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17 Participants with diabetes mellitus have preserved metabolic flexibility
  1. Peregrine Green,
  2. William D Watson,
  3. Neil Herring,
  4. Stefan Neubauer,
  5. Oliver J Rider
  1. Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, UK


Background Measurement of the Phosphocreatine/Adenosine Triphosphate (ATP) ratio along with the Creatine Kinase (CK) rate constant (CK kf ) allows calculation of the ATP delivery rate (CK flux). Metabolic flexibility may be impaired both in heart failure with reduced ejection fraction (HFrEF) and diabetes mellitus (DM). It is unknown to what extent flexibility can be influenced by artificially altering the substrate available for metabolism.

Purpose To examine cardiac function and energetics in diabetic participants with normal cardiac function and HFrEF, clamped on either fatty acid (FA) or glucose metabolism.

Methods Participants with non-insulin dependent diabetic mellitus (NIDDM) with both normal cardiac function (NHDM) and HFrEF (HFDM) were recruited and received intravenous infusions of either Intralipid (IL) or glucose-insulin (GI) at 2 separate visits, before undergoing multi-parametric cardiac MRI at 3 Tesla. Cardiac volume and function, PCR/ATP and CK kf were assessed. CK flux was calculated as CK k f x PCR/ATP x 5.7 μmol (g wet weight)−1 (assumed ATP concentration).

Results 15 NHDM participants (14 male, age 61.5 ± 7.3 years) and 9 HFDM participants (7 male, age 69.4 ± 7.8 years) were recruited. Left ventricular ejection fraction (LVEF) at rest was higher on IL compared to both baseline fasting and GI for NHDM (baseline 59.1±3.8%, GI 59.4±4.3%, IL 62.8±3.5%; p=<0.01), with a non-significant trend for HFDM (baseline 37.3±7.6%, GI 36.8±9.2%, IL 38.8±8.0%, p=0.12). For both NHDM and HFDM there was no difference in PCR/ATP (NHDM: GI 1.98±0.31, IL 1.97±0.24, p=0.99; HFDM: GI 1.82±0.36, IL 2.01±0.32, p=0.09) or CK flux (NHDM: GI 2.6±1.1 μmol (g wet weight)−1 s−1, IL 1.8±1.2 μmol (g wet weight)−1 s−1, p=0.08; HFDM: GI 1.6±1.7μmol (g wet weight)−1 s−1, IL 2.3±1.1 μmol (g wet weight)−1 s−1, p=0.39).

Conclusion Diabetic participants with HFrEF and normal cardiac function appear to have increased resting LVEF when clamped on FA as opposed to glucose metabolism, without a significant change in energetic status. This may imply that metabolic flexibility is relatively preserved in these groups.

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