Diabetes Forecast

Going Low: Hypoglycemia

How the brain responds to low blood glucose

By Andrew Curry , ,
digital illustration of femaile brain showing electrical activity


It was a morning like any other for Susan Carleton, 47, who was diagnosed with type 1 diabetes 44 years ago. She woke up around 6 a.m. and tested her blood glucose level; a quick glance told her she was at a low 60 mg/dl.

Carleton, a technical director who works from her home in Chandler, Arizona, figured she’d get a bite to eat and then take her short-acting breakfast insulin. “I remember dithering over breakfast, not choosing anything and then sitting down at my desk,” she says. “I kissed my husband goodbye, but my kids were still there. The next thing I remember is waking up at 2:30 in the afternoon with a stuffed animal in my arms.”

Looking back, Carleton says that terrifying day was the worst hypoglycemic episode of her 44 years living with diabetes, topping the hallucinations she had as a child and the bouts of near-paralysis she has experienced as an adult.

Sweet and Low

Hypoglycemia (from the Greek words for “under” and “sweet”) is what happens when the body’s blood glucose levels sink too low. The initial symptoms—shakiness, sweating, a pounding heart, and hunger—are the body’s warning light, an urgent demand for sugar.

When the call for help is ignored and the brain’s fuel runs out completely, the result can be disastrous—as Carleton discovered. “Acute hypoglycemia is pretty simple—you just stop getting fuel, and the brain turns off,” says Ewan McNay, PhD, a neuroscientist at the University at Albany–State University of New York. The result can be unconsciousness and coma, and even death: Surges of the hormones epinephrine and norepinephrine during a severe low can cause an abnormal heart rhythm, which can be fatal.

From Our Readers
My family and I were around daily to help my dad, who is getting older and has Parkinson’s disease and type 2 diabetes. One day, his blood sugar went so low he couldn’t move. We thought he was having a stroke, but it was a combination of medicine, limited appetite, and a cold. Things could have gone terribly wrong had we not been there to call for help.—Laura Soares

Carleton’s still not sure how she managed to survive. After she fell unconscious at her desk, her kids thought she was taking a nap and left for school, but not without putting a stuffed animal in her arms to keep her company. When she came to eight hours later, dizzy and disoriented, she had just enough energy to crawl to the kitchen and drink a glass of juice.

“Now when anything is vaguely low, I have my husband double-check it,” she says. She taught her children to recognize the symptoms of hypoglycemia, and now wears a continuous glucose monitor as additional security.

Brain Food

For many people with diabetes using insulin or one of the oral medications in the sulfonylurea or meglitinide class of drugs—Carleton’s experience may be frighteningly familiar. People with diabetes are urged to keep their blood glucose levels tightly controlled for their long-term good. Yet scrupulously avoiding high blood glucose means some people constantly risk the opposite, hypoglycemia. “Some patients on insulin or sulfonylureas, particularly those patients receiving higher doses than they need, may experience many episodes,” says Elizabeth Seaquist, MD, an endocrinologist at the University of Minnesota Medical School in Minneapolis. When that’s the case, medication therapy adjustments are needed.

Running on Empty

While most of the body can use a range of fuels to generate energy, breaking down fat or muscle when the food supply is low, our gray matter is picky. “The brain is fundamentally dependent on a continuous supply of glucose,” says McNay. “The brain is unique in that respect—other tissues can use alternative fuel, like fatty acids. The brain can’t do that. It needs that specific sugar.”

From Our Readers   
When I had a bad low, my son remembered his dad and me telling him if my blood sugar drops too low, I need sugar. He brought me a bag of Hershey Kisses and a Diet Coke. My sugar was so low I couldn’t get the paper off the chocolate, and I ate the candy, paper and all. I don’t know how many Hershey Kisses I ate, but eventually I had enough and my blood sugar came up. My son is now 15 years old and still talks about the time he “saved Mom’s life.”—Shelly Tullier

The body breaks down food to produce glucose, releasing it into the bloodstream to be transported to cells in the body. Ordinarily, the pancreas regulates how much glucose is in the blood. When there’s too much, the pancreas releases insulin, allowing the body to absorb glucose into the cells. Extra glucose is stored in the muscles and liver.

