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

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.

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

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

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

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

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

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

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).