Subclinical thyroid dysfunction and risk of diabetes

An international group of specialists, which included Italian clinicians, performed a systematic literature review with meta-analysis to test the relationship between the presence of subclinical thyroid dysfunction and the risk of developing type 2 diabetes. The results confirmed no relationship between alterations in gland function and the occurrence of metabolic disease.

Thyroid dysfunction and type 2 diabetes are widespread diseases, and some authors have hypothesized possible relationships between the presence of the former and the development of the latter. There can be two subclinical dysfunctions of the thyroid gland: subclinical hypothyroidism, which consists of an increase in TSH to which normal blood concentrations of FT4 correspond, and subclinical hyperthyroidism, in which blood concentrations of TSH are low while those of FT4 and FT3 are within normal limits. Subclinical hypothyroidism has been related to an increased risk of developing cardiovascular disease and an increased likelihood of death, and the other subclinical thyroid dysfunction has also been associated with adverse health consequences. Studies that have evaluated the relationship between thyroid disease and type 2 diabetes have provided mixed results. A survey of more than 30,000 people in Norway did not confirm an association between the two diseases, while other studies have shown a possible relationship between increased blood concentrations of TSH and the presence of insulin resistance. A limitation of such evidence is that it was produced with cross-sectional studies, and these do not allow evidence of the development of such associations over time. In addition, the relationship between thyroid disease and diabetes may be bidirectional, that is, the presence of the former may favor the development of the latter, but also vice versa, so by evaluating the association at a single time, it is difficult to understand which disease favored the appearance of the other. Few research studies have followed people with thyroid dysfunction over time to assess whether diabetes appeared, and almost always they have included subjects with clinically manifested altered function of the gland. To shed light on the possible association between subclinical thyroid dysfunction and type 2 diabetes, Alwan and colleagues performed a literature review with meta-analysis by individual data. Metanalysis by individual data is a statistical method aimed at summarizing evidence from clinical studies by combining not the results of those studies, as in traditional meta-analyses, but by pooling the data archives collected from the research itself and analyzing the overall case series. The authors searched the major network libraries of scientific literature for articles, published through Feb. 11, 2022, related to studies that had enrolled adult subjects with data on blood TSH concentrations at baseline and had followed these subjects over time, assessing the onset of type 2 diabetes. The development of this disease was defined according to American Diabetes Association criteria, namely: fasting blood glucose ≥ 7 mmol/L or glucose loading curve with blood glucose ≥ 11.1 mmol/L after 2 hours or glycated hemoglobin ≥ 6.5% or still taking medication to reduce blood glucose. Special care was taken to check the quality of the research and the data it had produced, and the most effective statistical methods were applied to highlight any relationships. By combining the case histories of 18 studies selected because they met the criteria set by the authors, a total population of 61,178 adults was collected. The mean age of these case histories was 58 years, the frequency of female sex was 49%, and the mean time for which they had been followed was 8.2 years. Considering the last available follow-up, no relationship was found either between the presence of subclinical hypothyroidism and the development of diabetes (odds ratio 1.02; 95% confidence interval 0.88-1.17; I2 = 0%), or between subclinical hyperthyroidism and the development of diabetes (odds ratio 1.03; 95% confidence interval 0.82-1.30; I2 = 0%), even when applying the appropriate adjustments for age and sex to the analysis. Another analysis that assessed time to event onset produced similar results. In fact, the hazard ratio for subclinical hypothyroidism was 0.98 (95% confidence interval la 95% 0.87-1.11) and that for subclinical hyperthyroidism was 1.07 (95% confidence interval la 95% 0.88-1.29). The results were robust in all subgroups and also in sensitivity analyses.

In their conclusions, Alwan and colleagues emphasized that the one they performed was the largest systematic literature review with meta-analysis for individual data ever done to prospectively test the relationship between subclinical thyroid dysfunction and type 2 diabetes. The authors also pointed out that their results showed no association between these diseases and that the translation of these outcomes into clinical practice does not justify screening for type 2 diabetes in people with subclinical thyroid dysfunction.

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