Phenotyping Type 2 Diabetes in Terms of Myocardial Insulin Resistance and Its Potential Cardiovascular Consequences: A New Strategy Based on F-FDG PET/CT

Overview

Journal J Pers Med

Date 2022 Jan 21

PMID 35055345

Authors

Jose Raul Herance

Rafael Simo

Mayra Alejandra Velasquez

Bruno Paun

Daniel Garcia-Leon

Carolina Aparicio

Roso Mares

Olga Simo-Servat

Joan Castell-Conesa

Cristina Hernandez

Santiago Aguade-Bruix

Affiliations

Soon will be listed here.

Abstract

Background: Systemic insulin resistance is generally postulated as an independent risk factor of cardiovascular events in type 2 diabetes (T2D). However, the role of myocardial insulin resistance (mIR) remains to be clarified.

Methods: Two F-FDG PET/CT scans were performed on forty-three T2D patients at baseline and after hyperinsulinemic-euglycemic clamp (HEC). Myocardial insulin sensitivity (mIS) was determined by measuring the increment in myocardial F-FDG uptake after HEC. Coronary artery calcium scoring (CACs) and myocardial radiodensity (mRD) were assessed by CT.

Results: After HEC, seventeen patients exhibited a strikingly enhancement of myocardial F-FDG uptake and twenty-six a marginal increase, thus revealing mIS and mIR, respectively. Patients with mIR showed higher mRD (HU: 38.95 [33.81-44.06] vs. 30.82 [21.48-38.02]; = 0.03) and CACs > 400 (AU: 52% vs. 29%; = 0.002) than patients with mIS. In addition, HOMA-IR and mIS only showed a correlation in those patients with mIR.

Conclusions: F-FDG PET combined with HEC is a reliable method for identifying patients with mIR. This subgroup of patients was found to be specifically at high risk of developing cardiovascular events and showed myocardial structural changes. Moreover, the gold-standard HOMA-IR index was only associated with mIR in this subgroup of patients. Our results open up a new avenue for stratifying patients with cardiovascular risk in T2D.

Citing Articles

Insights into Insulin Resistance and Calcification in the Myocardium in Type 2 Diabetes: A Coronary Artery Analysis.

Martin-Saladich Q, Simo R, Aguade-Bruix S, Simo-Servat O, Aparicio-Gomez C, Hernandez C Int J Mol Sci. 2023; 24(4).

PMID: 36834662 PMC: 9959651. DOI: 10.3390/ijms24043250.

Identification of Myocardial Insulin Resistance by Using Liver Tests: A Simple Approach for Clinical Practice.

Herance J, Martin-Saladich Q, Velasquez M, Hernandez C, Aparicio C, Ramirez-Serra C Int J Mol Sci. 2022; 23(15).

PMID: 35955920 PMC: 9369008. DOI: 10.3390/ijms23158783.

References

Kramer C, Zinman B, Gross J, Canani L, Rodrigues T, Azevedo M . Coronary artery calcium score prediction of all cause mortality and cardiovascular events in people with type 2 diabetes: systematic review and meta-analysis. BMJ. 2013; 346:f1654. DOI: 10.1136/bmj.f1654. View

Camici P, Ferrannini E, Opie L . Myocardial metabolism in ischemic heart disease: basic principles and application to imaging by positron emission tomography. Prog Cardiovasc Dis. 1989; 32(3):217-38. DOI: 10.1016/0033-0620(89)90027-3. View

Fedorov A, Beichel R, Kalpathy-Cramer J, Finet J, Fillion-Robin J, Pujol S . 3D Slicer as an image computing platform for the Quantitative Imaging Network. Magn Reson Imaging. 2012; 30(9):1323-41. PMC: 3466397. DOI: 10.1016/j.mri.2012.05.001. View

Budoff M, Raggi P, Beller G, Berman D, Druz R, Malik S . Noninvasive Cardiovascular Risk Assessment of the Asymptomatic Diabetic Patient: The Imaging Council of the American College of Cardiology. JACC Cardiovasc Imaging. 2016; 9(2):176-92. PMC: 5371352. DOI: 10.1016/j.jcmg.2015.11.011. View

