When Hypoglycemia Attacks

It was close to midnight by the time I returned home after a paramedic class “dinner.” I still lived in my parents’ house at the time, so I attempted to go in quietly. The moment I reached my room, I heard my phone ring and knew the precise timing was too close to be a coincidence. I silently cursed as I reached for the phone, assuming that my mother would be on the other end with some choice words for me. Instead of angry, her voice sounded weak.  

“Yaeli, I don’t feel well. I think my sugar is low. Can you come down to my room please?”

I hung up the phone and headed to her room. My mother has been dealing with insulin-dependent Type 1 diabetes since before I came along. As I grew up, I became accustomed to things like blood sugar checks 10 or more times a day. I always knew where the extra candy was kept and knew to leave her alone when she laid down on the couch and said, “I’ll be fine. I just need a few minutes.” She knew how to manage her high and low blood sugar spikes like a pro. That night, though, something was different.

“What’s wrong, mom?”

“My sugar is low. Really low. I already checked and it’s 18.”

“Your blood sugar is 18? How did you remember my phone number? How are you even conscious?”

“I’m not really sure. I was having some of those weird nightmares I get when my sugar is low, and they woke me up. So I figured I should check my sugar.“

She reached into the top drawer of her night table and handed me a plastic red box with what looked like a prescription label on it.

“Here, take this. Just in case…”

She didn’t have to finish her sentence. I knew “just in case” meant for use in the event of altered mental status, or worse. I looked down at the case again, and read the label: Glucagon 1mg/mL 1mL

I still wasn’t sure how she was able to function and had retained her ability for cognitive thought with a blood sugar of just 18 mg/dL. As long as she was stable at that moment, I was content, bu, I took the small case, “just in case,” and headed downstairs to the kitchen, where I hastily made a peanut butter and jelly sandwich, grabbed a handful of candy and bounded back upstairs. Over the next half hour, her blood sugar slowly but steadily climbed. When it hit around 100, she felt well enough to turn on the television, and we finally fell asleep watching cartoon reruns. Crisis averted this time, but why was my mother able to stay awake and relatively unscathed by an extremely low blood sugar that would have other diabetics combative, confused, seizing or unresponsive?

Definition

My mother’s “resistance” to hypoglycemia is related to a condition that occurs particularly in patients with Type 1/insulin-dependent diabetes called hypoglycemia unawareness. Her brain and central nervous system have, over the years, become desensitized to hypoglycemia due to repeated and sustained low blood glucose levels. The brain adapts to recurrent states of decreased glucose availability, and the deprived cells learn to function within, or close to, normal parameters even under duress.

The Event

Hypoglycemia unawareness can have more than one component or cause, and in most cases is due to several contributing factors. Although patients with this condition can be entirely unaware that they have extremely low blood sugar levels and may appear to have superhuman ability to retain intact neurological function (like my mother), they may also present with atypical symptoms ranging from general malaise, weakness, fatigue and difficulty concentrating to lightheadedness and headache. They can become increasingly emotionally charged and moody, as evidenced by increased anxiety, irritability and stubborn behavior, or excessive sadness or crying for seemingly no reason.

Pathophysiology

In a comparative study conducted on central glucose uptake and central glucose concentration levels, several groups were monitored during sessions of induced hypoglycemia. The group that typically maintained normal or near normal blood glucose levels exhibited significant decreases in central glucose uptake and central glucose concentration levels during these sessions of induced hypoglycemia. At the same markedly decreased blood glucose levels during these sessions, a group within the study that was classified as having chronic low glucose levels—such as those who have repeated or lengthened episodes of hypoglycemia—showed no change in central glucose uptake and central glucose concentration levels. 

This adaptation, while allowing patients with “years of experience at being hypoglycemic” to function at comparatively lower blood sugar levels, is dangerous. A patient who is “hypoglycemic unaware” and repeatedly experiences hypoglycemia will compensate much like an otherwise healthy patient in shock compensates until they suddenly and seemingly without warning experience acute decompensation.

In healthy patients and diabetics with the intact ability to sense changes in central glucose concentration, a cascade of events that signals and potentially corrects hypoglycemia begins with the autonomic nervous system. The autonomic nervous system is programmed to secrete two substances, epinephrine and glucagon, in response to falling plasma glucose levels as sensed by glucoreceptors within the brain. Epinephrine is a neurotransmitter and naturally occurring catecholamine that functions as a sympathetic nervous system stimulant and, once secreted, has broad, systemic effects on the body. As noted above, some patients with hypoglycemic unawareness will have no significant changes in plasma glucose levels in the brain. For these patients, therefore, the initial signal to involve the autonomic nervous system in correcting hypoglycemia never gets generated, as the hypoglycemia is unrecognized by glucoreceptors.

Under normal parameters, when plasma glucose levels fall below a specific concentration, a signal activates the autonomic nervous system to perform its role in correcting hypoglycemia by initiating release of epinephrine. Epinephrine is a neurotransmitter and naturally occurring catecholamine that functions broadly as a sympathetic nervous system stimulant. Within the sympathetic nervous system, which is a division of the autonomic nervous system, the release of epinephrine stimulates beta-adrenergic receptors and incites a “fight-or-flight” response. Systemic effects of epinephrine on the body include sweating, shaking, increased heart rate, weakness and dizziness, which alert the body to an impending crisis. These symptoms warn patients to eat something in an attempt to correct hypoglycemia before their condition requires EMS or other medical intervention.

