Skip to main content
Top
Published in: Diabetologia 6/2004

01-06-2004 | Article

Effects of metoprolol on QT interval and QT dispersion in Type 1 diabetic patients with abnormal albuminuria

Authors: E. Ebbehøj, H. Arildsen, K. W. Hansen, C. E. Mogensen, H. Mølgaard, P. L. Poulsen

Published in: Diabetologia | Issue 6/2004

Login to get access

Abstract

Aims/hypothesis

The excess mortality in diabetes is mainly due to cardiovascular causes and almost confined to patients with abnormal albuminuria. Compared to healthy subjects, diabetic patients have a prolonged QT interval and increased QT dispersion. In non-diabetic subjects, as well as in Type 1 diabetic patients with overt nephropathy, a prolonged QT interval and increased QT dispersion are associated with cardiac morbidity and mortality. There is an increasing number of studies on effects of beta blocker treatment on QT interval and QT dispersion in non-diabetic subjects. In contrast, there are no studies on the effects of beta blocker treatment on QT interval and QT dispersion in patients with diabetes. The aim of our study was to describe the effects of metoprolol treatment on QT interval and QT dispersion in a group of well-characterised Type 1 diabetic patients with elevated urine albumin excretion.

Methods

We studied the effects of 6 weeks of treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in a randomised, placebo-controlled, double blind, crossover trial including 20 Type 1 diabetic patients. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, 24-h ambulatory blood pressure recording and 24-h fractionated urine collections. On days of investigation 12-lead electrocardiograms were recorded and autonomic tests performed.

Results

We found strong associations between both daytime and night-time blood pressure and heart-rate-corrected QT interval dispersion (QTc dispersion). Heart rate variability parameters indicating sympathetic and parasympathetic modulation showed strong correlations with heart-rate-corrected QT interval (QTc interval) and with QTc dispersion. Beta blocker treatment caused a decrease in QTc interval but no change in QTc dispersion.

