Fatty liver largely explains associations of subclinical hypothyroidism with insulin resistance, metabolic syndrome, and subclinical coronary atherosclerosis

Abstract

Background: The association of subclinical hypothyroidism (SCH) with insulin resistance, metabolic syndrome (MS), and coronary atherosclerosis is uncertain. Objective: To investigate the role of increased intrahepatic fat in the association of SCH with insulin resistance, MS, and coronary atherosclerosis. Design, patients, and methods: We conducted a cross-sectional study in a sample of 753 subjects (46% males) aged 35-70 years with no history of diabetes, renal, hepatic, thyroid, or coronary heart disease, and were participants of the Genetics of Atherosclerotic Disease study. SCH was defined as a high serum TSH level with normal free thyroxine concentration. Fatty liver (FL), coronary artery calcification (CAC), and abdominal visceral adipose tissue were assessed by computed tomography. Cross-sectional associations of SCH with and without FL, with MS, insulin resistance, and subclinical atherosclerosis defined as a CAC score >0, were examined in logistic regression models. Results: SCH was observed in 17.7% of the population studied. The prevalence of FL was similar in both euthyroid and SCH subjects (31.8 vs 27.8%, P=0.371). SCH plus FL subjects were heavier and had more metabolic abnormalities compared with SCH plus normal liver subjects. In multivariate-adjusted logistic regression analyses, SCH plus FL was associated with MS (odds ratio (OR): 2.73, 95% CI: 1.26-5.92), insulin resistance (OR: 4.91, 95% CI: 1.63-14.75), and CAC score >0 (OR: 3.05, 95% CI: 1.20-7.76). SCH without FL showed no associations. Conclusion: SCH with FL is associated with increased odds of MS, insulin resistance, and CAC, independent of potential confounders.