Stress Strain Speckle‐Tacking Segmental Analysis Reveals Early Indications of Diastolic Dysfunction in a Type 2 Mouse Model of Diabetes Mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is becoming increasingly common, as there are currently 23.1 million people diagnosed and another 84.1 million adults diagnosed with pre‐diabetes in the United States alone. While many long‐term consequences are associated with T2DM, the leading cause of mortality is cardiovascular complications. Though reduction in ejection fraction and fractional shortening are well‐described indicators of cardiovascular dysfunction, these indices are usually present late in the progression of the pathology. Identification of predictors that can be observed earlier in the disease progression may aid in diagnosing and predicting future health outcomes for the patient. The goal of the current study was to evaluate cardiac contractile changes in a rodent model of type 2 diabetes mellitus using the well characterized db/db model mouse model. Db/Db FVB mice and wild‐type (WT) littermate controls were utilized for the study (WT = 22 and db/db = 14). Echocardiography, using the Vevo 2100 Imaging System, was implemented to evaluate cardiac function in both groups at 12 weeks of age. M‐mode was used for conventional measures of cardiac function, while B‐mode short and long axis images were used for stress strain speckle‐tracking analyses. In addition, Pulse Wave Doppler analyses were utilized to examine changes in flow across the mitral valve. At 12 weeks of age, db/db mice exhibit lower ejection fractions (P ≤ 0.05) and increased stroke volumes (P ≤ 0.0018) when compared to WT. Concomitantly, db/db mice presented with significant increases in both systolic and diastolic ventricular diameters and volumes, along with an increased LV mass (P ≤ 0.0001). To determine whether spatial differences in cardiac dysfunction was associated with T2DM, we assessed regional changes in cardiac function. Speckle‐tracking strain analyses revealed significant changes in radial displacement at systole in the short axis (P ≤ 0.0024) and diastole at both the short axis (P ≤ 0.033), and long axis (P ≤ 0.0001). Segmental analysis revealed that the lateral wall portion of the left ventricle, in all axes, was significantly altered during diabetic stress. In summary, echocardiography and specifically speckle‐tracking strain analysis has the potential to indicate early dysfunction of the left ventricle during the progression of type 2 diabetes mellitus through segmentally isolated cardiac function, potentially aiding in diagnosis and future outcomes.Support or Funding InformationR01 HL‐128485 (JMH), AHA‐17PRE33660333 (QAH), AHA 17PRE33660333 (QAH), and the Community Foundation for the Ohio Valley Whipkey Trust.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.