Cited by 322Thyroid Disorders and TreatmentsDiabetes, Cardiovascular Risks, and LipoproteinsGrowth Hormone and Insulin-like Growth Factors

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Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome

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Laclaustra, Martin, Moreno-Franco, Belen, Lou-Bonafonte, Jose Manuel, Mateo-Gallego, Rocio, Casasnovas, Jose Antonio, Guallar-Castillon, Pilar, Cenarro, Ana, Civeira, Fernando·2019·Diabetes Care

DOI 10.2337/dc18-1410

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Abstract

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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Self-citation
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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)
ORCID: Laclaustra, Martin
Cenarro, Ana
Civeira, Fernando
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
DOI: 10.2337/dc18-1410
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
Licence: cc-by
www.diabetesjournals.org/content/license (vor, 38 d)
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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Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome

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