ADA 2019: The Heart and Type 2 Diabetes
There is a well-established increased risk for heart failure (HF) in people with type 2 diabetes (T2D). T2D is an independent predictor for the development of HF. In addition, T2D is associated with worse clinical outcomes in the presence of HF, with a twofold increased risk of death. Myocardial metabolism in people with T2D is altered, which is thought to contribute to decreased cardiac output and higher risk for HF. A healthy heart consumes the most ATP of any organ by weight, and a steady source of energy is essential to its proper function. Ketones are the most efficient fuel and fatty acids are the least efficient, and their utilization is in a fine balance in the healthy heart. In people with T2D, the balance is disrupted and heart muscle is more reliant on fatty acid oxidation, is more insulin-resistant than in people without T2D, and has less glucose uptake. This increased use of fatty acid oxidation for fuel for heart muscle is inefficient and, in turn, leads to decreased cardiac output efficiency. The use of insulin in a T2D animal model resulted in increased cardiac muscle glucose utilization, which lead to improved cardiac output and stroke volume. SGLT2 inhibitors improve cardiac outcomes, including HF hospitalizations, but the pathophysiology for this effect is unclear as it seems to be due to more than just improved glycemic control or weight loss. There is some thought that SGLT2 inhibitors increase ketone utilization for cardiac muscle fuel. In animal models, it seems that, although ketone utilization is not increased and fatty acid utilization is not decreased, the relative amount of ketone utilization is higher. This excess ketone utilization with the use of SGLT2 inhibitors is thought to be the physiology behind improved HF outcomes.
The American Heart Association published its first official position statement regarding the association between HF and T2D as well as treatment recommendations. The statement acknowledges that recent clinical trials have demonstrated the shared pathophysiology between T2D and HF, the synergistic effect of managing both conditions, and the potential T2D treatments to improve HF outcomes. Not only does T2D confer a higher risk of HF, but the association likely goes both ways. Secondary analysis in the CHARM study and EMPHASIS-HF study showed that HF is associated with a twofold increased risk for developing T2D. Regardless of the directionality of the T2D and HF association, multimodal treatment has been shown to improve outcomes for both conditions.
Medications that make HF worse include NSAIDs, amiodarone, and pseudoephedrine; these should be avoided in any patient with HF. If there is reduced ejection fraction in HF, the use of diuretics to achieve a target dry weight is important. In addition, if possible, ACE inhibitors or ARBs, beta blockers, and mineralocorticoid receptor antagonists should be added to the therapeutic regimen. Endocrinologists and cardiologists need to work closely together to improve outcomes for their patients with T2D and HF. The new medication on the block is sacubitril/valsartan, and, although the PARADIGM-HF results have not been published in entirety, they are promising and will likely influence changes to HF therapy recommendations. Treatment of T2D in people with HF should be determined by glycemic control, age, and renal function. SGLT2 inhibitors have been associated with improved HF outcomes, while the cardiovascular benefits associated with GLP-1 receptor agonists are limited, in large part linked to coronary artery disease and not HF. Regarding HF with preserved ejection fraction, there have not been any trials to demonstrate any benefit of therapy.
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