Conclusions/interpretation

This study is the first to address the QTc interval and QTc dispersion in Type 1 diabetic patients treated with metoprolol. Beta blocker treatment caused a decrease in QTc interval but no change in QTc dispersion. These results may in part explain the pronounced cardioprotective effect of beta blocker treatment in diabetic patients with cardiovascular disease.
Literature
1.
go back to reference Schouten EG, Dekker JM, Meppelink P, Kok FJ, Vandenbroucke JP, Pool J (1991) QT interval prolongation predicts cardiovascular mortality in an apparently healthy population. Circulation 84:1516–1523PubMed Schouten EG, Dekker JM, Meppelink P, Kok FJ, Vandenbroucke JP, Pool J (1991) QT interval prolongation predicts cardiovascular mortality in an apparently healthy population. Circulation 84:1516–1523PubMed
2.
go back to reference Malik M, Batchvarov VN (2000) Measurement, interpretation and clinical potential of QT dispersion. J Am Coll Cardiol 36:1749–1766CrossRefPubMed Malik M, Batchvarov VN (2000) Measurement, interpretation and clinical potential of QT dispersion. J Am Coll Cardiol 36:1749–1766CrossRefPubMed
3.
go back to reference Langen KJ, Ziegler D, Weise F et al. (1997) Evaluation of QT interval length, QT dispersion and myocardial m-iodobenzylguanidine uptake in insulin-dependent diabetic patients with and without autonomic neuropathy. Clin Sci (Colch ) 93:325–333 Langen KJ, Ziegler D, Weise F et al. (1997) Evaluation of QT interval length, QT dispersion and myocardial m-iodobenzylguanidine uptake in insulin-dependent diabetic patients with and without autonomic neuropathy. Clin Sci (Colch ) 93:325–333
4.
go back to reference Elming H, Holm E, Jun L et al. (1998) The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens. Eur Heart J 19:1391–1400CrossRefPubMed Elming H, Holm E, Jun L et al. (1998) The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens. Eur Heart J 19:1391–1400CrossRefPubMed
5.
go back to reference Dekker JM, Schouten EG, Klootwijk P, Pool J, Kromhout D (1994) Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen Study. Circulation 90:779–785PubMed Dekker JM, Schouten EG, Klootwijk P, Pool J, Kromhout D (1994) Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen Study. Circulation 90:779–785PubMed
6.
go back to reference Chambers JB, Sampson MJ, Sprigings DC, Jackson G (1990) QT prolongation on the electrocardiogram in diabetic autonomic neuropathy. Diabet Med 7:105–110PubMed Chambers JB, Sampson MJ, Sprigings DC, Jackson G (1990) QT prolongation on the electrocardiogram in diabetic autonomic neuropathy. Diabet Med 7:105–110PubMed
7.
go back to reference Sivieri R, Veglio M, Chinaglia A, Scaglione P, Cavallo-Perin P (1993) Prevalence of QT prolongation in a type 1 diabetic population and its association with autonomic neuropathy. The Neuropathy Study Group of the Italian Society for the Study of Diabetes. Diabet Med 10:920–924PubMed Sivieri R, Veglio M, Chinaglia A, Scaglione P, Cavallo-Perin P (1993) Prevalence of QT prolongation in a type 1 diabetic population and its association with autonomic neuropathy. The Neuropathy Study Group of the Italian Society for the Study of Diabetes. Diabet Med 10:920–924PubMed
8.
go back to reference Arildsen H, May O, Christiansen EH, Damsgaard EM (1999) Increased QT dispersion in patients with insulin-dependent diabetes mellitus. Int J Cardiol 71:235–242CrossRefPubMed Arildsen H, May O, Christiansen EH, Damsgaard EM (1999) Increased QT dispersion in patients with insulin-dependent diabetes mellitus. Int J Cardiol 71:235–242CrossRefPubMed
9.
go back to reference Aytemir K, Aksoyek S, Ozer N, Gurlek A, Oto A (1998) QT dispersion and autonomic nervous system function in patients with type 1 diabetes. Int J Cardiol 65:45–50CrossRefPubMed Aytemir K, Aksoyek S, Ozer N, Gurlek A, Oto A (1998) QT dispersion and autonomic nervous system function in patients with type 1 diabetes. Int J Cardiol 65:45–50CrossRefPubMed
10.
go back to reference Sawicki PT, Dähne R, Bender R, Berger M (1996) Prolonged QT interval as a predictor of mortality in diabetic nephropathy. Diabetologia 39:77–81PubMed Sawicki PT, Dähne R, Bender R, Berger M (1996) Prolonged QT interval as a predictor of mortality in diabetic nephropathy. Diabetologia 39:77–81PubMed
11.
go back to reference Rossing P, Breum L, Major-Pedersen A et al. (2001) Prolonged QTc interval predicts mortality in patients with Type 1 diabetes mellitus. Diabet Med 18:199–205PubMed Rossing P, Breum L, Major-Pedersen A et al. (2001) Prolonged QTc interval predicts mortality in patients with Type 1 diabetes mellitus. Diabet Med 18:199–205PubMed
