[acb-diabetics] hypoglycemia-can be deadly

[Patricia LaFrance-Wolf]

C1991-2010 Diabetes Health 

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Dr. Robert Tanenberg 

 

Beware the Perils of Severe Hypoglycemia 

Robert J. Tanenberg, MD, FACP - Diabetes Health Advisory Board Member

May 13, 2010 

 

Over 80 years ago, famed diabetologist Elliot Joslin said about the
treatment of patients with 

type 1 diabetes

: "Ketoacidosis may kill a patient, but frequent hypoglycemic reactions will
ruin him."  Unfortunately, 

hypoglycemia

 continues to be the most difficult problem facing most patients, families,
and caregivers who deal with the management of 

type 1

 diabetes on a daily basis. Frequent hypoglycemia episodes not only can
"ruin," or adversely impact the quality of life for patients, but also, when
severe,

can cause seizures, coma, and even death.

 

A Tragic Case

 

Recently, our group published a case report in the journal Endocrine
Practice describing a tragic death from hypoglycemia that occurred while the
patient

slept in his own bed. Our patient, a 23-year-old man with type 1 diabetes
who had a history of recurrent severe hypoglycemia, was using an older model

 

insulin pump

 and wearing a separate, non-real-time continuous glucose monitoring (

CGM

) system. He was given the CGM in 2005 for the purpose of tracking his
nocturnal (nighttime) blood glucose values and making further 

insulin

 pump adjustments. After he was pronounced dead in the emergency room, our
diabetes nurse removed the pump and CGM to help us understand what happened.

His insulin pump was found to have been working correctly. What we learned
was that after supper, he had a heavy workout at a gym, followed by a late
snack.

Between 8 pm and midnight, he "stacked" five boluses of insulin, totaling
7.35 units (33% of his basal dose), in an attempt to keep his glucose values

in "tight" control. The downloaded sensor demonstrated that his glucose
values fell from about 200 mg/dL at midnight to under 50 mg/dL by 2:00 am,
and

to under 30 mg/dL by 5:00 am - three hours before he was found by his
parents.

 

Sadly, this is not a rare occurrence. In 1991, two British diabetes
specialists, describing 22 cases of unexplained sudden death in young
patients with

type 1 diabetes, coined the term "dead-in-bed syndrome." Studies from Europe
estimate that the "dead-in-bed" syndrome is responsible for six percent of

the deaths of patients under age 40 with type 1 diabetes.

 

To better understand how these tragedies may occur, one needs to first
understand hypoglycemia as a biological event. When 

blood sugars

 fall below normal, there are two important consequences, which are
identified by the blood sugar level at which they occur and the type of
symptoms involved.

 

Mild and Moderate Hypoglycemia

 

The first consequence triggers a prompt release of hormones that work to
raise the blood sugar. These so-called counter-regulatory hormones include
epinephrine

(adrenaline), glucagon, cortisol, and growth hormone. The clinical responses
to these hormones, which are well known to patients who have had
hypoglycemic

reactions, include sweating, palpitations, tremor, hunger, nervousness, and
tingling sensations. These "fight, or flight" symptoms are often called
sympathetic

or adrenergic to emphasize their origin in the autonomic nervous system and
from the adrenal gland. They are non-specific and may also occur in response

to other stressors.

 

When hormones are released normally (in response to a low or rapid fall in
blood sugar), patients experience the symptoms and usually take action by
eating

or drinking 

carbohydrates

. Typically, the symptoms resolve within five minutes as the blood sugar
rises.

 

Severe Hypoglycemia

 

However, if the hormones are not released and there are no warning symptoms,
the blood sugar will continue to fall.  As the blood sugar drops below 55
mg/dL,

the second consequence of hypoglycemia occurs. The brain becomes deprived of
glucose and can no longer function normally. This condition, called
neuroglycopenia,

leads to cognitive dysfunction that presents as confusion. There is a
slowing of reflexes, and the hypoglycemic individual loses the ability to
comprehend

and act appropriately. The patient is no longer able to treat the
hypoglycemia himself. The need for assistance from another person to treat
the hypoglycemia

fulfills the definition of severe hypoglycemia. When driving a car, for
example, patients with severe hypoglycemia often become lost even in a
familiar

neighborhood. If they are not able to quickly recognize the insulin reaction
and pull off the road, they may lose control of their vehicle, with
potentially

catastrophic consequences.

 

Loss of Protective Hormones 

 

Several hormonal changes occur in patients with type 1 diabetes. Usually
within a few years of the onset of the disease, the patient's pancreas fails
to

secrete glucagon when the blood sugar falls below 70 mg/dL. When this
happens, only epinephrine is left to respond to the 

low blood sugar

 until it drops below 60 mg/dL. At that level, cortisol and growth hormone
are secreted. Unfortunately, these hormones are "too little, too late" to
help

during the first 10 minutes of the insulin reaction.

