Angelica was a rocket scientist—literally. She worked at the famed NASA Jet Propulsion Laboratory (JPL) in Los Angeles. In a place filled with brainiacs, Angelica, an African American woman in her fifties, was among the brightest stars in the sky. She was part of the team that put the first landing rover, the Sojourner Truth, on Mars.
So, it was surprising that she was only now visiting me—her first-ever appointment with a cardiologist. I say that because she was fully aware that she had type 2 diabetes. What had escaped her—apparently her primary care doctor as well—was the relationship between diabetes and heart disease.
“I go to my doctor at least every six months to check my blood sugar levels,” she said. “Believe me, I’m not the kind of person who takes chances. I can’t in my profession. Everything at JPL is checked and rechecked. And I can assure you that I certainly don’t take any chances with my health,” she said.
“And your doctor never thought to check for signs of atherosclerosis?” I questioned.
“Well, no. But why should she have checked? I’ve never experienced chest pains or any other symptoms of heart disease,” she protested.
Exactly. That is the problem. Many doctors and their patients who suffer from diabetes are not aware that cardiovascular disease is a common comorbidity of diabetes, and this correlation over the past three decades has only grown stronger.
But let’s be clear: cardiologists are as big a part of the problem. Just as primary care doctors may not check for signs of atherosclerosis, many cardiologists may not check a patient’s blood sugar level.
The clear association between heart disease and diabetes is a phenomenon well known by medical researchers but not so much among medical practitioners in general and even less by their patients. A survey released by the American Heart Association found that only a third of diabetics realized that heart disease was among the “most serious” complications for which they were at risk, even though almost twice that number would experience a cardiovascular problem.
So, let’s state the facts once and for all: the 30.3 million adult Americans with diabetes have a risk of dying of a heart attack or stroke two to four times as great as that of someone who has already survived a heart attack. To frame it another way, at least 68 percent of people age sixty-five or older with diabetes die from some form of heart disease, and 16 percent die of stroke.
In addition to the 30.3 million Americans diagnosed with diabetes, more than twice as many—another 70 million with prediabetes (a condition characterized by slightly elevated blood glucose levels)—are also at high risk for coronary heart disease. Patients with or at high risk for diabetes and their doctors too often tend to treat heart disease as a separate concern. Worse, because silent heart disease is an asymptomatic coronary heart condition, diabetes patients and their doctors might not even consider it life threatening, despite the evidence to the contrary. While it’s understandable that for persons with diabetes the focus of their medical care is the treatment of diabetes, they should never ignore their heightened risk for heart disease.
In this chapter, we’ll also discuss kidney disease, which affects 37 million people in the United States (or 15 percent of adult Americans) and is the ninth leading cause of death. Like those with diabetes, people with kidney disease are also at risk for silent heart attacks—the ones that may go unnoticed—because both diseases can cause neuropathy, or damage to the peripheral nervous system. As a result, researchers believe that diabetics and kidney disease sufferers simply can’t feel when they have a heart attack.
People with diabetes cannot fully regulate their blood sugar levels, and if the disease isn’t monitored constantly, blood sugar can spike to abnormally high levels, a condition called hyperglycemia, or less often dip below normal, a condition called hypoglycemia. Both conditions are potentially life threatening and can lead to coma and death if not recognized and promptly treated.
In a sense, diabetes is not one but two disorders. Type 1 diabetes, formerly known as juvenile diabetes, is an immunological disease in which a person is born without the ability to produce insulin, a hormone made in your pancreas that is essential for your body to use glucose for cellular energy. In type 2 diabetes, formerly known as adult-onset diabetes, the pancreas still makes insulin but not enough, or the insulin doesn’t work in the body like it should, and blood sugar levels get too high. Another difference is that type 2 diabetes is a progressive disease and worsens over time. Eventually, most patients with prediabetes or type 2 diabetes will need to use a blood-sugar-controlling oral medication or injectable insulin (just like virtually all type 1 diabetes patients).
Both kinds of diabetes have a genetic connection. If your parents had type 1 or type 2 diabetes, you’re at greater risk of developing the disease. But as is the case with heart disease, the fact that you’re at a higher risk of the disease doesn’t mean you will get it. Lifestyle, diet, and other environmental factors are important determinants.
