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

Sections of ¹Clinical Physiology and Oncology/Pathology and of ²Nuclear Medicine, Department of Surgical Sciences, Karolinska Institutet, SE-171 76 Stockholm, Sweden; ³Turku Positron Emission Tomography Centre and ⁴Division 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 [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.

echocardiography; myocardial blood flow; positron emission tomography; rate-pressure product

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