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Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
The Effect of Glycemic Control on Left Ventricular Function in Clinical and Experimental Diabetes
Steven J Lavine1,2, Petar Prcevski3
1Wayne State University, St. Louis, Missouri, USA.
Insights
Poor glycemic control worsens left ventricular (LV) dysfunction in diabetes mellitus (DM). This study in canines and patients shows that uncontrolled blood sugar negatively impacts heart function, increasing heart failure risk.
Area of Science:
- Cardiology
- Endocrinology
- Diabetology
Background:
- Cardiovascular outcomes in diabetes mellitus (DM) remain suboptimal despite efforts to improve glycemic control, particularly with normal left ventricular (LV) function.
- The impact of glycemic control on pre-existing LV dysfunction in DM requires further investigation.
Purpose of the Study:
- To assess the effect of glycemic control on LV dysfunction in a canine model of DM and LV dysfunction.
- To evaluate the impact of glycemic control on LV function in patients with DM and pre-existing LV dysfunction.
Main Methods:
- A canine model was established with chronic LV dysfunction induced by coronary microsphere embolization, followed by induction of DM and assignment to good or poor glycemic control.
- Hemodynamic and Doppler echocardiographic data were collected in canines and in a cohort of patients with DM and reduced ejection fraction (EF), compared to non-DM controls.
- Patient data included laboratory results, medications, and adverse events.
Main Results:
- In canines, poor glycemic control (HbA1c = 8.05%) led to reduced LV mass and circumferential fiber shortening compared to those with LV dysfunction alone.
- Good glycemic control (HbA1c = 3.88%) maintained LV parameters similar to controls (HbA1c = 2.99%).
- Patients with DM and poor glycemic control exhibited reduced EF, impaired circumferential fiber shortening (0.93 vs 1.11, P < 0.001), and a higher incidence of heart failure compared to non-DM controls.
Conclusions:
- Poor glycemic control exerts an adverse effect on pre-existing left ventricular dysfunction in experimental models.
- These findings translate to patients with type 2 diabetes, where poor glycemic control exacerbates LV dysfunction and increases heart failure risk.
Background:
Glycemic control in diabetes mellitus (DM) has not improved cardiovascular outcomes with normal left ventricular (LV) function. We assessed the effect on LV dysfunction using a canine model of LV dysfunction and DM, and in patients with DM and LV dysfunction.
Methods:
Chronic LV dysfunction was produced by coronary microsphere embolization in 34 canines (15-25 kg). Following 8 weeks of stabilization, DM was induced in 24 canines and randomized to good or poor glycemic control for 3 months. Ten canines without DM were controls. Hemodynamic and Doppler echocardiographic data were obtained prior to and following pressure loading. We reviewed the Doppler-echocardiography at baseline and follow-up in 207 patients with DM with reduced ejection fraction (EF; median follow-up = 612 days) and 60 age- and sex-matched non-DM patients with normal EF. Laboratory results, medications, and incident adverse events from medical records were obtained.
Results:
EF = 43.8% ± 11.2% for all canines at 8 weeks. Canines with poor glycemic control (hemoglobin [Hb]A1c = 8.05% ± 3.02%) demonstrated reduced LV mass and rate-corrected velocity of circumferential fiber shortening, compared to those with LV dysfunction (1.36 ± 0.73 vs 0.88 ± 0.13 circumference per second, P < 0.01). Good glycemic control (HbA1c = 3.88% ± 0.89%) demonstrated similar LV parameters, compared to controls (HbA1c = 2.99% ± 0.44%). EF was similar among groups. Patients with vs without DM were followed for up to 3 years. Patients with DM and poor glycemic control had reduced EF, lower rate-corrected velocity of circumferential fiber shortening = 0.93 ± 0.26 vs 1.11 ± 0.26, P < 0.001), and greater incidence of heart failure.
Conclusions:
Poor glycemic control had an adverse effect on preexisting LV dysfunction experimentally and in patients with type 2 diabetes.
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