Download PDF
Horm Metab Res 2013; 45(06): 449-455
DOI: 10.1055/s-0033-1333752
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Oxidative Stress after a Carbohydrate Meal Contributes to the Deterioration of Diastolic Cardiac Function in Nonhypertensive Insulin-treated Patients with Moderately Well Controlled Type 2 Diabetes

H. von Bibra
1   Department of Endocrinology, Diabetes and Vascular Medicine, Teaching Hospital München-Bogenhausen of the Technische Universität, Munich, Germany
,
M. St John Sutton
2   Department of Medicine, Cardiovascular Division, University of ­Pennsylvania, School of Medicine, Philadelphia, PA, USA
,
T. Schuster
3   Institute for Statistics and Epidemiology in Medicine of the Technische Universität, Munich, Germany
,
A. Ceriello
4   Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
,
T. Siegmund
1   Department of Endocrinology, Diabetes and Vascular Medicine, Teaching Hospital München-Bogenhausen of the Technische Universität, Munich, Germany
,
P.-M. Schumm-Draeger
1   Department of Endocrinology, Diabetes and Vascular Medicine, Teaching Hospital München-Bogenhausen of the Technische Universität, Munich, Germany
› Author Affiliations
Further Information

Publication History

received 09 September 2012

accepted 10 January 2013

Publication Date:
20 February 2013 (online)

Also available at
    Permissions and Reprints

Abstract

The prevalence and prognostic importance of diastolic dysfunction in type 2 diabetes has only recently been appreciated. We tested the hypothesis that in insulin treated type 2 diabetes (D), carbohydrate consumption induces oxidative stress resulting in further impairment of diastolic function beyond structural myocardial stiffness. The effects of a pure carbohydrate breakfast (48 g) on oxidative stress and cardiac function were studied in the fasting and postmeal states in subjects without hypertension or overt cardiac disease (moderately well controlled D, n=21 and controls without D, n=20). Studied variables included systolic and early diastolic (E′) myocardial velocities, traditional metabolic and hemodynamic parameters, serum nitrotyrosine, and sVCAM-1. In D compared to control subjects, the postmeal increase (∆) in glucose (1.44±2.78 vs. 0.11±0.72 mmol/l, p=0.04) and ∆nitrotyrosine (0.34±0.37 vs.  − 0.23±0.47 nM/l, p<0.001) were significantly higher. sVCAM-1 was higher in fasting and postmeal (p=0.02). E′ was significantly lower in postmeal (7.3±1.3 vs. 9.6±1.3 cm/s, p<0.001) and fasting (p<0.001) whereas the rate pressure product was significantly higher (9 420±1 118 vs. 7 705±1 871 mm Hg/min, p<0.001). Multivariable regression models of the pooled data demonstrated that independent predictors for postmeal E′ were ∆nitrotyrosine and septal thickness (R2 0.466) and for fasting E′ age, ∆nitrotyrosine, and septal thickness (R2 0.400). In insulin requiring type 2 diabetes, carbohydrate consumption may induce oxidative stress that is associated with worsening diastolic function, indicating that this metabolic factor is an important determinant of diastolic dysfunction in the diabetic heart beyond the increase in structural myocardial stiffness.

Key words

diastolic function - type 2 diabetes - oxidative stress - postmeal hyperglycemia - tissue Doppler
 

