Abstract 16595: Insulin Replacement Attenuates Autonomic Impairment but Did Not Prevent Early Diastolic Dysfunction in a Model of Type 1 Diabetes
Introduction: Insulin replacement is the most widely used therapy for treatment of patients with Type 1 Diabetes Mellitus. However, despite a restricted glycemic control, diabetic patients are prone to chronic complications, such as cardiovascular disease. The mechanisms underlying this increased risk are not well understood.
Hypothesis: The insulin replacement therapy can prevent the cardiac and autonomic dysfunctions in a model of type 1 diabetes.
Methods:18 male Wistar rats (230-260g) were divided into 3 groups (n=6/group): control (C), diabetic (D, streptozotocin 50 mg/kg) and diabetic treated daily with insulin subcutaneously (DTI). At 30 days, cardiac function was assessed by echocardiogram and after the rats were cannulated and arterial pressure (AP) was recorded.
Results: The diabetic groups showed hyperglycemia (>350mg/dl) at the beginning of the protocol. Insulin therapy normalized the glycemia (DTI: 94±28 and C: 126±8 vs. D: 533±67 mg/dl). There was a reduction in the posterior wall thickness of the left ventricle at diastole (PWD) and in the relative wall thickness (RWT) in D group and these changes were not observed in DTI group (PWD- C: 0.122±0.008 and DTI: 0.126±0.004 vs. D: 0.086±0.006 cm and RWT- C: 0.42±0.021 and DTI: 0.4±0.013 vs. D: 0.35±0.014). Left ventricular mass was reduced in D group (D: 0.393±0.0510 vs. C: 0.581±0,054 and DTI: 0.586±0.049). The systolic function was not different (shortening fraction) between the groups. Regarding diastolic function, the isovolumetric relaxation time was not different between the groups, but there was a decrease in E/A wave ratio in the group of diabetic rats, which was not reversed by insulin treatment (D: 1.53±0.104 and DTI: 1.69±0.178 vs. C: 2.45±0.380). The baroreflex sensitivity was impaired in D group in relation to C and DTI groups (D: 1.05±0.110 vs. C: 1.39±0.100 and DTI: 1.36±0.09 bpm/mmHg). The insulin treatment normalized mean AP (DTI: 118±3.34 and C: 110±3.28 vs. D: 99±5.48 mmHg).
Conclusions: Treatment with insulin despite normalize blood glucose, baroreflex sensitivity, hemodynamics and cardiac morphometry, was not able to attenuate diastolic dysfunction, suggesting a remaining cardiovascular risk even after insulin replacement in this model of experimental diabetes type I.
Author Disclosures: S.C. Freitas: None. P.M. Dourado: None. I.C. Sanches: None. J.F. machi: None. M.C. Irigoyen: None. K. De angelis: None.
- © 2015 by American Heart Association, Inc.