How Obesity and Diabetes Affect the Heart


I may be a bit biased, but I think the heart is our most fascinating organ. Sure, you can argue that it’s the brain, without which our amazing hearts would be irrelevant. But, our cardiovascular system is so intricate and, dare I say perfect; our heart keeps it’s steady rhythm throughout life, never fatiguing or missing a beat (unless you’ve got an arrhythmia, of course…)

Given its importance, a priority should be placed on protecting this essential pump. However, statistics indicate that this is hardly the case worldwide — cardiovascular and heart disease are the leading causes of death from non-communicable disease; even surpassing cancer of any kind. Whether due to environmental, dietary, or lifestyle-related factors, people all around the globe fail to take adequate care of their hearts. Health, productivity, and lifespan suffer because of it.

Recently, I’ve been doing some (sort of mandatory) reading on two separate but similar conditions. Both are what is known as a cardiomyopathy — a disease of the heart muscle that causes it to be less efficient at pumping blood. More specifically, I’ve been reading about obesity and diabetes cardiomyopathy — heart dysfunction that is independently caused by either obesity or diabetes.

Obesity and diabetes are rampant, and are sometimes considered “twin epidemics” — as they more often than not occur in conjunction. While neither are neither necessary nor sufficient for each other to occur, the metabolic causes and consequences often overlap.

We usually think of obesity and diabetes in their metabolic terms — using phrases like high blood glucose, insulin resistance, and body fatness to typify them. However, both diseases can have profound adverse effects on the cardiovascular system which impair heart function. Below, I’ll discuss some of the main characteristics of and mechanisms that lead to obesity and diabetic cardiomyopathy.

One of the primary findings in both obesity and diabetes cardiomyopathy is something called left-ventricular diastolic dysfunction. In short, the main pumping chamber of the heart (the left ventricle, or LV) loses its ability to relax. Relaxation (diastole) is necessary for our heart to fill with blood, before contraction (systole) ejects the blood out of the aorta and into our circulation.

The obese/diabetic heart has reduced ability to relax, and therefore doesn’t fill properly. In turn, this can lead to systolic dysfunction —a reduced ability to contract and eject blood. The dangerous cycle only superimposes further dysfunction on itself.

This loss of function is accompanied by some pretty major structural changes to the heart. Diabetes and obesity can cause the walls of the heart to thicken — termed cardiac hypertrophy. These thick, muscular walls lose some of their elastic ability. Stiffer walls are worse at contracting and relaxing. Wall thickening occurs because individual heart cells (known as cardiomyocytes) actually grow larger themselves. As each cell grows (hypertrophies), the wall thickens in proportion.

Ventricle size also increases in diabetic and obesity cardiomyopathy, expanding in size and volume. This process is known as dilatation, and most often occurs in the left ventricle, though the right ventricle also experiences dilatation.

A final structural change involves something called fibrosis. Fibrosis of the heart is implicated in the process of thickening and stiffening. Our heart muscle is surrounded by something called extracellular matrix (ECM)— a layer composed of various proteins like collagen and elastin, vascular cells, and other immune and fibrotic cells that serve as a structural scaffold for the heart. In diabetes and obesity, the heart ECM becomes more fibrotic — meaning that an abnormal amount of ECM accumulates or the composition changes; leading to a stiffer, “fibrotic” heart.

This structural remodeling spells bad news for the heart. A large ventricle size may prevent adequate contraction, and thicker, stiffer walls prevent adequate contraction AND relaxation, which is further impaired by fibrosis. As a result, the heart becomes less efficient at pumping blood. This, when it progresses, is known as heart failure.

Normal (top) and hypertrophied/fibrotic heart (bottom) Source: Herum KM, Lunde IG, McCulloch AD et al. J Clin Med 2017

What causes all of these changes? Some of the pathophysiology is specific to either obesity or diabetes, but a lot of it is shared by both.

In obesity , one of the primary causes of left ventricular hypertrophy is an increased load on the heart. Obese individuals have a higher metabolic activity and increased lean/fat mass, and this increases total blood volume and a hypercirculatory state. An overall increase in blood volume means that the heart experiences a greater filling volume and elevated systolic/diastolic pressure. The heart must also work harder (i.e. generate more force) to eject blood against these increased pressures. Both of these changes mean that the left ventricle work rate and wall stress are increased, leading to a thicker, hypertrophied muscle. The heart, just like a bicep or tricep muscle, grows larger with “training.”

