Hypoglycemic Dangers to Heart Based on Number of Episodes

Uncontrolled hypoglycemic events among those with type 2 diabetes can increase the risk of adverse cardiovascular events.

With Aman Rajpal MD

A new study is a reminder that blood sugar levels can also be too low.

There is ample evidence that repeated, uncontrolled hypoglycemic events among those with type 2 diabetes can increase the risk of adverse cardiovascular events, from arrhythmias, to strokes, to myocardial infarction. One recent study found the risk of mortality from having one or more event at 3.1%. But at what point in that continuum does the risk increase? Is a single event a problem? Or does it take many? 

The issue of whether more hypoglycemia equals greater risk was the topic of a study presented at the virtual American Diabetes Association conference in mid-June, due to be published before the end of the year. Aman Rajpal MD, an assistant professor of medicine at Case Western Reserve University in Cleveland, Ohio and his co-investigators looked at records from a national database of more than 61 million people in 27 health networks, 4.9 million of whom had type 2 diabetes. The database dates from 1999.

Hypoglycemia was defined as blood sugar levels under 70 mg/dl – there were more than 182,000 patients in that category. Of the 40,810 patients who had more than 5 episodes of hypoglycemia:

  • Just under 6700 had cardiac arrhythmias, cerbrovascular accidents or acute myocardial infarction;
  • About 58% of those with more than five episodes were over 65 years of age
  • More than 53% were obese
  • Almost 94% had high blood pressure
  • 91% had high cholesterol
  • Just under half had coronary artery disease.

In the control group of those with 1-4 episodes of hypoglycemia, the percentages were similar except for the advanced age. In the controls, just 40% were senior citizens.

Among the patients with more hypoglycemic events who had a cardiovascular adverse event, the majority – 5100 – experienced arrhythmias, 330 had strokes, and 2310 had myocardial infarctions. More than a third of these occurrences happened in patients over 65, and a further fifth were between 45 and 64. In total, patients with more than 5 incidents per year were at a 61% greater risk of a cardiovascular event than the controls.

Also in the findings: people who are on insulin and sulfonylureas were more likely to have hypoglycemic effects than those on some of the newer drugs, such as DDP IV inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors.

Rajpal says that for decades we have known that keeping blood sugar low is vital to the health of those with type 2 diabetes and helps prevent cardiovascular disease. But overdoing that control to the point of hypoglycemia can cause the body to release cortisol and cause inflammation, he says. It can also cause activation of platelets and increase risk of clots. “Endothelial function can be disrupted and cause vasoconstriction. None of these things are good.”

Even in the physician community, Rajpal says, there are physicians who “still like to hammer hyperglycemia, but we have learned that hypoglycemia is also dangerous.” He points to the ACCORD trial during the first decade of this century, when the intensive glucose arm of the study was stopped, as they found a greater death rate among those subjects than the other arms. “I have to remind some doctors and patients that there is too low,” he notes.

Not that this is true for every patient, Rajpal says. “All of this is patient specific. We used to think that lower was always better, but now we understand that that is not necessarily true for every individual. Someone who is younger and has no other medical issues might be able to have more aggressive action on blood sugar. But if you are older and have comorbidities, then lower blood sugar might be bad. The question we haven’t answered is just how much hypoglycemia is dangerous.”

Physicians need to be concerned about more than demographic differences such as age that may alter a decision on how low blood sugar can go, says Rajpal. There is a tool commonly used around the world that looks at the many factors that can go into personalizing a care plan. Along with age, it includes duration of diabetes diagnosis, comorbidities, known vascular complications, and the kind of support a patient has.

One of the biggest dangers of ongoing hypoglycemic events that are not addressed is hypoglycemic unawareness, says Rajpal. As time goes on, the symptoms that occur when someone has dangerously low blood sugar such as shakiness, for example, disappear. “They will stop having physical reactions to low blood sugars, and this can drop so low without symptoms that patients die.”

In some ways, Rajpal thinks that hypoglycemia is worse than hyperglycemia. “With uncontrolled blood sugar, you have to have it for a period of time before you start to see the complications that come with it. But for hypoglycemia, you don’t need to have it for a long time. And even though we found that the highest risk was for those with five or more episodes, even those who are having fewer are still having adverse cardiac events.”

The answer is personalizing the treatment plans, he says. Patients who are 75 and still on sulfonylureas, have cardiac and kidney issues, and have been having hypoglycemic events are good candidates for another kind of drug.

This doesn’t always happen, though, says Rajpal. Right now he is working on a quality improvement project to track how many providers are mentioning a specific goal for blood sugar and talking about the dangers of hypoglycemia to patients. “We need to spend more time with patients. We may have limits due to financial constraints from insurance companies and time constraints imposed by health systems, but we need to be more worried about patient outcomes than those things.”

Paying attention to hypoglycemia doesn’t mean that a physician and patient should avoid tight A1c control, but there is such a thing as too much of a good thing. “I get patients referred by primary care providers and sometimes they have focused too much on blood sugar control. There is a decent amount of evidence on this, but what is missing is education for people to understand that hypoglycemia is bad. We talk about numbers and that more than 5 is bad, but we don’t talk about how low is bad.”

There is some help available from current technology allowing for continuous monitoring, with alerts when sugar levels are out of range, Rajpal says. “These are game changers, but we still need better education.”

Continue Reading:
Cardiovascular Complications, Hypoglycemia Common in Older Patients with Diabetes
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