C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients

• Published in: American journal of physiology: endocrinology and metabolism 2004-01, Vol.286 (1), p.E14-E19
• Main Authors: Johansson, Bo-Lennart, Sundell, Jan, Ekberg, Karin, Jonsson, Cathrine, Seppanen, Marko, Raitakari, Olli, Luotolahti, Matti, Nuutila, Pirjo, Wahren, John, Knuuti, Juhani
• Format: Article
• Language: English
• Subjects: Adenosine - physiology; Adult; Blood Glucose - physiology; Blood Pressure - physiology; C-Peptide - physiology; Coronary Circulation - physiology; Coronary Vessels - physiology; Cross-Over Studies; Diabetes Mellitus, Type 1 - physiopathology; Double-Blind Method; Echocardiography; Heart - diagnostic imaging; Humans; Insulin - physiology; Male; Medicin och hälsovetenskap; Reference Values; Regional Blood Flow; Tomography, Emission-Computed; Vasodilation - physiology
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00236.2003

Sections of 1 Clinical Physiology and Oncology/Pathology and of 2 Nuclear Medicine, Department of Surgical Sciences, Karolinska Institutet, SE-171 76 Stockholm, Sweden; 3 Turku Positron Emission Tomography Centre and 4 Division of Clinical Physiology, Turku University, Turku, FIN-20014 Finland Submitted 22 May 2003 ; accepted in final form 31 August 2003 Patients with type 1 (insulin-dependent) diabetes show reduced skeletal muscle blood flow and coronary vasodilatory function despite intensive insulin therapy and good metabolic control. Administration of proinsulin C-peptide increases skeletal muscle blood flow in these patients, but a possible influence of C-peptide on myocardial vasodilatory function in type 1 diabetes has not been investigated. Ten otherwise healthy young male type 1 diabetic patients (Hb A 1c 6.6%, range 5.7-7.9%) were studied on two consecutive days during normoinsulinemia and euglycemia in a double-blind, randomized, crossover design, receiving intravenous infusion of C-peptide (5 pmol·kg -1 ·min -1 ) for 120 min on one day and saline infusion on the other day. Myocardial blood flow (MBF) was measured at rest and during adenosine administration (140 µg·kg -1 ·min -1 ) both before and during the C-peptide or saline infusions by use of positron emission tomography and [ 15 O]H 2 O administration. Basal MBF was not significantly different in the patients compared with an age-matched control group, but adenosine-induced myocardial vasodilation was 30% lower ( P < 0.05) in the patients. During C-peptide administration, adenosine-stimulated MBF increased on average 35% more than during saline infusion ( P < 0.02) and reached values similar to those for the healthy controls. Moreover, as evaluated from transthoracal echocardiographic measurements, C-peptide infusion resulted in significant increases in both left ventricular ejection fraction (+5%, P < 0.05) and stroke volume (+7%, P < 0.05). It is concluded that short-term C-peptide infusion in physiological amounts increases the hyperemic MBF and left-ventricular function in type 1 diabetic patients. echocardiography; myocardial blood flow; positron emission tomography; rate-pressure product Address for reprint requests and other correspondence: B-L. Johansson, Dept. of Surgical Sciences, Division of Clinical Physiology N1:05, Karolinska Hospital, SE-171 76 Stockholm, Sweden.