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Preclinical and clinical evaluation of a new method to assess cardiac insulin resistance using nuclear imaging

  • ORIGINAL ARTICLE
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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Myocardial insulin resistance (IR) could be a predictive factor of cardiovascular events. This study aimed to introduce a new method using 123I-6-deoxy-6-iodo-d-glucose (6DIG), a pure tracer of glucose transport, for the assessment of IR using cardiac dynamic nuclear imaging.

Methods

The protocol evaluated first in rat-models consisted in two 6DIG injections and one of insulin associated with planar imaging and blood sampling. Compartmental modeling was used to analyze 6DIG kinetics in basal and insulin conditions and to obtain an index of IR. As a part of a translational approach, a clinical study was then performed in 5 healthy and 6 diabetic volunteers.

Results

In rodent models, the method revealed reproducible when performed twice at 7 days apart in the same animal. Rosiglitazone, an insulin-sensitizing drug, induced a significant increase of myocardial IR index in obese Zucker rats from 0.96 ± 0.18 to 2.26 ± 0.44 (P<.05) after 7 days of an oral treatment, and 6DIG IR indexes correlated with the gold standard IR index obtained through the hyperinsulinemic-euglycemic clamp (r=.68, P<.02). In human, a factorial analysis was applied on images to obtain vascular and myocardial kinetics before compartmental modeling. 1.5-fold to 2.2-fold decreases in mean cardiac IR indexes from healthy to diabetic volunteers were observed without reaching statistical significance.

Conclusions

These preclinical results demonstrate the reproducibility and sensibility of this novel imaging methodology. Although this first in-human study showed that this new method could be rapidly performed, larger studies need to be planned in order to confirm its performance.

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Abbreviations

6DIG:

6-Deoxy-6-iodo-d-glucose

IR:

Insulin resistance

T2D:

Type 2 diabetes

SPECT:

Single-photon emission computed tomography

ROI:

Region of interest

ID:

Injected dose

T 1/2 :

Radioactive half-life period

Bq:

Becquerel

HOMA:

Homeostatic model assessment of insulin resistance

QUICKI:

Quantitative insulin sensitivity check index

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Acknowledgments

We thank the staff of the Center of Clinical Investigation and the Nuclear Medicine department of CHU Grenoble Alpes.

Disclosures

Drs. Perret, Slimani, Barone-Rochette, Vollaire, Briat, Ahmadi, Henri, Desruet, Clerc, Broisat, Riou, Boucher, Frouin, Djaileb, Calizzano, Vanzetto, Fagret, and Ghezzi have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Univ. Grenoble Alpes, Inserm, CHU Grenoble Alpes, LRB U1039, 38000, Grenoble, France

    Pascale Perret, Lotfi Slimani, Gilles Barone-Rochette, Julien Vollaire, Arnaud Briat, Mitra Ahmadi, Marion Henri, Marie-Dominique Desruet, Romain Clerc, Alexis Broisat, Laurent Riou, Loïc Djaileb, Alex Calizzano, Gérald Vanzetto, Daniel Fagret & Catherine Ghezzi

  2. Univ. Grenoble Alpes, CNRS, CHU Grenoble Alpes, TIMC-IMAG, 38000, Grenoble, France

    François Boucher

  3. Inserm, U1288 LITO, Institut Curie, 91400, Orsay, France

    Frédérique Frouin

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  1. Pascale Perret
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Correspondence to Pascale Perret.

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Funding

This work was partly funded by the ANR-06-TecSan-005-01-GLUCIMAG and “Infrastructure d’avenir en Biologie Santé” ANR-11-INBS-0006 Grants.

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Perret, P., Slimani, L., Barone-Rochette, G. et al. Preclinical and clinical evaluation of a new method to assess cardiac insulin resistance using nuclear imaging. J. Nucl. Cardiol. 29, 1419–1429 (2022). https://doi.org/10.1007/s12350-020-02520-7

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