This editorial refers to ‘Improved diabetic control in advanced heart failure patients treated with left ventricular assist devices’ by Nir Uriel et al. published in this issue on page 195–199. Heart failure and diabetes often co-exist, and since the number of people with either diabetes or heart failure is increasing worldwide, the amount of patients suffering from both disorders will grow exponentially. The presence of diabetes in patients with heart failure is associated with increased hospitalization, cardiovascular morbidity, and mortality.1 Conversely, patients with heart failure have an increased risk of developing diabetes.2 Factors predictive of the onset of diabetes in patients with heart failure are the percentage glycated haemoglobin and body mass index. In addition, the decreased cardiac output characteristics for heart failure patients may represent an additional risk factor. The associated decrease in tissue perfusion, together with neurohumoral (adrenergic) activation, translates into a reduction in tissue delivery of glucose and insulin (reduced nutritive flow). Muscle glucose uptake depends on the amount of glucose delivered to the tissue and the fraction of glucose extracted.3 Thus, if vasoconstriction occurs in the capillary compartment of the muscle, the ability to extract glucose is reduced resulting in insulin resistance.4 Such a relationship is supported by the observations of Uriel et al.,5 published in the current issue of the European Journal of Heart Failure. The authors show an intriguing association between improvement in cardiac output and improved glucose regulation. In a relatively small study of only 15 patients with diabetes and advanced heart failure who were treated with left ventricular assist devices (LVADs), they demonstrated that after a period of only 4 months, both fasting glucose levels and the percentage glycated haemoglobin decreased significantly. Moreover, the average daily insulin dose was halved post-implantation and six patients needed no glucose-lowering treatment at all at follow-up. The authors suggest that increased blood flow to the peripheral and cardiac muscle may explain these results, although this was not measured directly. Alternatively, improved physical activity resulting in changes in fat and muscle mass, changes in neurohormonal activity6 and inflammation, or the reduced use and dose of diuretics2 may have accounted for the results. A few observations corroborate the findings of Uriel et al. In experimental studies, it has been observed that glucose metabolism is affected by heart failure, which is reversible after the improvement or normalization of cardiac output. In a study of 24 dogs with experimental heart failure, the increased cardiac glucose oxidation and decreased free fatty acid oxidation was reversed to normal values 10 days after recovery from heart failure.7 Furthermore, respiratory chain and metabolic genes were down-regulated in a rat heart failure model and returned to normal with unloading.8 Cardiac output can be improved by medical and device treatment and by heart transplantation. Cardiac resynchronization therapy has been shown to be beneficial for patients with diabetes and heart failure in several trials.9 Patients with diabetes who received cardiac resynchronization therapy experienced an improvement in outcome, similar to the benefits observed among patients without diabetes.10 Whether cardiac resynchronization affects glucose and insulin levels or insulin sensitivity has not yet been investigated. Cardiac output can also be improved by LVADs, as shown by Uriel et al. Previous studies which have investigated the effect of LVADs on whole-body metabolism have reported down-regulation of the expression of the glucose transporters 1 and 4 and mitochondrial proteins (uncoupling protein 3) in the failing heart,11 and the latter was reversed by mechanical unloading. Barton et al.12 observed that the messenger RNA of insulin-like growth factor-I which was elevated at the time of LVAD implantation returned to normal 1 year after explantation in patients who showed the recovery of left ventricular function. The recently updated heart failure guidelines state that the technical improvements and proven success of implantable LVADs have made them a reasonable treatment option which may be considered in patients with end-stage heart failure.7 The current recommendation is Class IIb with a level of evidence B, mainly based on the beneficial effects observed with the continuous-flow device (HeartMate II) in 200 heart failure patients.13 The effect of improved cardiac output on glucose regulation, as shown with LVAD treatment in the present study,5 seems beneficial. Future studies related to cardiac output should investigate whether this observed effect can be reproduced. For patients with diabetes, mechanical unloading may therefore have a two-fold beneficial effect: not only by improving haemodynamics, but also—secondary to this—by improving the metabolic disturbance, thereby possibly providing some treatment for diabetes. Conflict of interest: none declared.