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166 BASIC SKILLS IN INTERPRETING LABORATORY DATA
Target Organ Hormone
https://t.me/med1917
In summary, glucose concentrations are aected by any factor that can inuence glucose production or utilization, glucose
absorption from the GI tract, glycogen catabolism, or insulin
production or secretion. Fasting suppresses the rate of insulin secretion, and eating generally increases insulin secretion.
Hypothalamus
Releasing Hormone
Anterior Pituitary
Stimulating or Inhibitory Hormone
Target Organ
FIGURE 9-1. The hypothalamus may secrete a releasing
hormone in response to low levels of stimulating,
inhibitory, or target organ hormone. This releasing
hormone causes the release of a stimulating or
inhibitory hormone that, in turn, controls the release of
target organ hormone.
Increased insulin secretion lowers serum glucose concentrations,
whereas decreased secretion raises glucose concentrations.
1
e three most commonly encountered types of DM are as
follows:
1. Type 1 DM, formally known as insulin- dependent DM
2.
Type 2 DM, formerly known as adult- onset or noninsulindependent DM
2
3. Gestational DM (GDM)
Type 1 DM is characterized by a lack of endogenous insu-
lin, a predisposition to ketoacidosis, and abrupt onset. Some
patients present with ketoacidosis aer experiencing polyuria,
polyphagia, and polydipsia for several days. Typically, this type
of DM is diagnosed in children and adolescents but may also
occur at a later age. In contrast, patients with type 2 DM do not
normally depend on exogenous insulin to sustain life and are not
usually ketosis prone, but they are usually obese and >40 years
old. ere is an alarming increase in the number of children
and adolescents diagnosed with type 2 DM. Although there is a
genetic predisposition to the development of type 2 DM, environmental factors such as high- fat diet and sedentary lifestyle
contribute to the disorder. Patients with type 2 DM are both
insulin decient and insulin resistant (Table9-1).
1
Many patients with type 2 DM are asymptomatic, so diag-
nosis oen depends on laboratory studies. Concentrations of
ketone bodies in the blood and urine are typically low or absent,
even in the presence of hyperglycemia. is nding is common
because the lack of insulin is not severe enough to lead to abnormalities in lipolysis and signicant ketosis or acidosis.
Because of the chronicity of asymptomatic type 2 DM, many
patients with type 2 DM present with evidence of microvascular
TABLE 9-1. General Characteristics of Type 1 and Type 2 Diabetes Mellitus
CHARACTERISTICS TYPE 1 TYPE 2
Usual age of onset Childhood or adolescence
Rapidity of onset Abrupt Gradual
Family studies Increased prevalence of type 1 DM Increased prevalence of type 2 DM
Body weight Unusually thin Obesity is common
Islet cell antibodies and pancreatic
Yes No
cell- mediated immunity
Ketosis Possible Unlikely; if present, associated with
Insulin Markedly diminished early in disease
or totally absent
Symptoms Polyuria, polydipsia, polyphagia, weight
loss
Source
Diabetes Care 2021;44(suppl 1):S152S33.
>40 yr old
severe stress or infection
Levels may be low, normal, or high
(indicating insulin resistance)
May be asymptomatic; polyuria,
polydipsia, polyphagia may be present
CHAPTER 9 • EndoCRinE disoRdERs 167
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complications (neuropathy, nephropathy, and retinopathy) and
macrovascular complications (coronary artery, cerebral vascular,
and peripheral arterial disease) at the time of diagnosis. Type2
DM is oen discovered incidentally during glucose screening
sponsored by hospitals and other healthcare institutions.
1
Gestational DM, a third type of glucose intolerance, develops during the third trimester of pregnancy. Patients with GDM
have a 30% to 50% chance of developing type 2 DM later in life.2
Women with diabetes who become pregnant or women diagnosed with diabetes early in pregnancy are not included in this
category.
Diagnostic Laboratory Tests
C-Peptide
Categories of C- peptide values are as follows:
• Fasting range: 0.78 to 1.89 ng/mL (0.26 to 0.62 nmol/L)
• Range 1 hour aer a glucose load: 5 to 12 ng/mL
• During a glucose tolerance test: 1.66 to 3.97 nmol/L
Insulin is synthesized in the β cells of the islets of Langerhans as the precursor, proinsulin. Proinsulin is cleaved to
form C- peptide and insulin, which are both secreted in equimolar amounts into the portal circulation. By measuring the
levels of C- peptide, the level of insulin can also be calculated.
C- peptide levels are also used to evaluate residual β- cell function. High levels of C- peptide generally indicate high levels
of endogenous insulin production, which may be a response
to high levels of blood glucose caused by glucose intake and
insulin resistance. Also, high levels of C- peptide also are seen
with insulinomas (insulin- producing tumors) and may be seen
with hypokalemia, pregnancy, Cushing syndrome, and renal
failure. Low levels of C- peptide are associated with low levels of insulin production, which can occur when insucient
insulin is produced due to a decrease in the number of functional insulin- producing β cells associated with type 1 DM or
long- term type 2 DM or with suppression tests that involve
substances such as somatostatin.
A C- peptide test can be performed to distinguish between
type 1 and type 2 DM. A patient with type 1 DM has a low level
of insulin and C- peptide. A patient with newly diagnosed type
2 DM typically has a normal or high level of C- peptide. When a
patient has newly diagnosed type 1 or type 2 DM, C- peptide can
be used to help determine how much insulin the patient’s pancreas is still producing. With type 2 DM, the test may be ordered
to monitor the status of β- cell function and insulin production
over time and determine if insulin injections may be required.
A C- peptide test may dierentiate the cause of hypoglycemia,
such as excessive use of medicine to treat diabetes or a noncancerous growth (tumor) in the pancreas (insulinoma). Because
man- made (synthetic) insulin does not have C- peptide, a person
with a low blood sugar level from taking too much insulin has
a low C- peptide level but a high level of insulin. Insulinomas
are the most common cause of hypoglycemia resulting from
endogenous hyperinsulinism. A person with an insulinoma has
a high level of C- peptide in the blood when the he or she has a
high level of insulin.
3
Although they are produced at the same rate, C- peptide and
insulin leave the body by dierent routes. Insulin is processed
and eliminated by the liver and kidneys, whereas C- peptide is
removed primarily by the kidneys. e half- life of C- peptide
is 30 minutes as compared with the half- life of insulin, which
is 5 minutes. us, there is usually about ve times as much
C- peptide in the bloodstream as endogenous insulin.