The brain even has a fuel gauge built in—it’s called the hypothalamus, and it’s constantly sampling the fluid outside the brain to see if there’s enough blood glucose to carry on.

When food’s not immediately available—during a fast, say, or at night between meals—the hypothalamus releases hormones that prompt the body to release the glucose stored in the liver; when that runs out, the liver starts breaking down fat and muscle to supply glucose to fuel the brain. “When everything works right, you never even know this is happening,” Seaquist says. “The body has a really well-regulated way of preventing the blood sugar from getting low.”

Guessing Game

For people with diabetes, the system doesn’t work nearly as smoothly. They can’t rely on their pancreas to regulate blood glucose levels, either because their pancreas no longer produces insulin (type 1 diabetes) or because their body isn’t sensitive enough to insulin (type 2 diabetes).

Instead, many people with diabetes have to approximate, injecting insulin or taking other drugs and closely monitoring their blood glucose levels with test strips to keep their numbers in a narrow “safe” range. (The American Diabetes Association recommends between 80 and 130 mg/dl before a meal.)

From Our Readers
I was a counselor in training at a summer camp for people with type 1 diabetes. I was getting my campers together when I suddenly felt low. I tested earlier and was at 90 mg/dl. I thought, “I’ll be inside eating soon enough, so I should be fine.” Boy, was I wrong. I stood up and walked over to one of the older male counselors, tapped him on the shoulder and mumbled, “I am way too low.” Boom. Lights out. I fell right into his arms.

Immediately, I felt people holding my head up, placing things in my mouth, and rubbing my cheeks. I couldn’t open my eyes or say anything, but I could hear everything. It took 15 to 20 minutes for me to completely come back to reality.—Emily Clare

Staying in this safe zone can be tough. Injecting too much insulin can cause the body to take up too much blood glucose, reducing the brain’s glucose supply faster than the liver can respond. When that happens, the hypothalamus flashes the warning a little faster, engaging what’s called the “sympatho-adrenal response.” A flood of new hormones cause a wave of discomfort, a physical reminder to get food, fast. “Those responses are the basis of common hypoglycemia symptoms—tremor, sweating, agitation, hunger,” says Philip Cryer, MD, an endocrinologist at the Washington University School of Medicine in St. Louis.

There are as many versions of hypoglycemia symptoms as there are people with diabetes: Some people wind up soaked in sweat while others develop tremors or a pounding heart. Still others experience some combination of these or other symptoms. Those feelings are usually enough of a signal for the person to eat or drink a quick source of glucose, such as a half cup of juice, four glucose tablets, or a tablespoon of sugar or honey.

Caught Unawares

Yet not everyone feels these symptoms. Thanks to what may be an evolutionary defense mechanism, repeated bouts of hypoglycemia make it harder for some people to sense when they’re going too low. “People don’t always feel the warning signs, and that means they may not know to eat and break up an episode,” Cryer says.

Repeated hypoglycemia, it turns out, damps down the sympatho-adrenal response—the reactions in the brain that trigger the sweating, shaking, anxious “warning light” symptoms to switch on. Eventually, the brain’s warning light may not switch on at all. People on insulin and sulfonylureas and those with long-duration diabetes are at particular risk.

When the sympatho-adrenal response fails to warn people, they have what doctors call impaired hypoglycemia awareness, or hypoglycemia unawareness. For them, the first sign of hypoglycemia may be unconsciousness. McNay has seen patients come into his lab with their blood glucose at 40 mg/dl, close to comatose, and wonder aloud if they should drive home to get a bite to eat.

Ironically, tens of thousands of years ago, hypoglycemia unawareness might have been a good system: When you’re starving, it’s important to be able to concentrate on catching your next meal. There’s even evidence that repeated hypoglycemia makes you smarter, as the brain rewires itself to suck up glucose from the blood more efficiently—up to a point. “After a couple of episodes, the brain says, ‘Look, this is happening frequently, and I’ve got to protect myself so the next time it happens I don’t die,’ ” says McNay.

