Because Diabetes mellitus and heart failure are both prevalent conditions, and because diabetes can itself be a cause of heart failure, it is apportioned to you to consider the specific pathophysiology and management implications in patients with both diabetes and heart failure. It is this consideration that a 2019 review article by the American Heart Association addresses.
The prevalence of heart failure in patients with diabetes is four times higher than that of the general population. In fact, fasting hyperglycaemia, raised HbA1c levels, and insulin resistance are all associated with higher risk for heart failure. These associations reflect the specific metabolic and structural pathophysiological mechanisms of heart failure in patients with diabetes: an impaired glucose utilisation coerces the heart into a preferential fatty acid oxidation the ultimate consequence of which is diabetic cardiomyopathy.
Elevated levels of free fatty acids are the hallmarks of the cardiovascular pathophysiology of diabetes. These free fatty acids allow for:
- lipid to accumulate in cardiomyocytes
- increases in mitochondrial reactive oxygen species
- myocardial hypertrophy and increase in left ventricular mass
- higher rates of cardiomyocyte apoptosis
The mitochondria of the heart cells are metabolically altered, and this affects the entire workings of the cells, including their handling of calcium. Intracellular calcium is not only the critical mediator of myocardial contraction, but also a key regulator of mitochondrial and, in turn, overall cellular, metabolism. The diabetic heart is at once both fat laden and exposed to lipotoxicity. And the vasculature of those with diabetes is more highly atherogenic.
The increase in ventricular mass relates also to increased fibrosis due to cross-linking of collagen molecules under the influence of advanced glycation end-products courtesy of hyperglycaemia. The result is an increase in myocardial stiffness and impaired cardiac relaxation. A non-compliant, fatty heart resists fuller ventricular filling; and such diastolic dysfunction is an early functional manifestation of diabetic cardiomyopathy, present in 40-75% of patients with Diabetes mellitus. The hyperglycaemia also leads to activation of the renin-angiotensin-aldosterone system and its vasoconstrictive effects.
The diabetic heart then is at risk for both systolic and diastolic heart failure.
Dunlay SM, Givertz MM, Aguilar D, et al. Type 2 Diabetes Mellitus and Heart Failure, A Scientific Statement From the American Heart Association and Heart Failure Society of America [published correction appears in J Card Fail. 2019 Oct;25(10):851]. J Card Fail. 2019;25(8):584-619. doi:10.1016/j.cardfail.2019.05.007
