Verbesserung der Myokardfunktion durch verbesserte Stoffwechselkontrolle bei Typ-2-Diabetes

 

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Zusammenfassung

Hintergrund und Fragestellung: Bei Patienten mit Typ-2-Diabetes ist die myokardiale diastolische Dysfunktion ein häufiges und prognostisch ungünstiges Phänomen. In einer Kurz- und Langzeitstudie wurde die Hypothese getestet, dass die myokardiale Funktion durch bessere Blutzuckereinstellung kurz- und langfristig optimiert werden kann.

Methoden: In einer 3-wöchigen Kurz- und 52-wöchigen Langzeitstudie wurden bei 33 bzw. 50 Patienten durch intensivierte Insulintherapie niedrigere Blutzuckerwerte angestrebt. Vor und nach der Therapiemodifikation wurde die Myokardfunktion mittels gepulstem Gewebe-Doppler als systolische (Vs) und diastolische myokardiale Geschwindigkeit (Ve) bestimmt. Den 25 Patienten mit Therapieintensivierung in der Kurzzeitstudie standen als Kontrollgruppe 8 Patienten gegenüber und analog in der Langzeitstudie 39 vs. 11 Patienten.

Ergebnisse: In der Kurzzeitstudie reduzierte sich der Nüchternblutzucker unter intensivierter Insulintherapie um 69 ± 47 mg/dl (p < 0,01), assoziiert mit einem Anstieg der diastolischen Myokardgeschwindigkeit Ve von 8,0 ± 1,6 auf 8,8 ± 1,6 cm/s (p < 0,01) parallel zu Vs (6,2 ± 1,1 zu 6,6 ± 1,3 cm/s, p < 0,04). In der Kontrollgruppe blieben Blutzucker, Vs und Ve unverändert. In der Langzeitstudie sank der Blutzucker um 20 ± 43 mg/dl (p < 0,017) assoziiert mit einem Ve-Anstieg von 7,6 ±1,3 auf 8,3±1,7 cm/s (p < 0,002) parallel zum Trend in Vs (7,4 ± 0,9 zu 7,7 ± 0,9 cm/s, p < 0,07). In der Kontrollgruppe blieben Blutzucker und Myokardgeschwindigkeiten unverändert. Bei den gepoolten Daten korrelierte die Änderung von Ve signifikant mit der Veränderung des Blutzuckers (r = 0,49, p < 0,004 Kurzzeit- und r = 0,45; p < 0,002 Langzeitstudie).

Folgerungen: Die mit Gewebe-Doppler gemessene diastolische Myokardgeschwindigkeit als Maß für eine subklinisch reduzierte Myokardfunktion kann bei Typ-2-Diabetikern durch normnahe Stoffwechseleinstellung mittels intensivierter Insulintherapie verbessert werden.

Summary

Background: In patients with type 2 diabetes mellitus diastolic dysfunction is a frequent manifestation of myocardial disease with poor prognosis. The hypothesis that better glycemic control results in improved myocardial function was tested using tissue Doppler.

Methods: During a short-term (3 weeks) and a long-term (52 weeks) study, metabolic control and myocardial function were evaluated in 33 and 50 patients, respectively, with type 2 diabetes. Systolic (Vs) and diastolic (Ve) myocardial velocity were assessed by tissue Doppler. In the short-term study, antidiabetic therapy was intensified in 25 patients (Int3) and compared to those eight individuals with unchanged therapy (Con3), similarly to the long-term study with Int52 (n = 39) and Con52 (n = 11).

Results: In Int3, fasting serum glucose was reduced by 69±47 mg/dl (p < 0.01) compared to baseline and was associated with an increase of Ve from 8.0 ± 1.6 to 8.8 ± 1.6 cm/s (p < 0.01) and Vs from 6.2 ± 1.1 to 6.6 ± 1.3 cm/s, p < 0.04. In Con3, serum glucose and myocardial velocities were unchanged. In Int52, fasting serum glucose was reduced by 20 ± 43 mg/dl (p < 0.017) compared to baseline and was associated with an increase of Ve from 7.6 ± 1.3 to 8.3 ± 1.7 cm/s (p < 0.002) and a similar trend in Vs (p < 0.07). In Con52, serum glucose and myocardial velocities remained unchanged. Evaluating pooled data, the changes of diastolic myocardial velocity correlated significantly with the changes of serum glucose (r = 0.49, p < 0.004 short- and r = 0.45; p < 0.002 long-term study, respectively).

Conclusion: In patients with type 2 diabetes subclinical diastolic myocardial dysfunction, measured as diastolic myocardial velocity by tissue Doppler, improves with better glycemic control.

