sensitivity indices were associated with an increased prevalence of hyperuricemia compared with the lowest group (TFQI: OR = 1.18, 95% CI 1.04-1.35; PTFQI: OR = 1.20, 95% CI 1.05-1.36; TT4RI: OR = 1.17, 95% CI 1.08-1.27; TSHI: OR = 1.12, 95% CI 1.04-1.21). BMI significantly mediated 32.35%, 32.29%, 39.63%, and 37.68% of the associations of TFQI, PTFQI, TT4RI and TSHI with hyperuricemia, respectively.ConclusionsOur research revealed that BMI mediated the association between impaired sensitivity to thyroid hormones and hyperuricemia in the euthyroid population. These findings could provide useful evidence for understanding the interaction between impaired sensitivity to thyroid hormone and hyperuricemia in euthyroid individuals and suggest the clinical implications of weight control in terms of impaired thyroid hormones sensitivity.
| S-EPMC10320931 | biostudies-literature
Project description:The relationship between vitamin D deficiency and sensitivity to thyroid hormones was unclear. We aimed to explore the association of 25-hydroxyvitamin D (25(OH)D) levels with thyroid hormone sensitivity in euthyroid adults. A total of 3143 subjects were included. The serum 25(OH)D, free thyroxine (FT3), free thyrotropin (FT4), thyroid-stimulating hormone (TSH), and other clinical variables were measured. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. Thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyroid-stimulating hormone index (TSHI), thyrotrophic thyroxine resistance index (TT4RI), and FT3/FT4 were calculated to assess thyroid hormone sensitivity. Results showed that 58.8% of the participants had vitamin D deficiency. They had significantly higher levels of triglyceride, insulin, FT3, FT4, TSH, TFQI, PTFQI, TSHI, and TT4RI and lower levels of high-density lipoprotein cholesterol than those with sufficient vitamin D (all p < 0.05). Logistic regression analysis showed that the risk of impaired sensitivity to thyroid hormones evaluated by TFIQ, PTFQI, TSHI, and TT4RI increased by 68% (OR: 1.68; 95%CI: 1.45-1.95; and p < 0.001), 70% (OR: 1.70; 95%CI: 1.46-1.97; and p < 0.001), 66% (OR: 1.66; 95%CI: 1.43-1.92; and p < 0.001), and 50% (OR: 1.50; 95%CI: 1.30-1.74; and p < 0.001), respectively, in participants with vitamin D deficiency compared with those with sufficient vitamin D after adjusting for multiple confounders. In conclusion, in euthyroid populations, vitamin D deficiency was associated with impaired sensitivity to thyroid hormones.
| S-EPMC10490158 | biostudies-literature
Project description:BackgroundAbnormalities in thyroid function affect bowel health. However, the relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation remain unclear. Thus, the aim of this study was to investigate the relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation in euthyroid US adults.MethodsThe data for this population-based study were taken from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 datasets. The relationships between thyroid hormone concentrations and the risk of developing chronic diarrhea and constipation were examined via multivariate regression. Smoothed curve fitting and threshold effects analysis were used to test for nonlinear relationships and inflection points.ResultsThis study involved 4999 participants ranging in age from 20 to 80 years. Multivariate logistic regression analysis revealed a significant positive correlation between FT3 concentrations and the risk of developing chronic diarrhea [1.37 (1.00, 1.88), P=0.049]. Multivariate linear regression analysis revealed a significant positive correlation between FT3 concentrations and the number of bowel movements [0.84 (0.39, 1.28), P<0.001]. Using smoothed curve fitting and the two-stage regression model, we found a nonlinear relationship between FT4 concentrations and chronic diarrhea, with a breakpoint of 0.79 ng/dl.ConclusionsThere were associations between thyroid hormone concentrations and abnormal bowel habits, particularly between FT3 concentrations and the risk of developing chronic diarrhea. A higher FT3 level was associated with an increased risk of developing chronic diarrhea and more frequent bowel movements. To validate our results, further large-scale prospective studies are needed.