 

Patients with both a diminished glucagon and a diminished epinephrine
response have a 25-fold increase in the frequency of severe hypoglycemia.
Diabetes

specialists use the term hypoglycemic unawareness to describe patients who
have lost the ability to trigger the classic sympathetic symptoms. Sleep,
which

naturally suppresses epinephrine, makes the patient vulnerable to severe
nocturnal hypoglycemia. 

 

If the blood sugar drops falls below 30 mg/dL, it may lead to seizures,
coma, and ultimately death (as it did in our patient). Occasionally,
patients with

tightly controlled type1 diabetes (e.g., 

A1c

 under 6.5%) may be reasonably lucid with blood sugars below 40 mg/dL.
Apparently, the brain has a capability to lower the natural clinical set
point. This

situation places the patient in great danger. The only treatment is to back
off on glycemic control (in other words, raise the target blood sugars),
which

should raise the set point back to normal. In fact, it is well known that
each episode of severe hypoglycemia increases the possibility of a future
episode

occurring at an even lower blood glucose level. Our patient had experienced
an earlier episode of severe hypoglycemia that was successfully treated with

intravenous dextrose by the local rescue squad. It was for this reason that
the CGM study was ordered.

 

Causes of Hypoglycemia

 

In type 1 diabetes, the most common cause of hypoglycemia is a mismatch of
insulin, food intake, and physical activity. Whenever there is a change in
the

amount of food or 

exercise

 in a nondiabetic individual, the body adjusts by changing the hormones to
keep the glucose as close to normal as possible. This is why people without
diabetes

rarely become hypoglycemic when fasting or running marathons. In patients
taking insulin, however, vigorous physical activity may cause hypoglycemia
both

during the activity and for several hours afterward. In fact, late afternoon
exercise is a well known cause of nocturnal hypoglycemia. Regimens using the

newer analogue insulins (e.g., glargine and lispro) reduce the incidence of
hypoglycemia compared to those using regular and NPH insulin. But any
insulin,

even when dosed correctly, can cause severe hypoglycemia. If patients taking
insulin increase their physical activity, they must either eat more or
reduce

the insulin dose before and after their activity. Similarly, patients on
insulin who eat much less than usual need to reduce their insulin dose to
prevent

hypoglycemia. Furthermore, the indiscriminate use of alcohol can also lead
to severe hypoglycemia.

 

Treatment of Hypoglycemia 

 

Mild hypoglycemia should be treated with 15 grams of fast-acting
carbohydrate, such as four ounces of juice or three to four dextrose
tablets. If the blood

sugar is still low in 10 to 15 minutes another 15 grams of carbohydrate
should be given (known as the Rule of 15). Moderate hypoglycemia typically
responds

to oral carbohydrates, but may take as long as 30 minutes to fully resolve.
Frequent fingerstick blood glucose testing is mandatory to be sure the
glucose

does not continue to fall.

 

Patients with severe hypoglycemia who are not yet comatose may respond to
liquid or buccal oral carbohydrates, but injectable glucagon is the best
treatment

in the home setting. Since glucagon may not raise the glucose levels to
normal, giving fast-acting carbohydrates after the patient becomes more
responsive

is essential. Rescue squads and emergency room physicians administer
50-percent dextrose intravenously, which usually reverses the condition very
quickly.

In some cases, repeated doses of intravenous dextrose are needed.

 

Prevention of Severe Hypoglycemia

 

To help prevent severe hypoglycemia, diabetes specialists recommend the
following:

 

list of 5 items

. For physically active persons, it is important to check fingerstick blood
sugars after exercise in anticipation of possible hypoglycemia. It is
especially

important to check at bedtime and 3:00 am if the activity is after 4:00 pm. 

. Bedtime insulin should be decreased after exercise. 

. Physicians should be cautious about recommending near-normal blood glucose
control and A1c targets to patients with type 1 diabetes and a history of
hypoglycemia,

particularly if they sleep alone. 

. If severe hypoglycemia occurs, the physician should raise the glucose
targets immediately to prevent another episode. 

. Patients with nocturnal hypoglycemia, hypoglycemic unawareness, and/or a
history of seizures are candidates for the newer real-time subcutaneous
sensors

with low glucose alarms. 

list end

 

Final Thoughts

 

Our purpose in publishing this tragic case is twofold. First, we want to
better inform physicians and patients of this potential danger. Severe
hypoglycemia,

in very rare cases, can lead to death while driving a car, swimming in the
ocean, or even sleeping in ones' own bed. If patients who take insulin learn

nothing else, they should learn to always test their blood sugar at bedtime,
before driving, and any time there is a change in activity or food intake.

Early treatment of mild hypoglycemia must be emphasized so that progression
to more severe consequences can be avoided. As physicians and diabetes
educators

learn more about the hazards of nocturnal hypoglycemia, they will educate
their patients to anticipate and prevent it.

 

Second, my colleagues and I are hoping that this tragic case report will add
to the growing literature that supports the need for real-time glucose
sensors

in all patients on insulin with a history of hypoglycemia.  These data are
essential to convince all insurance carriers to reimburse this new
life-saving

technology. In my opinion, if our patient had been wearing a real-time
sensor four years ago, he would be alive today.

 

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