3
Diabetes-Related Autoantibody Testing
Diabetes- related (islet) autoantibody testing is used to distinguish
between autoimmune type 1 DM and type 2 DM, allowing for
early initiation of the most appropriate treatment, which may
minimize disease complications. e four most commonly
used autoantibody tests are islet cell cytoplasmic autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA),
insulinoma- associated-2 autoantibodies (IA-2A), and insulin
autoantibodies (IAA). Of these, ICA and GADA, which are
autoantibodies directed against islet cell proteins or β- cell
antigen, are present in 70% to 80% of adult patients with type 1
DM. IA-2A autoantibodies are present in approximately 60% of
adult patients with type 1 DM. e majority of people, 95% or
more, with new- onset type 1 DM will have at least one islet autoantibody.2 Some people who have type 1 DM will never develop
detectable amounts of islet autoantibodies, but this is rare.
e autoantibodies seen in children are oen dierent than
those seen in adults. IAA is usually the rst marker to appear
in young children. As the disease evolves, IAA may disappear
and ICA, GADA, and IA-2A become more important. Approximately 50% of children with new- onset type 1 DM will be IAA
positive.
A combination of these autoantibodies may be ordered when
a person is newly diagnosed with diabetes and the healthcare
provider wants to distinguish between type 1 and type 2 DM. In
addition, these tests may be used when the diagnosis is unclear
in persons with diabetes who have been diagnosed as type 2 DM,
but who have great diculty in controlling their glucose levels
with oral medications. If ICA, GADA, and IA-2A are present in
a person with symptoms of DM, the diagnosis of type 1 DM is
conrmed. Likewise, if IAA is present in a child with DM who
is not insulin- treated, type 1 DM is the cause. If no diabetesrelated autoantibodies are present, then it is unlikely that the
diabetes is type 1 DM.
Latent autoimmune diabetes in adults (LADA) is a slowprogressing form of autoimmune diabetes. Patients may present
with characteristics of both type 1 and type 2 DM.
features of type 1 diabetes seen in LADA include a lower body
mass index (BMI) compared with what is typical in type2 DM
and autoimmunity against one or more of the following antibodies: ICA, autoantibodies to glutamic acid decarboxylase (GAD),
IA-2, and IAA
6,7
ent in LADA include older age at onset and insulin resistance or
deciency. Characteristics of LADA tend to include an intermediate level of β- cell dysfunction between those in type1 and type
2 DM, faster decline of C- peptide compared with type 2 DM,
and a level of insulin resistance that is comparable to type 1 DM.8
β- cell decline is variable in LADA, as measured by C- peptide
8,9
levels.
2
4,5
e clinical
e characteristics of type 2 DM that may pres-
168 BASIC SKILLS IN INTERPRETING LABORATORY DATA
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Laboratory Tests to Assess Glucose Control
e two most common methods used for evaluating glucose
homeostasis are the fasting plasma glucose (FPG) and glycated
hemoglobin (A1c) tests. e oral glucose tolerance test (OGTT)
is most commonly used to diagnosis GDM.
With all blood tests, proper collection and storage of the sample and performance of the procedure are important. Improper
collection and storage of samples for glucose determinations
can lead to false results and interpretations. Aer collection,
red blood cells (RBCs) and white blood cells (WBCs) continue
to metabolize glucose in the sample tube. is process occurs
unless (1) the RBCs can be separated from the serum using
serum separator tubes or (2) the metabolism is inhibited using
sodium uoride–containing (gray- top) tubes or refrigeration of
the specimen. Without such precautions, the glucose concentration drops by 5 to 10 mg/dL (0.3 to 0.6 mmol/L) per hour, and
the measured glucose level does not reect the patient’s FPG at
collection time. In vitro, metabolic loss of glucose is hastened in
samples of patients with leukocytosis or leukemia.
Fasting Plasma Glucose and Two-Hour Postprandial
Glucose
e categories of FPG values are as follows:
•
FPG <100 mg/dL (5.6 mmol/L) represents normal fasting
glucose
•
FPG ≥100 (5.6 mmol/L) and <126 mg/dL (7 mmol/L) repre-
sents prediabetes (previously termed impaired fasting glucose)
•
FPG ≥126 mg/dL (7 mmol/L) represents provisional diagno-
sis of diabetes (the diagnosis must be conrmed as described
in Table9-2)
An FPG concentration measures the ability of endogenous
or exogenous insulin to prevent fasting hyperglycemia by regulating glucose anabolism and catabolism. FPG may be used to
monitor therapy in patients being treated for glucose abnormalities. For this test, the patient maintains his or her usual diet,
and the assay is performed on awakening (before breakfast).
2
2
10-15
is timing allows for an 8- hour fast. An FPG >126 mg/dL
(>7mmol/L), in abnormal test results from the same sample or
in two separate test samples, is diagnostic for DM. If the initial
single test is an abnormal FPG result, either the same or a different test can be taken on a dierent day to conrm the diagnosis for DM.
Testing in asymptomatic people should be considered in
adults of any age who are overweight or obese (BMI ≥25 kg/m2
or ≥23 kg/m2 for individuals of Asian-Pacic descent) with one
or more risk factors2:
• First- degree relative with diabetes
•
High- risk ethnic groups (eg, high- risk ethnic groups:
Hispanic, African American, Native American, South or East
Asian, or Pacic Island descent)
• History of cardiovascular disease
•
Hypertension (≥140/90 mm Hg or on therapy for
hypertension)
•
High- density lipoprotein cholesterol level of 35 mg/dL
(0.90mmol/L) and/or a triglyceride level of 250 mg/dL
(2.82mmol/L)
• Women with polycystic ovary syndrome
• Physical inactivity• A1c ≥5.7%, impaired glucose tolerance,
or elevated fasting glucose on a previous testing (should be
tested annually)
• Polycystic ovary syndrome
•
Other clinical conditions associated with insulin resistance
(eg, severe obesity, acanthosis nigricans)
Patients with prediabetes (A1C ≥5.7% [39 mmol/mol],
impaired glucose tolerance [IGT]; impaired fasting glucose
[IFG]) should be tested yearly. Women who were diagnosed
with GDM should have lifelong testing at least every 3 years.
Individuals without these risk factors should be screened no
later than 45 years of age. If results are normal, testing should be
repeated at a minimum of 3- year intervals, with consideration
of more frequent testing depending on initial results and risk
TABLE 9-2. Diagnosis of DM Based on Fasting Plasma Glucose Concentration, Oral Glucose Tolerance
Test, or Glycosylated Hemoglobin
VENOUS PLASMA GLUCOSE AFTER 75- g
OGTTa (mg/dL)
LEVEL OF GLUCOSE
TOLERANCE FPG
“Normal”
<100
NA
<140 <5.7%
A1c30, 60, or 90 min 2 hr
Prediabetes 100–125 NA 140–199 5.7%–6.4%
DM
GDM
NA = not applicable.
a
Multiply number by 0.056 to convert glucose to International System (SI) units (mmol/L).
Source
Diabetes Care 2021;44(suppl 1):S152S33.
