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PreprintCited by 5Cardiovascular Function and Risk FactorsDiabetes, Cardiovascular Risks, and LipoproteinsCardiac Imaging and Diagnostics

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Sex-specific differences in myocardial glucose metabolic rate in non-diabetic, pre-diabetic and type 2 diabetic subjects

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Succurro, Elena, Vizza, Patrizia, Cicone, Francesco, Cassano, Velia, Massimino, Mattia, Giofrè, Federica, Fiorentino, Teresa Vanessa, Perticone, Maria, Sciacqua, Angela, Guzzi, Pietro Hiram, Veltri, Pierangelo, Andreozzi, Francesco, Cascini, Giuseppe Lucio, Sesti, Giorgio·2023·Cardiovascular Diabetology
DOI 10.21203/rs.3.rs-3596006/v1PMC PMC11055246

Preprint — published as 10.1186/s12933-024-02246-7

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Abstract

Background Evidence has shown that women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than men with T2DM. Subjects with either T2DM or prediabetes exhibit myocardial insulin resistance, but it is still unsettled whether sex-related differences in myocardial insulin resistance occur in diabetic and prediabetic subjects. Methods we aimed to evaluate sex-related differences in myocardial glucose metabolic rate (MRGlu), assessed using dynamic PET with 18 F-FDG combined with euglycemic-hyperinsulinemic clamp, in subjects with normal glucose tolerance (NGT; n = 20), prediabetes (n = 11), and T2DM (n = 26). Results Women with prediabetes or T2DM exhibited greater relative differences in myocardial MRGlu than men with prediabetes or T2DM when compared with their NGT counterparts. As compared with women with NGT, those with prediabetes exhibited an age-adjusted 35% decrease in myocardial MRGlu (P = 0.04) and women with T2DM a 74% decrease (P = 0.006), respectively. Conversely, as compared with men with NGT, men with T2DM exhibited a 40% reduction in myocardial MRGlu (P = 0.004), while no significant difference was observed between men with NGT and prediabetes. The statistical test for interaction between sex and glucose tolerance on myocardial MRGlu (P < 0.0001) was significant suggesting a sex-specific association. Conclusions Our data suggest that deterioration of glucose homeostasis in women is associated with a greater impairment in myocardial glucose metabolism as compared with men. The sex-specific myocardial insulin resistance could be an important factor responsible for the greater effect of T2DM on the excess risk of cardiovascular disease in women than in men.

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Research works printed but not linked: 38

