The OGTT is more sensitive than fasting
glucose in the course of type 2 diabetes, resulting in lack of equivalence
between the fasting and 2-hour glucose value.
For epidemiological or screening purpose the fasting or 2h post load
value may be used. For clinical purpose diagnosis should be confirmed by
repeating the test on another day. For dysglycemic condition both IGT and IFG
should be determined. These patients with IFG or IGT are called predibetics. In
type 2 diabetes where diabetes occurs at least 4 to 7 years before clinical
diagnosis, or for people at high risk of diabetes, screening is recommended.
Fasting glucose should be measured in all asymptomatic people at 45 years of
age (or younger in subjects at increased risk), with follow-up testing every 3
years.
OGTT is
standard method to evaluate individuals and establish values for healthy and
disease subjects. Although more sensitive than FPG determinations, glucose
tolerance testing is affected by various factors resulting in poor
reproducibility. So OGTT should be performed on two separate occasions before
saying abnormal. The following conditions should be met for performing OGTT:
a. Discontinue
when possible medications known to affect glucose tolerance e.g. thiazides,
oral contraceptives, corticosteroids, etc.
b. Perform in
the morning after 3 days of unrestricted diet (containing at least 150 g of
carbohydrate per day) and activity
c. Perform the
test after a 10 to 16 hour fast only in ambulatory subjects
d. Smoking
should be avoided during the test or in previous 3 days.
e. Should not
be performed on hospital, acutely ill, or inactive patients.
f.
Test should begin between 7 AM and 9 AM
g. Plasma
glucose should be measured fasting, then every 30 minutes for 2 hours after an
oral glucose load.
h. For
non-pregnant adults the recommended load is 75 g, for children 1.75 g/kg body
weight
i.
The glucose should be dissolved in 300 mL of water and
ingested over 5 minutes.
An OGTT is rarely necessary for the diagnosis of diabetes mellitus and is
not recommended by ADA for routine clinical use. An FPG value less than 100
mg/dL or a random glucose concentration less than 140 mg/dL is sufficient to
rule out the diagnosis of diabetes mellitus. An OGTT is indicated in following
situations:
a. Diagnosis
of GDM
b. Diagnosis
of Prediabetics
c. Evaluation
of patient with unexplained nephropathy, neuropathy, retinopathy, with RBS
>140 mg/dL.
d. High risk
population during epidemiological data
Intravenous Glucose tolerance test
Poor absorption of orally administered glucose may result in a flat
tolerance curve. Some patients are unable to tolerate a large oral carbohydrate
or may have altered gastric physiology. In these patients an intravenous
glucose tolerance test may be performed to eliminate the factors related to the
rate of glucose absorption. In addition, measurement of first-phase insulin
response can identify subgroups at greatest risk of progression to type 1
diabetes.
Preparation of patients is the same as for OGTT. The dose of glucose is
0.5 g/kg of body weight (maximum 35 g), given as a 25 g/dL solution. The dose
is administered intravenously over 3 minutes and blood is collected every 10
minutes for 1 hour. If insulin assay are performed a specimen is also obtained
5 minutes after the start of injection. Blood glucose concentration should decrease
in an exponential manner if normal. The rate of disappearance <1% per minute
is diagnostic as diabetes but in normal it is >1.5% per minute.
According
to ADA, FPG was the preferred test for diagnosing diabetes and
prediabetes however, OGTT could be required for further diagnosing IFG or when
diabetes was still suspected despite of normal FPG. But WHO states individuals
with IFG should also undergo an OGTT to exclude IGT or diabetes.
In 2003 ADA further
lowered the FPG from 110 – 125 mg/dl to 100 -125 mg/dl. But WHO still defines
IFG at 110-125 mg/dl.
In 2010 ADA defined new term Glycated Hb (HbA1c) equal
or greater 6.5% for diagnosis of diabetes along with FPG and 2 hour glucose
level after OGTT.
IFG is diagnosed when FPG is 100-125 mg/dl
IGT diagnosed when 2 hour glucose level 140-199 mg/dl and HbA1c 5.7-6.4%
and FPG <100 mg/dl
Diabetes diagnosed when any one of the following is identified and if
positive subsequent testing should be done in next day for confirmation.
1. FPG ≥126 mg/dl and Presence of sign and
symptoms
2. Random
level ≥200 mg/dl
or
3. 2 hour
glucose level >200 mg/dl after 75 gram OGTT
4. HbA1c ≥6.5%
At present HbA1c alone is not recommended by WHO for diagnosis of
diabetes but used for monitoring glucose value of 3 month.
Limitations
of HbA1c determination include specific hemoglobinopathies that interfere with
AbA1c assay (eg, HbF falsely increases and sickle cell hemoglobin/HbC lowers
HbA1c). Diseases changing the turnover of red blood cells like hemolysis,
shortened RBC life, cirrhosis, acute or chronic blood loss, or transfusions,
may also lead to abnormally low HbA1c levels giving false negative diagnosis. During
iron deficiency HbA1c value increases giving false positive diagnosis. In these
patients and during pregnancy, traditional diagnostic test based on glucose
criteria and not HbA1c should be used.
In summary it is reasonable to consider as stated by ADA, an HbA1c range
of 5.7 to 6.4% for identifying high risk groups i.e. prediabetes and values
higher than 6.5% can be used for diagnosing diabetes. Current estimate indicate
that most individuals up to 70% with prediabetes eventually develop diabetes.
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