≥126
>92 >180 (1 hr) >153
NA
>200 ≥6.5%
CHAPTER 9 • EndoCRinE disoRdERs 169
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status. e American Diabetes Association (ADA) also recommends that individuals from high- risk groups aged >30years be
screened for DM every 3 years.
2
Oral Glucose Tolerance Test
e categories for the 75- g OGTT are as follows:
•
represents normal glucose tolerance
• 2- hour PG 140 to 199 mg/dL (7.8 to 11 mmol/L) represents
prediabetes (previously termed impaired glucose tolerance)
•
2- hour PG ≥200 mg/dL (≥11.1 mmol/L) represents provisional diagnosis of diabetes
e OGTT can be used to assess patients who have signs and
symptoms of DM but whose FPG is normal or suggests prediabetes (<126 mg/dL or <7 mmol/L). e OGTT measures both
the ability of the pancreas to secrete insulin following a glucose
load and the body’s response to insulin. Interpretation of the test
is based on the plasma glucose concentrations drawn before and
during the exam. is exam may also be used in diagnosing DM
with onset during pregnancy if the disease threatens the health
of the mother and fetus.
e OGTT is performed by giving a standard 75- g dose of
an oral glucose solution over 5 minutes aer an overnight fast.
e pediatric dose is 1.75 g/kg up to a maximum of 75g. Blood
samples commonly are drawn before the glucose load and at
120minutes aer the glucose load. e samples should be collected into tubes containing sodium uoride unless the assay
will be performed immediately.2 If the patient vomits the test
dose, the exam is invalid and must be repeated.
Pregnant women with risk factors such as overweight or
obese with a BMI >25; family history of type 2 DM; hypertension; hyperlipidemia; and high- risk ethnic groups (eg, Hispanic,
African American, Native American, South or East Asian, or
Pacic Island descent) should be screened at the rst prenatal
visit using standard diagnostic criteria for type 2 DM. Pregnant
women not previously known to have DM or risk factors can be
screened for GDM at 24 to 28 weeks’ gestation. GDM diagnosis
can be accomplished with either of two strategies:
1. e “one- step” 75- g OGTT
2.
e older “two- step” approach with a 50- g (nonfasting) screen
followed by a 100- g OGTT for women who screen positive
One-Step Strategy
A 75- g OGTT is performed with plasma glucose measurement
when the patient is fasting and at 1 and 2 hours.2 e OGTT
should be performed in the morning aer an overnight fast of
at least 8 hours. e diagnosis of GDM is made when any of the
following plasma glucose values are met or exceeded:
• FPG ≥92 mg/dL (5.1 mmol/L)
• OGTT value at 1 hour ≥180 mg/dL (10 mmol/L)
• OGTT value at 2 hours ≥153 mg/dL16 (8.5 mmol/L)
Two-Step Strategy
Step 1: Perform a 50- g OGTT (nonfasting), with plasma glucose
measurement at 1 hour. If the plasma glucose level measured
1hour aer the load is ≥130, 135, or 140 mg/dL (7.2, 7.5, or
7.8 mmol/L, respectively), proceed to a 100- g OGTT. Cuto
values of 130, 135, and 140are all used clinically for screening.
e lower values are more sensitive but less specic for GDM.
Step 2: e 100- g OGTT should be performed when the
patient is fasting.2 e diagnosis of GDM is made when at
least two of the following four plasma glucose levels are met
or exceeded (measured fasting and at 1, 2, and 3 hours during
OGTT):
• Fasting: 95 mg/dL (5.3 mmol/L)
• 1 hour: 180 mg/dL (10.0 mmol/L)
• 2 hours: 155 mg/dL (8.6 mmol/L)
• 3 hours: 140 mg/dL (7.8 mmol/L)
Glycated Hemoglobin
Normal range: 4% to 5.6%
Glycated hemoglobin (A1c), also known as glycosylated A1c, is
a component of the hemoglobin molecule. During the 120- day
lifespan of an RBC, glucose is irreversibly bound to the hemoglobin moieties in proportion to the average serum glucose. e
process is called glycosylation. Measurement of A1c is, therefore,
indicative of glucose control during the preceding 3 months.
e entire hemoglobin A1 molecule— composed of A1a, A1b,
and A1c— is not used because subfractions A1a and A1b are
more susceptible to nonglucose adducts in the blood of patients
with opiate addiction, lead poisoning, uremia, and alcoholism.14
Because the test measures a component of hemoglobin, the
specimen analyzed is RBC and not serum or plasma.
Results are not aected by daily uctuations in the blood glucose concentration, and a fasting sample is not required. Results
can reect overall patient compliance to various treatment regimens. With most assays, 95% of a normal individual’s hemoglobin is 4% to 5.6% glycated; a level of 5.7% to 6.4% indicates
prediabetes, and a level of ≥6.5% indicates diabetes. An A1c
≥7% suggests less- than- ideal glucose control for most patients.
Patients with A1c of ≥9%are considered to have poorly controlled glucose levels.
For years, the A1c has been used to monitor glucose control
in people already diagnosed with DM. Initially, it was not recommended for diagnosis because the test variability from laboratory to laboratory was too great for a diagnostic test. e A1c
cut- point of ≥6.5% identies one- third fewer cases of undiagnosed DM than a fasting glucose cut- point of ≥126 mg/dL. However, the lower sensitivity of the test at the cut- point is oset by
the test’s greater practicality, and wider use of this more convenient test may result in an increase in the number of diagnoses.
A few situations confound interpretation of test results. False
elevations in A1c may be noted with uremia, chronic alcohol
intake, and hypertriglyceridemia.16 Recent blood transfusion,
use of drugs that stimulate erythropoiesis, and end- stage kidney
disease may also compromise the accuracy of the A1C result.2
Patients who have diseases with chronic or episodic hemolysis
(eg, sickle cell disease and thalassemia) generally have spuriously
low A1c concentrations caused by the predominance of young
RBCs (which carry less A1c) in the circulation. In splenectomized patients and those with polycythemia, A1c is increased.
16
2
170 BASIC SKILLS IN INTERPRETING LABORATORY DATA
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If these disorders are stable, the test still can be used, but values
must be compared with the patient’s previous results rather than
published normal values. Both falsely elevated and falsely lowered measurements of A1c may also occur during pregnancy.
erefore, A1c should not be used to screen for GDM.
16
e A1C test should be performed using a method that is
certied by the NGSP (www.ngsp.org). Although point- of- care
(POC) A1C assays may be NGSP certied and cleared by the
U.S. Food and Drug Administration (FDA) for use in monitoring glycemic control in people with diabetes in both Clinical
Laboratory Improvement Amendments (CLIA)- regulated and
CLIA- waived settings, only those POC A1C assays that are also
cleared by the FDA for use in the diagnosis of diabetes should
be used for this purpose, and only in the clinical settings for
which they are cleared. POC A1C assays may be more generally applied for the assessment of glycemic control in the clinic.