  1. Vaduganathan M, Mensah GA, Turco JV, Fuster V, Roth GA. The Global Burden of Cardiovascular Diseases and Risk: A Compass for Future Health. J Am Coll Cardiol. 2022;80:2361–71. · DOI
  2. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. · DOI · Paper page
  3. Heald AH, Stedman M, Davies M, Livingston M, Alshames R, Lunt M, et al. Estimating life years lost to diabetes: outcomes from analysis of National Diabetes Audit and Office of National Statistics data. Cardiovasc Endocrinol Metab. 2020;9:183–5. · DOI
  4. Succurro E, Fiorentino TV, Miceli S, Perticone M, Sciacqua A, Andreozzi F, Sesti G. Relative Risk of Cardiovascular Disease Is Higher in Women With Type 2 Diabetes, but Not in Those With Prediabetes, as Compared With Men. Diabetes Care. 2020;43:3070–78. · DOI
  5. Juutilainen A, Kortelainen S, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Gender difference in the impact of type 2 diabetes on coronary heart disease risk. Diabetes Care. 2004;27:2898–904. · DOI
  6. Shah AD, Langenber Langenberg C, Rapsomaniki E, Denaxas S, Pujades-Rodriguez M, Gale CP, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1–9 million people. Lancet Diabetes Endocrinol. 2015;3:105–13. · DOI · Paper page
  7. Bragg F, Holmes MV, Iona A, Guo Y, Du H, Chen Y, et al. China Kadoorie Biobank Collaborative Group. Association between diabetes and cause-specific mortality in rural and urban areas of China. JAMA. 2017;317:280–89. · DOI
  8. Peters SA, Huxley RR, Woodward M. Diabetes as risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858,507 individuals and 28,203 coronary events. Diabetologia. 2014;57:1542–51. · DOI · Paper page
  9. Prospective Studies Collaboration and Asia Pacific Cohort Studies Collaboration. Sex-specific relevance of diabetes to occlusive vascular and other mortality: a collaborative meta-analysis of individual data from 980793 adults from 68 prospective studies. Lancet Diabetes Endocrinol. 2018;6:538–46. · DOI
  10. Kautzky-Willer A, Leutner M, Harreiter J. Sex differences in type 2 diabetes. Diabetologia. 2023;66:986–1002. · DOI · Paper page
  11. Succurro E, Miceli S, Fiorentino TV, Sciacqua A, Perticone M, Andreozzi F, Sesti G. Sex-specific differences in left ventricular mass and myocardial energetic efficiency in non-diabetic, pre-diabetic and newly diagnosed type 2 diabetic subjects. Cardiovasc Diabetol. 2021;20:60. · DOI
  12. Tramunt B, Smati S, Grandgeorge N, Lenfant F, Arnal JF, Montagner A, et al. Sex differences in metabolic regulation and diabetes susceptibility. Diabetologia. 2020;63:453–61. · DOI · Paper page
  13. Succurro E, Marini MA, Riccio A, Fiorentino TV, Perticone M, Sciacqua A, et al. Sex-differences in insulin sensitivity and insulin secretion in subjects with impaired fasting glucose and impaired glucose tolerance. Diabetes Res Clin Pract. 2022;194:110185. · DOI
  14. Yoshida Y, Chen Z, Baudier RL, Krousel-Wood M, Anderson AH, Fonseca VA, et al. Sex Differences in the Progression of Metabolic Risk Factors in Diabetes Development. JAMA Netw Open. 2022;5:e2222070. · DOI
  15. Wright AK, Kontopantelis E, Emsley R, Buchan I, Mamas MA, Sattar N, Ashcroft DM, et al. Cardiovascular risk and risk factor management in type 2 diabetes mellitus. Circulation. 2019;139:2742–53. · DOI
  16. Iozzo P, Chareonthaitawee P, Dutka D, Betteridge DJ, Ferrannini E, Camici PG. Independent association of type 2 diabetes and coronary artery disease with myocardial insulin resistance. Diabetes. 2002;51:3020–4. · DOI
  17. Succurro E, Pedace E, Andreozzi F, Papa A, Vizza P, Fiorentino TV, et al. Reduction in Global Myocardial Glucose Metabolism in Subjects With 1-Hour Postload Hyperglycemia and Impaired Glucose Tolerance. Diabetes Care. 2020;43:669–76. · DOI
  18. Ohtake T, Yokoyama I, Watanabe T, Momose T, Serezawa T, Nishikawa J, et al. Myocardial glucose metabolism in noninsulin-dependent diabetes mellitus patients evaluated by FDG-PET. J Nucl Med. 1995;36:456–63.
  19. Hu L, Qiu C, Wang X, Shao X, Wang Y. The association between diabetes mellitus and reduction in myocardial glucose uptake: a population-based 18F-FDG PET/CT study. BMC Cardiovasc Disord. 2018;18:203. · DOI
  20. Nielsen R, Jorsal A, Iversen P, Tolbod L, Bouchelouche K, Sørensen J, et al. Heart failure patients with prediabetes and newly diagnosed diabetes display abnormalities in myocardial metabolism. J Nucl Cardiol. 2018;25:169–76. · DOI
  21. Succurro E, Vizza P, Papa A, Cicone F, Monea G, Tradigo G, et al. Metabolic Syndrome Is Associated With Impaired Insulin-Stimulated Myocardial Glucose Metabolic Rate in Individuals With Type 2 Diabetes: A Cardiac Dynamic 18 F-FDG-PET Study. Front Cardiovasc Med. 2022;9:924787. · DOI
  22. Devesa A, Fuster V, Vazirani R, García-Lunar I, Oliva B, España S, et al. Cardiac Insulin Resistance in Subjects With Metabolic Syndrome Traits and Early Subclinical Atherosclerosis. Diabetes Care. 2023;46:2050–57. · DOI
  23. Succurro E, Cicone F, Papa A, Miceli S, Vizza P, Fiorentino TV, et al. Impaired insulin-stimulated myocardial glucose metabolic rate is associated with reduced estimated myocardial energetic efficiency in subjects with different degrees of glucose tolerance. Cardiovasc Diabetol. 2023;22:4. · DOI
  24. Kofoed KF, Carstensen S, Hove JD, Freiberg J, Bangsgaard R, Holm S, et al. Low whole-body insulin sensitivity in patients with ischaemic heart disease is associated with impaired myocardial glucose uptake predictive of poor outcome after revascularisation. Eur J Nucl Med Mol Imaging. 2002;29:991–8. · DOI
  25. Losi MA, Izzo R, Mancusi C, Wang W, Roman MJ, Lee ET, et al. Depressed myocardial energetic efficiency increases risk of incident heart failure: The Strong Heart Study. J Clin Med. 2019;8:1044. · DOI
  26. de Simone G, Izzo R, Losi MA, Stabile E, Rozza F, Canciello G, et al. Depressed myocardial energetic efficiency is associated with increased cardiovascular risk in hypertensive left ventricular hypertrophy. J Hypertens. 2016;34:1846–53. · DOI
  27. Tang K, Lin J, Ji X, Lin T, Sun D, Zheng X, et al. Non-alcoholic fatty liver disease with reduced myocardial FDG uptake is associated with coronary atherosclerosis. J Nucl Cardiol. 2021;28:610–20. · DOI
  28. El Sayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, on behalf of the American Diabetes Association, et al. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46(Suppl 1):19–S40.
  29. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237:E214–23.
  30. Carson RE. Tracer kinetic modeling in PET. Positron Emission Tomography. London: Springer; 2005. pp. 127–59. · DOI
  31. Vizza P, Guzzi PH, Veltri P, Papa A, Cascini GL, Sesti G, Succurro E. Experiences on quantitative cardiac pet analysis. 2016 IEEE International Conference on Bioinformatics and Biomedicine (BIBM). Shenzen, China, 2016. p. 1148-53.
  32. Tura A, Pacini G, Moro E, Vrbíková J, Bendlová B, Kautzky-Willer A. Sex- and age-related differences of metabolic parameters in impaired glucose metabolism and type 2 diabetes compared to normal glucose tolerance. Diabetes Res Clin Pract. 2018;146:67–75. · DOI
  33. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991;114:345–52. · DOI · Paper page
  34. Cook SA, Varela-Carver A, Mongillo M, Kleinert C, Khan MT, Leccisotti L, et al. Abnormal myocardial insulin signalling in type 2 diabetes and left-ventricular dysfunction. Eur Heart J. 2010;31:100–11. · DOI
  35. Tan Y, Zhang Z, Zheng C, Wintergerst KA, Keller BB, Cai L. Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence. Nat Rev Cardiol. 2020;17:585–607. · DOI
  36. Sesti G. Pathophysiology of insulin resistance. Best Pract Res Clin Endocrinol Metab. 2006;20:665–79. · DOI
  37. Juszczyk A, Jankowska K, Zawiślak B, Surdacki A, Chyrchel B. Depressed cardiac mechanical energetic efficiency: a contributor to cardiovascular risk in common metabolic diseases-from mechanisms to clinical applications. J Clin Med. 2020;9:2681. · DOI
  38. Gerber BL, Ordoubadi FF, Wijns W, Vanoverschelde JL, Knuuti MJ, Janier M, et al. 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 Concerted Action Multicenter Study on Use of (18)F-Fluoro-Deoxyglucose Positron Emission Tomography for the Detection of Myocardial Viability. Eur Heart J. 2001;22:1691–701. · DOI

