Thyroid hormone status in women at mid-life: Its roles in insulin resistance, obesity and inflammation.

Abstract

<italic>Objective</italic>. This three paper dissertation reports an investigation of the association between thyroid function and insulin resistance, metabolic syndrome and C-reactive protein, all risk factors for type 2 diabetes and cardiovascular disease. <italic>Research design and methods</italic>. The first study examined the association between thyroid function and its interaction with gender in relation to insulin resistance and metabolic syndrome. Subjects included individuals over 39 years of age from the Third National Health and Nutrition Examination Survey (NHANES III), a cross-sectional health survey (1988-1994) of a representative sample of the U.S. population. The second study described the 4-year change in serum thyroid-stimulating hormone (TSH) in mid-aged women and related the baseline TSH and change in TSH to insulin resistance using 5-year data from The Study of Women's Health Across the Nation (SWAN), a multi-ethnic study of the natural history of menopausal transition. The third study examined the influence of TSH and thyroid function on the association between body mass index (BMI) and 5-year change in C-reactive protein (hsCRP) in the SWAN population. <italic>Results</italic>. The analyses of NHANES III data did not reveal a significant association between TSH and insulin resistance, overall or by gender. However, individuals had a 2% (adjusted odds ratio 1.02, 95% CI, 1.00-1.03) increase in the odds of having metabolic syndrome for each 1 mU/L increase in serum TSH (p<0.01). Euthyroid individuals had a 14% (adjusted OR 1.14, 95% CI, 1.06-1.23) increase in the odds of having metabolic syndrome for every 1mU/L increase in serum TSH (p<0.01). In the SWAN population, higher baseline TSH was associated with a greater annual increase in insulin resistance (beta=0.035, 95% CI, 0.004-0.102, p<0.03). Women with baseline subclinical hypothyroidism had a greater 5-year increase in hsCRP with increasingly greater BMI as compared to euthyroid women (p=0.05 for interaction term). The BMI-TSH interaction was not significant, however, in women who used exogenous reproductive hormones at anytime during the study. Chinese and Hispanic women were more likely to have an undiagnosed TSH > 5.0 uIU/ml (OR=2.75, 95%CI 1.52-5.02 and OR=1.7, 95%CI 0.75-3.85, respectively) while African American women were more likely to have an undiagnosed TSH < 0.1 (OR=1.7, 95%CI 0.43-6.80) as compared to Caucasian women. <italic>Conclusion</italic>. We demonstrated an important the role of thyroid disease in health as it relates to type 2 diabetes and cardiovascular disease through the influence of TSH on insulin resistance and chronic inflammation.