What Are The Signs And Symptoms Of Diabetic Cardiomyopathy?

Diabetes can put you at risk of several serious health problems, especially when it’s left untreated. Consistently high blood sugar levels impact every part of your body, but they are particularly threatening to the heart and the blood vessels — and cardiovascular disease remains the leading cause of death among people with diabetes. The most common heart problems in diabetespatients include coronary artery disease, stroke, and heart failure.

The American Heart Association defines diabetic cardiomyopathy as a clinical condition of ventricular dysfunction (dysfunction of the heart’s pumping chambers) in the absence of high blood pressure or coronary atherosclerosis (a disease in which plaque builds up inside your arteries). In around 25 percent of the patients, DCM leads to heart failure.

What is cardiomyopathy?

Cardiomyopathy is a group of heart muscle diseases characterized by changes in heart structure. These changes affect the heart’s ability to pump blood and it can often lead to heart failure, a condition in which the heart is not able to meet the demands of the body.

There are many possible causes of cardiomyopathy. Some are genetic, while others can happen as a consequence of another systematic disease like diabetes. Although the causes differ, cardiomyopathy usually presents as one of four types: dilated, hypertrophic restrictive and arrhythmic. These are usually called phenotypes, a set of observable characteristics of some condition. DCM usually presents as dilated cardiomyopathy in which the heart walls stretch

How and why does diabetes cause cardiomyopathy?

In type 1 diabetes mellitus (T1DM) the pancreas doesn’t produce enough insulin, one of the most important hormones that allows sugars to enter cells where they can then be used as fuel. Type 2 diabetes (T2DM) is characterized by insulin resistance, meaning that the body doesn’t respond to insulin in the way it’s supposed to.

The result of both type 1 and type 2 is elevated blood glucose levels over a prolonged period, which leads to many changes in the organism. That way both T1DM and T2DM can lead to diabetic cardiomyopathy, which can result in heart failure.

The development of DCM is silent and complex, depending on several factors and through several mechanisms. It’s called silent because it’s characterized by an unusually long symptomless stage (the so-called latent period). During that time, a number of important metabolic and structural changes happen. The changes can be observed on the cellular level and within the structure of the whole heart. Let's look at some of the most important changes.

Changes on the cellular level

• A decrease in glucose uptake by the heart cells. Normal heart cells get most of their energy from fatty acids and glucose. As a consequence of low insulin levels and lower number of glucose transporters (proteins through which the glucose enters the cells, something like cell gates for glucose; in that analogy insulin would be the key for the gate), the heart cells start to take only the fatty acids. This disrupts balance and causes many changes. High blood sugar (hyperglycemia) causes the mitochondria (cell organelle responsible for cellular respiration) to produce superoxide, a very reactive molecule that can damage the DNA and the proteins.
• Formation of reactive oxygen species (ROS), leading to oxidative stress. The excess of blood glucose starts to react and form chemical bonds with proteins around it. After a series of reactions, these altered proteins lead to the formation of ROS, very reactive species that can damage any molecule they come in contact with, including DNA. These altered proteins also activate pathways that lead to an inflammatory response and a decrease in contractile proteins. This is very important since the contraction of the heart is based on the contraction of those proteins. Inflammation also plays a big role in the development of DCM.
• A change in the way the heart cells communicate with each other (changes in calcium signaling).
• Formation of toxic protein structures that lead to the death of the heart cells. This happens through the misfolding of proteins. Every protein has a 3D structure and molecules that help it fold into that structure. Sometimes the event of folding can result in unintended protein structures that might be toxic.  
• Degradation of the extracellular matrix. Heart cells are surrounded by a meshwork of proteins called the cardiac extracellular matrix. These proteins are very important for the heart’s function, allowing normal contractions by positioning every heart cell. That leads to a coordinated response to an electrical stimulus. Disruption of the web that holds and positions the heart cells affects the way in which the heart contracts.

Changes in the heart structure

• Left ventricular hypertrophy (LVH). Your heart is a muscular pump that features four chambers. Two upper chambers, the atria, collect the blood, passing it to the lower pumping chambers called ventricles. The left ventricle is the heart’s main pumping chamber that pumps oxygenated blood from the lungs to every other part of the body. Hypertrophy is the term used to describe the enlargement and abnormal thickening of the left ventricle. This reduces its ability to pump blood and it’s a risk factor for heart failure. In DCM it mostly happens in patients who have type 2 diabetes, and obesity plays a big role. The fat tissue produces leptin and resistin, hormones that regulate feelings of hunger and satiety. However, they also influence many other cells and through still unknown mechanisms lead to the hypertrophy of the heart muscle. It’s also believed that insulin acts as a growth factor in the heart.
• Heart fibrosis. Scarring of the heart, characterized by extra collagenous tissue.

What are the symptoms of diabetic cardiomyopathy?

Diabetic cardiomyopathy is characterized by a long asymptomatic phase. In that phase, also called the latent period, the heart goes through the changes described above, but it takes some time for structural and metabolical changes to present with symptoms. 

Diabetic cardiomyopathy can present as restrictive or dilated cardiomyopathy type. In dilated CM the ventricle becomes enlarged. The walls of one or both ventricles stretch (dilate) and become thinner, making it harder for the ventricle to contract and pump blood effectively. 

In restrictive CM the ventricular walls become stiff, and normal tissue is replaced with scar tissue. In diabetic CM both of these changes happen on the left ventricle. While both can lead to heart failure, there is an important difference in the ejection fraction. Ejection fraction (EF) is a measurement of the percentage of blood leaving your heart each time it contracts. When becoming symptomatic, DCM patients with a dilated type present as heart failure with reduced ejection fraction, while the restrictive phenotype has a normal EF. This requires different therapeutic approaches.

Early signs

Before the symptoms start the show, a physician can observe some of the following signs:

• Left ventricular hypertrophy. Imaging methods such as echocardiogram show the thickening of the heart walls (thicker than 1.1cm).
• Left ventricular diastolic dysfunction. The heart works through cycles, each consisting of the muscle relaxation and filling with blood, called diastole, followed by a contraction that pumps the blood out of the chamber, called systole. LV diastolic dysfunction means that the left ventricle doesn’t fill with blood the way its meant to. Scarring of the heart tissue (fibrosis) plays a big part in diastolic dysfunction. Studies have shown that between 40 to 75 percent of T1DM and T2DM have diastolic dysfunction. Once diastolic dysfunction is diagnosed all measures should be taken to prevent the progression of DCM to systolic dysfunction and consequently heart failure.

Later manifestations

• Enlargement of the left ventricle.
• Systolic dysfunction. The ability of the left ventricle to contract and pump blood is reduced. This usually happens after diastolic dysfunction and leads to heart failure
• Symptomatic heart failure.

Symptoms of heart failure

Once diabetic CM has progressed, symptoms typical of heart failure occur. That includes:

• Breathlessness, coughing or wheezing. This happens because fluid builds up in the lungs.
• Fatigue, weakness or tiredness. Every cell in our body requires oxygen for its metabolical processes. In heart failure the heart can’t pump enough oxygen-rich blood to meet the energy demands of the body, leaving you with a feeling of fatigue and general lack of energy.
• Swelling of the legs and the ankles. The heart doesn’t have enough strength to force used blood back up from the lower parts of the body, resulting in the fluid build-up.