Abstract
BackgroundThe association of thyroid function with risk of type 2 diabetes remains elusive. We aimed to investigate the association of thyroid function with incident diabetes and progression from prediabetes to diabetes in a population-based prospective cohort study.MethodsWe included 8452 participants (mean age 65 years) with thyroid function measurement, defined by thyroid-stimulating hormone (TSH) and free thyroxine (FT4), and longitudinal assessment of diabetes incidence. Cox-models were used to investigate the association of TSH and FT4 with diabetes and progression from prediabetes to diabetes. Multivariable models were adjusted for age, sex, high-density lipoprotein cholesterol, and glucose at baseline, amongst others.ResultsDuring a mean follow-up of 7.9 years, 798 diabetes cases occurred. Higher TSH levels were associated with a higher diabetes risk (hazard ratio [HR] 1.13; 95 % confidence interval [CI], 1.08–1.18, per logTSH), even within the reference range of thyroid function (HR 1.24; 95 % CI, 1.06–1.45). Higher FT4 levels were associated with a lower diabetes risk amongst all participants (HR 0.96; 95 % CI, 0.93–0.99, per 1 pmol/L) and in participants within the reference range of thyroid function (HR 0.96; 95 % CI, 0.92–0.99). The risk of progression from prediabetes to diabetes was higher with low-normal thyroid function (HR 1.32; 95 % CI, 1.06–1.64 for TSH and HR 0.91; 95 % CI, 0.86–0.97 for FT4). Absolute risk of developing diabetes type 2 in participants with prediabetes decreased from 35 % to almost 15 % with higher FT4 levels within the normal range.ConclusionsLow and low-normal thyroid function are risk factors for incident diabetes, especially in individuals with prediabetes. Future studies should investigate whether screening for and treatment of (subclinical) hypothyroidism is beneficial in subjects at risk of developing diabetes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0693-4) contains supplementary material, which is available to authorized users.
Highlights
The association of thyroid function with risk of type 2 diabetes remains elusive
The Rotterdam Study consists of three independent cohorts: RS Cohort I (RSI), including 7983 participants aged ≥ 55 years, RS Cohort II (RSII), including 3011 participants aged ≥ 55 years, and RS Cohort III (RSIII), including 3932 participants aged ≥ 45 years
We included a total of 8452 participants with thyroid function measurements and who were free of diabetes at baseline (Fig. 1)
Summary
The association of thyroid function with risk of type 2 diabetes remains elusive. The role of auto-immunity has been well-recognized in the link between auto-immune thyroid disease and type 1 diabetes mellitus [2]. Excess thyroid hormone (i.e. hyperthyroidism) causes increased liver gluconeogenesis and peripheral insulin resistance and is associated with glucose intolerance [10,11,12,13]. Lack of thyroid hormone is associated with a decrease in peripheral insulin sensitivity and glucose intolerance [14] and treatment of hypothyroidism has been shown to improve insulin sensitivity [14, 15]
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