Objective: Few prospective studies have assessed whether persons with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. We conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroid dysfunction and incident diabetes.
Methods: We performed a systematic review of the literature in Medline, Embase, and the Cochrane Library from inception to February 11 2022. A two-stage individual participant data analysis was conducted to compare participants with subclinical hypothyroidism and subclinical hyperthyroidism versus euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up.
Results: Among 61,178 adults from 18 studies, mean age was 58 years, 49% were females, and mean follow-up time was 8.2 years. At last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (OR=1.02, 95% confidence interval (CI): 0.88-1.17, I2=0%), or subclinical hyperthyroidism and incidence of diabetes (OR=1.03, 95% CI: 0.82-1.30, I2=0%), in age- and sex-adjusted analyses. Time-to-event analysis showed similar results (hazard ratio for subclinical hypothyroidism: 0.98, 95% CI: 0.87-1.11; hazard ratio for subclinical hyperthyroidism: 1.07, 95% CI: 0.88-1.29). The results were robust in all subgroup and sensitivity analyses.
Conclusions: This is the largest systematic review and individual participant data analysis to date investigating the prospective association between subclinical thyroid dysfunction and diabetes. We did not find an association between subclinical thyroid dysfunction and incident diabetes. Our results do not support screening patients with subclinical thyroid dysfunction for diabetes.