7158 Incidence Of Undiagnosed Diabetes Mellitus Among Individuals With Thyroid Function Tests Within The Normal Range: A Retrospective NHANES Analysis
Authors: Alvi Zara Zafar , Karnchanasorn Rudruidee , Ou Horng-Yih , Chuang Lee-Ming , Gianoukakis Andrew George , Chiu Ken C 
Published: October 2024

Abstract
Disclosure: Z.Z. Alvi: None. R. Karnchanasorn: None. H. Ou: None. L. Chuang: None. A.G. Gianoukakis: None. K.C. Chiu: None.
The euthyroid state is difficult to determine on an individual level because of individual set point variability within the wide reference ranges. This raises a concern for mild thyroid dysfunction in seemingly euthyroid individuals. The thyroid hormone is one of the key hormonal regulators of energy metabolism, while diabetes mellitus (DM) is a disorder of dysregulated fuel metabolism. Thus, thyroid hormones can affect glucose metabolism. Here, we analyze the incidence of undiagnosed DM using pair combinations of TSH and a thyroid hormone level. We used the National Health and Nutrition Examination Survey 2007-2012 database of representative, noninstitutionalized adults (aged 20 years or older) with available BMI, thyroid function, and defined glucose tolerance states by HbA1c, fasting, or 2-hour post-challenged glucose. Individuals with known thyroid disease and/or known DM were excluded from the study. Based on the tertiles of TSH and the corresponding thyroid hormone, 3x3 tables were constructed. Using the subjects within the second tertile of TSH and the corresponding thyroid hormone as the reference, the odds ratio (OR) for diabetes for each cell was calculated using a sample-weighted analysis. The adjusted ORs were also computed considering age, gender, BMI, race/ethnicity, current smoker, current alcohol consumption, and family history of DM. Among the 6843 qualifying subjects, 488 individuals were found to have undiagnosed DM. The incidence of DM varied across paired TSH/thyroid hormone tertiles. Incidence of DM was 4.77%, 4.13%, and 6.80% (P&lt;0.001) for increasing TSH and decreasing FT4 tertile pairs; 4.15%, 3.08%, and 5.61% (P&lt;0.001) for increasing TSH and decreasing TT4 tertile pairs; 4.13%, 4.64%, and 6.01% (P&lt;0.001) for increasing TSH and decreasing FT3 paired tertiles; and 3.34%, 4.29%, and 6.08% (P&lt;0.001) for increasing TSH and decreasing TT3 tertile pairs. Using the second tertile as a reference, a U-shaped relationship between undiagnosed DM and thyroid function within the normal range was highlighted by the higher Adjusted Odds Ratio (AOD) for the lowest and highest tertile pairs of TSH/Free T4 (1.358; 1.352-1.364 and 1.291; 1.286-1.296 respectively) and TSH/Total T4 (1.605; 1.597-1.613 and 1.631; 1.624-1.638 respectively). For TSH/Free T3 and TSH/Total T3 tertile pairs, increased incidence of DM was noted for the lowest tertiles of TSH paired with the highest FT3 & TT3 tertiles only (1.435; 1.429-1.442 and 1.098; 1.093-1.103 respectively). Sensitivity analysis excluding those with any out-of-range thyroid function levels confirmed the above results. Our results identify a U-shaped relationship between the incidence of undiagnosed DM and thyroid function across the normal reference range. Additional studies are warranted to confirm and further investigate this relationship and its clinical implications.
Presentation: 6/1/2024