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

Abstract

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.

A systematic review and meta-analysis investigating the relationship between metabolic syndrome and the incidence of thyroid diseases

“…Although it is widely accepted that there is an association between type 1 diabetes and thyroid dysfunction, and consequently guidelines recommend screening individuals with type 1 diabetes for thyroid disorders [ 38 ], the association is less evident for type 2 diabetes. Results from cross-sectional studies and longitudinal studies assessing the risk of diabetes among individuals with thyroid disorders have been inconclusive [ 12 , 19 , 20 , 22 , 39 – 41 ]. However, very few studies have assessed the association in the inverse direction, i.e., by examining whether individuals with type 2 diabetes are at an increased risk of developing thyroid disease.…”

“…However, the temporal relationship between thyroid disorders and MetS remains unclear [ 18 ]. Evidence from longitudinal studies in this field is relatively scarce, and most studies have investigated whether thyroid disorders are prospectively associated with the development of MetS or its components [ 19 – 22 ]. Interestingly, one study reported evidence of an association between subclinical hypothyroidism and prevalent, but not incident, MetS [ 20 ].…”

Subclinical Hypothyroidism in Patients with Obesity and Metabolic Syndrome: A Narrative Review

“…Thyroid hormone (TH) controls food intake by regulating appetite and thermogenesis and influences glucose and lipid metabolism and adipogenesis [ 5 ]. MetS, obesity and SHypo are frequent conditions among the adult population and to date, various studies and meta-analyses have been published to assess the relationship between these disorders with controversial results [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. Some meta-analyses assessed the relationship between SHypo and MetS, as well as its components.…”

Helicobacter pylori infection increase the risk of subclinical hyperthyroidism in middle-aged and elderly women independent of dietary factors: Results from the Tianjin chronic low-grade systemic inflammation and health cohort study in China

“…The common causes of subclinical hyperthyroidism include toxic multinodular goiter, toxic adenoma, Graves’ disease, and some exogenous causes ( 4 ). The prevalence of subclinical hyperthyroidism in the general population is 1%–3% ( 5 , 6 ), which varies by age, sex, race, genetic predisposition, iodine status, and the definition of subclinical hyperthyroidism ( 7 ). Women, older individuals, and those living in iodine-deficient regions were more frequent ( 8 ).…”