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Thyroid Function Is Associated with Components of the Metabolic Syndrome in Euthyroid Subjects

Departments of Endocrinology (A.R., T.P.L., B.H.R.W.) and Internal Medicine (S.J.L.B., R.O.B.G.), University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands

Address all correspondence and requests for reprints to: Bruce H. R. Wolffenbuttel, M.D., Ph.D., Department of Endocrinology, University Medical Center Groningen and University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands. E-mail: bwo{at}int.umcg.nl.

Context: Thyroid disease and the metabolic syndrome are both associated with cardiovascular disease.

Objective: The aim of this study was to explore the hypothesis that thyroid function, in euthyroid subjects, is associated with components of the metabolic syndrome, including serum lipid concentrations and insulin resistance.

Methods: A total of 2703 adult inhabitants of a middle-sized city in The Netherlands participated in this cross-sectional study. Subjects who were not euthyroid were excluded, as were subjects taking thyroid medication, medication for diabetes, and subjects for whom medication data were not available (n = 1122). Homeostasis model assessment for insulin resistance (HOMA-IR) (mU_*mmol/liter²) was calculated as fasting insulin (mU/liter) times fasting glucose (mmol/liter) divided by 22.5. The metabolic syndrome was defined according to National Cholesterol Education Program’s Adult Treatment Panel III criteria.

Results: After adjustment for age and sex, free T₄ (FT4) was significantly associated with total cholesterol [standardized ß (ß) = –0.059; P = 0.014], low-density lipoprotein cholesterol (ß = –0.068; P = 0.004), high-density lipoprotein cholesterol (ß = 0.100; P < 0.001), and triglycerides (ß = –0.102; P < 0.001). Both FT4 and TSH were significantly associated with HOMA-IR (ß = –0.133; P < 0.001 and ß = 0.055; P = 0.024, respectively). Median HOMA-IR increased from 1.42 in the highest tertile of FT4 to 1.66 in the lowest tertile of FT4. FT4 was significantly related to four of five components of the metabolic syndrome (abdominal obesity, triglycerides, high-density lipoprotein cholesterol, and blood pressure), independent of insulin resistance.

Conclusions: We have demonstrated an association between FT4 levels within the normal reference range and lipids, in accordance with the earlier observed association between (sub)clinical hypothyroidism and hyperlipidemia. Moreover, low normal FT4 levels were significantly associated with increased insulin resistance. These findings are consistent with an increased cardiovascular risk in subjects with low normal thyroid function.

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