P279Impaired LV diastolic function in long term type 1 diabetes is associated with advanced glycation endproducts

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Purpose: The LV function in long term (40 years duration) type 1 diabetes without symptoms is not well known. Therefore we assessed LV systolic and diastolic function in such a cohort, and studied if advanced glycation endproducts (AGE) were associated with these parameters. AGEs contribute in the development of diabetic vascular complications and have also been suggested as a mechanism for a specific diabetic cardiomyopathy.Methods: 27 (54±7 years) patients with type 1 diabetes of 40±3 years duration from the cohort "Oslo study" underwent clinical examination, standard echocardiography and tissue velocity imaging (TVI), and were compared with 26 age and sex matched healthy controls (55±6 years ). LV ejection fraction (EF) were measured by two-dimensional (2D) echo and tricuspidal annular systolic excursion (TAPSE) by M-mode as a measure for right heart systolic function. LV diastolic function was assessed by peak early (E) and atrial (A) diastolic transmitral velocities by pulsed Doppler, and TVI E` as an average of early diastolic septal and lateral TVI velocities. E/E' and E/A ratio were then calculated. Systolic S by TVI was measured at septum and lateral LV wall from four chamber view and averaged. All echocardiograhic recordings were analyzed by the same investigator, who was blinded to the clinical status of the participants.The AGE modification methylglyoxal derived hydroimidazolone was analyzed in serum by immunoassay.Results: There were no significant difference in age, body mass index, EF, TAPSE or systolic blood pressure between the diabetics and the controls, and the ECGs were normal in both groups. The diabetic patients had lower diastolic blood pressure and increased heart rate, 65±8 vs 73±9 mmHg (p <0.01) and 76 ± 10 vs 67 ± 10 beats/min (p<0.01), respectively. Systolic S was significantly lower in the diabetics compared to the controls, 6.9±1.6 cm/s vs 7.9±1.5 cm/s (p<0.05), and transmitral E and E/E' were significant higher in the diabetics, 0.8±0,1 m/s vs 0.7±0.2 m/s (p<0,01) and 7.2±2 vs 6.0±1.5 (p<0.05), respectively. Hydroimidazalone (AGE) correlated significantly with E/E`, R=0.45 (p<0.05), but not with S.Conclusion: The present study has demonstrated a reduced LV systolic function by TVI and increased E/E`, which reflects increased LV filling pressures and thus LV diastolic dysfunction in this cohort of diabetics type I of 40 years duration compared to controls. The association betwen E/E`and metylglyoxal derived hydroimidazalone may suggest AGEs as a mechanism for the enhanced LV filling pressure in these patients-perhaps by inducing stiffening of LV connective tissue.

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