Follow-Up Report on the Diagnosis of Diabetes Mellitus

In 1997, an International Expert Committee was convened to reexamine the classification and diagnostic criteria of diabetes, which were based on the 1979 publication of the National Diabetes Data Group (1) and subsequent WHO study group (2). As a result of its deliberations, the Committee recommended several changes to the diagnostic criteria for diabetes and for lesser degrees of impaired glucose regulation (IFG/IGT) (3). The following were the major changes or issues addressed. 1) The use of a fasting plasma glucose (FPG) test for the diagnosis of diabetes was recommended, and the cut point separating diabetes from nondiabetes was lowered from FPG 140 mg/dl (7.8 mmol/l) to 126 mg/dl (7.0 mmol/l). (All glycemic values represent venous plasma.) This change was based on data that showed an increase in prevalence and incidence of diabetic retinopathy beginning at approximately a FPG of 126 mg/dl, as well as on the desire to reduce the discrepancy that existed in the number of cases detected by the FPG cut point of 140 mg/dl and the 2-h value in the OGTT (2-h plasma glucose [2-h PG]) of 200 mg/dl (11.1 mmol/l). 2) Normal FPG was defined as 110 mg/dl (6.1 mmol/l). 3) The use of HbA1c (A1C) as a diagnostic test for diabetes was not recommended. The primary reason for this decision was a lack of standardized methodology resulting in varying nondiabetic reference ranges among laboratories. 4) Although the OGTT (which consists of an FPG and 2-h PG value) was recognized as a valid way to diagnose diabetes, the use of the test for diagnostic purposes in clinical practice was discouraged for several reasons (e.g., inconvenience, less reproducibility, greater cost). The diagnostic category of impaired glucose tolerance (IGT) was retained to describe people whose FPG was 126 mg/dl but whose 2-h PG after a 75-g oral glucose challenge was 140–199 mg/dl. 5) The range of FPG levels between “normal” and that diagnostic for diabetes was named “impaired fasting glucose” (IFG). IFG identified people whose FPG ranged from 110 mg/dl (6.1 mmol/l) to 125 mg/dl (6.9 mmol/l). This construct was established so that there would be a fasting category analogous to IGT. The WHO consultation (4) also adopted most of the above conclusions. The two significant differences were that, whenever feasible, individuals with IFG should receive an OGTT to exclude the presence of diabetes, and the adoption of different criteria for the diagnosis of gestational diabetes. Since the 1997 Expert Committee report, many new data related to the diagnosis of diabetes have been published. First, many analyses of both old and new epidemiological data have examined the equivalence of the FPG and the 2-h PG to predict diabetes, and questions have been raised about the preference of the FPG test over the 2-h PG to diagnose diabetes (5– 7). Second, the IGT category has now been associated with cardiovascular disease (CVD) risk factors (8–10) and CVD events (10,11), whereas IFG is much less strongly associated with CVD events and CVD mortality (10,11). Third, the National Glycosylated Hemoglobin Standardization Program (NGSP) has now ensured that most laboratories in the U.S. perform the assays using standardized controls and report glycated hemoglobin results in a manner traceable to the assay used in the Diabetes Control and Complications Trial (DCCT) (12). These development s have improved as say performance and now allow caregivers and patients to compare reported results obtained among laboratories. Additional studies have suggested that the A1C may assist in diagnosing diabetes (13–17). Finally, data from major clinical trials that tested whether the progression from IGT to diabetes could be delayed or prevented by a treatment intervention have produced concordant results: intensive lifestyle modification (nutritional and exercise interventions) (18,19), metformin (19,20), and acarbose (20,21) were effective to variable degrees. In addition, a thiazolidinedione drug (troglitazone) reduced the incidence of diabetes in high-risk women with prior gestational diabetes (22). An inherent difficulty in the diagnosis of diabetes is the present lack of an identified unique qualitative biological marker that separates all people with diabetes from all nondiabetic individuals. The closest such characteristic for practical purposes is diabetic retinopathy, but this suffers from the obvious defect that in most diabetic patients, retinopathy usually becomes evident years after the recognized onset of diabetes. The lack of a suitable, unique marker of diabetes has led to reliance on the metabolic abnormality historically associated with the disease, i.e., hyperglycemia (as measured by the FPG or 2-h PG) as the most useful diagnostic test. The selection of diagnostic cut points for these tests rests on two ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●