Subclinical thyroid dysfunction and incident diabetes: a systematic review and an individual participant data analysis of prospective cohort studies

Heba Alwan, Fanny Villoz, Martin Feller, Robin P.F. Dullaart, Stephan J.L. Bakker, Robin P. Peeters, Maryam Kavousi, Douglas C. Bauer, Anne R. Cappola, Bu B. Yeap, John P. Walsh, Suzanne J. Brown, Graziano Ceresini, Luigi Ferrucci, Jacobijn Gussekloo, Stella Trompet, Massimo Iacoviello, Jae Hoon Moon, Salman Razvi, Isabela M. BensenorFereidoun Azizi, Atieh Amouzegar, Sergio Valdés, Natalia Colomo, Nick J. Wareham, J. Wouter Jukema, Rudi G.J. Westendorp, Ki Woong Kim, Nicolas Rodondi, Cinzia Del Giovane

Research output: Contribution to journalReview articlepeer-review

Abstract

Objective: Few prospective studies have assessed whether individuals with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. In this study, 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 vs euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up. Results: Among 61 178 adults from 18 studies, 49% were females, mean age was 58 years, and mean follow-up time was 8.2 years. At the last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (odds ratio (OR) = 1.02, 95% 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 sub-group 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. Significance statement: Evidence is conflicting regarding whether an association exists between subclinical thyroid dysfunction and incident diabetes. We therefore aimed to investigate whether individuals with subclinical thyroid dysfunction are more prone to develop diabetes in the long run as compared to euthyroid individuals. We included data from 18 international cohort studies with 61 178 adults and a mean follow-up time of 8.2 years. We did not find an association between subclinical hypothyroidism or subclinical hyperthyroidism at baseline and incident diabetes at follow-up. Our results have clinical implications as they neither support screening patients with subclinical thyroid dysfunction for diabetes nor treating them in the hope of preventing diabetes in the future.

Original languageEnglish
Pages (from-to)S35-S46
Number of pages12
JournalEuropean Journal of Endocrinology
Volume187
Issue number5
DOIs
Publication statusPublished - 1 Nov 2022

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