Portable analyzers are available that can provide A1c results at
the POC within 5 to 8 minutes.16 e ADA recommends A1c
testing one to two times a year for patients with good glycemic
control and quarterly in patients with poor control or whose
therapy has changed.
2
Fructosamine
Normal range: 170 to 285 µmol/L
Fructosamine is a general term that is applied to any glycosyl-
ated protein. Unlike the A1c test, only glycosylated proteins
in the serum or plasma (eg, albumin)— not erythrocytes— are
measured. In patients without diabetes, the unstable complex
dissociates into glucose and protein. erefore, only small quan
tities of fructosamine circulate. In patients with DM, higher
glucose concentrations favor the generation of more stable
glycation, and higher concentrations of fructosamine are found.
Fructosamine has no known inherent toxicological activity
but can be used as a marker of medium- term glucose control.
Fructosamine correlates with glucose control over 2 to 3 weeks
based on the half- lives of albumin (14 to 20 days) and other
serum proteins (2.5 to 23 days). As a result, high- fructosamine
concentrations may alert caregivers to deteriorating glycemic
control earlier than increases in A1c.
Falsely elevated results may occur for the following reasons:
•
Serum (not whole blood) hemoglobin concentrations are
>100 mg/dL (normally <15 mg/dL)
• Serum bilirubin is >4 mg/dL
• Serum ascorbic acid is >5 mg/dL
Methyldopa and calcium dobesilate (the latter is used outside the United States to minimize myocardial damage aer an
acute infarction) may also cause falsely elevated results. Serum
fructosamine concentrations are lower in obese patients with
DM as compared with lean patients with DM.18 Falsely low
fructosamine levels can be observed in patients with low serum
protein or albumin levels. Some clinicians advocate the use of
fructosamine concentrations as a monitoring tool for short- term
changes in glycemic control (eg, GDM, recent addition of medication). A fructosamine test can be used as an alternative test
in cases in which the A1C may be unreliable, such as blood loss
or hemolytic anemia, sickle cell anemia, or other hemoglobin
17
variants. e hemoglobin A1c test is also less reliable and the
fructosamine test may be preferred.
18
Urine Glucose
Normal range: negative
Glucose “spills” into the urine when the serum glucose concentration exceeds the renal threshold for glucose reabsorption
(normally 180 mg/dL). However, a poor correlation exists
between urine glucose and concurrent serum glucose concentrations. is poor correlation occurs because urine is “produced”
hours before it is tested unless the inconvenient double- void
method (urine is collected 30 minutes aer emptying of the
bladder) is used. Furthermore, the renal threshold varies among
patients and tends to increase in diabetes over time, especially
if renal function is declining. Urine testing gradually has been
replaced by convenient ngerstick blood sugar testing. Urine
glucose testing should be recommended only if a patient is
unable or unwilling to perform blood glucose monitoring.
Self-Monitoring Tests for Blood Glucose
Blood glucose meters and reagent test strips are commercially
available so that patients may perform blood glucose monitoring
at home. ese systems are also used in hospitals, where healthcare providers rely on quick results for determining insulin
requirements. e meters currently marketed are lightweight,
relatively inexpensive, accurate, and user friendly.
e rst generation of self- monitoring blood glucose (SMBG)
meters relied on a photometric analysis that was based on a dyerelated reaction. is method, also termed reectance photom-
etry, light reectance, or enzyme photometry, involves a chemical
reaction between capillary blood and a chemical on the strip
that produces a change in color. e amount of color reected
from the strip is measured photometrically. e reected color
is directly related to the amount of glucose in the blood. e
darker color the test strip, the higher the glucose concentration.
e disadvantages of this method are that the test strip has to
be developed aer a precise interval (aer the blood is washed
away), a large sample size of blood (>12 µL) is required, and the
meter requires frequent calibration.
21
Most SMBG meters today utilize an electrochemical or
enzyme electrode process, which determines glucose levels by
measuring an electrical charge produced by the glucose- reagent
reaction. ese second- generation glucose meters can further
be subdivided according to the electrochemical principle used:
amperometry or colorimetry.
21
Amperometry biosensor technology requires a large sample
size (4 to 10 µL). Amperometric technology measures only a
small percentage of the glucose and uses a multiplier to convert
it to a numerical value. erefore, blood glucose readings may be
aected by environmental temperature, hematocrit (Hct), medications, and other factors. Also, small samples may result in
inaccurate readings because of a weak signal being generated.
e colorimetry method involves converting the glucose
sample into an electrochemical charge, which is then captured for measurement. An advantage of this system is that a
small amount of blood (eg, 0.3 mL) is enough to determine the
blood glucose level. e colorimetry method is not inuenced
20
19
22
CHAPTER 9 • EndoCRinE disoRdERs 171
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by changes in temperature and Hct levels. ese monitors can
use blood samples extracted from the arm and thigh, too. At
these alternative sites, there are fewer capillaries and nerve endings, allowing for a less painful needle stick. Some examples of
second- generation glucometers that use the colorimetry method
include Nova Max Plus, OneTouch Verio, and FreeStyle Lite. A
chart that lists the current glucose meters and their features can
be found at http://main.diabetes.org/dforg/pdfs/2020/2020-cg
-blood-glucose-meters.pdf.
22
Although new SMBG meters report results as plasma values,
older meters may report results as whole blood values, which are
approximately 10% to 15% lower than plasma values. e ADA
recommends whole blood fasting readings of 80 to 130 mg/dL
(4.4 to 6.7 mmol/L) and postprandial readings of <180 mg/dL.
Special features of glucose meters. Blood glucose testing can
bechallenging for adults with poor vision or limited dexterity and children with small hands. Patients should try several
meters by checking their ease of use with the lancing device
and lancets, test strips, packaging, and meter features before
committing to one. Many meters like the Glucocard Shine
Express, Advocate Redi-Code Plus Speaking Meter, and For
a Test N’GO Advance Voice oer an audio function that is
available in several dierent languages. Individuals with visual
impairment may benet from larger display screen, screen
backlight, or test strip port light. Examples of meters that oer
a screen backlight include the FreeStyle Lite, Presto, Presto
Pro, OneTouch Ultra 2, and Contour Next Link USB.
22
Some children are more comfortable monitoring their blood
glucose than others. Some children may like glucometers that
come in bright or “cool” colors. Many “auto- code” or “no- code”
meters, which do not require manually programming the meter
to recognize a specic group of test strips, are ideal choices for
children who are learning how to monitor their blood glucose
levels. Parents should select a meter that requires a small blood
sample size.
