What to Know About Peripheral Artery Disease—and Its Connection to Diabetes

When we think of clogged arteries, most of us think about 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.

The arteries that branch out and feed into our arms and legs make up the bulk of what we call peripheral arteries. 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. But exactly why that happens remains unclear.
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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

In the U.S., nearly 12 million people have PAD, 1 in 3 of whom also have Type 1 or Type 2 diabetes, according to the 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.

There are risk factors for peripheral artery disease beyond diabetes: being older and having high cholesterol, high blood pressure, and chronic kidney disease all elevate the chances that someone will be diagnosed with PAD. “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.

So how exactly does diabetes lead to blockages in blood vessels?

“Inflammation is key,” Aday says. Diabetes causes a persistent state of inflammation, which can be measured by blood tests like that for C-reactive protein. Some studies show that high levels of this protein enhance clotting within arteries, making them even more susceptible to narrowing and blockages.

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. Also, protein kinase C (PKC), a key arbiter of generating these reactive oxygen molecules, has been shown to harm the structure and function of blood vessels.

Kim emphasizes the negative impact of diabetes on endothelial cells, which line the inner layer of blood vessels. When healthy, they produce a gaseous molecule called nitric oxide, which not only helps blood vessels stretch and recoil as needed, but also mellows chemical signals that cue our bodies to inappropriately 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. Many people have diseased arteries before receiving a diabetes diagnosis, which is then exacerbated by poor blood-sugar control. 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. But studies have consistently found that the duration of diabetes corresponds with the extent 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.

Race and ethnicity also play a role in developing this duo of diseases. “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.

Read More: People With Diabetes Are More Vulnerable to Heart Disease. How to Reduce the Risk

Warning signs and symptoms

About five years ago, Steve Shipley, who was in his early 60s at the time, noticed several blisters under his toes after umpiring softball. Diagnosed with Type 1 diabetes in 1977, he tried to remain active, coaching basketball and softball at a Tennessee high school, while also playing and refereeing those sports recreationally.

“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.

But after a couple of days, the blisters looked 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.

For a few more days he remained cautiously optimistic that the wounds would eventually heal, and kept a watchful eye on his feet. Then one evening, when he noticed his toe turning dark, he went right back to the podiatrist, who had to perform an emergency surgery. “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 one of many patients who hardly experience symptoms while their peripheral arteries insidiously build up plaque. By the time more obvious symptoms appear, blood vessels can become critically blocked, and the situation limb-threatening.

“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. These painful sensations might be localized to specific areas depending on which vessels are involved. “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.

There are other signs to watch for. “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. And in cases of poor diabetes management, PAD can progress to patients having blisters, non-healing foot ulcers, infections, and tissue death, ultimately requiring amputations.

However, as Goodney points out, not everyone with PAD will experience pain or other obvious symptoms. 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.

During these visits, medical providers also ask detailed questions about diabetes management, lifestyle factors like smoking and diet, and movement difficulties. A doctor might order a noninvasive test called the ankle-brachial index, which can help determine the severity of arterial disease. This test is usually done in a resting position, but patients are sometimes asked to run on a treadmill to better locate symptoms.

In addition to the ankle-brachial index, an anatomic evaluation may be needed to visualize the location and extent of blockages more precisely. “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.

Read More: The Link Between Type 2 Diabetes and Psychiatric Disorders


There are several treatment options for peripheral artery disease. Many people with PAD are instructed to start 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.

In conjunction with exercise and lifestyle modifications, American Heart Association/American College of Cardiology guidelines recommend that patients with PAD should be started on medications. “We start patients on anti-platelet therapy with aspirin or clopidogrel, high-intensity statins for lipid lowering, and high-blood-pressure medications,” Kim says. Studies have shown that adhering to a rigorous medication regimen may not only improve some of the plaques but also reduce the overall risk of heart attacks, strokes, limb loss, and death.

Depending on the extent of blockages, however, medications alone may be insufficient, and surgical interventions may be necessary. “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. Diabetes-related amputation can cause intense feelings of guilt, low body image and self-esteem, and depression. It’s often a good idea for these patients to seek behavioral health services.

Shipley felt self-conscious for months following his toe-amputation surgery. “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.”

The emotional burden was even heavier around people 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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Contributor: Lala Tanmoy Das