Recent evidence revealed a diurnal variation in FPG,
with mean FPG higher in the morning than in the afternoon, indicating
that many cases of undiagnosed diabetes would be missed in patients seen
in the afternoon. Glucose concentrations decrease ex vivo with time in
whole blood because of glycolysis. The rate of glycolysis, reported to
average 5% to 7% [~0.6 mmol/L (10 mg/dL)] per hour, varies with the
glucose concentration, temperature, white blood cell count, and other
factors. Glycolysis can be attenuated by inhibition of enolase with
sodium fluoride (2.5 mg fluoride/mL of blood) or, less commonly, lithium
iodoacetate (0.5 mg/mL of blood). These reagents can be used alone or,
more commonly, with anticoagulants such as potassium oxalate, EDTA,
citrate, or lithium heparin. Although fluoride maintains long-term
glucose stability, the rate of decline of glucose in the first hour
after sample collection in tubes with and without fluoride is virtually
identical. (Note that leukocytosis will increase glycolysis even in the
presence of fluoride if the white cell count is very high). After four
hours, the glucose concentration is stable in whole blood for 72 hours
at room temperature in the presence of fluoride. In separated,
nonhemolyzed, sterile serum without fluoride, the glucose concentration
is stable for fourteen days at 25°C and 4°C.
Glucose can be
measured in whole blood, serum, or plasma, but plasma is recommended for
diagnosis. The molality of glucose (ie, amount of glucose per unit
water mass) in whole blood and plasma is identical. Although red blood
cells are essentially freely permeable to glucose (glucose is taken up
by facilitated transport), the concentration of water (kg/L) in plasma
is ~11% higher than that of whole blood. Therefore, glucose
concentrations in plasma are ~11% higher than whole blood if the
hematocrit is normal. Glucose concentrations in heparinized plasma are
reported to be 5% lower than in serum. The reasons for the latter
difference are not apparent but may be attributable to the shift in
fluid from erythrocytes to plasma caused by anticoagulants. The glucose
concentrations during an OGTT in capillary blood are significantly
higher than those in venous blood [mean of 1.7 mmol/L (30 mg/dL),
equivalent to 20% to 25%], but the mean difference in fasting samples is
only 0.1 mmol/L (2 mg/dL).
Although methods for glucose analysis
exhibit low imprecision at the diagnostic decision limits of 7.0 mmol/L
[(126 mg/dL), fasting] and 11.1 mmol/L [(200 mg/dL), postglucose load],
the relatively large intraindividual biological variability (CVs of ~5%
to 7%) may produce classification errors. On the basis of biological
variation, glucose analysis should have analytical imprecision <3.4%,
bias <2.6%, and total error <8.0%.1,2
Like a
fasting glucose level >125 mg/dL, a two-hour postprandial glucose
>200 mg/dL is virtually diagnostic of diabetes mellitus and obviates
the need for a glucose tolerance test. An oral glucose tolerance test
(OGTT) is not necessary in the setting of sufficiently high fasting and
two-hour postprandial results.
Other causes of high glucose
(serum or plasma) include nonfasting specimen; recent or current IV
infusions of glucose; stress states such as myocardial infarct,5 brain damage, CVA,6
convulsive episodes, trauma, general anesthesia; Cushing disease;
acromegaly; pheochromocytoma; glucagonoma; severe liver disease;
pancreatitis; drugs (thiazide and other diuretics, corticoids, many
others are reported to affect glucose).
The danger of hypoglycemia (low glucose) is lack of a steady supply of glucose to the brain (neuroglycopenia).
Causes of low glucose:
Excess insulin, including rare insulin autoimmune hypoglycemia,
surreptitious insulin injection, and sulfonylurea use; glycolysis in
specimens overheated or old; serum permitted to stand on clot in red-top
tube for chemistry profile. Very prompt removal of plasma and analysis
is needed in cases of marked leukocytosis. Hypoglycemia should be
confirmed by specimens drawn in fluoride tubes (gray-top tubes).
With hypoglycemia, symptoms must be correlated with plasma glucose.
Three
major groups of hypoglycemia are defined: reactive, fasting, and
surreptitious. The reactive group includes alimentary hyperinsulinism,
prediabetic, endocrine deficiency, and idiopathic functional groups.7 Postprandial hypoglycemia
may occur after gastrointestinal surgery, and is described with
hereditary fructose intolerance, galactosemia, and leucine sensitivity.
•
Pancreatic islet cell tumors (insulinomas) - cause hypoglycemia in
fasting individuals or after exercise. Measurement of simultaneous
glucose, C-peptide, and insulin levels at the time of spontaneous
hypoglycemia help to differentiate insulinoma from other conditions. The
glucose:insulin ratio is useful in the diagnosis of insulinoma: insulin
levels inappropriately increased for plasma glucose. An intravenous
tolbutamide test with plasma glucose and serum insulin determinations
may be used for evaluation of insulin-secreting islet cell tumors. The
test is positive in approximately 75% of patients with these tumors.7 Glucagon and leucine stimulation tests are less frequently utilized.
• Extrapancreatic tumors-rare bulky fibromas, sarcomas, mesotheliomas, and carcinomas, including hepatoma and adrenal tumors
• Adrenal insufficiency (Addison disease), including congenital adrenal hyperplasia
• Hypopituitarism, isolated growth hormone or ACTH deficiency
• Starvation, malabsorption-but starvation does not cause hypoglycemia in normal persons
•
Drugs including insulin (see above), oral hypoglycemic agents, and
alcoholism, especially with starvation. Ethanolism is a common cause of
hypoglycemia. Other drugs can depress glucose levels.
• Liver damage, including fulminant hepatic necrosis (hepatitis, toxicity), and severe congestive failure
•
Tumor-induced hypoglycemia appears to be caused by increased production
of an insulin-like substance (insulin-like growth factor II) by the
tumor. This substance induces increased utilization of glucose by the
peripheral tissues and the tumor, and impairs the counterregulatory
effect of growth hormone by suppressing growth hormone secretion.8,9
Infancy and childhood:
Infants with tremor, convulsions and/or respiratory distress should
have stat glucose, particularly in the presence of maternal diabetes,
hemolytic disease of the newborn (erythroblastosis fetalis); babies too
large or small for gestational age should also have glucose level
measured in the first 24 hours of life. A large number of entities
relate to neonatal hypoglycemia, including glycogen storage diseases,
galactosemia, hereditary fructose intolerance, ketotic hypoglycemia of
infancy, fructose-1,6-diphosphatase deficiency, carnitine deficiency (a
treatable disease presenting as Reye syndrome), and nesidioblastosis.