Literatur

• 1 Appleton C P, Hatle L K. The natural history of left ventricular filling abnormalities: assessment by two-dimensional and Doppler echocardiography.  Echocardiography. 1992;  9 438-457
  Google Scholar
• 2 Aurigemma G P, Silver K H, Priest M A, Gaasch W H. Geometric changes allow normal ejection fraction despite depressed myocardial shortening in hypertensive left ventricular hypertrophy.  J Am Coll Cardiol. 1995;  26 195-202
  Google Scholar
• 3 Avgeropoulou C, Illmann A, Schumm-Draeger P M, Kallikazaros J, von Bibra H. Assessment of arterio-ventriculo coupling in well controlled type 2 diabetes mellitus and controls by tissue doppler and wave intensity approach.  Brit J Diabetes Vasc Dis. 2006;  6 271-278
  Google Scholar
• 4 Bella J N, Palmieri V, Roman M J. et al . 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
  Google Scholar
• 5 von Bibra H, Tuchnitz A, Klein A, Schneider-Eicke J, Schömig A, Schwaiger M. Regional diastolic function by pulsed Doppler myocardial mapping for the detection of left ventricular ischemia during pharmacologic stress testing - a comparison with stress echocardiography and perfusion scintigraphy.  J Am Coll Cardiol. 2000;  36 444-452
  Google Scholar
• 6 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
  Google Scholar
• 7 von Bibra H, Thrainsdottir I S, 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
  Google Scholar
• 8 Brownlee M. Glycation products and the pathogenesis of diabetic complications.  Diabetes Care. 1992;  15 1835-1843
  Google Scholar
• 9 Celentano A, Vaccaro O, Tammaro P, Galderisi M, Crivaro M, Oliviero M. et al . Early abnormalities of cardiac function in non-insulin-dependent diabetes mellitus and impaired glucose tolerance.  Am J Cardiol. 1995;  76 1173-1176
  Google Scholar
• 10 Devereux R B, Roman M J, Liu J E. et al . Congestive heart failure despite normal left ventricular systolic function in a population-based sample: the strong heart study.  Am J Cardiol. 2000;  86 1090-1096
  Google Scholar
• 11 Diamant M, Lamb H J, Groeneveld Y. et al . Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus.  J Am Coll Cardiol. 2003;  42 328-335
  Google Scholar
• 12 Diamant M, Tushuizen M E. The metabolic syndrome and endothelial dysfunction: common highway to type 2 diabetes and CVD?.  Curr Diab Rep. 2006;  6 279-286
  Google Scholar
• 13 Fang Z Y, Yuda S, Anderson V. et al . Echocardiographic detection of early diabetic myocardial disease.  J Am Coll Cardiol. 2003;  41 611-617
  Google Scholar
• 14 Fischer M, Baessler A, Hense H W. et al . Prevalence of left ventricular diastolic dysfunction in the community. Results from a Doppler echocardiographic-based survey of a population sample.  Eur Heart J. 2003;  24 320-328
  Google Scholar
• 15 Fukuta H, Sane D C, Brucks S, Little W C. Statin therapy may be associated with lower mortality in patients with diastolic heart failure - a preliminary report.  Circulation. 2005;  112 357-363
  Google Scholar
• 16 Gæde P, Vedel P, Larsen N, Jensen G VH, Parving H -H, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.  N Engl J Med. 2003;  348 383-393
  Google Scholar
• 17 Gaenzer H, Neumayr G, Marschang P. et al . Effect of insulin therapy on endothelium-dependent dilatation in type 2 diabetes.  Am J Cardiol. 2002;  89 431-414
  Google Scholar
• 18 Gilbert J C, Glantz S A. Determinants of left ventricular filling and of the diastolic pressure-volume relation.  Circulation Research. 1989;  64 827-851
  Google Scholar
• 19 Hansen A, Johansson B L, Wahren J, von Bibra H. Beneficial effects of C-peptide on myocardial function in patients with type 1 diabetes.  Diabetes. 2002;  51 3077-3082
  Google Scholar
• 20 Jain A, Avendano G, Dharamsey S. et al . Left ventricular diastolic function in hypertension and role of plasma glucose and insulin. Comparison with diabetic heart.  Circulation. 1996;  93 1396-1402
  Google Scholar
• 21 Liu J E, Palmieri V, Roman M J. et al . The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: The strong heart study.  J Am Coll Cardiol. 2001;  37 1943-1949
  Google Scholar
• 22 Poirier P, Bogaty P, Garneau C, Marois L, Dumesnil J G. Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: Importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy.  Diabetes Care. 2001;  24 5-10
  Google Scholar
• 23 Rask-Madsen C, Ihleman N, Krarup T. et al . Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease.  Diabetes. 2001;  50 2611-2618
  Google Scholar
• 24 Saraiva R M, Duarte D M, Duarte M P. et al . Tissue Doppler imaging identifies asymptomatic normotensive diabetics with diastolic dysfunction and reduced exercise tolerance.  Echocardiography. 2005;  22 561-567
  Google Scholar
• 25 Sohn D W, Chai I H, Lee D J. et al . Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function.  J Am Coll Cardiol. 1997;  30 474-480
  Google Scholar
• 26 Strauer B E, Motz W, Vogt M, Schwartzkopf B. Impaired coronary flow reserve in NIDDM. A possible role for diabetic cardiomyopathy in humans.  Diabetes. 1997;  46 (Suppl 2) 119-124
  Google Scholar
• 27 Vinereanu D, Nicolaides E, Tweddel A. et al . Subclinical left ventricular dysfunction in asymptomatic patients with type 2 diabetes mellitus, related to serum lipids and glycated haemoglobin.  Clinical Science. 2003;  105 591-599
  Google Scholar
• 28 Wiernsperger N F. In defense of microvascular constriction in diabetes.  Clin Hemorheol Microcirc. 2001;  25 55-62
  Google Scholar
• 29 Williams S B, Goldfine A B, Timimi F K, Ting H H, Roddy M A, Creafer M A. Acute hyperglycemia attenuates endothelium-dependent vasodilatation in humans.  Circulation. 1998;  97 1695-1701
  Google Scholar

Prof. Dr. Helene von Bibra

Abt. für Endokrinologie, Diabetologie und Angiologie, Städt. Klinikum GmbH, München-Bogenhausen

Englschalkingerstraße 77

81925 München

Phone: 0049/89/92702118

Fax: 0049/89/92702116

Email: von-Bibra@extern.lrz-muenchen.de