Hypoglycemia
Defining hypoglycemia
No single glucose value alone serves to define the medical condition termed
hypoglycemia for all people and purposes. Throughout the 24 hour cycles of
eating, digestion, and fasting, blood plasma glucose levels are generally
maintained within a range of 70-140 mg/dL (3.9-7.8 mmol/L) for healthy humans.
Although 60 or 70 mg/dL (3.3 or 3.9 mmol/L) is commonly cited as the lower limit
of normal glucose, different values (typically below 40, 50, 60, or 70 mg/dL)
have been defined as low for different populations, clinical purposes, or
circumstances.
The precise level of glucose considered low enough to define hypoglycemia is
dependent on (1) the measurement method, (2) the age of the person, (3) presence
or absence of effects, and (4) the purpose of the definition. While there is no
disagreement as to the normal range of blood sugar, debate continues as to what
degree of hypoglycemia warrants medical evaluation or treatment, or can cause
harm.
This article expresses glucose in milligrams per deciliter (mg/dL or mg/100
mL) as is customary in the United States, while millimoles per
itre (mmol/L or
mM) are the
I
(International System) units used in most of the rest of the world. Glucose
concentrations expressed as mg/dL can be converted to mmol/L by dividing by 18.0
g/mol (the
molar mass of glucose). For example, a glucose concentration of 90 mg/dL is
5.0 mmol/L or 5.0 mM.
Measurement method
Blood glucose levels discussed in this article are
enous
lasma
or serum levels measured by standard, automated
glucose oxidase methods used in
medical laboratories. For clinical purposes, plasma and serum levels are
similar enough to be interchangeable.
rterial plasma
or serum levels are slightly higher than venous levels, and
apillary
levels are typically in between.
This difference between arterial and venous levels is small in the fasting state
but is amplified and can be greater than 10% in the postprandial state.
On the other hand, whole blood glucose levels (e.g., by
fingerprick meters) are about 10%-15% lower than venous plasma levels.
Furthermore, available
fingerstick glucose meters are only warranted to be accurate to within 15%
of a simultaneous laboratory value under optimal conditions, and home use in the
investigation of hypoglycemia is fraught with misleading low numbers.
In other words, a meter glucose reading of 39 mg/dL could be properly obtained
from a person whose laboratory serum glucose was 53 mg/dL; even wider variations
can occur with "real world" home use. Ironically, most meters sold are routinely
tested for accuracy at the high-end of the scale, sometimes up to 800 mg/dL,
despite the fact that there is little immediate danger from
hyperglycemia, whereas there is very real immediate danger from
hypoglycemia, making accuracy at the low-end extremely critical.
Two other factors significantly affect glucose measurement: hematocrit and
delay after phlebotomy. The disparity between venous and whole blood
concentrations is greater when the
ematocrit
is high,
as in newborn infants, or adults with
polycythemia. High neonatal hematocrits are particularly likely to confound
glucose measurement by meter. Second, unless the specimen is drawn into a
fluoride tube or processed immediately to separate the serum or plasma from
the cells, the measurable glucose will be gradually lowered by in vitro
metabolism of the glucose at a rate of approximately 7 mg/dL/hr, or even more in
the presence of
leukocytosis.
Age differences
Surveys of healthy children and adults show that plasma glucoses below 60
mg/dL (3.3 mM) or above 100 mg/dL (5.6 mM) are found in less than 5% of samples
after an overnight fast.
In infants and young children up to 10% have been found to be below 60 mg/dL
after an overnight fast.[itation
needed] As the duration of fasting is extended, plasma
glucose levels can fall further, even in healthy people. In other words, many
healthy people can occasionally have glucose levels in the hypoglycemic range
without symptoms or disease.
The normal range of newborn blood sugars continues to be debated. Surveys and
experience have revealed blood sugars often below 40 mg/dL (2.2 mM), rarely
below 30 mg/dL (1.7 mM),[itation
needed] in apparently healthy full-term infants on the
first day after birth. It has been proposed that newborn brains are able to use
alternate fuels when glucose levels are low more readily than adults. Experts
continue to debate the significance and risk of such levels, though the trend
has been to recommend maintenance of glucose levels above 60-70 mg/dL after the
first day after birth. In ill,
undersized, or
premature newborns, low blood sugars are even more common, but there is a
consensus that sugars should be maintained at least above 50 mg/dL[itation
needed] (2.8 mM) in such circumstances. Some experts
advocate 70 mg/dL[itation
needed] as a therapeutic target, especially in
circumstances such as
hyperinsulinism where alternate fuels may be less available.
Presence or absence of effects
Research in healthy adults shows that mental efficiency declines slightly but
measurably as blood glucose falls below 65 mg/dL (3.6 mM) in many people.
ormonal
defense mechanisms (drenaline
and lucagon)
are activated as it drops below a threshold level (about 55 mg/dL for most
people), producing the typical symptoms of shakiness and
ysphoria.
On the other hand, obvious impairment does not often occur until the glucose
falls below 40 mg/dL, and up to 10% of the population may occasionally have
glucose levels below 65 in the morning without apparent effects. Brain effects
of hypoglycemia, termed neuroglycopenia, determine whether a given low glucose
is a "problem" for that person, and hence some people tend to use the term
hypoglycemia only when a moderately low glucose is accompanied by symptoms.
Even this criterion is complicated by the facts that A) hypoglycemic symptoms
are vague and can be produced by other conditions; B) people with persistently
or recurrently low glucose levels can lose their threshold symptoms so that
severe neuroglycopenic impairment can occur without much warning; and C) many
measurement methods (especially glucose meters) are imprecise at low levels.
Diabetic hypoglycemia represents a special case with respect to the
relationship of measured glucose and hypoglycemic symptoms for several reasons.
Although home glucose meter readings are sometimes misleading, the probability
that a low reading accompanied by symptoms represents real hypoglycemia is
higher in a person who takes insulin. Second, the hypoglycemia has a greater
chance of progressing to more serious impairment if not treated, compared to
most other forms of hypoglycemia that occur in adults. Third, because glucose
levels are above normal most of the time in people with diabetes, hypoglycemic
symptoms may occur at higher thresholds than in people who are normoglycemic
most of the time. For all of these reasons, people with diabetes usually use
higher meter glucose thresholds to determine hypoglycemia.
Purpose of definition
For all of the reasons explained in the above paragraphs, deciding whether a
blood glucose in the borderline range of 45-75 mg/dL (2.5-4.2 mM) represents
clinically problematic hypoglycemia is not always simple. This leads people to
use different "cutoff levels" of glucose in different contexts and for different
purposes.
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