Abstract
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.