| S-EPMC11524803 | biostudies-literature
Project description:Background This study aimed to examine the associations of thyroid hormone sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, thyroid feedback quantile-based index by FT4 (TFQIFT4), thyroid-stimulating hormone index (TSHI), and thyrotrophic thyroxine resistance index (TT4RI) with all-cause mortality in euthyroid adults. Methods The study included 6243 euthyroid adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. FT3/FT4 ratio, TFQIFT4, TSHI, and TT4RI were calculated. The multivariable Cox proportional hazard regression, restricted cubic spline (RCS), and subgroup analysis were conducted. Results Individuals in quartile 4th (Q4) had lower all-cause mortality than those in quartile 1st (Q1) of FT3/FT4 ratio (OR 0.70, 95% CI (0.51, 0.94)). Regarding TFQIFT4, individuals in Q4 of TFQIFT4 had a 43% higher all-cause mortality than those in Q1 (OR 1.43, 95% CI (1.05, 1.96)) (P <0.05, all). Compared with participants in Q1, no associations of TSHI and TT4RI with mortality were found. TFQIFT4 was linearly and positively associated with mortality. However, the FT3/FT4 ratio showed a U-shaped association with mortality. Conclusions Increased risk for all-cause mortality was positively associated with TFQIFT4, suggesting that increased risk for all-cause mortality was associated with decreased central sensitivity to thyroid hormones. Furthermore, the FT3/FT4 ratio showed a U-shaped association with mortality, with an inflection point at 0.5. However, more cohort studies are needed to validate the conclusions.
| S-EPMC10895331 | biostudies-literature
Project description:BackgroundThyroid disease and metabolic syndrome are both associated with cardiovascular disease. The aim of this study was to investigate the correlation between thyroid hormones and obesity sub-phenotypes using nationwide data from Korea, a country known to be iodine replete.MethodsThis study was based on data obtained from the sixth Korea National Health and Nutrition Examination Survey, administered from 2013 to 2015. A total of 13,873 participants aged ≥19 years were included, and classified into four groups: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO) by body fat on the basis of body mass index and metabolic health.ResultsAt baseline, serum free thyroxine (fT4) values were significantly higher in the MHNO phenotype (MHNO, 1.27±0.01 ng/dL; MHO, 1.25±0.01 ng/dL; MUNO, 1.24±0.01 ng/dL; MUO, 1.24±0.01 ng/dL, P<0.001) in total study population. However, this significant association no longer remained after adjustment for age, urine iodine concentration, and smoking (P=0.085). After adjustment for confounders, statistically significant association was observed between lower thyroid stimulating hormone (TSH) and MHNO phenotype (P=0.044). In men participants (not women), higher fT4 values were significantly associated with MHNO phenotype (P<0.001). However, no significant association was observed between thyroid function (TSH or fT4) and obesity phenotypes in groups classified by age (cutoff age of 55 years).ConclusionAlthough there was a difference by age and sex, we found that the decrease of TSH and the increase of fT4 values were associated with MHNO.
| S-EPMC6943265 | biostudies-literature
Project description:AimThyroid dysfunction is closely associated with periodontitis. We aim to explore the association between sensitivity to thyroid hormones (THs) and periodontitis and to investigate the mediating role of serum 25-hydroxyvitamin D[25(OH)D] in this relationship in Chinese euthyroid populations.MethodsThis population-based retrospective study included 2,530 euthyroid participants. Central sensitivity to THs was assessed by the thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyrotrophic thyroxine resistance index (TT4RI) and thyroid-stimulating hormone index (TSHI), while FT3/FT4 was evaluated to assess peripheral sensitivity. Multivariable regression analysis and restricted cubic spline were performed to explore the association between sensitivity to THs and periodontitis. Threshold effect and subgroup analysis were also conducted. Mediation analysis was performed to estimate direct and indirect effects through 25(OH)D.ResultsMultivariable regression analysis indicated that central sensitivity to THs indices(per SD increase) were positively associated with periodontitis risk [TFQI: OR=1.19,95% CI (1.09, 1.31); PTFQI: OR=1.22, 95% CI(1.12,1.34); TSHI: OR=1.36, 95% CI (1.21,1.52); TT4RI: OR=1.43, 95% CI (1.25,1.63)](all P value<0.001). TT4RI only had a non-linear relationship with periodontitis in euthyroid participants. Subgroup analysis showed that no significant correlations were founded among those aged over 65 years or with hypertension/diabetes. Mediation analysis revealed that the proportions mediated by 25(OH)D on the association of TFQI, PTFQI,TSHI, TT4RI and periodontitis risk were 16.37%, 16.43%, 9.93% and 10.21%, respectively.ConclusionsImpaired central sensitivity to THs is positively associated with periodontitis in euthyroid and serum 25(OH)D might be one of its biological mechanisms.