But while the brain can find ways to wring the most out of low blood glucose, it can’t run on empty. “What can happen is they can have a glucose level that is below the level where they can think clearly and not know it,” Seaquist says. “When your first symptom is unconsciousness, that’s not a good way to live.”

The Sweet Spot

Controlling blood glucose puts people with diabetes in a difficult position. Just ask Kelly Reeser, RD, LDN, CDE. As a dietitian and diabetes educator at a U.S. Department of Veterans Affairs hospital in Chicago, she sees the long-term consequences of high blood glucose, from kidney damage to amputations, firsthand.

That’s why Reeser—who was diagnosed with type 1 diabetes when she was 5—is fanatical about tight blood glucose control and keeping her A1C, a common measurement of long-term blood glucose levels, low. “I know what all the complications are, and it makes me nervous,” she says. “I have a bigger fear of high blood sugar than low blood sugar.”

Though she now uses a continuous glucose monitor to alert her when she goes too low, Reeser, 28, has had some close calls. “I’ve woken up more than once with paramedics in my bedroom and not known what was going on,” she says. Once, she lost consciousness while driving home from a workout and woke up in the wrong lane of a Chicago street, facing the grille of a semitrailer through her windshield. “My blood sugar was 100 when I got in the car, and it must have crashed while I was driving,” she says. “That was definitely my worst low.”

Indeed, evidence suggests her struggle to keep her A1C low puts her at risk of hypoglycemic attacks. “There’s clear evidence that with a lower A1C, there’s a higher frequency of hypoglycemia,” Cryer says. “If somebody has an episode that requires help from somebody else, it’s a clinical red flag—they need to find the problem and fix it. They need a glycemic goal that does not cause impaired awareness.” For some, that may mean shooting for an A1C target above the generally recommended 7 percent.

Researchers have made strides in understanding how hypoglycemia works—and are working on finding a cure for hypoglycemia unawareness. Encouragingly, researchers now think hypoglycemia, if successfully treated and reversed, does no permanent damage to the brain.

And there’s increasing evidence that hypoglycemia unawareness can be reversed in most people by avoiding low blood glucose levels for about two weeks, though it can occur again later. As anyone with diabetes knows, that’s easier said than done. “Whatever happens to the brain is quite fluid—if [people] avoid hypoglycemia, they get the ability to recognize symptoms back,” says McNay. “It’s just so hard to completely avoid hypoglycemia.”

Until a cure is found, Cryer says, it’s critical to educate people with diabetes about hypoglycemia. Along with that, an intimate understanding of how diabetes medications work is a must. “Intensive patient education has been shown to reduce the frequency of hypos,” he says. “We should be teaching people exactly how their drugs work, and what to do when they tend to be low.”

What’s Your Risk?

Of everyone with diabetes, children seem to be the most vulnerable to hypoglycemia, possibly because they have less fuel on reserve, says neuroscientist Ewan McNay, PhD, of the University at Albany–State University of New York. In adults, those with type 2 experience severe hypoglycemia at a third of the rate of those with type 1. Philip Cryer, MD, an endocrinologist with the Washington University School of Medicine, says that’s no reason to dismiss the dangers for type 2s, though. “There are 10 to 20 times more people with type 2, so the absolute frequency is actually much higher,” he says.

5 Facts to Know About Going Low

  1. Blood glucose is considered low when it’s at 70 mg/dl or below.
  2. Alcohol can cause hypoglycemia soon after drinking and for up to 24 hours after that. If you’re drinking alcohol, it’s important to do frequent blood glucose checks.
  3. Exercise can cause blood glucose to drop immediately—and for up to 24 hours post-workout.
  4. If your medications put you at risk for hypoglycemia, test before driving. If you’re running low, be sure to treat before getting behind the wheel.
  5. Skipping or delaying meals can be a trigger for lows. Carry fast-acting sources of glucose just in case.

Readers share their hypoglycemia stories here. Tell us yours!



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