Oral Glucose Tolerance Test

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The oral glucose tolerance test (OGTT) has for many years been the accepted standard for the diagnosis of diabetes. It is, however, time consuming and inconvenient requiring considerable preparation. Many would therefore regard it as unsuitable for widespread use among people with risk factors for diabetes. Unless conducted in the inpatient setting, the recent dietary intake and duration of the pre-test fast cannot be standardised in the way the protocol demands, and these factors can affect the results54,55. Paired OGTTs performed two to six weeks apart have shown that among people who are diagnosed as having diabetes in an initial OGTT, 95% of values in the second OGTT lie within ±20% of the initial fasting glucose and ±36% of the initial 2 h glucose56.

It is recommended that the OGTT should be administered in the morning after at least three days of unrestricted diet (greater than 150 g of carbohydrate

Engelgau et al.50

At sensitivity of 90%*: At specificity of 90%: Optimal:

Median specificity 76-78%

Median specificity 48-52% (according to age group) Median sensitivity 49-52% Median sensitivity 73-76%

Qiao et al.51

Cut-off 5.8 mmol/l Cut-off 5.2 mmol/l

Sensitivity 63%, specificity 85%** Sensitivity 78%, specificity 62%**

daily) and usual physical activity. A reasonable carbohydrate containing meal (30-50 g) should be consumed on the evening before the test. The test should be preceded by an overnight fast of 8-14 hours, during which water may be drunk. Smoking should not be permitted during the test. The presence of factors that influence interpretation of the results of the test should be recorded (e.g. medications, inactivity, infection, etc.).

There is also little published evidence supporting the appropriate glucose amount. These are currently 75 g anhydrose glucose for adults and 1.75 g of glucose per kg body weight, up to a total of 75 g of glucose for children. The origin of these recommendations is a mid-Atlantic compromise between the 50 g and 100 g used in Europe and the USA before international standardisation. When glucose monohydrate is used, the corresponding amount is 82.5 g, which may give rise to confusion and another potential source of measurement error.

Fasting blood glucose measurement

The ADA Expert Committee recommended using the fasting glucose alone as a diagnostic criterion, thus simplifying fieldwork and reducing the burden on participants. The WHO, by contrast, recommended retention of the OGTT.

A new intermediate group of individuals whose glucose levels, although not meeting criteria for diabetes, are too high to be considered normal was established based on fasting blood glucose measurement and called impaired fasting glucose. Although this is conceptually similar to the definition of IGT based on intermediate 2 h PG values, the thresholds chosen were not selected to be comparable along the considerations underlying the agreement on the diagnostic FPG threshold for diabetes (see above). Table 2.1 shows that the range of glucose values between the lower and upper 2 h cut-offs for IGT is constant across the different biological specimen categories at 3.3 mmol/l. However, the range for the fasting glucose cut-points for IFG is 0.9 mmol/l in plasma and 0.5 mmol/l in whole blood. As the definition of IGT is broader, it is likely that IGT will identify more people as having impaired glucose homeostasis than IFG.

When both tests, FPG and 2 h PG, are applied on the same individual a 3 x 3 table emerges to classify their glucose intolerance status (Table 2.5).

Fasting versus oral glucose tolerance testing

The ADA diabetes classification document has received a lot of attention, with its recommendations to perform diabetes diagnosis generally with fasting plasma glucose alone. This was a deviation from the 1985 WHO recommendations and not completely followed by the new WHO statement which supported the retention of the OGTT unless circumstances prevented it from being performed. Furthermore, the WHO retained the recommendation for epidemiological studies to restrict diabetes screening to the 2 h post-OGTT value in situations where the fasting state of the participants cannot be assured.

In a situation of partial overlap of the distributions of fasting and 2 h diabetes values in a population, any algorithm utilising several tests in parallel (such as scoring individuals using their fasting and 2 h glucose values for classification by whichever meets the diabetes criterion) will yield increased numbers. Table 2.5 shows how different criteria used together would classify patients with different blood glucose levels, and how changing thresholds would affect glucose intolerance groups.

There is complete agreement in classifying individuals at either extreme of the glucose distribution (the grey shaded areas in Table 2.5). However, for individuals with a FPG between 6.1 and 7.8 mmol/l and a 2 h glucose between 7.8 and 11.1 mmol/l, how they are classified depends on the criteria used. This discordance between the classification systems means that if either criterion was used alone, it would inevitably identify different groups of individuals. This will also impact on incidence and prevalence rates. A number of recent studies have shown that using FPG would result in the misclassification of a significant proportion of people with diabetes (when defined according to the 2 h level)57-67. It is likely that all these people are at risk of diabetes-related complications; in other words they can be considered as being genuinely diabetic and therefore the OGTT may be necessary to exclude diabetes in anyone with a positive screening blood test. Approximately 35% of all people with newly diagnosed diabetes still have a normal fasting glucose, whereas 15-20% have a normal 2 h value. This distribution differs between men and women, with women being more commonly diagnosed on the basis of the 2 h glucose level68. This is also

Table 2.5. Diagnostic category of individuals with different glucose cut-off levels according to WHO (1985), ADA (1997) and WHO (1998) classification criteria.

2 h plasma glucose (mmol/l)

plasma glucose (mmol/l)

Table 2.5. Diagnostic category of individuals with different glucose cut-off levels according to WHO (1985), ADA (1997) and WHO (1998) classification criteria.

2 h plasma glucose (mmol/l)

plasma glucose (mmol/l)

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