Serum insulin is associated with right ventricle function parameters and lung volumes in subjects free of cardiovascular disease

in European Journal of Endocrinology
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  • 1 Department of Diagnostic and Interventional Radiology, Universitäts Klinikum Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • 2 Department of Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany
  • 3 Chair of Epidemiology, Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany
  • 4 Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  • 5 Department of Neuroradiology, Universitäts Klinikum Freiburg, Freiburg, Germany
  • 6 German Diabetes Center, Institute for Biometrics and Epidemiology, Düsseldorf, Germany
  • 7 German Center for Diabetes Research (DZD), partner site Neuherberg, Neuherberg, Germany
  • 8 Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Inner City Clinic, University Hospital of Munich, Ludwig-Maximilians-Universität, Munich, Germany
  • 9 Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich/Neuherberg, Germany

Correspondence should be addressed to B Mujaj; Email: blerim.mujaj@uniklinik-freiburg.de
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Background

Diabetes mellitus is an established risk factor for cardiovascular diseases. Even impaired levels of glucose and insulin might harm organ function prior to diabetes onset. Whether serum glucose or insulin plays a direct role in cardiac dysfunction or lung volume reduction remains unclear. The aim was to investigate the relationship between glucose and insulin with the right ventricle and lung volumes within KORA-MRI FF4 study.

Methods

From the KORA-MRI FF4 cohort study 337 subjects (mean age 55.7 ± 9.1 years; 43% women) underwent a whole-body 3T MRI scan. Cardiac parameters derived from a cine-steady-state free precession sequence using cvi42. MRI-based lung volumes derived semi-automatically using an in-house algorithm. Fasting serum glucose, fasting insulin levels, and HOMA index were calculated in all study subjects. Linear regression analyses were performed to assess the relationships between glucose and insulin levels with right ventricle volumes and lung volumes adjusted for age, sex, BMI, and cardiovascular risk factors.

Results

In univariate and multivariate-adjusted models, high serum insulin was inversely associated with end-diastolic volume (β = −12.43, P < 0.001), end-systolic volume (β = −7.12, P < 0.001), stroke volume (β = −5.32, P < 0.001), but not with ejection fraction. The association remained significant after additional adjustment for lung volumes. Similarly, serum insulin was inversely associated with lung volume (β = −0.15, P = 0.04). Sensitivity analysis confirmed results after excluding subjects with known diabetes.

Conclusions

Serum insulin was inversely associated with right ventricle function and lung volumes in subjects from the general population free of cardiovascular disease, suggesting that increased insulin levels may contribute to subclinical cardiopulmonary circulation impairment.

 

     European Society of Endocrinology

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  • 1

    American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2009 32 (Supplement 1) S62S 6 7. (https://doi.org/10.2337/dc09-S062)

    • Search Google Scholar
    • Export Citation
  • 2

    Nano J, Dhana K, Asllanaj E, Sijbrands E, Ikram MA, Dehghan A, Muka T & Franco OH Trajectories of BMI before diagnosis of Type 2 diabetes: the Rotterdam Study. Obesity 2020 28 114911 56. (https://doi.org/10.1002/oby.22802)

    • Search Google Scholar
    • Export Citation
  • 3

    Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Després J-P & Fullerton HJ Heart disease and stroke statistics-2016 update. Circulation 2016 133 38.e360. (https://doi.org/10.1161/CIR.0000000000000350)

    • Search Google Scholar
    • Export Citation
  • 4

    Low Wang CC, Hess CN, Hiatt WR & Goldfine AB Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus – mechanisms, management, and clinical considerations. Circulation 2016 133 24592 502. (https://doi.org/10.1161/CIRCULATIONAHA.116.022194)

    • Search Google Scholar
    • Export Citation
  • 5

    Willson C, Watanabe M, Tsuji-Hosokawa A & Makino A Pulmonary vascular dysfunction in metabolic syndrome. Journal of Physiology 2019 597 112111 41. (https://doi.org/10.1113/JP275856)