Cutler C, Bailey E, Kumar V, Schwarz S, Bom H, Hatazawa J . Global Issues of Radiopharmaceutical Access and Availability: A Nuclear Medicine Global Initiative Project. J Nucl Med. 2020; 62(3):422-430. PMC: 8049350. DOI: 10.2967/jnumed.120.247197. View

Gerber B, Ordoubadi F, Wijns W, Vanoverschelde J, Knuuti M, Janier M . Positron emission tomography using(18)F-fluoro-deoxyglucose and euglycaemic hyperinsulinaemic glucose clamp: optimal criteria for the prediction of recovery of post-ischaemic left ventricular dysfunction. Results from the European Community.... Eur Heart J. 2001; 22(18):1691-701. DOI: 10.1053/euhj.2000.2585. View

Dilsizian V, Bacharach S, Beanlands R, Bergmann S, Delbeke D, Dorbala S . ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. J Nucl Cardiol. 2016; 23(5):1187-1226. DOI: 10.1007/s12350-016-0522-3. View

Voipio-Pulkki L, Nuutila P, Knuuti M, Ruotsalainen U, Haaparanta M, Teras M . Heart and skeletal muscle glucose disposal in type 2 diabetic patients as determined by positron emission tomography. J Nucl Med. 1993; 34(12):2064-7. View

Fu F, Zhao K, Li J, Xu J, Zhang Y, Liu C . Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure. Sci Rep. 2015; 5:17927. PMC: 4677294. DOI: 10.1038/srep17927. View

10.

Qi Y, Xu Z, Zhu Q, Thomas C, Kumar R, Feng H . Myocardial loss of IRS1 and IRS2 causes heart failure and is controlled by p38α MAPK during insulin resistance. Diabetes. 2013; 62(11):3887-900. PMC: 3806607. DOI: 10.2337/db13-0095. View

11.

Witteles R, Fowler M . Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options. J Am Coll Cardiol. 2008; 51(2):93-102. DOI: 10.1016/j.jacc.2007.10.021. View

12.

Fedorov A, Clunie D, Ulrich E, Bauer C, Wahle A, Brown B . DICOM for quantitative imaging biomarker development: a standards based approach to sharing clinical data and structured PET/CT analysis results in head and neck cancer research. PeerJ. 2016; 4:e2057. PMC: 4888317. DOI: 10.7717/peerj.2057. View

13.

Godsland I, Lecamwasam K, Johnston D . A systematic evaluation of the insulin resistance syndrome as an independent risk factor for cardiovascular disease mortality and derivation of a clinical index. Metabolism. 2011; 60(10):1442-8. DOI: 10.1016/j.metabol.2011.02.012. View

14.

Farre M, Perez-Mana C, Papaseit E, Menoyo E, Perez M, Martin S . Bilastine vs. hydroxyzine: occupation of brain histamine H1 -receptors evaluated by positron emission tomography in healthy volunteers. Br J Clin Pharmacol. 2014; 78(5):970-80. PMC: 4243871. DOI: 10.1111/bcp.12421. View

15.

Bax J, Visser F, Poldermans D, Van Lingen A, Elhendy A, Boersma E . Feasibility, safety and image quality of cardiac FDG studies during hyperinsulinaemic-euglycaemic clamping. Eur J Nucl Med Mol Imaging. 2002; 29(4):452-7. DOI: 10.1007/s00259-001-0757-2. View

16.

Feng H, Wang X, Chen J, Cui J, Gao T, Gao Y . Nuclear Imaging of Glucose Metabolism: Beyond F-FDG. Contrast Media Mol Imaging. 2019; 2019:7954854. PMC: 6458935. DOI: 10.1155/2019/7954854. View

17.

Knuuti M, Nuutila P, Ruotsalainen U, Saraste M, Harkonen R, Ahonen A . Euglycemic hyperinsulinemic clamp and oral glucose load in stimulating myocardial glucose utilization during positron emission tomography. J Nucl Med. 1992; 33(7):1255-62. View