Prevalence and Incidence of Thyroid Dysfunction in Type 1 Diabetes, Type 2 Diabetes and Latent Autoimmune Diabetes of Adults

The Fremantle Diabetes Study Phase II

Kirsten E. Peters; Stephen A. Paul Chubb; David G. Bruce; Wendy A. Davis; Timothy M. E. Davis

Disclosures

Clin Endocrinol. 2020;92(4):373-382. 

In This Article

Materials and Methods

Patients

The FDS2 is a prospective community-based study of 1668 people with diabetes.[23] Details of recruitment and data collection have been published.[23,24] In brief, classification of diabetes type was based on age at diagnosis, nature of first presentation, diabetes treatment history, body mass index (BMI), evidence of ketonaemia, autoantibody positivity, serum insulin and C-peptide concentrations, and genotyping in those with high monogenic diabetes risk scores.[24] There were 1617 eligible participants, including 130 (8.0%) with type 1 diabetes, 1408 (87.1%) with type 2 diabetes, and 79 (4.9%) with latent autoimmune diabetes of adults (LADA). Patients with secondary/monogenic diabetes, taking amiodarone/lithium, or with missing medication data/blood samples were excluded (Figure 1). The FDS2 protocol was approved by the Southern Metropolitan Area Health Service Human Research Ethics Committee. All subjects gave informed consent before participation.

Clinical and Biochemical Data

At baseline, all participants completed a detailed questionnaire, underwent a physical examination and had blood and urine taken for routine fasting biochemical tests. Each participant was invited to return for biennial clinical and biochemical assessments interspersed with biennial postal questionnaires. Fasting serum samples taken at each assessment were stored at −80°C for future analyses. The cohort was followed from baseline (2008-2011) until end-June 2016 through these assessments and linkage with the Western Australia Data Linkage System (WADLS).[25]

Serum thyrotropin, FT4 and thyroperoxidase antibodies (anti-TPO) were measured by automated electrochemiluminescence immunoassays (Cobas E601 analyser, Roche Diagnostics Australia). Between-run imprecision, expressed as coefficients of variation, was ≤4.7% for FT4, ≤3.5% for TSH and ≤8.1% for anti-TPO. Reference intervals were 0.34–5.1 mIU/L for TSH and 12–22 pmol/L for FT4, based on a study of 300 healthy blood donors from the Fremantle area, and <35 U/L for anti-TPO as recommended by the manufacturer. Thyroid function testing was performed on baseline and Year 4 stored serum samples, while anti-TPO was assessed at baseline only. As thyroid function tests were carried out some time after the assessment, neither the participants nor their health professionals were routinely advised of the results. Other usual care biochemical tests were performed using standard automated methods. Chronic complications were ascertained using standard criteria.[23]

Known prevalent thyroid disease was defined as self-reported thyroid medication use at baseline and/or prior hospitalization for/with thyroid disease ascertained from the WADLS. This included a history of hypothyroidism, Hashimoto's thyroiditis, Graves' disease, nodular goitre, taking thyroxine and/or liothyronine or antithyroid medications, and/or thyroidectomy or [131]I therapy. In patients without known prevalent thyroid disease, an abnormal TSH at baseline defined undiagnosed hypo- or hyperthyroidism. Overt hypothyroidism was defined as an elevated TSH and subnormal FT4, subclinical hypothyroidism as an elevated TSH but normal FT4, overt hyperthyroidism as a subnormal TSH and elevated FT4, and subclinical hyperthyroidism as a subnormal TSH and normal FT4.[11] 'Any prevalent thyroid disease' included participants with known prevalent thyroid disease and those with an abnormal TSH.

Known incident thyroid disease was defined as initiation of thyroid medication and/or a new hospitalization for/with thyroid disease between entry and end-June 2016 in participants without thyroid disease at baseline. An abnormal TSH at follow-up defined new undiagnosed hypothyroidism/hyperthyroidism as described for prevalent undiagnosed thyroid disease. 'Any incident thyroid disease' included participants with known incident thyroid disease and those with an abnormal TSH concentration at follow-up who were euthyroid at baseline. As FDS2 is an observational study, decisions relating to the management of thyroid disease during the period of observation were made solely by the participants' usual care clinicians.

Statistical Analysis

Data are summarized as proportions, mean ± SD, geometric mean (SD range) or median [interquartile range] as appropriate. For independent samples, two-way comparisons for proportions were by Fisher's exact test, for normally distributed variables by Student's t test and for non-normally distributed variables by Mann-Whitney U test. Two related but not normally distributed groups were compared using the Wilcoxon signed rank test. All statistical analyses were performed using SPSS for Windows (version 25; SPSS Inc).

The incidence of new-onset thyroid disease was assessed in patients who had TSH measured at entry and Year 4. The incidence of known thyroid disease was determined by dividing the number of cases with a new event (hospitalization for/with thyroid disease or those who self-reported commencing thyroid medication) by the follow-up period, a summation of all follow-up times to end-June 2016, death, or thyroid disease, whichever came first. Dates of hospitalizations were obtained from the WADLS, while the date of the Year 2 or Year 4 FDS2 visit was used as a proxy for starting thyroid medication. As a secondary measure, the incidence of any thyroid disease, including those with an abnormal follow-up TSH plus those with known incident disease, was assessed by dividing the number of cases by the length of follow-up between study entry and Year 4.

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