    • Search Google Scholar
    • Export Citation
  • 6

    Kenny HC & Abel ED Heart failure in type 2 diabetes mellitus. Circulation Research 2019 124 1211 41. (https://doi.org/10.1161/CIRCRESAHA.118.311371)

    • Search Google Scholar
    • Export Citation
  • 7

    Patscheider H, Lorbeer R, Auweter S, Schafnitzel A, Bayerl C, Curta A, Rathmann W, Heier M, Mesinger C & Peters A Subclinical changes in MRI-determined right ventricular volumes and function in subjects with prediabetes and diabetes. European Radiology 2018 28 31053113. (https://doi.org/10.1007/s00330-017-5185-1)

    • Search Google Scholar
    • Export Citation
  • 8

    Wallace TM, Levy JC & Matthews DR Use and abuse of HOMA modeling. Diabetes Care 2004 27 148714 95. (https://doi.org/10.2337/diacare.27.6.1487)

  • 9

    Velagaleti RS, Gona P, Chuang ML, Salton CJ, Fox CS, Blease SJ, Yeon SB, Manning WJ & O’Donnell CJ Relations of insulin resistance and glycemic abnormalities to cardiovascular magnetic resonance measures of cardiac structure and function: the Framingham Heart Study. Circulation: Cardiovascular Imaging 2010 3 2572 63. (https://doi.org/10.1161/CIRCIMAGING.109.911438)

    • Search Google Scholar
    • Export Citation
  • 10

    Demmer RT, Allison MA, Cai J, Kaplan RC, Desai AA, Hurwitz BE, Newman JC, Shah SJ, Swett K & Talavera GA Association of impaired glucose regulation and insulin resistance with cardiac structure and function: results from ECHO-SOL (echocardiographic study of latinos). Circulation: Cardiovascular Imaging 2016 9 e005032. (https://doi.org/10.1161/CIRCIMAGING.116.005032)

    • Search Google Scholar
    • Export Citation
  • 11

    Fontes-Carvalho R, Ladeiras-Lopes R, Bettencourt P, Leite-Moreira A & Azevedo A Diastolic dysfunction in the diabetic continuum: association with insulin resistance, metabolic syndrome and type 2 diabetes. Cardiovascular Diabetology 2015 14 4. (https://doi.org/10.1186/s12933-014-0168-x)

    • Search Google Scholar
    • Export Citation
  • 12

    Cauwenberghs N, Knez J, Thijs L, Haddad F, Vanassche T, Yang WY, Wei FF, Staessen JA & Kuznetsova T Relation of insulin resistance to longitudinal changes in left ventricular structure and function in a general population. Journal of the American Heart Association 2018 7 e008315. (https://doi.org/10.1161/JAHA.117.008315)

    • Search Google Scholar
    • Export Citation
  • 13

    Markus MRP, Rospleszcz S, Ittermann T, Baumeister SE, Schipf S, Siewert-Markus U, Lorbeer R, Storz C, Ptushkina V & Peters A Glucose and insulin levels are associated with arterial stiffness and concentric remodeling of the heart. Cardiovascular Diabetology 2019 18 145. (https://doi.org/10.1186/s12933-019-0948-4)

    • Search Google Scholar
    • Export Citation
  • 14

    Shah SJ Pulmonary hypertension. JAMA 2012 308 136613 74. (https://doi.org/10.1001/jama.2012.12347)

  • 15

    Mueller J, Karrasch S, Lorbeer R, Ivanovska T, Pomschar A, Kunz WG, von Krüchten R, Peters A, Bamberg F & Schulz H Automated MR-based lung volume segmentation in population-based whole-body MR imaging: correlation with clinical characteristics, pulmonary function testing and obstructive lung disease. European Radiology 2019 29 15951 606. (https://doi.org/10.1007/s00330-018-5659-9)

    • Search Google Scholar
    • Export Citation
  • 16

    Holle R, Happich M, Lowel H, Wichmann HEMONICA/KORA Study Group. KORA – a research platform for population based health research. Gesundheitswesen 2005 67 (Supplement 1) S19S 25. (https://doi.org/10.1055/s-2005-858235)