Metadata

Authors
Succurro, E., Vizza, P., Cicone, F., Cassano, V., Massimino, M., Giofrè, F., Fiorentino, T. V., Perticone, M., Sciacqua, A., Guzzi, P. H., Veltri, P., Andreozzi, F., Cascini, G. L., & Sesti, G.
Affiliations
  • Magna Graecia University (IT)
  • University of Calabria (IT)
  • Sapienza University of Rome (IT)
Corresponding author
Succurro, Elena
ORCID
Venue
Cardiovascular Diabetology
Publisher
Research Square Platform LLC
Published
2023-11-15
Volume
23
Issue
1
Pages
144-144
ISSN
1475-2840 (ISSN-L)
DOI
10.21203/rs.3.rs-3596006/v1
PMC
PMC11055246
OpenAlex
W4395659583
Cited by
5
References
1
Citations by year
2026: 2 · 2025: 2 · 2024: 1
FWCI
1.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Cardiovascular Diabetology (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
  • Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
Keywords
sex differences, myocardial glucose metabolism, type 2 diabetes, prediabetes, myocardial insulin resistance, cardiovascular disease risk in women, glucose tolerance
MeSH terms
Adult, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Energy Metabolism, Female, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Myocardium, Prediabetic State, Sex Factors, Glucose Clamp Technique, Biomarkers, Case-Control Studies, Radiopharmaceuticals, Fluorodeoxyglucose F18, Positron-Emission Tomography

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