Most meters hold from 100 to 450 test results, although a
few save over 1,000. is makes it easier to track blood glucose
control over time. Many meters on the market have computerdownload capabilities through a USB connection.
22
Generally, blood glucose concentrations determined by these
methods are clinically useful estimates of corresponding plasma
glucose concentrations measured by the laboratory. erefore,
at- home blood glucose monitoring is preferred to urine testing.22 At- home blood testing claries the relationship between
symptomatology and blood glucose concentrations. e best
meter for a patient is an individual decision. Patients should be
encouraged to try dierent brands of meters to nd the device
with which they are most comfortable.
20
e use of continuous glucose monitoring (CGM) is recognized as the standard of care for individuals with type 1 diabetes
and a subset of those with type 2 diabetes requiring insulin therapy.23 CGM provides readings every few minutes throughout
the day. is method allows patients and providers an opportunity to observe trends in glucose levels throughout the day
and make the appropriate adjustments to medication, meal, or
exercise regimens. A small, sterile, disposable glucose- sensing
device called a sensor is inserted into the subcutaneous tissue.
is sensor measures the change in glucose levels in interstitial
uid and sends the information to a reader that can store from
3 to 90 days of data. Real- time CGM systems include Dexcom
G5 and Dexcom G6 sensors (manufactured by Dexcom); Eversense CGM System (manufactured by Senseonics) and Guardian
Connect CGM System (manufactured by Medtronic Diabetes).
Monitors are typically calibrated daily by entering at least two
blood glucose readings obtained at dierent times using a standard blood glucose meter. e monitors have an alert system to
warn patients if their blood glucose level is dangerously low or
high. e monitor may be part of an insulin pump or a separate
device that can be carried in a pocket or purse. Smartphone apps
2
are also used in conjunction with CGMs. e FreeStyle Libre
Flash Glucose Monitoring System and FreeStyle Libre 2 System (Abbott Diabetes Care) are the only intermittently scanned
system currently available. Aer the sensor is inserted, there is
a 12- hour warm- up time, and no initial or daily calibration is
required during the 14- day wear period. Unlike with the realtime CGM system, the patient has to purposely scan the sensor
to obtain changes in glucose levels.
23,24
Quality control, which consists of control solution testing, calibration, and system maintenance, is a necessary component of accurate glucose testing. Control solutions can be
purchased to assess the accuracy of the test strip. Control
solutions should be used every time a new container of test
strips is opened, when the blood glucose meter is mishandled or dropped, or whenever the accuracy of the results is
questioned. e technique of verifying accuracy operates the
same way that the patient analyzes a drop of blood. A few
meters require manual calibration prior to use, but most have
an automatic calibration mode for ease of use. In photometric meters, the blood sample intended for the strip may come
in contact with the meter and soil the optic window resulting in inaccurate results.21 Pharmacists should guide patients
through the instructions for cleaning the meter that is usually
provided by the manufacturer.
20
Factors aecting glucose readings. User error is the most
common reason for inaccurate results. Some of the most common errors include not putting enough blood on the reagent
portion of the strip. Patients should be asked periodically to
demonstrate how they operate the meter.
25
Environmental factors such as temperature, humidity, altitude, and light may inuence the accuracy of glucose readings.
Exposing glucometers to extremes of temperature can alter
battery life and performance. erefore, glucometers should
be stored at room temperature to ensure accuracy (most will
function at temperatures between 50°F and 104°F). Temperature changes and humidity may decrease the shelf life of test
strips, resulting in inaccurate test results. Test strips should not
be stored in areas of high humidity, such as a bathroom, or in
areas with notable temperature changes, such as the car. Individuals should check the expiration date of the test strips. Because
test strips are costly, patients are oen tempted to use expired
strips, which result in inaccurate readings.
26,27
Most test strips
expire within 90 to 180 days aer being opened.
172 BASIC SKILLS IN INTERPRETING LABORATORY DATA
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At higher altitudes, changes in oxygen content and temper-
ature alter glucose testing results. Results of studies evaluating the accuracy of glucometers at altitudes >10,000 feet have
revealed major alterations in blood glucose levels. ese changes
are attributed to variations in metabolic rate, hydration, diet,
physical exercise, Hct, and temperature associated with higher
altitudes. Patients should be educated on how to use glucometers
at high altitudes. Changes in light exposure can also alter results
with photometric glucometers.26 Additional variables such as
hypotension, hypoxia, high triglyceride concentrations, and
various drugs can alter readings; each patient should be evaluated for the presence of such variables and medication- related
25-27
eects.
Accuracy of glucose readings. e FDA requires 95% of all
meter test results to be within 20% of the actual blood glucose
level for results ≥75 mg/dL (4.2 mmol/L). An actual blood glucose that is 100 mg/dL (5.6 mmol/L) could show on a meter as
being between 80 and 120 mg/dL (4.4 to 6.7 mmol/L) and still
be considered accurate. e FDA is currently reviewing more
stringent standards that will require 98% of meter test results
to be within 15% of the actual blood glucose level for results
≥75 mg/dL (4.2 mmol/L). For example, an actual blood glucose result of 100 mg/dL (5.6 mmol/L) could potentially show
on a meter as any value between 85 and 115 mg/dL (4.7 to
6.4mmol/L) and meet the standard.
28
e guidelines for results in the hypoglycemic range, dened
as a blood glucose level <72mg/dL (4.2 mmol/L), stipulate that
98% of test results must be within ±15 mg/dL of the actual
blood glucose level. erefore, if an actual blood glucose level
is 60 mg/dL, the guidance says the reading would need to be
between 45 and 75 mg/dL (2.5 to 4.2 mmol/L) to meet accuracy standards.
28,29
e FDA guidance also recommends that meter boxes and
test strip vials include easy- to- understand accuracy data— both
on the outside of the package and on the insert inside. e FDA
does not regularly monitor blood glucose meters or strips once
they enter the commercial market. is means some companies
may not maintain the same level of quality and accuracy as when
the products were initially approved.
28,29
Frequency of glucose monitoring. Glucose monitoring require-
ments may vary based on the pharmacologic therapy administered. It is generally unnecessary in patients who manage their
diabetes with diet alone or who take oral medications that do
not cause hypoglycemia. Patients taking insulin injections twice
a day should check blood glucose levels at least twice a day.
Patients on intensive insulin therapy should monitor blood glucose levels three to four times a day. Patients on insulin pumps
need monitoring four to six times a day to determine the eectiveness of the basal and bolus doses. In general, premeal glucose measurements are needed to monitor the eectiveness of
the basal insulin dose (eg, glargine or detemir) dose. Two- hour
postprandial glucose (PPG) readings are needed to monitor
rapid- acting insulins (eg, lispro, glulisine, aspart, and Afrezza
inhaled). Oral blood glucose–lowering agents, such as metformin, thiazolidinediones, sitagliptin, and glipizide, are evaluated using 2- hour postprandial readings. Pregnancy requires
frequent monitoring of blood glucose levels four to six times a
day to ensure tight control. Premeal testing is required during
acute illness to determine the need for supplemental insulin.
