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Letters |
1
Department of Clinical Biochemistry, North Manchester General Hospital, Manchester M8 5RB, UK,
2
Department of Clinical Chemistry, Royal Liverpool University Hospital, Liverpool L7 8XP, UK
a Author for correspondence. Fax 44-161-720-2886.
To the Editor:
In his editorial article (1), Dr. Sacks welcomes the
new guidelines for diagnosis of diabetes published recently by the
American Diabetes Association (ADA) (2). Replacement of the
oral glucose tolerance test (OGTT) by measurement of fasting plasma
glucose (FPG) on more than one occasion certainly simplifies the
diagnostic procedure, and the chosen FPG cutoff of 
7.0 mmol/L (126
mg/dL) appears to be almost as sensitive for diabetes detection as the
OGTT 2-h plasma glucose (2hPG). Unfortunately, the situation is not
quite as simple as that.
We recently conducted a survey of 401 nonpregnant subjects having OGTT because of suspected diabetes mellitus (3). The OGTT was performed according to WHO protocol and interpreted on the basis of the 2hPG value. The prevalence of diabetes in this population according to the results of the OGTT was 44.4%, compared with 41.4% by the ADA FPG criterion. This is in line with the ADA's data on the different sensitivities of the two tests and suggests that they are giving approximately the same answers. However, when we compared results by the two methods for individual patients, the agreement was not always so good. Of 178 patients positive for diabetes by 2hPG, only 139 were positive by the ADA FPG criterion, which means the latter gave 39 (22%) false negatives if the OGTT 2hPG is regarded as the reference method. This discrepancy was not immediately apparent in the prevalence figures because 27 other subjects were falsely positive by the ADA criterion, and these partially balanced the false negatives. In its overall view of the situation, the ADA seems to have omitted considering in any detail the possibility of a substantial number of individual discrepancies within the population. Furthermore, subjects whose FPG is lower than 6.1 mmol/L (110 mg/dL) are regarded by the ADA criteria as normal; available evidence, however, suggests that an appreciable proportion of diabetics have FPG below this (4)(5), and our recent survey confirms it. Eighteen out of 178 subjects with a diabetic OGTT 2hPG had FPG below 6.1 mmol/L (110 mg/dL).
Owing to the change from the OGTT to FPG, the term impaired glucose tolerance (IGT) has had to be replaced by impaired fasting glucose (IFG), the latter being FPG in the range 6.1–6.9 mmol/L (110–125 mg/dL) inclusive. In our survey, 94 subjects fell into the IGT category, but only 27 of these met the criteria for IFG. Therefore, the two categories cannot really be regarded as equivalent.
Similar discrepancies between the two methods of classification were recently reported by Harris et al. (6). In an assessment of the prevalence of undiagnosed diabetes in a population, the ADA criteria detected 4.4% compared with 6.4% by WHO criteria; however, 1.0% of the ADA figure were subjects classified by WHO as IGT or normal, and 3.0% of the WHO "diabetics" were classified as IFG or normal by the ADA method. This means that in their study almost one-half of those diagnosed as diabetic by WHO were considered nondiabetic by ADA.
Although we welcome attempts to simplify diagnostic testing for diabetes, it should be realized that although the proposed ADA changes may not greatly affect population prevalence figures for diabetes, the identities of the subjects constituting the various categories may show some differences, and some patients classified as diabetic by one method may not be by the other procedure. We fully accept that in many cases it is unnecessary to perform an OGTT to make a diagnosis, but we believe that comparison of the new ADA and WHO 1985 systems would reveal considerable numbers of diagnostic discrepancies at the lower levels of glucose intolerance. The argument that the new criterion should increase the number of diagnosed patients is only valid if one assumes that hitherto they would have been assessed solely on the higher FPG cutoff. Although there may be valid arguments for changing the protocol for diagnosing diabetes, clinical chemists should not fall into the trap of thinking that the new ADA criteria are a straightforward substitute for the OGTT and will produce the same results for individual patients. An epidemiologist wanting to ascertain the diabetes prevalence in a population might be forgiven for taking this view, but try convincing the patient who might now be told he is no longer diabetic based on ADA criteria after being diagnosed as such by the OGTT and perhaps having had restrictions placed on his life insurance or even his driving license!