Type 2 diabetes patients also commonly have a condition called insulin resistance. While they’re able to make insulin, their bodies can’t use it properly to move glucose into the cells. So, the amount of glucose in the blood rises. The pancreas then makes more insulin to try to overcome this problem.
But in order to develop insulin resistance and type 2 diabetes, you must also have a genetic abnormality. Along the same lines, some people with type 2 don’t produce enough insulin; that is also due to a genetic abnormality. That is, not everyone can develop type 2 diabetes. Additionally, not everyone with a genetic abnormality will develop type 2 diabetes; other genetic risk factors and lifestyle choices influence the development.
Insulin resistance has a strong correlation with obesity, but scientists aren’t exactly clear how it works. Indeed, when bariatric surgery became popular in the first decade of the twenty-first century as a means of treating extreme obesity, a surprising side effect in many patients with diabetes was that the disease instantly disappeared. They no longer had to take insulin. Since bariatric surgery involves several different techniques in which the capacity of the stomach is shrunk, on the face of it that should have no impact on diabetes, since insulin is produced in the pancreas. While there is no known cure for diabetes per se, bariatric surgery for some patients does, indeed, appear to cure the disease for reasons still unknown.
Diabetes was well known although not well understood by the ancients, and only recently has its connection to heart disease been identified. In the history of diabetes treatment, one date stands out: everything can be categorized as falling before 1921 or afterward.
More than three thousand years ago, the Egyptians were writing about a physical condition characterized by excessive urination, thirst, and weight loss—all traits of type 1 diabetes. Around the same time Ayurvedic physicians in India identified the disease and called it amadhumeha, or honey urine, as they noted that the urine of its sufferers attracted ants. The term “diabetes,” from the ancient Greek word for “to pass through,” was first used in 250 BC by Apollonius of Memphis, a reference to excessive urination associated with the disease. In the fifth century AD, Chinese physicians had already figured out the two types of diabetes.
In the Middle Ages, physicians thought the disease was a condition of the kidneys, because of its association with excessive urination. Physicians treated it with a wildly imaginative array of regimens, from a diet of rancid animal foods to smoking tobacco to exercise on horseback to wearing warm flannel clothes. But give credit to the medieval doctors for discovering that metformin (known then as goat’s rue or French lilac) was effective in treating diabetes. Fast-forward a few centuries, and metformin again would become available in 1995 in the United States as a treatment approved by the Food and Drug Administration for pre–type 2 diabetes.
By the late eighteenth century, English and Italian physicians, through autopsies, had observed that damage to the pancreas, not kidneys, was likely the cause of diabetes. And then came the first breakthrough in 1910, when Sir Edward Albert Sharpey-Schafer found that people with diabetes were deficient in a single chemical normally produced by the pancreas. He proposed calling this substance insulin and described the endocrine role it played in metabolism.
Then, in 1921, Frederick Grant Banting and Charles Herbert Best demonstrated that they could reverse induced diabetes in dogs by giving them an extract from the pancreases of healthy dogs. Eureka! They went on to purify the hormone insulin from bovine pancreases, and the first patient treated successfully was a fourteen-year-old boy with type 1 diabetes, Leonard Thompson, who weighed only sixty-five pounds at the time because of his disease. By 1924, insulin was in mass production and being distributed around the world. The insulin that Banting and Best developed nearly a century ago is essentially the same as is used today.
What is the link between diabetes and coronary heart disease, including asymptomatic silent heart disease? Over time, high blood glucose from type 2 diabetes can damage blood vessels and the nerves that control the heart and blood vessels. The longer one has type 2 diabetes, the greater the chances of developing heart disease.
People with type 1 diabetes are also at increased risk for heart disease, though the reasons for this are less clear. A recent study reported in the New England Journal of Medicine found solid evidence that aggressively lowering a person’s blood sugar level can cut the risk of heart attack and stroke nearly in half, at least for type 1 diabetes. Whether stringent glucose control also halves cardiovascular disease in type 2 diabetes is being studied by the National Institutes of Health.