12.
go back to reference Veglio M, Borra M, Stevens LK, Fuller JH, Perin PC (1999) The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complications Study Group. Diabetologia 42:68–75PubMed Veglio M, Borra M, Stevens LK, Fuller JH, Perin PC (1999) The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complications Study Group. Diabetologia 42:68–75PubMed
13.
go back to reference Borch-Johnsen K, Kreiner S, Deckert T (1986) Mortality of type 1 (insulin-dependent) diabetes mellitus in Denmark: a study of relative mortality in 2930 Danish type 1 diabetic patients diagnosed from 1933 to 1972. Diabetologia 29:767–772PubMed Borch-Johnsen K, Kreiner S, Deckert T (1986) Mortality of type 1 (insulin-dependent) diabetes mellitus in Denmark: a study of relative mortality in 2930 Danish type 1 diabetic patients diagnosed from 1933 to 1972. Diabetologia 29:767–772PubMed
14.
go back to reference Borch-Johnsen K, Kreiner S (1987) Proteinuria: value as predictor of cardiovascular mortality in insulin dependent diabetes mellitus. BMJ (Clin Res Ed) 294:1651–1654 Borch-Johnsen K, Kreiner S (1987) Proteinuria: value as predictor of cardiovascular mortality in insulin dependent diabetes mellitus. BMJ (Clin Res Ed) 294:1651–1654
15.
go back to reference Robinson RT, Harris ND, Ireland RH, Lee S, Newman C, Heller SR (2003) Mechanisms of abnormal cardiac repolarization during insulin-induced hypoglycemia. Diabetes 52:1469–1474 Robinson RT, Harris ND, Ireland RH, Lee S, Newman C, Heller SR (2003) Mechanisms of abnormal cardiac repolarization during insulin-induced hypoglycemia. Diabetes 52:1469–1474
16.
go back to reference Edvardsson N, Olsson SB (1981) Effects of acute and chronic beta-receptor blockade on ventricular repolarisation in man. Br Heart J 45:628–636PubMed Edvardsson N, Olsson SB (1981) Effects of acute and chronic beta-receptor blockade on ventricular repolarisation in man. Br Heart J 45:628–636PubMed
17.
go back to reference Bonnar CE, Davie AP, Caruana L et al. (1999) QT dispersion in patients with chronic heart failure: beta blockers are associated with a reduction in QT dispersion. Heart 81:297–302PubMed Bonnar CE, Davie AP, Caruana L et al. (1999) QT dispersion in patients with chronic heart failure: beta blockers are associated with a reduction in QT dispersion. Heart 81:297–302PubMed
18.
go back to reference Fesmire SI, Marcoux LG, Lyyski DS, Sprague MK, Kennedy HL, Eichhorn EJ (1999) Effect of selective versus nonselective beta blockade on QT dispersion in patients with nonischemic dilated cardiomyopathy. Am J Cardiol 84:350–354, A9CrossRefPubMed Fesmire SI, Marcoux LG, Lyyski DS, Sprague MK, Kennedy HL, Eichhorn EJ (1999) Effect of selective versus nonselective beta blockade on QT dispersion in patients with nonischemic dilated cardiomyopathy. Am J Cardiol 84:350–354, A9CrossRefPubMed
19.
go back to reference Ebbehoj E, Poulsen PL, Hansen KW, Knudsen ST, Molgaard H, Mogensen CE (2002) Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in Type I diabetic patients with abnormal albuminuria. Diabetologia 45:965–975 Ebbehoj E, Poulsen PL, Hansen KW, Knudsen ST, Molgaard H, Mogensen CE (2002) Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in Type I diabetic patients with abnormal albuminuria. Diabetologia 45:965–975
20.
go back to reference Poulsen PL, Ebbehoj E, Arildsen H et al. (2001) Increased QTc dispersion is related to blunted circadian blood pressure variation in normoalbuminuric type 1 diabetic patients. Diabetes 50:837–842PubMed Poulsen PL, Ebbehoj E, Arildsen H et al. (2001) Increased QTc dispersion is related to blunted circadian blood pressure variation in normoalbuminuric type 1 diabetic patients. Diabetes 50:837–842PubMed
21.
go back to reference Ewing DJ, Martyn CN, Young RJ, Clarke BF (1985) The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 8:491–498PubMed Ewing DJ, Martyn CN, Young RJ, Clarke BF (1985) The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 8:491–498PubMed
22.
go back to reference Christensen CK, Ørskov C (1984) Rapid screening PEG radioimmunoassay for quantification of pathological microalbuminuria. Diabetic Nephropathy 3:92–94 Christensen CK, Ørskov C (1984) Rapid screening PEG radioimmunoassay for quantification of pathological microalbuminuria. Diabetic Nephropathy 3:92–94
23.
go back to reference Mayet J, Shahi M, McGrath K et al. (1996) Left ventricular hypertrophy and QT dispersion in hypertension. Hypertension 28:791–796PubMed Mayet J, Shahi M, McGrath K et al. (1996) Left ventricular hypertrophy and QT dispersion in hypertension. Hypertension 28:791–796PubMed
