How Peripheral Artery Disease Impacts People With Diabetes

WWhen we think about clogged arterials, many of us immediately think of the heart. “But buildup of fatty plaques can happen in any artery, including those that carry blood away from the heart,” says Dr. Samuel Kim, a preventive cardiologist and lipidologist at Weill Cornell Medicine in New York.

What we refer to as peripheral arteries is the majority of what we mean. And the narrowing in these vessels is referred to as peripheral artery disease (PAD), a common condition in which the legs or arms don’t receive sufficient blood flow. “Interestingly, arteries in our legs and feet clog up much more readily than those in our arms and hands,” Kim says. It is not clear why this happens.

It’s possible to have PAD without plaque buildup in the heart and brain vessels, which are harbingers of heart attacks and strokes. “Even though these diseases can occur separately,” says Dr. Philip Goodney, a vascular surgeon at Dartmouth Hitchcock Medical Center in Lebanon, N.H., “it is not at all uncommon for these disease entities to travel together.” As a result, patients with symptoms of coronary or cerebrovascular disease will often get evaluated for PAD, and vice versa.

The Diabetes Connection

According to The American Diabetes Association, close to 12 million Americans have PAD. 1 in 3 also has Type 1 or Type 2 diabetes. World Journal of Diabetes. While data is insufficient to show if either type is more concretely linked to PAD, “Type 2 diabetes is more common, simply because there are more Type 2 diabetic patients,” Kim says.

The risk factors that increase the likelihood of developing peripheral arterial disease include being over 65, having high cholesterol, high bloodpressure, chronic kidney disease, and high blood pressure. “But smoking and diabetes are the top two,” says Dr. Aaron Aday, a cardiologist and vascular-medicine specialist at Vanderbilt University Medical Center in Nashville.

What causes diabetes to cause blockages of blood vessels?

“Inflammation is key,” Aday says. A persistent state of inflammation is caused by diabetes. Blood tests such as the C-reactive protein can measure this. Research has shown that elevated levels of this protein may increase the risk of clotting in the arteries and make them susceptible to blocking or narrowing.

In addition, having high levels of sugar in blood—such as when diabetes is inadequately controlled—produces a lot of reactive oxygen species, which are fairly unstable molecules that ricochet within cells and damage vital components such as DNA and RNA. It has also been demonstrated that protein kinase C(PKC) is a critical arbiter for generating reactive oxygen molecules. This can cause damage to blood vessels’ structure and functions.

Kim emphasizes diabetes’ negative effects on endothelial cell, the cells that line blood vessels’ inner layer. Endothelial cells, when healthy, produce a gaseous substance called nitric dioxide, which helps blood vessels stretch, recoil, and also slows down chemical signals that can cause our bodies to incorrectly clot blood. However, when exposed to high amounts of sugar, these cells lose their ability to modulate nitric oxide levels—and the complex architecture of blood vessels, along with their astonishing pliability, is severely compromised.

While having diabetes can heighten someone’s risk of developing PAD, the relationship doesn’t go just one way. People can develop arteries disease before they are diagnosed with diabetes. This is often exacerbated when blood sugar levels drop. Lifestyle factors including smoking, unhealthy diet, and physical inactivity—coupled with genetic factors such as high levels of lipoprotein(a) and familial hyper-cholesterolemia—can fray the linings of blood vessels long before diabetes is officially diagnosed. Studies have shown that diabetes duration is related to the severity of arterial damage. Plus, each 1% rise in HbA1c—a test that measures the amount of sugars chemically bound to blood cells (compared with sugars just floating around in bloodstreams as measured by a regular blood-glucose test)—is associated with an almost 30% increased risk of being diagnosed with PAD.

This duo of disease can also be caused by race and ethnicity. “If you have diabetes and you’re Black, your risk of PAD is almost twice as high as Caucasians,” says Dr. J. Antonio Gutierrez, an interventional cardiologist at Duke Health who is also involved in patient-outreach activities among minority communities outside of Durham, N.C. Hispanics, Puerto-Ricans, and Mexicans are also at increased risk, he says.

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Watch out for warning signs and symptoms

Steve Shipley was in his 60s when he noticed blisters beneath his feet after he had been umpiring softball five years earlier. After being diagnosed in 1977 with Type 1 diabetes, he attempted to keep active. In addition to coaching and refereeing softball, he also played basketball.

“I noticed the blisters and thought, ‘Well, it’s probably from the shoes rubbing against that area,’ so I didn’t pay too much attention to it,” he says. Plus, he’d never had anything like it before, or experienced any unusual pain or cramps in his legs.