  • References

  • 1 von Bibra H, St John Sutton M. Diastolic dysfunction in diabetes and the metabolic syndrome – promising potential for diagnosis and prognosis. Diabetologia 2010; 53: 1033-1045
    CrossrefPubMedGoogle Scholar
  • 2 Fang ZY. Diabetic cardiomyopathy: evidence, mechanisms and therapeutic implications. Endocr Rev 2004; 25: 543-567
    CrossrefPubMedGoogle Scholar
  • 3 Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95 783 individuals followed for 12.4 years. Diabetes Care 1999; 22: 233-240
    CrossrefPubMedGoogle Scholar
  • 4 Colette C, Monnier L. Acute glucose fluctuations and chronic sustained hyperglycemia as risk factors for cardiovascular diseases in patients with type 2 diabetes. Horm Metab Res 2007; 39: 683-686
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Chiasson JL. Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial. Endocr Pract 2006; 12 (Suppl. 01) 25-30
    CrossrefPubMedGoogle Scholar
  • 6 von Bibra H, Siegmund T, Ceriello A, Volozhyna M, Schumm-Draeger PM. Optimized postmeal glucose control is associated with improved cardiac/vascular function – comparison of three insulin regimens in well controlled type 2 diabetes. Hormone Metab Res 2009; 41: 109-115
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Ceriello A, Quagliaro L., Piconi L, Assaloni R, Da Ros R, Maier A, Esposito K, Giugliano D. Effect of postmeal hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes 2004; 53: 701-710
    CrossrefPubMedGoogle Scholar
  • 8 Esposito K, Guigliano D, Nappo F. Marfella R for the Campanian Hyperglycemia Study Group . Regression of carotid atherosclerosis by control of postmeal hyperglycemia in type 2 diabetes mellitus. Circulation 2004; 110: 214-219
    CrossrefPubMedGoogle Scholar
  • 9 Ritchie RH. Evidence for a causal role of oxidative stress in the myocardial complications of insulin resistance. Heart, Lung & Circulations 2009; 18: 11-18
    PubMedGoogle Scholar
  • 10 Witteles RM, Fowler MB. Insulin-resistant cardiomyopathy. J Am Coll Cardiol 2008; 51: 93-102
    CrossrefPubMedGoogle Scholar
  • 11 von Bibra H, Thrainsdottir IS, Hansen A, Dounis V, Malmberg K, Rydén L. Tissue Doppler imaging for the detection and quantitation of myocardial dysfunction in patients with type 2 diabetes mellitus: A methodological study. Diabetes Vasc Dis Res 2005; 2: 483-487
    PubMedGoogle Scholar
  • 12 Xu J, Zou MH. Molecular insights and therapeutic targets for diabetic endothelial dysfunction. Circulation 2009; 120: 1266-1286
    CrossrefPubMedGoogle Scholar
  • 13 von Bibra H, Hansen A, Dounis V, Bystedt T, Malmberg K, Rydén L. Insulin based improved metabolic control augments myocardial diastolic function and perfusion in patients with type 2 diabetes mellitus. Heart 2004; 90: 1483-1484
    CrossrefPubMedGoogle Scholar
  • 14 Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813-820
    CrossrefPubMedGoogle Scholar
  • 15 Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase-C dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 2000; 49: 1939-1945
    CrossrefPubMedGoogle Scholar
  • 16 Forst T, Hohberg H, Pfützner A. Cardiovascular effects of disturbed insulin activity in metabolic syndrome and in type 2 diabetic patients. Horm Metab Res 2009; 41: 123-131
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Poirier P, Garneau C, Bogaty P, Nadeau A, Marois L, Brochu C, Gingras C, Fortin C, Jobin J, Dumesnil JG. Impact of left ventricular diastolic dysfunction on maximal treadmill performance in normotensive subjects with well-controlled type 2 diabetes mellitus. l Am J Cardiol 2000; 85: 473-477
    PubMedGoogle Scholar
  • 18 Bella JN, Palmieri V, Roman MJ, Liu JE, Welty TK, Lee ET, Fabsitz RR, Howard BV, Devereux RB. Mitral ratio of peak early to late diastolic filling velocity as a predictor of mortality in middle-aged and elderly adults. The Strong Heart Study. Circulation 2002; 105: 1928-1933