24.
go back to reference Yunus A, Gillis AM, Traboulsi M et al. (1997) Effect of coronary angioplasty on precordial QT dispersion. Am J Cardiol 79:1339–1342CrossRefPubMed Yunus A, Gillis AM, Traboulsi M et al. (1997) Effect of coronary angioplasty on precordial QT dispersion. Am J Cardiol 79:1339–1342CrossRefPubMed
25.
go back to reference Veglio M, Giunti S, Stevens LK, Fuller JH, Perin PC (2002) Prevalence of Q-T interval dispersion in Type 1 diabetes and its relation with cardiac ischemia : The EURODIAB IDDM Complications Study Group. Diabetes Care 25:702–707PubMed Veglio M, Giunti S, Stevens LK, Fuller JH, Perin PC (2002) Prevalence of Q-T interval dispersion in Type 1 diabetes and its relation with cardiac ischemia : The EURODIAB IDDM Complications Study Group. Diabetes Care 25:702–707PubMed
26.
go back to reference Rana BS, Band MM, Ogston S, Morris AD, Pringle SD, Struthers AD (2002) Relation of QT interval dispersion to the number of different cardiac abnormalities in diabetes mellitus. Am J Cardiol 90:483–487CrossRefPubMed Rana BS, Band MM, Ogston S, Morris AD, Pringle SD, Struthers AD (2002) Relation of QT interval dispersion to the number of different cardiac abnormalities in diabetes mellitus. Am J Cardiol 90:483–487CrossRefPubMed
27.
go back to reference Mølgaard H, Christensen PD, Hermansen K, Sørensen KE, Christensen CK, Mogensen CE (1994) Early recognition of autonomic dysfunction in microalbuminuria: significance for cardiovascular mortality in diabetes mellitus? Diabetologia 37:788–796PubMed Mølgaard H, Christensen PD, Hermansen K, Sørensen KE, Christensen CK, Mogensen CE (1994) Early recognition of autonomic dysfunction in microalbuminuria: significance for cardiovascular mortality in diabetes mellitus? Diabetologia 37:788–796PubMed
28.
go back to reference Frattola A, Parati G, Gamba P et al. (1997) Time and frequency domain estimates of spontaneous baroreflex sensitivity provide early detection of autonomic dysfunction in diabetes mellitus. Diabetologia 40:1470–1475 Frattola A, Parati G, Gamba P et al. (1997) Time and frequency domain estimates of spontaneous baroreflex sensitivity provide early detection of autonomic dysfunction in diabetes mellitus. Diabetologia 40:1470–1475
29.
go back to reference Barr CS, Naas AA, Fenwick M, Struthers AD (1997) Enalapril reduces QTc dispersion in mild congestive heart failure secondary to coronary artery disease. Am J Cardiol 79:328–333CrossRefPubMed Barr CS, Naas AA, Fenwick M, Struthers AD (1997) Enalapril reduces QTc dispersion in mild congestive heart failure secondary to coronary artery disease. Am J Cardiol 79:328–333CrossRefPubMed
30.
go back to reference Ranade V, Molnar J, Khokher T, Agarwal A, Mosnaim A, Somberg JC (1999) Effect of angiotensin-converting enzyme therapy on QT interval dispersion. Am J Ther 6:257–261PubMed Ranade V, Molnar J, Khokher T, Agarwal A, Mosnaim A, Somberg JC (1999) Effect of angiotensin-converting enzyme therapy on QT interval dispersion. Am J Ther 6:257–261PubMed
31.
go back to reference Kassotis J, Mongwa M, Reddy CV (2003) Effects of angiotensin-converting enzyme inhibitor therapy on QT dispersion post acute myocardial infarction. Pacing Clin Electrophysiol 26:843–848PubMed Kassotis J, Mongwa M, Reddy CV (2003) Effects of angiotensin-converting enzyme inhibitor therapy on QT dispersion post acute myocardial infarction. Pacing Clin Electrophysiol 26:843–848PubMed
32.
go back to reference Heller SR (2002) Abnormalities of the electrocardiogram during hypoglycaemia: the cause of the dead in bed syndrome? Int J Clin Pract Suppl 129:27–32PubMed Heller SR (2002) Abnormalities of the electrocardiogram during hypoglycaemia: the cause of the dead in bed syndrome? Int J Clin Pract Suppl 129:27–32PubMed
33.
go back to reference Robinson RT, Harris ND, Ireland RH, MacDonald IA, Heller SR (2004) Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with Type 1 diabetes. Diabetologia 47:312–315CrossRefPubMed Robinson RT, Harris ND, Ireland RH, MacDonald IA, Heller SR (2004) Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with Type 1 diabetes. Diabetologia 47:312–315CrossRefPubMed
Metadata
Title
Effects of metoprolol on QT interval and QT dispersion in Type 1 diabetic patients with abnormal albuminuria
Authors
E. Ebbehøj
H. Arildsen
K. W. Hansen
C. E. Mogensen
H. Mølgaard
P. L. Poulsen
Publication date
01-06-2004
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 6/2004
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1422-7

Other articles of this Issue 6/2004

Diabetologia 6/2004 Go to the issue