Association between thyroid dysfunction and type 2 diabetes: a meta-analysis of prospective observational studies

Background: Diabetes mellitus and thyroid disease are two areas of broad interest in the field of endocrinology and metabolism. Variation of thyroid hormone concentration, even within the normal range, may portend the onset of type 2 diabetes mellitus (T2DM), especially among those with prediabetes. However, current evidence is mixed. Methods: Prospective studies which assessed diabetes incidence were identified using a database search of MEDLINE and Embase through May 1, 2021. The Sidik-Jonkman random-effects model and cubic spline model were used to evaluate the associations and dose-response relationships between thyroid function/hormone levels and risk of T2DM and cardiovascular disease (CVD) risk among T2DM patients. Results: A total of 12 prospective studies were included. We found that high baseline TSH levels were related to a 17% higher risk of T2DM (RR 1.17, 95% CI 1.01, 1.36; I-2=78%, P<0.01), compared with normal TSH levels. Low FT3 (RR 1.40, 95% CI 1.09, 1.80; I-2=59%, P=0.03) and low FT4 (RR 1.33, 95% CI 1.04, 1.71; I-2=62%, P=0.02) levels were significantly associated with risk of T2DM. The cubic spline model indicated a J-shaped relationship with TSH, but inverted-J-shaped relationships with FT3 and FT4. CVD events and all-cause deaths were prospectively evaluated in four studies, but were not associated with abnormal thyroid function. Conclusions: Our meta-analysis determined that abnormal thyroid hormone level is associated with an increased risk of T2DM, showing a J-shaped relationship with TSH and inverted-J-shaped relationships with FT3 and FT4.