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; M. St John Sutton; T. Schuster; A. Ceriello; T. Siegmund; P.-M. Schumm-Draeger

doi:10.1055/s-0033-1333752

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2013; 45(06): 449-455
DOI: 10.1055/s-0033-1333752

Humans, Clinical

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

¹Department of Endocrinology, Diabetes and Vascular Medicine, Teaching Hospital München-Bogenhausen of the Technische Universität, Munich, Germany

,

M. St John Sutton

²Department of Medicine, Cardiovascular Division, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA

,

T. Schuster

³Institute for Statistics and Epidemiology in Medicine of the Technische Universität, Munich, Germany

,

A. Ceriello

⁴Institut 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

¹Department of Endocrinology, Diabetes and Vascular Medicine, Teaching Hospital München-Bogenhausen of the Technische Universität, Munich, Germany

,

P.-M. Schumm-Draeger

¹Department of Endocrinology, Diabetes and Vascular Medicine, Teaching Hospital München-Bogenhausen of the Technische Universität, Munich, Germany

› Author Affiliations

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

Full Text

References

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
2 Fang ZY. Diabetic cardiomyopathy: evidence, mechanisms and therapeutic implications. Endocr Rev 2004; 25: 543-567
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
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
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
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
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
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
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
10 Witteles RM, Fowler MB. Insulin-resistant cardiomyopathy. J Am Coll Cardiol 2008; 51: 93-102
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
12 Xu J, Zou MH. Molecular insights and therapeutic targets for diabetic endothelial dysfunction. Circulation 2009; 120: 1266-1286
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
14 Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813-820
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
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
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
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
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
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
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
22 Taegtmeyer H, McNulty P, Young ME. Adaptation and maladaptation of the heart in diabetes. I. General concepts. Circulation 2002; 105: 1727-1733
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
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
25 Boudina S, Abel ED. Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes. Physiology 2006; 21: 250-258
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
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
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
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
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
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
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
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