Henrik Wiggers

Cardiovascular and Metabolic Effects of 48-Hour Glucagon-like Peptide 1 Infusion in Compensated Chronic Heart Failure Patients

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  • Department of Pharmacology
  • The Department of Cardiological Medicine B
  • Biomedical Radio Isotope Techniques
  • The Department of Endocrinology and Diabetes
  • Medical Research Laboratory
  • Centre for Clinical Pharmacology
Objectives: The incretin hormone, glucagon-like peptide-1 (GLP-1), and its analogues are currently emerging as anti-diabetic medications. GLP-1 improves ejection fraction (LVEF) in dogs with heart failure and in patients with acute myocardial infarction. We studied metabolic and cardiovascular effects of 48-hour GLP-1 infusions in congestive heart failure (CHF) patients. Methods: In a randomized, double-blind cross-over design, 20 non-diabetic CHF patients with ischemic heart disease, EF 30+/-2%, NYHA II and III (n=14 and 6) received 48-hour GLP-1 (0.7 pmolkg(-1)min(-1)) and placebo-infusion. At 0 and 48 hours, LVEF, diastolic function, tissue-Doppler regional myocardial function, exercise testing, non-invasive cardiac output, and brain natriuretic peptide (BNP) were measured. Blood pressure, heart rate, and metabolic parameters were recorded. Results: Fifteen patients completed the protocol. GLP-1 increased insulin (90+/-17 pmol/L vs. 69+/-12 pmol/L; p=0.025) and lowered glucose levels (5.2+/-0.1 mmol/L vs. 5.6+/-0.1 mmol/L; p<0.01). Heart rate (67+/-2 beats/min vs. 65+/-2 beats/min; p=0.016) and diastolic blood pressure (71+/-2 mmHg vs. 68+/-2 mmHg; p=0.008) increased during GLP-1 treatment. Cardiac index (1.5+/-0.1 Lmin(-1)m(-2) vs. 1.7+/-0.2 Lmin(-1)m(-2); p=0.54) and LVEF (30+/-2 % vs. 30+/-2 %; p=0.93), tissue-Doppler indices, body weight, and BNP remained unchanged. Hypoglycemic events were observed in eight patients. Conclusion: GLP-1 infusion increased circulating insulin levels and reduced plasma glucose concentration but had no major cardiovascular effects in non-diabetic patients with compensated CHF. The impact of minor increases in heart rate and diastolic blood pressure during GLP-1 infusion requires further studies. Hypoglycemia was frequent and calls for caution in non-diabetic CHF patients. Key words: Metabolism, GLP-1, non diabetics, insulin resistance.
Original languageEnglish
JournalAmerican Journal of Physiology: Heart and Circulatory Physiology
Volume298
Issue3
Pages (from-to)H1096-102
Number of pages7
ISSN0363-6135
DOIs
Publication statusPublished - 2010

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