Endocrine Abstracts

Background: Skin autofluorescence (SAF), measured with the AGE-reader, predicts cardiovascular disease (CVD) and type 2 diabetes (T2D). Thyroid hormone levels (TH) may affect this association. In the present study, we examined whether TH predict 4-years risk of T2D, CVD and mortality in the general population independently of SAF.

Methods: We included 28245 participants (age 44±12 years, BMI 25.9±4.3 kg/m²) of the Dutch Lifelines Cohort Study, who had SAF and TH (TSH, FT4, FT3, Roche Modular E170 Analyzer) measured, and were not known to have diabetes or CVD at baseline, or using medication influencing TH (including levothyroxine). Diagnosis of incident T2D was by self-report, or fasting blood glucose≥7.0 mmol/l or HbA1c≥6.5% at follow-up; diagnosis of incident CVD was by self-report. Metabolic syndrome (MetS) was defined by NCEP-ATPIII criteria. Mortality was ascertained with the Municipal Personal Records Database. The influence of TH on the composite outcome of incident T2D, CVD and mortality, and these outcomes separately, was evaluated with logistic regression.

Results: After a median follow-up of 4 (range 1–9) years, 325 participants had died, 415 developed CVD, and 377 developed T2D. For the composite outcome, TH were identical in cases vs. non-cases. Subjects with incident T2D were significantly older (54 vs 44 years), had lower FT4 compared to no-diabetes (15.2±2.1 vs 15.6±2.1 pmol/l, P<0.0001), but similar FT3 and TSH, while those with new-onset CVD were older (57 vs 44 years) and had borderline significantly higher FT4 levels (15.9±2.1 vs 15.7±2.2, P=0.06). Logistic regression showed that each 1.0 pmol/l lower level of FT4 was associated with an 11% higher T2D risk, adjusted for SAF, age and gender. After further adjustment for presence of MetS, glucose and/or HbA1c, FT4 retained its significance (OR 0.92, P=0.006). In contrast, each 1.0 pmol/l higher FT4 was associated with a 5% increased CVD risk (P=0.02), adjusted for SAF, age and gender but this association lost its significance when adjusting further for blood pressure and cholesterol. In the multivariate models, higher FT3 was associated with increased T2D and CVD risk; there was no association between TSH and outcome.

Conclusions/interpretations: Serum FT4 levels have opposite effects on risk of development of T2D and CVD in the general population, independent of SAF, and presence of metabolic syndrome. Next steps will be to elucidate underlying mechanism(s).