30-37
Diagnosis of Hyperglycemia
e diagnosis of patients with hyperglycemia commonly falls
into one of three categories: (1) DM or prediabetes, (2) diabetic
ketoacidosis (DKA), and (3) hyperosmolar hyperglycemia state
2
(HHS).
Diabetes Mellitus or Prediabetes
Goals of therapy. Once DM is diagnosed, the clinician needs
to establish a therapeutic goal with respect to glucose control.
e ADA recommends that an A1C goal for many nonpregnant adults of <7% (53 mmol/mol) is appropriate. On the
basis of provider judgment and patient preference, achieving lower A1C levels (eg, <6.5%) may be acceptable if it can
be achieved safely without signicant hypoglycemia or other
adverse eects of treatment. Less stringent A1C goals (eg, <8%
[64mmol/mol]) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced
microvascular or macrovascular complications, extensive
comorbid conditions, or long- standing diabetes in whom the
goal is dicult to achieve despite diabetes self- management
education, appropriate glucose monitoring, and eective doses
of multiple glucose- lowering agents, including insulin.
Diabetic Ketoacidosis
Insulin deciency can result in impaired glucose use by peripheral tissues and the liver. Prolonged insulin deciency results in
protein breakdown and increased glucose production (gluconeogenesis) by the liver and an increased release of counterregulatory hormones such as glucagon, catecholamines
(eg, epinephrine and norepinephrine), cortisol, and growth
hormones. In the face of lipolysis, free fatty acids are converted
by the liver to ketone bodies (β- hydroxybutyric acid and acetoacetic acid), which can result in metabolic acidosis. DKA, which
occurs most commonly in patients with type 1 DM, is initiated
by insulin deciency (Minicase 1). e most common causes
of DKA include the following38:
• Infections, illness, and emotional stress
• Nonadherence or inadequate insulin dosage
• Undiagnosed type 1 DM
• Unknown or no precipitating event
Clinically, patients with DKA typically present with dehydration, lethargy, acetone- smelling breath, abdominal pain, tachycardia, orthostatic hypotension, tachypnea, and, occasionally,
mild hypothermia and lethargy or coma. Because of a patient’s
tendency toward low body temperatures, fever strongly suggests
infection as a precipitant of DKA. DKA is typically associated
with a high glucose concentration. is concentration is typically >250 mg/dL or 13.9 mmol/L; however, in the setting of
sodium- glucose cotransporter-2 (SGLT2) inhibitors use and
other uncommon conditions, the blood glucose can be in the
normal range (euglycemic DKA).
39
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MINICASE 1
Diabetic Ketoacidosis
Rena M. is a 40- year- old woman with a 2- year history of type 2DM.
She presents to the ED with a pH of 7.25, HCO3 of 9, and blood
glucose of 180 mg/dL. Her husband brought her to the ED after
finding her “out of it” when attempting to wake her. She was vomiting
and unable to eat over the last 24 hours, and she experienced
labored breathing, fever, chills, and unusual fatigue.
Approximately 1 year ago, her provider started her on Janumet
(sitagliptin–metformin, 50 mg/1,000 mg) at breakfast and dinner.
At her most recent clinic appointment 1 month ago, her laboratory
results indicated that her HbA1c has dropped from 9.2 to 7.8
since starting sitagliptin–metformin. Her doctor decided to add
dapagliflozin 10 mg to her regimen to obtain an HbA1c below 7%.
Rena M. also takes atorvastatin 40 mg at bedtime for elevated
cholesterol and lisinopril 10 mg daily and hydrochlorothiazide
25 mg daily for hypertension. She has tolerated all of her
medications and adheres to the indicated daily schedule. Physical
examination reveals a lethargic woman with vital signs including
BP 116/68mm Hg (which dropped to 95/50 when standing); HR 105
beats/min; respiratory rate (RR) 30 breaths/min (deep and regular);
and an oral temperature 101.4°F (38.6°C). Her skin turgor is poor, her
mucous membranes are dry, and she is disoriented and confused.
Her laboratory results are as follows:
• Sodium, 142 mEq/L (136 to 142 mEq/L)
• Potassium, 5 mEq/L (3.8 to 5 mEq/L)
• Chloride, 99 mEq/L (95 to 103 mEq/L)
• BUN, 28 mg/dL (8 to 23 mg/dL)
• SCr, 1.8 mg/dL (0.6 to 1.2 mg/dL)
• Phosphorus, 2.7 mg/dL (2.3 to 4.7 mg/dL)
• Amylase, 200 International Units/L (30 to 220
International Units/L)
• pH, 7.25 (7.38 to 7.44)
• Bicarbonate, 9 mEq/L (21 to 28 mEq/L)
• Hct, 52% (36% to 45%)
• WBC count, 16 × 10
3
10
cells/mm3)
• Calcium, 9 mg/dL (9.2 to 11 mg/dL)
• Glucose, 180 mg/dL (70 to 110 mg/dL)
• Ketones, 3+ at 1:8 serum dilution (normal = 0)
• Osmolality, 304 mOsm/kg (280 to 295 mOsm/kg)
• Triglycerides, 174 mg/dL (10 to 150 mg/dL)
• Lipase, 1.4 units/mL (<1.5 units/mL)
• Magnesium, 2 mEq/L (1.3 to 2.1 mEq/L)
A urine screen with Multistix indicates a large (160 mg/dL) amount
of ketones (the highest designation on the strip).
QUESTION: Based on clinical and laboratory findings, what is
the most likely diagnosis for this patient? What precipitated
this metabolic disorder? Can an interpretation of any results be
influenced by her acidosis or hyperglycemia? Are there potential
medication interferences with any laboratory tests?
DISCUSSION: The patient has type 2 DM and presents with DKA,
which is less commonly observed in patients with type 2 DM
compared with type 1 DM. Since 2014, the FDA has received many
reports of DKA in patients treated with SGLT2 inhibitors. TheFDA
3
cells/mm3 (4.8 to 10.8 ×
reports that DKA case presentations associated with SGLT2
inhibitors are atypical in that glucose levels can be normal or mildly
elevated, whereas patients with a typical DKA presentation (type
1 DM or type 2 DM) typically have glucose levels >300 mg/dL.
This patient has a fever, which suggest a potential infection. She
should be examined for infection by obtaining a urinalysis and blood
culture. The cause of preserved euglycemia could be greater urinary
loss of glucose triggered by counterregulatory hormones, hepatic
glucose production observed during a fasting state, or the SGLT2
inhibitor. A key physiologic determinant is the quantity of food she
ingested before development of DKA. That is, when patients are well
fed, their liver contains large amounts of glycogen, which primes the
liver to produce glucose and suppress ketogenesis. However, when
patients have been vomiting and unable to eat, the liver is depleted
of glycogen and primed to produce ketones. Thus, patients such
as Rena M. with euglycemic ketoacidosis are usually in the fasting
state before they become ill.