Increased wall stress and elevated ventricular work rate means the heart has a higher demand for oxygen. In diabetes and obesity, as we will see later, oxygen supply may be reduced and therefore, the heart may be “starved” of oxygen.

Obesity and diabetes are often characterized by insulin resistance — the muscles and other tissues in the body fail to respond properly to insulin, and therefore blood glucose uptake and utilization is impaired. Insulin resistance leads to hyperglycemia, or high blood glucose. High blood glucose (blood sugar) can wreak havoc on the cardiovascular system — it increases oxidative stress and inflammation, reduces blood vessel function, and can lead to the production of advanced-glycation end products (AGEs). AGEs can be thought of as “sticky” molecules that attach to and cross-link proteins in the body, rendering them dysfunctional.

Insulin resistance also leads to a metabolic shift in the heart. Normally, the heart metabolizes glucose as a fuel substrate, but can use fatty acids (and ketones) in some situations. Without proper insulin action, however, glucose can’t be transported into the myocytes.

Thus, the heart shifts from glucose oxidation to primarily fatty acid oxidation. For one, this increases the oxygen demand of the heart, since fatty acids require more oxygen for their metabolism than does glucose. Secondly, an increased flux of fatty acids into the myocytes can lead to something known as lipotoxicity and dyslipidemia; when supply of these molecules outpaces demand or utilization. Toxic byproducts of fatty acids and triglycerides can promote myocyte cell death and cardiac dysfunction.

Pathways of of fatty acid and glucose metabolism in the heart. Source:

Inflammation — characterized by increased presence of proinflammatory molecules in the heart, is also upregulated in both obesity and diabetes. This can be due to hyperglycemia, insulin resistance, or production of inflammatory molecules in adipose (fat) tissue. Inflammation contributes in part to the cardiac hypertrophy and fibrosis involved in cardiac dysfunction.

A final shared mechanism among obesity and diabetes is overactivation of neurohumoral systems; including the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS).

In the body, RAAS has several effects — causing vasoconstriction of blood vessels and sodium/fluid retention in order to maintain blood pressure. The main player here is angiotensin II (ANG II), which causes these effects by activating its receptors throughout the cardiovascular system.

RAAS is overactive in both obesity and diabetes. Several components of RAAS are found in high quantities in adipose tissue, meaning obese individuals have higher levels of angiotensin II than normal-weight individuals (even those with hypertension or cardiomyopathy). In diabetes, RAAS is also overactivated due to hyperglycemia, insulin resistance, and other factors.

When RAAS is chronically overactive, it has adverse including vasoconstriction of blood vessels, stimulation of reactive oxygen species (ROS), cell proliferation, and fibrosis, among other actions. Angiotensin II is actually a growth factor in the cardiovascular system, and high levels can promote cardiac hypertrophy.

Increased RAAS and insulin resistance can also lead to SNS activation. In the cardiovascular system, SNS activation induces many of the similar pathways as RAAS, including vasoconstriction, heart contractility, inflammation and oxidative stress, and cell proliferation.

One final common pathway involved in cardiomyopathy in obesity and diabetes involves (and perhaps begins with) endothelial dysfunction. Normally, our blood vessels intricately regulate blood flow (and pressure) through vasoconstriction and vasodilation (relaxation). A healthy balance of molecules that promote dilation (nitric oxide, NO) and constriction (endothelin-1, ET-1) fine-tunes vascular tone to meet our metabolic needs. Many of the above mechanisms (RAAS, inflammation, hyperglycemia, SNS activation) can impair endothelial function. While it contributes to cardiomyopathy, endothelial dysfunction is also implicated in the progression of atherosclerosis, and has other effects such as reducing exercise capacity and cognitive function.

While these are only some of the mechanisms behind cardiomyopathy resulting from obesity and diabetes, the description illustrates a beautifully complex interaction between metabolic diseases and the cardiovascular system. Sometimes we isolate various diseases without thinking in terms of integrated systems physiology.

This means that to improve the health of individuals/nations, we can’t target just one aspect of any disease or physiological system, nor can we point to one definitive cause for our ailments. Optimizing our body in all aspects; improving metabolic, cardiovascular, and even cognitive health are necessary for optimal wellness.

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