Tuesday, November 13, 2012

OGTT : Introduction and Procedure

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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