After a few days the blisters got worse. “I made an appointment with my podiatrist, and we decided to try these platform shoes with Velcro straps designed to prevent any rubbing of the toes,” he says. However, Shipley soon realized that the blisters weren’t healing.

He remained hopeful that his wounds would heal over the next few days and kept an eye on what was happening to his feet for a while longer. He noticed that his right toe was turning darker and he called the podiatrist who performed an emergency procedure. “I’m glad I went when I did, because if I’d waited any longer, I might’ve lost my entire leg instead of just one toe,” he says.

Shipley is among many people who do not experience any symptoms but have their peripheral arteries gradually build up plaque. The situation can quickly become life-threatening when blood vessels are blocked before more symptoms show up.

“Only a third of patients have the classic textbook symptoms,” says Gutierrez, “but for others, the symptoms may be a lot more subtle.” Most commonly, these people experience throbbing pain, cramping, or a burning sensation in their legs—particularly in their calves—with walking or exercise, and find that it improves within a few minutes of resting. Depending on the vessel involved, these painful sensations may be specific to a particular area. “You could have buttock pain, which would mean it’s a proximal vessel you could be dealing with, or pain in your thighs or somewhere further down your feet,” Kim says.

Other signs you should be aware of are: “Patients may experience some degree of hair loss on their lower legs, changes in skin and toenails, and/or temperature differences between their feet,” Aday says. Poor diabetes management can lead to PAD, which could cause blisters, nonhealing feet ulcers, infection, tissue death and eventually, amputations.

Goodney points out that not all people with PAD experience pain. Many people with diabetes also have problems with their nerves, he says, “which limits their detection of some of those symptoms or warning signs.” That means it’s not unusual for those with peripheral artery disease to have no idea they have the condition.


Given that symptoms aren’t reliable, Goodney stresses the importance of routine evaluation. “One of the most important things patients with diabetes can do is to make sure that they get a diabetic foot exam on a yearly basis,” he says.

These visits are where medical professionals ask questions regarding diabetes management, lifestyle factors such as smoking, diet and movements. An ankle-brachial Index, a noninvasive test that can be used to determine the extent of arterial disease may be requested by doctors. The test is performed in resting positions, although patients may be asked to walk on treadmills to help locate their symptoms.

To visualize blockages and their location more accurately, an anatomical evaluation is required in addition to the index at the ankle. “That can be done through ultrasound, CT scan with contrast, or magnetic resonance angiography,” Kim says. Along with the patient’s history and physical exam, these scans may better inform the nuances of treatment plans.

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The treatment

Peripheral artery disease can be treated in a variety of ways. People with peripheral artery disease (PAD) are often instructed to begin supervised exercise therapy. “You push people to exercise beyond the boundaries of what they can tolerate,” Kim says. “The idea here is that over time, your body builds collateral blood vessels that take detours around the clogged vessel.” Such a program can be done at home—by going on walks for short to moderate distances—or in rehabilitation centers. “At the same time, it’s also important to ensure that people’s diabetes is properly managed, their blood pressure is under control, they’ve stopped smoking, and they’re eating healthfully to lower cholesterol,” Aday says.

American College of Cardiology/American Heart Association guidelines suggest that PAD patients should start taking medications in conjunction with lifestyle changes and exercise. “We start patients on anti-platelet therapy with aspirin or clopidogrel, high-intensity statins for lipid lowering, and high-blood-pressure medications,” Kim says. Research has shown that strict medication management can not only reduce some plaques but may also lower the risk of stroke, heart attack, and limb loss.

However, depending on how severe the blockage is, medication alone might not be enough. Surgery may be required. “We can help reopen arteries with things like balloons, stents, or catheters where patients can have quite dramatic effects,” Goodney says. “But for those with more advanced disease who have failed balloons and stents, we can help rebuild the arteries, similar to a bypass surgery.”

In some time-sensitive scenarios, amputation may be necessary. “When a patient is very ill, and all solutions to rebuild their arteries are used up without success, then removing a limb may be the only avenue left to get rid of severe pain or a life-threatening infection,” Goodney says. Amputations due to diabetes can lead to intense guilt and low self-esteem and body image. It’s often a good idea for these patients to seek behavioral health services.

Shipley was self-conscious for several months after his toe-amputation. “It makes you feel different,” he recalls. “For example, if I was at the pool or if I didn’t have my shoes on and somebody came to the door, I’d make sure I put them on before seeing them.”

Even more emotional weight was placed on those living at home. “Ironically, when I first had it, our granddaughter was only a couple of years old, and I was really afraid that the missing toe would scare her,” he says. But by accident, she noticed it one day and said, “‘Papaw, I would give you my toe if I could.’ And from that moment, my mental outlook changed completely.”

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