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Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome
Open accessAbstract
OBJECTIVE: Diabetes prevalence and incidence increase among individuals with hypothyroidism but also among those with hyperthyroxinemia, which seems contradictory. Both high free thyroxine (fT4) and high thyroid-stimulating hormone (TSH) are present in the resistance to thyroid hormone syndrome. A mild acquired resistance to thyroid hormone might occur in the general population and be associated with diabetes. We aimed to analyze the association of resistance to thyroid hormone indices (the Thyroid Feedback Quantile-based Index [TFQI], proposed in this work, and the previously used Thyrotroph T4 Resistance Index and TSH Index) with diabetes. RESEARCH DESIGN AND METHODS: We calculated the aforementioned resistance to thyroid hormone indices based on a U.S. representative sample of 5,129 individuals ≥20 years of age participating in the 2007–2008 National Health and Nutrition Examination Survey (NHANES). Also, to approximate TFQI, a U.S.-referenced Parametric TFQI (PTFQI) can be calculated with the spreadsheet formula =NORM.DIST(fT4_cell_in_pmol_per_L,10.075,2.155,TRUE)+NORM.DIST(LN(TSH_cell_in_mIU_per_L),0.4654,0.7744,TRUE)−1. Outcomes of interest were glycohemoglobin ≥6.5%, diabetes medication, diabetes-related deaths (diabetes as contributing cause of death), and additionally, in a fasting subsample, diabetes and metabolic syndrome. Logistic and Poisson regressions were adjusted for sex, age, and race/ethnicity. RESULTS: Odd ratios for the fourth versus the first quartile of TFQI were 1.73 (95% CI 1.32, 2.27) (Ptrend = 0.002) for positive glycohemoglobin and 1.66 (95% CI 1.31, 2.10) (Ptrend = 0.001) for medication. Diabetes-related death rate ratio for TFQI being above versus below the median was 4.81 (95% CI 1.01, 22.94) (Ptrend = 0.015). Further adjustment for BMI and restriction to normothyroid individuals yielded similar results. Per 1 SD in TFQI, odds increased 1.13 (95% CI 1.02, 1.25) for diabetes and 1.16 (95% CI 1.02, 1.31) for metabolic syndrome. The other resistance to thyroid hormone indices showed similar associations for diabetes-related deaths and metabolic syndrome. CONCLUSIONS: Higher values in resistance to thyroid hormone indices are associated with obesity, metabolic syndrome, diabetes, and diabetes-related mortality. Resistance to thyroid hormone may reflect energy balance problems driving type 2 diabetes. These indices may facilitate monitoring treatments focused on energy balance.
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“Population-based reference intervals for thyroid test variables are, therefore, much broader than the rather narrow within-subject variance and consequently are less useful for monitoring an individual patient.108–113”
In the citing paper
“Results from systematic studies in healthy mono- and dizygotic twins, repetitive sampling studies, and the testing of individuals or (sub-)populations in different regions have shown markedly narrower within-subject variability (e.g., during monthly sampling) than between-subject variations.”
In the citing paper
“Such studies reveal that heritability accounts for 30% to 65% of the variance in TSH, fT4, fT3, and the fT4 × TSH product.”
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Reduced Sensitivity to Thyroid Hormone Is Associated with Diabetes and Hypertension
Mehran, L., Delbari, N., Amouzegar, A., Hasheminia, M., Tohidi, M., & Azizi, F. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab646 · Cited by 116
Sun, Y. J., Teng, D., Zhao, L., Shi, X., Li, Y., Shan, Z., Teng, W., & the Thyroid Disorders, I. S. A. D. E. S. G. (. (2022) · Thyroid · doi:10.1089/thy.2021.0500 · Cited by 100
Van Uytfanghe, K., Ehrenkranz, J., Halsall, D., Hoff, K., Loh, T. P., Spencer, C. A., Köhrle, J., & ATA Thyroid Function Tests Writing Group (2023) · Thyroid® · doi:10.1089/thy.2023.0169 · Cited by 100
“113”
Sensitivity to Thyroid Hormone Indices Are Closely Associated With NAFLD
Lai, S., Li, J., Wang, Z., Wang, W., & Guan, H. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.766419 · Cited by 71
Sensitivity to Thyroid Hormones and Risk of Prediabetes: A Cross-Sectional Study
Liu, B., Wang, Z., Fu, J., Guan, H., Lyu, Z., & Wang, W. J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.657114 · Cited by 67
Metadata
- Authors
- Laclaustra, M., Moreno-Franco, B., Lou-Bonafonte, J. M., Mateo-Gallego, R., Casasnovas, J. A., Guallar-Castillon, P., Cenarro, A., & Civeira, F.
- Affiliations
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Universidad de Zaragoza, Zaragoza, Spain
- Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid-IdiPaz, and CIBERESP, Madrid, Spain
- Universidad de Zaragoza (ES)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2018-12-14
- Volume
- 42
- Issue
- 2
- Pages
- 303-310
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2904867458
- Cited by
- 322
- References
- 40
- Citations by year
- 2026: 53 · 2025: 70 · 2024: 82 · 2023: 60 · 2022: 31 · 2021: 14 · 2020: 9 · 2019: 3
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- green
- zaguan.unizar.es
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Zaguan (University of Zaragoza Repository) (submittedVersion, cc-by)
- Funders
- Instituto de Salud Carlos III (PI14/00009, PI17/01709)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- thyroid hormone resistance, thyroid feedback quantile-based index, thyroid-stimulating hormone, free thyroxine, diabetes mellitus, metabolic syndrome, diabetes mortality, obesity, energy balance, type 2 diabetes
- MeSH terms
- Adult, Aged, Aged, 80 and over, Diabetes Mellitus, Type 2, Female, Humans, Hyperthyroidism, Hypothyroidism, Male, Middle Aged, Mortality, Nutrition Surveys, Obesity, Thyroid Hormones, Thyrotropin, United States, Incidence, Prevalence, Thyroid Hormone Resistance Syndrome, Metabolic Syndrome, Young Adult
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