| S-EPMC11557418 | biostudies-literature
Project description:BackgroundThyrotropin (TSH) levels display a positive association with body mass index (BMI), and the prevalence of isolated hyperthyrotropinemia is higher in obese adolescents compared to their normal weight controls. However, the metabolic significance of the higher TSH in obese adolescents is less clear. The objective of this study was to determine the relationship between TSH concentrations and insulin sensitivity, lipids, and adipokines in euthyroid, non-diabetic, obese adolescents.MethodsThirty-six euthyroid, non-diabetic, obese adolescents between the ages of 12 and 18 years underwent a 75 g oral glucose tolerance test. Insulin sensitivity (Si) and pancreatic β-cell function as assessed by disposition index (DI) were measured using the oral glucose minimal model approach. Cholesterol (total, low-density lipoprotein [LDL-C], and high-density lipoprotein [HDL-C]), triglycerides (TG), interleukin-6 (IL-6), total and high molecular weight (HMW) adiponectin, and retinol binding protein-4 (RBP4) were also determined. Associations between measures of thyroid function and Si, DI, lipids, and adipokines were computed using Pearson's correlation coefficient and multiple regression analysis.ResultsThe mean age of the subjects was 14.3±1.88 years, and the mean BMI was 32.5±4.65 kg/m2; 97% were non-Hispanic white and 47% were male. The mean TSH was 2.7±1.2 mIU/L. Increasing serum TSH was correlated with decreasing Si (log Si) in the entire cohort (p=0.03), but this relationship persisted only in males (p=0.02). The correlation between TSH and Si in males remained significant after adjusting for BMI (p=0.02). There was no correlation between TSH and pancreatic β-cell function as assessed by DI (p=0.48). TSH correlated positively with LDL-C (p=0.04) and IL-6 (p=0.03), but these associations vanished or weakened after adjusting for BMI (LDL-C p-value=0.44; IL-6 p-value=0.07).ConclusionsThis study suggests a sex-specific association between TSH and insulin sensitivity in euthyroid, non-diabetic, obese adolescent males. Prospective studies are warranted to explore further this sexual dimorphism in the relationship between thyroid function and insulin sensitivity and to determine if obese adolescents with insulin resistance receiving thyroid supplements for hypothyroidism would benefit from targeting TSH levels in the lower half of normal range.
| S-EPMC4426325 | biostudies-literature
Project description: Not available
| S-EPMC11581855 | biostudies-literature
Project description:Background/aimOperating far from its equilibrium resting point, the thyroid gland requires stimulation via feedback-controlled pituitary thyrotropin (TSH) secretion to maintain adequate hormone supply. We explored and defined variations in the expression of control mechanisms and physiological responses across the euthyroid reference range.MethodsWe analyzed the relational equilibria between thyroid parameters defining thyroid production and thyroid conversion in a group of 271 thyroid-healthy subjects and 86 untreated patients with thyroid autoimmune disease.ResultsIn the euthyroid controls, the FT3-FT4 (free triiodothyronine-free thyroxine) ratio was strongly associated with the FT4-TSH ratio (tau = -0.22, p < 0.001, even after correcting for spurious correlation), linking T4 to T3 conversion with TSH-standardized T4 production. Using a homeostatic model, we estimated both global deiodinase activity and maximum thyroid capacity. Both parameters were nonlinearly and inversely associated, trending in opposite directions across the euthyroid reference range. Within the panel of controls, the subgroup with a relatively lower thyroid capacity (<2.5 pmol/s) displayed lower FT4 levels, but maintained FT3 at the same concentrations as patients with higher functional and anatomical capacity. The relationships were preserved when extended to the subclinical range in the diseased sample.ConclusionThe euthyroid panel does not follow a homogeneous pattern to produce random variation among thyroid hormones and TSH, but forms a heterogeneous group that progressively displays distinctly different levels of homeostatic control across the euthyroid range. This suggests a concept of relational stability with implications for definition of euthyroidism and disease classification.
| S-EPMC5091265 | biostudies-literature