Jean-Marie Ekoe,1 Paul Zimmet2
!Centre de Recherche CHUM, Montreal, Canada 2International Diabetes Institute, Melbourne, Australia
Diabetes mellitus may present with clear and classical symptoms (thirst, polyuria or ketoacidosis) or may be accompanied by specific complications. The lack of sensitivity and specificity of some of these 'diabetic symptoms' has already been discussed (see previous chapter). However, when the symptoms and/or specific complications are present, the diagnosis of diabetes is confirmed by a single, unequivocally elevated blood glucose measurement as shown in Figure 3.1 (1). Severe hyperglycemia found under conditions of acute infective, traumatic or other stress may be transitory and should not in itself be regarded as diagnostic of diabetes. If a diagnosis of diabetes is made, one must feel confident that the diagnosis is fully established since the consequences for the individual are considerable and lifelong (2). For the asymptomatic persons at least one additional plasma/blood glucose measurement with a value in the diabetic range is essential, either fasting, from a random (casual) sample, or from the oral glucose tolerance (OGTT). Levels of blood glucose below which a diagnosis of diabetes is virtually excluded have also been defined (Figure 3.1).
If different samples fail to confirm the diagnosis of diabetes mellitus, the person should be reassessed and retested until the diagnostic situation becomes clear. Additional factors such as family history, age, ethnicity, adiposity and concomitant disorders should be considered before deciding on a diagnostic or therapeutic course of action (2). A single abnormal blood glucose value should never be used as the sole basis of diagnosis of diabetes in an asymptomatic subject. An alternative to the single blood glucose estimation or OGTT has long been sought to simplify the diagnosis of diabetes. Glycated hemoglobin reflecting average glycemia over a period of weeks, was thought to provide such a test. In certain cases, it gives equal or almost equal sensitivity and specificity to glucose measurement. However, lack of standardization and its unavailability in many parts of the world make it difficult to recommend it as a good alternative at this time (2,3).
In a collaborative study involving nine British towns over 2 years, of 254 newly diagnosed cases of diabetes aged 18-50 years, 81% were diagnosed on one single random/casual blood glucose measurement of 11.1 mmol/l (200 mg/dl) or more (4). Furthermore, a diagnosis of diabetes was established from casual blood glucose estimation without any glucose tolerance test in 800 patients (90%) attending the Diabetic Clinic at King's College Hospital in London (5).
When symptoms are lacking and blood glucose levels are less markedly elevated (e.g., glucose concentration in a casual or random blood sample between 4.4 and 10.0 mmol/l for venous whole blood), measurements made after fasting or after a glucose load may be necessary to confirm or refute the diagnosis of diabetes. An entire investigation is needed if symptoms are questionable. In case of a medical, obstetrical or family history of diabetes, a single elevated blood glucose measurement may or may not be decisive. An oral glucose tolerance test (OGTT) is indicated in this situation (Table 3.1). Table 3.2 shows the diagnostic values of OGTT for diabetes mellitus and other categories of glucose tolerance abnormalities.
Collecting and interpreting epidemiologic data implies a complete understanding of diagnostic methods and the criteria applied. It is therefore appropriate to review briefly the indications of one
of the most widely used and misused methods of diagnosis: the OGTT.
THE DEMONSTRATION OF AN ABNORMAL BLOOD GLUCOSE LEVEL USING AN ORAL GLUCOSE TOLERANCE TEST (OGTT)
No marker other than a high blood glucose level has been discovered to identify the diabetic state. The diagnosis depends heavily on the demonstration of abnormal blood glucose levels. Symptoms and signs of diabetes and urine glucose tests are non-specific tests for diabetes although they should be taken into account when present.
Before performing the OGTT, it has been assumed that a random (or casual) blood glucose level should be obtained (Figure 3.1). Plasma venous glucose levels greater than 11.1 mmol/l (200 mg/dl) are usually diagnostic irrespective of time of day or status of fasting, provided the elevated blood glucose values are confirmed.
The Oral Glucose Tolerance Test (OGTT)
Conn and Fajans believed that the diagnosis of diabetes in a completely asymptomatic patient could be made only on the basis of a carefully performed glucose tolerance test (6, 7). Ten years earlier, Soskin believed that the OGTT was 'practically worthless as it was used and inter preted' (8). These conflicting statements illustrate the fact that, as a clinical diagnostic tool, the OGTT has been grossly overemphasized and misused. It is now apparent that the OGTT is useful in clearly defined situations as summarized in Table 3.1. For instance, the OGTT has been of prime importance in many epidemiological surveys of diabetes and is still one of the best instruments in such studies.
However, from a clinical viewpoint, the OGTT may be performed in specific circumstances. An equivocal random or casual blood glucose level (the diabetes mellitus uncertain zone as defined by the 1985 WHO Study Group on Diabetes Mellitus, Figure 3.1) deserves an OGTT. The establishment of a diagnosis is highly necessary in this situation. The OGTT might also be included as part of a special clinical investigation, or be needed for medico-legal reasons. If an OGTT is performed, it is sufficient to measure the blood glucose values while fasting and at 2 h after a 75 g oral glucose load (Annexes 1 and 2) (2). For children the oral glucose load is related to body weight, i.e. 1.75 g/kg.
Diabetes in children usually presents with severe symptoms, very high blood glucose levels, marked glycosuria, and ketonuria. In most children the diagnosis is confirmed without delay by blood glucose measurements and treatment (insulin injections) is initiated immediately. A small proportion of children and adolescents, however, present with less severe symptoms and may require a fasting blood glucose and/or an OGTT for diagnosis. Diagnostic interpretations of the fasting and 2 h post-load concentrations in non-pregnant subjects are shown in Table 3.2. The diagnostic criteria in children are the same as for adults but in
Table 3.1 Indications of oral glucose tolerance test (OGTT)
1. When a 'random' blood glucose is equivocal e-g-:
Fasting blood glucose: * > 6.1 -7.0 mmol/l < (IFG) Post-prandial blood glucose: * > 7.8-11.0 mmol/1
2. As part of special clinical investigation e.g.:
Fasting glycosuria in pregnancy
Data collection in certain endocrine or other diseases
3. For experimental and epidemiological purposes
4. To exclude diabetes mellitus or impaired glucose tolerance
IFG: Impaired Fasting Glycemia *: Venous plasma values
DIABETES MELLITUS: DIAGNOSIS AND CLASSIFICATION Table 3.2 Values for diagnosis of diabetes mellitus and other categories of hyperglycemia
Diabetes mellitus (DM): Fasting or
2 h post-glucose load or both
Impaired glucose tolerance (IGT): Fasting concentration (if measured) and
2 h post-glucose load
Impaired fasting glycemia (IFG): Fasting i h (if measured)
Glucose concentration mmol/l (mg/dl)
Whole blood Plasma
For epidemiological or population screening purposes, the fasting of 2 h value after 75 g oral glucose may be used alone. Glucose concentrations should not be determined on serum unless red cells are immediately removed, otherwise glycolysis will result in an unpredictable underestimation of the true concentrations. Glucose preservatives do not totally prevent glycolysis. If whole blood glucose is used, the sample should be kept at 0-4 °C or centrifuged immediately, or assayed immediately.
practice, an OGTT is rarely required to make a diagnosis of Type 1 diabetes.
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