582a6171a230d0af21d999fb8f3350f8 pmc_35055345.pdf 32735d99746e79d2435ebb9c23d0368dc01aff19 pmc_35055345.pdf 5da66a727a1e384e2f2f5500e1643fbb64d438ce629b1840188ae1eb48839729 pmc_35055345.pdf Title: Phenotyping Type 2 Diabetes in Terms of Myocardial Insulin Resistance and Its Potential Cardiovascular Consequences: A New Strategy Based on 18F-FDG PET/CT Subject: 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 18F-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 18F-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 18F-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]; p = 0.03) and CACs > 400 (AU: 52% vs. 29%; p = 0.002) than patients with mIS. In addition, HOMA-IR and mIS only showed a correlation in those patients with mIR. Conclusions: 18F-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. Keywords: myocardial insulin resistance; type 2 diabetes; cardiovascular risk; 18F-FDG PET/CT Author: José Raul Herance, Rafael Simó, Mayra Alejandra Velasquez, Bruno Paun, Daniel García-Leon, Carolina Aparicio, Roso Marés, Olga Simó-Servat, Joan Castell-Conesa, Cristina Hernández and Santiago Aguadé-Bruix Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sun Jan 2 10:41:08 2022 CET ModDate: Sun Jan 2 10:45:54 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 7 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 638434 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QDCWHF+EURM10 Type 1 Builtin yes yes no 10 0 JYPLJJ+VnURWPalladioL-Bold Type 1 Custom yes yes no 14 0 MSGOYU+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 QRIHCG+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 HWOSXV+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 UIJACC+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 56 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 59 0 JYUNWZ+CMSY10 Type 1 Builtin yes yes no 81 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 85 0 HMKJCH+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 98 0 HMKJCJ+PalatinoLinotype TrueType WinAnsi yes yes no 101 0 HMKJCL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 104 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 111 0 HMKJCH+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 120 0 HMKJCI+PalatinoLinotype CID TrueType Identity-H yes yes yes 123 0 HMKJCJ+PalatinoLinotype TrueType WinAnsi yes yes no 129 0 HMKJCL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 132 0 HMKLGB+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 135 0 YVYBFX+VnURWPalladioL Type 1 Custom yes yes no 145 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-07-01 02:26:47 CEST RepresentationInformation: pmc_35055345.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-01-31 03:36:41 CET Size: 638434 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 241 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4923ab24 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: Subjects Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Characterization of Myocardial Insulin Resistance (mIR) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: PET/CT Acquisition Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Data Processing and Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Info: Title: Phenotyping Type 2 Diabetes in Terms of Myocardial Insulin Resistance and Its Potential Cardiovascular Consequences: A New Strategy Based on 18F-FDG PET/CT Author: José Raul Herance, Rafael Simó, Mayra Alejandra Velasquez, Bruno Paun, Daniel García-Leon, Carolina Aparicio, Roso Marés, Olga Simó-Servat, Joan Castell-Conesa, Cristina Hernández and Santiago Aguadé-Bruix Subject: 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 18F-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 18F-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 18F-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]; p = 0.03) and CACs > 400 (AU: 52% vs. 29%; p = 0.002) than patients with mIS. In addition, HOMA-IR and mIS only showed a correlation in those patients with mIR. Conclusions: 18F-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. 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