    • Search Google Scholar
    • Export Citation
  • 17

    Bamberg F, Hetterich H, Rospleszcz S, Lorbeer R, Auweter SD, Schlett CL, Schafnitzel A, Bayerl C, Schindler A & Saam T Subclinical disease burden as assessed by whole-body MRI in subjects with prediabetes, subjects with diabetes, and normal control subjects from the general population: the KORA-MRI Study. Diabetes 2017 66 1581 69. (https://doi.org/10.2337/db16-0630)

    • Search Google Scholar
    • Export Citation
  • 18

    World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013 310 2191219 4. (https://doi.org/10.1001/jama.2013.281053)

    • Search Google Scholar
    • Export Citation
  • 19

    Schulz-Menger J, Bluemke DA, Bremerich J, Flamm SD, Fogel MA, Friedrich MG, Kim RJ, von Knobelsdorff-Brenkenhoff F, Kramer CM & Pennell DJ Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing. Journal of Cardiovascular Magnetic Resonance 2013 15 35. (https://doi.org/10.1186/1532-429X-15-35)

    • Search Google Scholar
    • Export Citation
  • 20

    Kawel-Boehm N, Maceira A, Valsangiacomo-Buechel ER, Vogel-Claussen J, Turkbey EB, Williams R, Plein S, Tee M, Eng J & Bluemke DA Normal values for cardiovascular magnetic resonance in adults and children. Journal of Cardiovascular Magnetic Resonance 2015 17 29. (https://doi.org/10.1186/s12968-015-0111-7)

    • Search Google Scholar
    • Export Citation
  • 21

    Ivanovska T, Hegenscheid K, Laqua R, Kühn JP, Gläser S, Ewert R, Hosten N, Puls R & Völzke H A fast and accurate automatic lung segmentation and volumetry method for MR data used in epidemiological studies. Computerized Medical Imaging and Graphics 2012 36 2812 93. (https://doi.org/10.1016/j.compmedimag.2011.10.001)

    • Search Google Scholar
    • Export Citation
  • 22

    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF & Turner RC Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985 28 41241 9. (https://doi.org/10.1007/BF00280883)

    • Search Google Scholar
    • Export Citation
  • 23

    Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia. Geneva: WHO. (available at: https://www.who.int/diabetes/publications/diagnosis_diabetes2006/en/)

    • Search Google Scholar
    • Export Citation
  • 24

    Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, Kusek JW, Eggers P, Van Lente F & Greene T A new equation to estimate glomerular filtration rate. Annals of Internal Medicine 2009 150 6046 12. (https://doi.org/10.7326/0003-4819-150-9-200905050-00006)

    • Search Google Scholar
    • Export Citation
  • 25

    Shah RV, Abbasi SA, Heydari B, Rickers C, Jacobs DR Jr, Wang L, Kwong RY, Bluemke DA, Lima JAC & Jerosch-Herold M Insulin resistance, subclinical left ventricular remodeling, and the obesity paradox: MESA (Multi-Ethnic Study of Atherosclerosis). Journal of the American College of Cardiology 2013 61 16981 706. (https://doi.org/10.1016/j.jacc.2013.01.053)

    • Search Google Scholar
    • Export Citation
  • 26

    Szablewski L Glucose transporters in healthy heart and in cardiac disease. International Journal of Cardiology 2017 230 707 5. (https://doi.org/10.1016/j.ijcard.2016.12.083)

    • Search Google Scholar
    • Export Citation
  • 27

    Gibbs EM, Stock JL, McCoid SC, Stukenbrok HA, Pessin JE, Stevenson RW, Milici AJ & McNeish JD Glycemic improvement in diabetic db/db mice by overexpression of the human insulin-regulatable glucose transporter (GLUT4). Journal of Clinical Investigation 1995 95 1512151 8. (https://doi.org/10.1172/JCI117823)