References
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, Fax 617-278-6921 e-mail dsacks{at}bics.bwh.harvard.edu
a Author for correspondence. Fax 44-161-720-2886.
To the Editor:
It is widely recognized that diagnosis of diabetes mellitus by fasting plasma glucose (FPG) and the oral glucose tolerance test (OGTT) are not equivalent. This disparity was one of the two primary motivations for revising the diagnostic criteria and lowering the FPG threshold [the other was to encourage use of the FPG instead of the OGTT (see below)] (1). Despite this change, the Expert Committee recognized the lack of correlation between the two tests and conceded that simultaneous measurement of FPG and 2-h postload glucose would lead to some diagnostic discrepancies. Two large studies (2)(3) published after the editorial was written, one by a member of the Expert Committee (2), clearly demonstrate this predicament.
Furthermore, it was acknowledged that diagnosing diabetes by the FPG alone would yield a prevalence lower than that obtained by the OGTT [see Table 4 in the report by the American Diabetes Association (1)]. The OGTT is more sensitive than the FPG because, as previously indicated (4), impaired release of insulin in response to glucose develops early in the course of type 2 diabetes; increased fasting glucose is a later manifestation. Thus, the observation by Wiener and Roberts that 18 of the 178 subjects with a "diabetic" OGTT had FPG <6.1 mmol/L (110 mg/dL) is not unexpected and corroborates the findings by Tanaka et al. in 2121 individuals (3).
An element of fundamental importance that confounds interpretation of their data was omitted from the letter by Wiener and Roberts; namely, the lack of reproducibility of the OGTT. This finding has been documented by multiple studies. For example, a group of 334 apparently healthy volunteers underwent six OGTTs over a period of 1 year. Using US Public Health Service criteria (the study antedated the recommendations of the 1979 National Diabetes Data Group), 29 subjects (9%) had abnormal results on at least one test, but none had all six tests abnormal (5). Moreover, of the seven individuals who were classified with diabetes, six were diagnostic on only one of the OGTTs. Another evaluation in 26 healthy subjects and 32 offspring of conjugal diabetic parents demonstrated that only about 50% of two OGTTs were reproducible (6). More recently, 524 subjects without a history of diabetes mellitus were evaluated with two OGTTs performed 2–6 weeks apart (7). Of the 198 patients classified with impaired glucose tolerance by the first OGTT using WHO criteria, 78 (39%) and 25 (13%) were classified with normal glucose tolerance and diabetes, respectively, by the second OGTT. Thus, if the initial OGTT is used as the gold standard, a repeat OGTT will "misclassify" ~50% of subjects with initial values near the cutoff. For this reason, the National Diabetes Data Group emphasized that it was imperative (emphasis added) that the OGTT be abnormal on more than one occasion for a diagnosis of diabetes to be established (8).
These factors were recognized in the Report of the Expert Committee on the Diagnosis and Classification of Diabetes (1). The principal reason to diagnose and treat diabetes is to decrease the risk of complications. Accordingly, the revised cutoff for FPG was established on the basis of the risk for the development of complications of diabetes. Analysis of several studies revealed that the approximate thresholds for increased risk of retinopathy and microvascular and macrovascular disease were 6.9 mmol/L (125 mg/dL) and 11.1 mmol/L (200 mg/dL) for fasting and 2-h postload glucose concentrations, respectively (1). Thus, FPG and the OGTT have approximately equal predictive value for the most pertinent and practical clinical outcome of diabetes, namely the development of long-term complications. Since it is less complex, less expensive, more reproducible, more readily obtained, and more acceptable to patients than the OGTT, the FPG should be the primary strategy for the assessment of glycemia.
Notwithstanding this recommendation, measurement of blood glucose concentrations is an imperfect method for identifying individuals with diabetes mellitus (4). Blood glucose concentrations are a continuum, and there is no absolute threshold for the development of complications, necessitating a somewhat arbitrary choice of cutoff. The advent of molecular and immunological assays that are capable of accurately diagnosing diabetes is eagerly awaited.
References
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