CORRESPONDENCE: RESEARCH CORRESPONDENCE
Diabetes Lowers Aerobic Capacity in Heart Failure
Amit S. Tibb, MD,
Pierre V. Ennezat, MD,
Jennifer A. Chen, MS,
Ali Haider, MS,
Susheel Gundewar, MD,
Vlad Cotarlan, MD,
Vimla S. Aggarwal, MD,
Ashok Talreja, MD and
Thierry H. Le Jemtel, MD*
* Tulane University School of Medicine, 1430 Tulane Avenue, SL 48, New Orleans, LA 70112 (Email: lejemtel{at}tulane.edu).
To the Editor: Patients with chronic heart failure (CHF) due to left ventricular (LV) systolic dysfunction develop skeletal muscle alterations that contribute to lower peak aerobic capacity (1). Patients with type 2 diabetes develop skeletal muscle alterations similar to those of patients with CHF (2). To test the hypothesis that diabetes may further reduce peak aerobic capacity in patients with CHF, we prospectively measured peak oxygen uptake (peak VO2) in 156 diabetic and nondiabetic patients with CHF who were matched for age and gender.
A total of 156 patients met inclusion/exclusion criteria and agreed to participate in the study. We first identified 204 patients with CHF and diabetes among the 689 patients with LV ejection fraction <40% in our CHF clinic and then attempted to match these 204 diabetic patients for age and gender to the 485 remaining nondiabetic patients. We found age and gender matches for 106 of the 204 patients. Informed consent and complete data were obtained in 78 of the 106 matched patients. Inclusion criteria included: steady clinical state, ability to perform a maximal exercise test, and therapy consistent with current CHF guidelines. Exclusion criteria were: exertional angina or arrhythmias; systolic or diastolic blood pressure >160 and 90 mm Hg, respectively; joint, pulmonary, or peripheral arterial disease; participation in a training program; and active tobacco use. Glycosylated hemoglobin was measured in all patients. They had all undergone coronary angiography. Chronic kidney disease was defined by a creatinine clearance <50 ml/min (3). All patients were familiar with exercise testing and measurement of expired gas.
Patients who met inclusion and exclusion criteria underwent evaluation of baseline physical activity. Plasma B-type natriuretic peptide (BNP) level and peak VO2 were determined within one week of evaluation of physical activity. The average number of daily steps was used to quantify baseline physical activity (4). It was recorded daily and averaged over seven consecutive days. Ejection fraction was assessed by echocardiography. Plasma levels of BNP were measured using the triage immunoassay (Biosite Inc., San Diego, California). Peak VO2 was measured during a symptom-limited treadmill exercise test. Patients who discontinued exercising for other than shortness of breath and fatigue or did not reach a respiratory exchange ratio >1.0 were excluded. Peak VO2 was compared in diabetics and nondiabetics using the t test for two independent samples. Multiple linear regression analysis was performed to assess the effect of diabetes on peak VO2 controlling for hypertension, coronary artery disease (CAD), chronic kidney disease, BNP plasma level, LV ejection fraction, physical activity, and glycosylated hemoglobin. We aimed to have a minimum of 15 patients for each parameter that we anticipated to include in our regression model.
Baseline characteristics and medications are summarized in Table 1. Hypertension and CAD were more prevalent in diabetics than in nondiabetics. Plasma BNP level, ejection fraction, body mass index, prevalence of chronic kidney disease, number of daily steps, and therapeutic regimen (except for aspirin) were similar in diabetics and nondiabetics. Peak VO2 was substantially lower in diabetic than in nondiabetic patients: 13.1 (SD 3.6) versus 18.9 (SD 4.2) ml/kg/min (p = 0.001) (Fig. 1). Peak heart rate and ventilatory threshold were similar in diabetics and nondiabetics. The difference in peak VO2 between diabetics and nondiabetics was 5.5 ml/kg/min (p < 0.001) after controlling for baseline characteristics.
View larger version (13K):
[in this window]
[in a new window]
|
Figure 1 Individual peak oxygen uptake (peak VO2) values in diabetic (DM) and nondiabetic (N-DM) patients with chronic heart failure due to left ventricular systolic dysfunction. Mean peak VO2 is significantly lower in DM than in N-DM patients.
