title: C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients.
abstract: 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 A1c 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 microg.kg-1.min-1) both before and during the C-peptide or saline infusions by use of positron emission tomography and [15O]H2O 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.
authors.affiliation: Department of Surgical Sciences, Division of Clinical Physiology N1:05, Karolinska Institutet, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Bo-Lennart
authors.initials: BL
authors.lastname: Johansson
authors.forename: Jan
authors.initials: J
authors.lastname: Sundell
authors.forename: Karin
authors.initials: K
authors.lastname: Ekberg
authors.forename: Cathrine
authors.initials: C
authors.lastname: Jonsson
authors.forename: Marko
authors.initials: M
authors.lastname: Seppänen
authors.forename: Olli
authors.initials: O
authors.lastname: Raitakari
authors.forename: Matti
authors.initials: M
authors.lastname: Luotolahti
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.forename: John
authors.initials: J
authors.lastname: Wahren
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000328:Adult; D001786:Blood Glucose / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002096:C-Peptide / Q000502:physiology*; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004311:Double-Blind Method; D004452:Echocardiography; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D007328:Insulin / Q000502:physiology; D008297:Male; D012016:Reference Values; D012039:Regional Blood Flow; D014055:Tomography, Emission-Computed; D014664:Vasodilation / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D000241:Adenosine