    CrossrefPubMedGoogle Scholar
  • 19 Westermann D, Kasner M, Stendijk P, Spillmann F, Riad A, Weitmann K, Hoffmann W, Poller W, Pauschinger M, Schultheiss HP, Tschöpe C. Role of left ventricular stiffness in heart failure with normal ejection fraction. Circulation 2008; 117: 2051-2060
    CrossrefPubMedGoogle Scholar
  • 20 van Heerebeek L, Hamdani N, Handoko ML, Falcao-Pires I, Musters RJ, Kupreishvili K, Ijsselmuiden AJ, Schalkwijk CG, Bronzwaer JG, Diamant M, Borbély A, van der Velden J, Stienen GJ, Laarman GJ, Niessen HW, Paulus WJ. Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation 2008; 117: 43-51
    CrossrefPubMedGoogle Scholar
  • 21 Scognamiglio R, Negut C, Vigili De Kreuzenberg S, Tiengo A, Avogaro A. Postprandial myocardial perfusion in healthy subjects and in type 2 diabetic patients. Circulation 2005; 112: 179-184
    CrossrefPubMedGoogle Scholar
  • 22 Taegtmeyer H, McNulty P, Young ME. Adaptation and maladaptation of the heart in diabetes. I. General concepts. Circulation 2002; 105: 1727-1733
    CrossrefPubMedGoogle Scholar
  • 23 Yu CM, Sanderson JE, Marwick TH, Oh JK. Tissue Doppler Imaging. A new prognosticator for cardiovascular disease. J Am Coll Cardiol 2007; 49: 1903-1914
    CrossrefPubMedGoogle Scholar
  • 24 Falk Peterson K, Dufour S, Savage DB, Bilz S, Solomon G, Yonemitsu S, Cline GW, Befroy D, Zemany L, Kahn BB, Papademetris X, Rothman DL, Shulman GI. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proc Natl Acad Sci USA 2007; 104: 12587-12594
    CrossrefPubMedGoogle Scholar
  • 25 Boudina S, Abel ED. Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes. Physiology 2006; 21: 250-258
    CrossrefPubMedGoogle Scholar
  • 26 Hansen A, Johansson BL, Warren C, von Bibra H. C-peptide exerts beneficial effects on myocardial blood flow and function in patients with type 1 diabetes. Diabetes 2002; 51: 3077-3082
    CrossrefPubMedGoogle Scholar
  • 27 von Bibra H, Diamant M, Scheffer PG, Siegmund T, Schumm-Draeger P-M. Rosiglitazone, but not glimepiride, improves myocardial diastolic function in association with a reduction of oxidative stress and inflammation in patients with type 2 diabetes mellitus. Diabetes Vasc Dis Res 2008; 5: 310-318
    CrossrefPubMedGoogle Scholar
  • 28 Rudofsky G, Roeder E, Merle T, Hildebrand M, Nawroth PP, Wolfrum C. Weight loss improves endothelial function independent of ADMA reduction in severe obesity. Horm Metab Res 2011; 43: 343-348
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 von Bibra H, St John Sutton M. Impact of diabetes on postinfarction heart failure and left ventricular remodeling. Curr Heart Fail Rep 2011; 8: 242-251
    CrossrefPubMedGoogle Scholar
  • 30 Irribarren C, Karter AJ, Go AS, Ferrara A, Liu JY, Sidney S, Selby JV. Glycemic control and heart failure among adult patients with diabetes. Circulation 2001; 103: 2668-2673
    CrossrefPubMedGoogle Scholar
  • 31 Schwarz PE, Greaves CJ, Lindstrom J, Yates T, Davies MJ. Nonpharmacological interventions for the prevention of type 2 diabetes mellitus. Nat Rev Endocrinol 2012; 8: 363-373
    PubMedGoogle Scholar
  • 32 Lindstrom J, Neumann A, Sheppard KE, Gilis-Januszewska A, Greaves CJ, Handke U, Pajunen P, Puhl S, Polonen A, Rissanen A, Roden M, Stemper T, Telle-Hjellset V, Tuomilehto J, Velickiene D, Schwarz PE. for the IMAGE, Group . Take action to prevent diabetes – the IMAGE toolkit for the prevention of type 2 diabetes in Europe. Horm Metab Res 2010; 42 (Suppl. 01) S37-S55
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Ouwens DM, Diamant M. Myocardial insulin action and the contribution of insulin resistance to the pathogenesis of diabetic cardiomyopathy. Arch Phys Biochem 2007; 113: 76-85
    PubMedGoogle Scholar