|
|
Our data extend the findings of Guazzi et al. (5) to a larger and more controlled patient population. Our data also provide the first evidence that diabetes is an independent determinant of peak VO2 in patients with CHF. Guazzi et al. (5) studied 40 diabetic and nondiabetic patients with CHF. Half of the patients were receiving angiotensin-converting enzyme inhibitors, and none were receiving beta-adrenergic blockade. Guazzi et al. (5) did not measure baseline physical activity nor consider whether differences in comorbid conditions could account for the lower peak VO2 of diabetic patients. The difference in peak VO2 was lower in the Guazzi et al. (5) study than in ours: 3.0 versus 5.5 ml/kg/min. Tighter diabetes control with aggressive insulin therapy may have contributed to the smaller difference in peak VO2 between diabetics and nondiabetics in the Guazzi et al. (5) study. Glycosylated hemoglobin was <7% in every one of the Guazzi et al. (5) patients, whereas it averaged 7.5% in our patients. Insulin therapy improves peak VO2 in patients with diabetes and CHF (6,7). Diabetes is associated with cardiac, vascular, metabolic, and skeletal muscle alterations that all tend to reduce peak VO2 (8). High-energy phosphate metabolism is impaired in skeletal muscles from patients with diabetes in the absence of CAD or LV dysfunction (2). Phosphocreatinine loss, pH decline, and deoxygenation occur sooner in exercising skeletal muscles of diabetics than in controls. Alterations in energy metabolism contribute to reduce peak aerobic capacity in CHF (9,10). The coexistence of diabetes and CHF may further alter skeletal muscle energy metabolism and reduce peak aerobic capacity. A major limitation of our study is the absence of longitudinal data with tighter diabetes control.
In summary, diabetes negatively impacts on and is an independent determinant of peak aerobic capacity in patients with CHF. Diabetes needs to be taken into consideration when evaluating functional capacity in patients with CHF.
 |
Footnotes
|
|---|
Please note: Dr. Le Jemtel is on the Speaker’s Bureau of Scios, Glaxo SmithKline, and Astra Zeneca, and does consultation work for Novartis.
|
References
|
|---|
1. Massie B, Conway M, Yonge R, et al. Skeletal muscle metabolism in patients with congestive heart failurerelation to clinical severity and blood flow. Circulation 1987;76:1009-1019.[Abstract/Free Full Text]
2. Scheuermann-Freestone M, Madsen PL, Manners D, et al. Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes Circulation 2003;107:3040-3046.[Abstract/Free Full Text]
3. Gault MH, Longerich LL, Harnett JD, Wesolowski C. Predicting glomerular function from adjusted serum creatinine Nephron 1992;62:249-256.[Web of Science][Medline]
4. Tudor-Locke C, Burkett L, Reis JP, Ainsworth BE, Macera CA, Wilson DK. How many days of pedometer monitoring predict weekly physical activity in adults? Prev Med 2005;40:293-298.[CrossRef][Web of Science][Medline]
5. Guazzi M, Brambilla R, Pontone G, Agostoni P, Guazzi MD. Effect of non-insulin-dependent diabetes mellitus on pulmonary function and exercise tolerance in chronic congestive heart failure Am J Cardiol 2002;89:191-197.[CrossRef][Web of Science][Medline]
6. Guazzi M, Tumminello G, Matturri M, Guazzi MD. Insulin ameliorates exercise ventilatory efficiency and oxygen uptake in patients with heart failure-type 2 diabetes comorbidity J Am Coll Cardiol 2003;42:1044-1050.[Abstract/Free Full Text]
7. Levy WC, Hirsch IB. Diabetes and heart failureis insulin therapy the answer?. J Am Coll Cardiol 2003;42:1051-1053.[Free Full Text]
8. Estacio RO, Regensteiner JG, Wolfel EE, Jeffers B, Dickenson M, Schrier RW. The association between diabetic complications and exercise capacity in NIDDM patients Diabetes Care 1998;21:291-295.[Abstract]
9. Mancini DM, Coyle E, Coggan A, et al. Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure Circulation 1989;80:1338-1346.[Abstract/Free Full Text]
10. Okita K, Yonezawa K, Nishijima H, et al. Skeletal muscle metabolism limits exercise capacity in patients with chronic heart failure Circulation 1998;98:1886-1891.[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
M. R. MacDonald, P. S. Jhund, M. C. Petrie, J. D. Lewsey, N. M. Hawkins, S. Bhagra, N. Munoz, F. Varyani, A. Redpath, J. Chalmers, et al.
Discordant Short- and Long-Term Outcomes Associated With Diabetes in Patients With Heart Failure: Importance of Age and Sex: A Population Study of 5.1 Million People in Scotland
Circ Heart Fail,
November 1, 2008;
1(4):
234 - 241.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. MacDonald, M. C. Petrie, F. Varyani, J. Ostergren, E. L. Michelson, J. B. Young, S. D. Solomon, C. B. Granger, K. Swedberg, S. Yusuf, et al.
Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: An analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme
Eur. Heart J.,
June 1, 2008;
29(11):
1377 - 1385.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. MacDonald, M. C. Petrie, N. M. Hawkins, J. R. Petrie, M. Fisher, R. McKelvie, D. Aguilar, H. Krum, and J. J.V. McMurray
Diabetes, left ventricular systolic dysfunction, and chronic heart failure
Eur. Heart J.,
May 2, 2008;
29(10):
1224 - 1240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Ingle, P. Reddy, A. L. Clark, and J. G.F. Cleland
Diabetes Lowers Six-Minute Walk Test Performance in Heart Failure
J. Am. Coll. Cardiol.,
May 2, 2006;
47(9):
1909 - 1910.
[Full Text]
[PDF]
|
|
|
|
Top
References