Clinically, Rena M. presents with typical signs of ketoacidosis,
which include difficulty breathing, nausea, vomiting, abdominal
pain, confusion, and unusual fatigue and sleepiness. Her decreased
skin turgor, dry mucous membranes, tachycardia (HR 105 beats/
min), and orthostatic hypotension are consistent with dehydration,
a common condition in patients with DKA. Her breathing is rapid
and deep. Although she is not comatose, she is lethargic, confused,
and disoriented. Chemically, she probably has a total body deficit of
sodium and potassium despite serum concentration results within
normal limits.
The decreased intravascular volume associated with DKA causes
hemoconcentration on electrolytes. Therefore, these values do
not reflect total body stores, and the clinician can expect them to
decline rapidly if unsupplemented fluids are infused. Although her
phosphorus concentration is in the normal range (lower end), it likely
will decrease after rehydration and insulin. Serial electrolyte testing
should be done every 3 to 4 hours during the first 24 hours.
Serial glucose, ketones, and acid- base measurements, typical
of DKA, should show gradual improvement with proper therapy.
Potassium balance is altered in patients with DKA because
of combined urinary and GI losses. Although total potassium
is depleted, the serum potassium concentration may be high,
normal, or low, depending on the degree of acidosis. Her metabolic
acidosis has resulted in an extracellular shifting of potassium,
causing an elevated serum potassium concentration. Potassium
supplementation may be withheld for the first hour or until serum
levels begin to drop. Potassium replacement should begin when
potassium levels reach normal. Low serum potassium in the face
of pronounced acidosis suggests severe potassium depletion
that requires early, aggressive therapy to prevent life- threatening
hypokalemia during treatment.
Decreased intravascular volume has led to a hemoconcentrated
Hct and BUN, which is also elevated by decreased renal perfusion
(prerenal azotemia), although intrinsic renal causes should be
considered if SCr is also elevated. Fortunately, as is probably
thecase with this patient, high SCr may be an artifact caused by the
Continued
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MINICASE 1 (cont’d)
influence of ketone bodies on the assay. If so, SCr concentrations
should decline with ketone concentrations.
She may be exhibiting leukocytosis unrelated to infection, but no
lab data were provided in the case to actually rule out infection. Her
estimated plasma osmolarity based on the osmolarity estimation
DKA is also characterized by low venous bicarbonate (0 to
15mEq/L), a decreased arterial pH (<7.0 to 7.2), and the presence of an anion gap (>12) (see Chapter13 for more information
on anion gap). Glucose spilling in the urine can lead to osmotic
diuresis, resulting in hypotonic uid losses, dehydration, and electrolyte loss. Sodium and potassium concentrations may be low,
normal, or high on initial presentation. Sodium concentrations
are reective of the amount of total body water and sodium lost
and replaced. In the presence of hyperglycemia, sodium concentrations may be decreased because of the movement of water from
the intracellular space to the extracellular space. e potassium
level reects a balance between the amount of potassium lost in
the urine and insulin deciency, which causes higher concentrations of serum potassium as potassium shis from intracellular
spaces to extracellular uid. Hypertonicity and acidosis can cause
potassium to move from the intracellular space to the extracellular space, resulting in elevated potassium levels. Patients with low
or normal potassium levels on presentation should be placed on
intravenous (IV) potassium replacement and monitored closely
because DKA and its subsequent treatment can result in a low
serum potassium and total body potassium levels that may place
the patient at risk for cardiac dysrhythmia.
38,39
e phosphate level is usually normal or slightly elevated but
may decrease during treatment and should be monitored.38 Creatinine and blood urea nitrogen (BUN) are usually elevated due
to dehydration with an increased BUN to Scr ratio. ese levels
usually return to normal aer rehydration unless there was preexisting renal insuciency. Hemoglobin, Hct, and total protein
levels are mildly elevated due to decreased plasma volume and
dehydration. Amylase levels may be increased due to increased
secretion by the salivary glands. Liver function tests are usually
elevated but return to normal in 3 to 4 weeks.
Serum osmolality is typically elevated at 300 to
320 mOsm/kg (normally, 280 to 295 mOsm/kg). Serum
osmolarity ( milliosmoles/liter), which is practically equivalent to osmolality (milliosmoles/kilogram), can be estimated
using the following formula:
serum osmolarity (mOsm/L) = (2′sodium) +
glucose/18 + BUN/2.8
where glucose and BUN units are expressed as milligrams/
deciliter.
Blood and urine ketones. Ketones are present in the blood and
urine of patients with DKA, as the name of this disorder implies.
Formation of ketone bodies results from fat metabolism. ree
formula would be (2 × 142) + (180/18) + (28/2.8) = 304 mOsm/L, which
is approximately equal to the actual measured laboratory result.
The serum ketone results still would have to be interpreted as real
and significant, given all of the other signs and symptoms. A urine
screen also indicated the presence of ketones.
principal ketone bodies include acetoacetate, acetone, and
β- hydroxybutyrate, which is the predominant ketone in the
blood of patients with DKA.38 DKA can be prevented if patients
are educated about detection of hyperglycemia and ketonuria.
It is recommended that all patients with DM test their urine for
ketones during acute illness or stress when blood glucose levels
are consistently >250 mg/dL (14 mmol/L), during pregnancy,
or when any symptoms of ketoacidosis— such as nausea, vomiting, or abdominal pain— are present.
40
All of the commercially available urine testing methods are
based on the reaction of acetoacetic acid with sodium nitroprusside (nitroferricyanide) in a strongly basic medium. e
colors range from beige or bu- pink for a “negative” reading
to pink and pink- purple for a “positive” reading (Acetest, Ketostix, Laboratorystix, and Multistix). ese nitroprusside- based
(nitroferricyanide) assays do not detect β- hydroxybutyric acid
and are 15 to 20 times more sensitive to acetoacetate than to acetone. In a few situations (eg, severe hypovolemia, hypotension,
low partial pressure of oxygen [pO2], and alcoholism) where
β- hydroxybutyrate predominates, assessment of ketones may
be falsely low. As DKA resolves, β- hydroxybutyric acid is converted to acetoacetate, the assay- reactive ketone body. erefore,
a stronger reaction may be encountered in laboratory results.
However, this reaction does not necessarily mean a worsening
of the ketoacidotic state.