    • Search Google Scholar
    • Export Citation
  • 28

    Witteles RM & Fowler MB Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options. Journal of the American College of Cardiology 2008 51 93102. (https://doi.org/10.1016/j.jacc.2007.10.021)

    • Search Google Scholar
    • Export Citation
  • 29

    Mujaj B, Bos D, Kavousi M, van der Lugt A, Staessen JA, Franco OH & Vernooij MW Serum insulin levels are associated with vulnerable plaque components in the carotid artery: the Rotterdam Study. European Journal of Endocrinology 2020 182 3433 50. (https://doi.org/10.1530/EJE-19-0620)

    • Search Google Scholar
    • Export Citation
  • 30

    Kolodgie FD, Gold HK, Burke AP, Fowler DR, Kruth HS, Weber DK, Farb A, Guerrero LJ, Hayase M & Kutys R Intraplaque hemorrhage and progression of coronary atheroma. New England Journal of Medicine 2003 349 23162 32 5. (https://doi.org/10.1056/NEJMoa035655)

    • Search Google Scholar
    • Export Citation
  • 31

    Ford ES, Zhao G & Li C Pre-diabetes and the risk for cardiovascular disease: a systematic review of the evidence. Journal of the American College of Cardiology 2010 55 1310131 7. (https://doi.org/10.1016/j.jacc.2009.10.060)

    • Search Google Scholar
    • Export Citation
  • 32

    Michelakis ED, Wilkins MR & Rabinovitch M Emerging concepts and translational priorities in pulmonary arterial hypertension. Circulation 2008 118 148614 95. (https://doi.org/10.1161/CIRCULATIONAHA.106.673988)

    • Search Google Scholar
    • Export Citation
  • 33

    He Z, Opland DM, Way KJ, Ueki K, Bodyak N, Kang PM, Izumo S, Kulkarni RN, Wang B & Liao R Regulation of vascular endothelial growth factor expression and vascularization in the myocardium by insulin receptor and PI3K/Akt pathways in insulin resistance and ischemia. Arteriosclerosis, Thrombosis, and Vascular Biology 2006 26 7877 93. (https://doi.org/10.1161/01.ATV.0000209500.15801.4e)

    • Search Google Scholar
    • Export Citation
  • 34

    Kaner RJ, Ladetto JV, Singh R, Fukuda N, Matthay MA & Crystal RG Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. American Journal of Respiratory Cell and Molecular Biology 2000 22 6576 6 4. (https://doi.org/10.1165/ajrcmb.22.6.3779)

    • Search Google Scholar
    • Export Citation
  • 35

    Partovian C, Adnot S, Raffestin B, Louzier V, Levame M, Mavier IM, Lemarchand P & Eddahibi S Adenovirus-mediated lung vascular endothelial growth factor overexpression protects against hypoxic pulmonary hypertension in rats. American Journal of Respiratory Cell and Molecular Biology 2000 23 7627 7 1. (https://doi.org/10.1165/ajrcmb.23.6.4106)

    • Search Google Scholar
    • Export Citation
  • 36

    Gómez A, Bialostozky D, Zajarias A, Santos E, Palomar A, Martínez ML & Sandoval J Right ventricular ischemia in patients with primary pulmonary hypertension. Journal of the American College of Cardiology 2001 38 113711 42. (https://doi.org/10.1016/s0735-1097(0101496-6)

    • Search Google Scholar
    • Export Citation
  • 37

    Thrainsdottir IS, Aspelund T, Hardarson T, Malmberg K, Sigurdsson G, Thorgeirsson G, Gudnason V & Rydén L Glucose abnormalities and heart failure predict poor prognosis in the population-based Reykjavík Study. European Journal of Cardiovascular Prevention and Rehabilitation 2005 12 4654 71. (https://doi.org/10.1097/01.hjr.0000173105.91356.4d)

    • Search Google Scholar
    • Export Citation
  • 38

    Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant CAmerican Heart Association & National Heart, Lung, and Blood Institute. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004 109 43343 8. (https://doi.org/10.1161/01.CIR.0000111245.75752.C6)

    • Search Google Scholar
    • Export Citation