A CLINICAL APPROACH FOR THE DIAGNOSIS OF DIABETES-MELLITUS - AN ANALYSIS USING GLYCOSYLATED HEMOGLOBIN LEVELS

Objective.-To determine whether a glycosylated hemoglobin level can be used in place of an oral glucose tolerance test (OGTT) to diagnose di abetes. Data Sources/Study Selection.-An augmented MEDLINE search was performed to identify all reports from 1966 through June 1994 in which glycosylated hemoglobin levels were measured concurrently with perfor mance of OGTTs in the same study, The corresponding authors were conta cted and asked to provide individual data for all subjects tested. A t otal of 31 investigators representing 34 possible studies responded, a nd 18 were able to provide us with the data requested, Overall fasting plasma glucose concentrations, 2-hour postdextrose glucose concentrat ions, and glycosylated hemoglobin levels were available from 11 276 in dividuals. Data Extraction-To define normal glucose tolerance, impaire d glucose tolerance (IGT), and diabetes, modified World Health Organiz ation criteria were used. Data Synthesis.-An analysis of the methods u sed for measurement of glycosylated hemoglobin levels revealed that th e HbA(1c) assay showed the least variance in normal subjects. Therefor e, only data from the 8984 subjects who had HbA(1c) levels measured we re used. When we used the mean HbA(1c) level plus 4 SDs as a cutpoint, the sensitivity was 36% and specificity was 100% compared with the re sults of the OGTT, Because of the lack of agreement between OGTT resul ts and HbA(1c) levels, models were created to analyze the distribution of HbA(1c) levels in each study, Using these models, we identified 3 subpopulations. The third subpopulation was likely to represent subjec ts with diabetes. When we applied an HbA(1c) level of 7.0% as a cutpoi nt, the sensitivity was 99.6% for the third subpopulation. When this c utpoint was reapplied to the OGTT results, of those subjects with an H bA(1c) level of at least 7.0%, 89% had diabetes, 7% had IGT, and 4% we re normal. Conclusions.-Although the OGTT is the ''gold standard'' for diagnosing diabetes, it is known to be poorly reproducible and is oft en not performed. Not only is use of an HbA(1c) level to diagnose diab etes more convenient, but therapeutic decisions are based on this valu e, regardless of the findings on the OGTT. An HbA(1c) level of 7.0% or higher often requires pharmacological intervention and is most often associated with the diagnosis of diabetes by World Health Organization standards. An HbA(1c) level below 7.0% would generally be treated wit h diet and exercise, regardless of the diagnosis of IGT or diabetes by OGTT. Thus, measurement of HbA(1c) levels may represent a reasonable approach to identifying treatment-requiring diabetes.