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. 2024 Dec 24;26(1):37.
doi: 10.3390/ijms26010037.

The Interplay Between High Cumulative Doses of Radioactive Iodine and Type 2 Diabetes Mellitus: A Complex Cardiovascular Challenge

Adina Elena Stanciu  1   2 , Madalina Lucica Bolovan  1 , Adina Zamfir-Chiru-Anton  3 , Catalina Voiosu  4   5 , Pradeep Kumar Dabla  6 , Marcel Marian Stanciu  7 , Nafija Serdarevic  8 , Mirela Gherghe  9   10
Affiliations

The Interplay Between High Cumulative Doses of Radioactive Iodine and Type 2 Diabetes Mellitus: A Complex Cardiovascular Challenge

Adina Elena Stanciu et al. Int J Mol Sci. .

Abstract

Starting from the metabolic profile of type 2 diabetes mellitus (T2DM), we hypothesized that the mechanisms of ¹³¹I-induced cardiotoxicity differ between patients diagnosed with differentiated thyroid cancer (DTC) with/without T2DM, with metformin potentially acting as a cardioprotective agent by mitigating inflammation in patients with T2DM. To address this hypothesis, we quantified, using ELISA, the serum concentration of several key biomarkers that reflect cardiac injury (NT-proBNP, NT-proANP, ST2/IL-33R, and cTn I) in 74 female patients with DTC/-T2DM and 25 with DTC/+T2DM treated with metformin. All patients received a cumulative oral dose of 131I exceeding 150 mCi (5.55 GBq) over approximately 53 months. Our results showed the following: (i) In DTC/-T2DM patients, high-cumulative 131I doses promote a pro-inflammatory state that accelerates the development of cardiotoxicity. Monitoring NT-proBNP, ST2/IL-33R, and cTn I in these patients may help identify those at risk of developing cardiac complications. (ii) In patients with DTC/+T2DM, high-cumulative 131I doses lead to the release of NT-proANP (r = 0.63), which signals that the atria are under significant stress. (iii) In patients with DTC/+T2DM, metformin suppresses inflammation, leading to a dose-dependent reduction in cTn I (r = -0.59). Monitoring cTn I and NT-proANP, and considering the use of metformin as part of the therapeutic strategy, could help manage cardiotoxicity in T2DM patients undergoing 131I therapy.

Keywords: cardiac biomarkers; cardiotoxicity; differentiated thyroid cancer; metformin; radioiodine; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Correlations between (A) the cumulative doses of 131I and NT-proBNP, (B) the cumulative doses of 131I and cTn I and (C) the cumulative doses of 131I and ST2/IL-33R in differentiated thyroid cancer patients without type 2 diabetes mellitus; (“—” fitted linear regression curve, “- - -” equality line).
Figure 2
Figure 2
Correlations between (A) NLR and NT-proBNP, (B) NLR and cTn I, (C) NLR and ST2/IL-33R, and between (D) PLR and NT-proBNP, (E) PLR and cTn I, (F) PLR and ST2/IL-33R in differentiated thyroid cancer patients without type 2 diabetes mellitus; (“—” fitted linear regression curve, “- - -” equality line).
Figure 3
Figure 3
Correlations between (A) ST2/IL-33 and NT-proBNP, (B) cTn I and NT-proBNP, and (C) cTn I and ST2/IL-33R in differentiated thyroid cancer patients without type 2 diabetes mellitus; (“—” fitted linear regression curve, “- - -” equality line).
Figure 4
Figure 4
Correlations between (A) the cumulative doses of 131I and absolute lymphocyte count, and (B) the cumulative doses of 131I and absolute neutrophile count in differentiated thyroid cancer patients with type 2 diabetes mellitus; (“—” fitted linear regression curve, “- - -” equality line).
Figure 5
Figure 5
Correlations between (A) BMI and absolute platelet count, (B) BMI and SII, (C) BMI and NT-proBNP, and (D) BMI and ST2/IL-33R in differentiated thyroid cancer patients with type 2 diabetes mellitus; (“—” fitted linear regression curve, “- - -” equality line).
Figure 6
Figure 6
Correlation between (A) NT-proANP and the cumulative dose of 131I, and (B) NT-proANP and PLR in differentiated thyroid cancer patients with type 2 diabetes mellitus; (“—” fitted linear regression curve, “- - -” equality line).
Figure 7
Figure 7
Correlation between (A) the metformin dose and NLR, (B) the metformin dose and cTn I, (C) the metformin dose and PLR, and (D) the metformin dose and SII in differentiated thyroid cancer patients with type 2 diabetes mellitus; (“—” fitted linear regression curve, “- - -” equality line).
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