41
Clinicians must keep in mind that ketonuria may also result
from starvation, high- fat diets, fever, and anesthesia, but these
conditions are not associated with hyperglycemia. Levodopa,
mesna, acetylcysteine (irrigation), methyldopa, phenazopyridine, pyrazinamide, valproic acid, captopril, and high- dose
aspirin may cause false- positive results with urine ketone
42-44
tests.
e inuence of these drugs on serum ketone tests
has not been studied extensively. If the ketone concentration
is increased, a typical series of dipstick results includes the
following results:
1. Negative
2. Trace (5 mg/dL)
3. Small (15 mg/dL)
4. Moderate (40 mg/dL)
5. Large (80 mg/dL)
6. Very large (160 mg/dL)
False- negative readings have been reported when test strips
have been exposed to air for an extended period of time or
when urine specimens have been highly acidic, such as aer
CHAPTER 9 • EndoCRinE disoRdERs 175
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large intakes of ascorbic acid.40 Urine ketone tests should not
be used for diagnosing or monitoring the treatment of DKA.
Acetoacetic and β- hydroxybutyric acids concentrations in
urine greatly exceed blood concentrations. erefore, the presence of ketone bodies in urine cannot be used to diagnose DKA.
Conversely, during recovery from ketoacidosis, ketone bodies
may be detected in urine long aer blood concentrations have
43,45
fallen.
In addition, urine testing only provides an estimate of
blood ketone levels 2 to 4 hours before testing and depends on
the person being able to pass urine.
40,41
Blood β- ketone testing can provide a patient with an early
warning of impending DKA.
45,46
While blood β- ketone testing
is routinely conducted in a medical setting, patients may also
use an at- home kit to test for ketones in blood. While instructions may vary, kits will include some kind of device for the
patient to prick their nger (similar to blood glucose testing).
e brands of meters currently marketed are CareTouch, KetoMojo, Nova Max Plus, and Precision Xtra. All of these meters
can also be used to measure blood glucose levels. Patients should
purchase the glucose strips made for their meter to use this
feature. In addition, each meter can be tested against control.
Aβ- hydroxybutyric acid level <0.6 mmol/L is considered normal. Patients with levels between 0.6 and 1 mmol/L should take
additional insulin and increase their uid intake to ush out
the ketones. Patients should contact their physician if levels are
between 1 and 3 mmol/L. Patients should be advised to report
to the emergency department (ED) immediately if their levels
are >3 mmol/L.
46
Hyperosmolar Hyperglycemia State
Hyperosmolar hyperglycemia state (HHS) is a condition that
occurs most frequently in elderly patients with type 2 DM, and
it is usually precipitated by stress or illness when such patients
do not drink enough to keep up with osmotic diuresis. Patients
usually present with severe hyperglycemia (glucose concentrations >600 mg/dL or >33.3 mmol/L); decreased mentation
(eg, lethargy, confusion, dehydration); neurologic manifestations (eg, seizures and hemisensory decits); and an absence of
ketosis. Insulin deciency is not as severe in HHS as in DKA.
erefore, lipolysis, which is necessary for the formation of
ketone bodies, does not occur (Minicase 2). e absence of
ketosis results in signicantly milder GI symptoms than patients
with DKA. erefore, patients oen fail to seek medical attention. Patients with HHS tend to have much higher blood glucose
concentrations than in DKA and are usually more dehydrated
on presentation than patients with DKA due to impairment in
the thirst mechanism, which results in prolonged diuresis and
dehydration.
In some cases, patients are taking medications that cause glucose intolerance (eg, diuretics, steroids, and phenytoin). Stroke
and infection are disease- related predisposing factors. Initially,
electrolytes are within normal ranges, but BUN routinely is
elevated. Serum osmolalities characteristically are higher than
those in DKA— in the range of 320 to 400 mOsm/kg. Serum
electrolytes (eg, magnesium, phosphorus, and calcium) are typi
cally abnormal and should be monitored until they return to
normal range.
46-48
47,48
Hypoglycemia
Hypoglycemia is dened as a blood glucose level of
70 mg/dL (3.9 mmol/L) or lower.
•
Level 1 (mild) hypoglycemia: blood glucose is <70 mg/dL
but ≥54 mg/dL.
•
Level 2 (moderate) hypoglycemia: Blood glucose is <54 mg/dL.
• Level 3 (severe) hypoglycemia: A person is unable to function
because of mental or physical changes. ey need help from
another person. In this case, blood glucose is oen <40 mg/dL.
e classication of hypoglycemia is based on an individual’s
ability to self- treat. Mild hypoglycemia is characterized by symptoms such as sweating, trembling, shaking, rapid heartbeat, heavy
breathing, and diculty concentrating. e symptoms associated
with mild hypoglycemia vary in severity and do not imply that
the symptoms experienced by the individual are minor or easily
tolerated. Although patients may experience profuse sweating,
dizziness, and lack of coordination, they still may be able to selftreat. ese symptoms resolve aer consuming readily absorb
able carbohydrates (eg, fruit juice, milk, or hard candy).
Other Laboratory Tests Used in the
Management of Diabetes Mellitus
e 2021 ADA standards recommend urinalysis for detection of proteinuria should be obtained in patients with DM on
a yearly basis.50 is should begin at the time of diagnosis in
patients with type 2 DM and 5 years aer diagnosis in patients
with type 1 DM.50 A quantitative test for urine protein should
follow a positive result on urinalysis. If urinalysis is negative
for proteinuria, testing for increased albumin excretion (previously termed microalbuminuria) should be obtained. Increased
albumin excretion indicates glomerular damage and is predictive of clinical nephropathy.
ree methods are available to screen for increased albumin
excretion. One method is measurement of the urine albumin
to creatinine ratio in a spot urine sample. is method is convenient in the clinical setting because it requires only one urine
sample. A morning sample is preferred to take into account the
diurnal variation of albumin excretion. A second method is a
24- hour urine collection for determination of albumin excretion. is method may be tedious and accuracy relies on proper
collection techniques. An advantage of this method is that renal
function can simultaneously be quantied. A third alternative
method to the 24- hour collection is a timed urine collection
for albumin. Moderately increased albuminuria is dened as a
urinary albumin excretion of 30 to 299 mcg/mL on a spot urine
sample, 30 to 299 mg/24hr on a 24- hour urine collection, or
20 to 199 mcg/min on a timed urine collection. Transient rises
in albumin excretion can be associated with exercise, hyperglycemia, hypertension, urinary tract infection, heart failure,
and fever. erefore, if any of these conditions are present, they
may result in false- positive results on screening tests. Variability
exists in the excretion of albumin; thus, moderately increased
-
albuminuria must be conrmed in two repeated tests in a 3- to
6- month period. Two of three positive screening tests for moderately increased albuminuria conrm the diagnosis.
50
-
16,49
50
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