The release of epinephrine also stimulates the release of glucagon from alpha cells in the pancreas. Glucagon, a hormone, then travels through the body toward the liver, where it signals the start of two processes: gluconeogenesis and glycogenolysis. Gluconeogenesis, the synthesis of glucose from non-carbohydrate sources within the body, and glycogenolysis, a process that synthesizes glycogen molecules and stores them in the liver, aid in the natural rise of the body’s blood glucose level without ingestion of any added sugar or carbohydrate. Generally, patients who have had insulin-dependent diabetes for 10 or more years lack glycogen stores within the liver and lack the ability to carry out both gluconeogenesis and glycogenolysis due to prolonged and repeated depletion of all available glycogen. 

Patients who have lived with insulin-dependent diabetes for a significant length of time often suffer from a number of other complications and diabetes-related illnesses. One complication than can cause hypoglycemia unawareness is autonomic neuropathy, which is classified by damage and impaired function of the autonomic nerves. Autonomic nervous tissue and autonomic nervous system dysfunction impede the body’s ability to compensate for hypoglycemia, which therefore goes hand in hand with hypoglycemia unawareness.

In this patient population, damage to the autonomic nervous system makes epinephrine and glucagon secretion lessened or completely absent,  so the presence of autonomic mediated signs and symptoms of low blood sugar are drastically altered or non-existent. A run of low blood sugars in a short period of time will also blunt autonomic nervous system transmission and signaling due to rebound desensitization from the repeated “signal overload,” further amplifying any existing damage. Patients who are taking beta-blockers also suffer from hypoglycemia unawareness, because their medications decrease or prevent the autonomic nervous system’s ability to stimulate beta receptors to compensate for a drop in blood glucose levels, a pharmacologically caused pathology that mimics the biological mechanisms of autonomic neuropathy.  

Precautions

People like my mother with long-term diabetes, and even those who have been practicing self-care strategies for a quarter century or more, often become used to taking care of diabetes-related emergencies on their own, and their families can be lulled into a false sense of security concerning diabetes emergencies. Both patients and family members may underestimate the severity of the situation and choose to not take medically appropriate action. 

Any patient with insulin-dependent diabetes mellitus may present with atypical or absent signs of hypoglycemia. They can be aware that “not feeling well” is indicative of hypoglycemia. Listen to these patients; they know their bodies.  They might be walking and talking, and may have activated 9-1-1 themselves. They may have already eaten a sandwich, had a sugar-enriched drink, and even given themselves a shot of glucagon, which does not immediately raise blood glucose. A patient who does not eat subsequent to glucagon self-administration may, as a result of not providing the body with an adequate amount of carbohydrate and sugar to be used in maintaining appropriate glucose levels, experience repeated symptoms after administration of the hormone. Additionally, even when the patient did not feel it was necessary to self-administer glucagon, there is always a possibility of hypoglycemia returning after their body has metabolized the glucose from any food or drink initially ingested.

Early Detection and Early Correction

New biomedical technologies like continuous glucose monitoring systems (CGMS) are being used to help avoid extreme hypoglycemia. A CGMS indicates blood glucose trends and approximates blood glucose levels by measuring electrical impedance using an algorithm for the approximation. There is, however, about a 20-minute lag in glucose readings, which is why the technology is marketed only for indicating trends rather than exact glucose levels. (Patients are cautioned to use finger-sticks to monitor their sugar levels as well, especially when falling or rising quickly.) When the receiver unit senses a downward or upward trend in glucose levels, it alarms at preset levels. These systems are commonly used in conjunction with insulin pump therapy, and may either have separate electronic receivers or be integrated with the pump and read on the pump screen. Each of these units has a small transmitter unit commonly inserted on the patient's thigh, back of the upper arm or abdomen.

My mother has continued to experience episodes of hypoglycemia unawareness, although she now wears a CGMS at all times to aid in the prompt diagnosis of severe hypoglycemia. On Christmas Eve, 2009, she discovered a major drawback of the Abbott Navigator CGMS system.  Each sensor of the Navigator system is changed every five days. After insertion, each new sensor requires 10 hours of calibration time before it begins to display blood sugar trends.

Conclusion

Don’t be fooled by the absence of typical symptoms of hypoglycemia. Gather both clinical signs and empirical data and rely on the interpretation of both in order to treat patients experiencing possible hypoglycemia. Even though they might not appear to be in crisis, their lives may depend on prompt treatment based on the strong investigative skills and high index of suspicion formed by a healthcare provider like you.

 
Bibliography

Cryer P. Symptoms of hypoglycemia, thresholds for their occurrence, and hypoglycemia unawareness. Endocrinology & Metabolism Clinics of North America 28(3):495-500, 1999.

Hoeldtke RD, Boden G. Epinephrine secretion, hypoglycemia unawareness, and diabetic autonomic neuropathy. Ann Intern Med 120(6): 512-517, Mar 15, 1994.

Boyle PJ, Kempers SF, O'Connor AM, Nagy, RJ. Brain glucose uptake and unawareness of hypoglycemia in patients with insulin-dependent diabetes mellitus. N Engl J Med 6(333):1726-1732, Dec 28, 1995.

Yael Nelson, MICP, has worked as a paramedic since 2005 in Newark, NJ. She is an instructor of several EMS-related disciplines. Contact her at Judges5.27@gmail.com or YaelL.Nelson@gmail.com.