Authors:
G. Nallur Shivu¹, T.T. Phan², K. Abozguia², I. Ahmed², R. Weaver², M. Nassimizadeh², A. Wagenmakers², M. Stevens², M. Frenneaux², ¹University of Birmingham - Birmingham - United Kingdom, ²University of Birmingham - Birmingham - United Kingdom,

Background: Heart failure is common in diabetes and is often secondary to epicardial coronary artery disease (CAD) and/or hypertension. However in diabetes, left ventricular (LV) dysfunction is often disproportionate to the extent of the CAD suggesting additional pathogenetic mechanisms. We propose that in diabetes, impaired cardiac energetics plays a patho-physiological role in the development of heart failure and contributes to increased mortality.

Methods: We used 31P cardiac magnetic resonance spectroscopy to measure myocardial energetic status in subjects with type 1 diabetes mellitus (T1DM) without heart failure. Coronary artery disease was excluded by history, exercise tolerance test and Stress Magnetic Resonance Imaging using adenosine. 10 asymptomatic subjects with T1DM (mean + 1SD age 34.6±5.4 y, diabetes duration 19 y) and 12 age matched healthy controls (HC) (age 32.9±5.5 y) were recruited into the study.

Results: LV Ejection Fraction (LVEF) was 59.3±6.3% in the T1DM subjects and VO2 max was 36.9ml/kg/min ± 8.0 (98.9% of predicted). In the HC, the corresponding values were 62.0±5.8% (p=0.42 vs T1DM) and 44.9 ml/kg/min ± 4.5 (114% of predicted) (p= 0.01 vs T1DM), respectively. In T1DM subjects, Phosphocreatine/ γ Adenosine Triphosphate (PCr/γ ATP) ratio was reduced by 36% compared to HC, 1.4±0.1 and 2.2±0.1, respectively (P < 0.001) (figure).

Conclusion: Subjects with T1DM exhibit a marked impairment of cardiac energetics in the absence of CAD and heart failure. We speculate that this impairment may reflect increased utilisation of free fatty acids for energy production. Alterations of substrate metabolism and impairment of energy production may contribute to enhanced cardiac risk in diabetes.