Type 2 diabetes and cardiovascular disease share deep molecular roots in the regulation of sugar and fat throughout the body. That relationship seems logical, because diabetes involves the way food is metabolized, a process that involves cholesterols, which can cause blood vessels to clog.
There is one positive side to the diabetes–heart disease connection. The same avoidance of risk factors for heart disease also appears to prevent or delay the onset of type 2 diabetes. A large National Institutes of Health–sponsored study, the Diabetes Prevention Program, and other studies have proven that modest weight-reduction and a thirty-minute exercise routine five days a week can reduce the development of type 2 diabetes over three years by more than 50 percent. Even people with diabetes frequently have abnormalities in blood pressure and lipid levels that can be detected and treated to prevent cardiovascular disease.
By the way, that was good news for my patient Angelica. She already was pursuing a lifestyle of moderate exercise, stress reduction (yoga, in her case), and a whole-foods diet—all good for treating diabetes and heart disease.
In the last ten years, large-scale research studies around the world have shown that optimal control of low-density lipoprotein (LDL) (the “bad” cholesterol) levels and blood pressure can prevent adverse cardiovascular outcomes by 30 to 50 percent. The American Diabetes Association and the American Heart Association recommend an LDL cholesterol goal in all adults with diabetes of less than 100 mg/dL. In people who already have heart disease, a more desirable LDL cholesterol goal should be less than 70 mg/dL, based on evidence from more recent studies. The blood pressure goal in all patients with diabetes is less than 130/80 mmHg. In most patients with diabetes, reaching these targets for blood pressure could require two or more medications. Fortunately, we have safe and effective medications available to help patients meet their lipid and blood pressure goals.
Being the space scientist that she was, Angelica was interested in future treatments for patients with both diabetes and heart disease. Immunotherapy, stem cell therapy, genetic engineering, and artificial pancreases were all lines of research being pursued, I told her.
One of the most exciting developments on the near horizon is from a bioengineering team at the University of California, Los Angeles, school of medicine that has developed a type of “smart” skin patch that monitors a patient’s blood sugar automatically—probably reducing the need for injections. It helps to keep blood sugar at normal levels and reduces the risk of hypoglycemia. The device has been successfully tested in the lab, and preclinical trials on humans could begin in 2020.
“You know, Dr. Karpman, you can count me in for anything that’s smart,” chuckled Angelica. In the meantime, we agreed to keep her diabetes and cardiovascular disease in check by keeping her cholesterol levels and blood pressure under control and continuing her healthy lifestyle regimen.
As with diabetes, doctors have long known that some families have more members with kidney disease than others. Kidney disease is an inherited risk factor, and heart disease is the most common cause of death among people who have kidney disease. What’s the connection? When the heart is no longer pumping efficiently, it becomes congested with blood, causing pressure to build up in the main vein connected to the kidneys and leading to blood congestion in the kidneys too. The kidneys also suffer from the reduced supply of oxygenated blood.
When the kidneys become impaired, the hormone system, which regulates blood pressure, goes into overdrive in an attempt to increase blood supply to the kidneys. The heart then has to pump against higher pressure in the arteries and eventually suffers from the increase in workload.
If you have diabetes and have a brother, sister, or parent with diabetic kidney disease, the chance that you will develop kidney disease is higher. Genes might be part of the reason that African American, Hispanic, Pacific Islander, Native American, and Native Alaskan people have higher risks. If you have diabetes but do not have a relative with diabetic kidney disease, you have a lower chance of developing that condition over the course of your lifetime.
As with diabetes, researchers are pursuing how genes affect kidney disease and its correlation with heart disease, and for one researcher the quest is personal. “My grandfather had hypertension for 45 years,” says Dr. Sun Woo Kang, a South Korean–born nephrologist and researcher with a fellowship from the National Kidney Foundation. “My father has had diabetes and hypertension for 25 years. He also had heart bypass surgery. Then, it was recently discovered that I had certain precursors for cardiovascular or kidney disease similar to my father, and my father’s father. I became even more interested in human genetics as it relates to cardiovascular disease and kidney disease,” he said in an interview published on the National Kidney Foundation’s website. Kang’s study—one of many looking at the genetic connection between chronic kidney disease and chronic heart disease—is currently underway at the Center for Human Genetics and Genomics at the University of California, San Diego.