Diabetic cardiomyopathy

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Diabetic cardiomyopathy
A hollow circle with a thick blue border and a clear centre
Universal blue circle symbol for diabetes.[1]
SpecialtyCardiology

Diabetic cardiomyopathy is a disorder of the

diabetes. It can lead to inability of the heart to circulate blood through the body effectively, a state known as heart failure(HF),[2] with accumulation of fluid in the lungs (pulmonary edema) or legs (peripheral edema). Most heart failure in people with diabetes results from coronary artery disease, and diabetic cardiomyopathy is only said to exist if there is no coronary artery disease to explain the heart muscle disorder.[3]

Signs and symptoms

One particularity of diabetic cardiomyopathy is the long latent phase, during which the disease progresses but is completely asymptomatic. In most cases, diabetic cardiomyopathy is detected with concomitant

systole. After the development of systolic dysfunction, left ventricular dilation and symptomatic heart failure
, the jugular venous pressure may become elevated, the apical impulse would be displaced downward and to the left. Systolic mitral murmur is not uncommon in these cases. These changes are accompanied by a variety of electrocardiographic changes that may be associated with diabetic cardiomyopathy in 60% of patients without structural heart disease, although usually not in the early asymptomatic phase. Later in the progression, a prolonged QT interval may be indicative of fibrosis. Given that diabetic cardiomyopathy's definition excludes concomitant atherosclerosis or hypertension, there are no changes in perfusion or in atrial natriuretic peptide levels up until the very late stages of the disease,[4] when the hypertrophy and fibrosis become very pronounced.

Pathophysiology

Defects in cellular processes such as

heart cells, prominent interstitial fibrosis and decreased or preserved systolic function[5] in the presence of a diastolic dysfunction.[6][7][8]

While it has been evident for a long time that the complications seen in diabetes are related to the hyperglycemia associated to it, several factors have been implicated in the pathogenesis of the disease. Etiologically, four main causes are responsible for the development of heart failure in diabetic cardiomyopathy: microangiopathy and related endothelial dysfunction, autonomic neuropathy, metabolic alterations that include abnormal glucose use and increased fatty acid oxidation, generation and accumulation of free radicals, and alterations in ion homeostasis, especially calcium transients.[citation needed] Additional effects include inflammation and upregulation of local angiotensin systems.

Diabetic cardiomyopathy may be associated with restrictive (

HFREF). HFPEF results predominantly from hyperinsulinemia, hyperglycemia, lipotoxicity, AGEs and microvascular rarefication. HFREF is associated with autoimmunity, hyperglycemia, lipotoxicity, microvascular rarefication and AGE formation.[9]

Microangiopathy

Microangiopathy can be characterized as subendothelial and endothelial fibrosis in the coronary microvasculature of the heart. This endothelial dysfunction leads to impaired myocardial blood flow reserve as evidence by echocardiography.[10] About 50% of diabetics with diabetic cardiomyopathy show pathologic evidence for microangiopathy such as sub-endothelial and endothelial fibrosis, compared to only 21% of non-diabetic heart failure patients.[11] Over the years, several hypotheses were postulated to explain the endothelial dysfunction observed in diabetes. It was hypothesized that the extracellular hyperglycemia leads to an intracellular hyperglycemia in cells unable to regulate their glucose uptake, most predominantly, endothelial cells. Indeed, while

myocytes have mechanisms allowing them to internalize their glucose
transporter, endothelial cells do not possess this ability. The consequences of increased intracellular glucose concentration are fourfold, all resulting from increasing concentration of
glyceraldehyde-3-phosphate reaction which is inhibited by mechanisms activated by increased free radical formation, common in diabetes.[12]
Four pathways, enumerated below all explain part of the diabetic complications. First, it has been widely reported since the 1960s that hyperglycemia causes an increase in the flux through
NAD(P)H oxidase production of free radicals further damaging the surrounding cells.[16] Finally, exported glycation products bind extracellular proteins and alter the matrix, cell-matrix interactions and promote fibrosis.[17] A major source of increased myocardial stiffness is crosslinking between AGEs and collagen. In fact, a hallmark of uncontrolled diabetes is glycated products in the serum and can be used as a marker for diabetic microangiopathy.[18]

Autonomic neuropathy

While the heart can function without help from the nervous system, it is highly innervated with autonomic nerves, regulating the heart beat according to demand in a fast manner, prior to hormonal release. The autonomic innervations of the myocardium in diabetic cardiomyopathy are altered and contribute to myocardial dysfunction. Unlike the brain, the peripheral nervous system does not benefit from a barrier protecting it from the circulating levels of glucose. Just like endothelial cells, nerve cells cannot regulate their glucose uptake and suffer the same type of damages listed above. Therefore, the diabetic heart shows clear denervation as the pathology progresses. This denervation correlates with echocardiographic evidence of diastolic dysfunction and results in a decline of survival in patients with diabetes from 85% to 44%. Other causes of denervation are ischemia from microvascular disease and thus appear following the development of microangiopathy.[citation needed]

Inflammation

Diabetes is associated with increased inflammation, which is mediated by generation of abnormal fatty acids, AGEs and other mechanisms.[19] The resulting cytokine profile promotes hypertrophy and apoptosis of cardiomyocytes, abnormal calcium signaling, impaired myocardial contractility and myocardial fibrosis.[20] Additionally, it may lead to microvascular dysfunction, either directly or via endothelial damage, thereby promoting myocardial ischemia.[21]

Diagnosis

Diagnostic approaches for diabetic cardiomyopathy include echocardiography, cardiac MRI investigations, Multi‐slice computed tomography (MsCT), and nuclear imaging.[22] Potential risks of the investigation (e.g. exposure to radiation) and diagnostic utility should be weighed for an optimised personalised procedure.[22]

Treatment

At present, there is no effective specific treatment available for diabetic cardiomyopathy.[23] Treatment rationale centers around intense glycemic control through diet and preferential use of certain medications in diabetic patients at high risk for developing cardiovascular disease or heart failure. A rationale for therapeutic decision making in individuals with coexistent diabetes mellitus and HF is less clear because there is a possibility that additional factors beyond glycemia might contribute to the increased HF risk in diabetes mellitus.

NYHA Class III or IV heart failure secondary to fluid retention.[25]

As with most other heart diseases,

ACE inhibitors can also be administered. An analysis of major clinical trials shows that diabetic patients with heart failure benefit from such a therapy to a similar degree as non-diabetics.[26] Similarly, beta blockers are also common in the treatment of heart failure concurrently with ACE inhibitors.[24]

References

  1. ^ "Diabetes Blue Circle Symbol". International Diabetes Federation. 17 March 2006. Archived from the original on 5 August 2007.
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