An Alternative Approach to the Diagnosis of Diabetes With a Review of the Literature

T wo thoughtful articles in the May 1994 issue of Diabetes Care argued the case for screening for type II diabetes (1, 2). Harris and Modan (1) pointed out that 1) large population surveys repeatedly show that approximately one-half of people with type II diabetes are undiagnosed; 2) type II diabetes (i.e., hyperglycemia) is present for ~10 years before the diagnosis is made; 3) complications are often present at the time of diagnosis; 4) diabetes (of which type II accounts for 90% of cases) exacts a dreadful toll on the population (e.g., 15% of all blindness, 35% of all end stage renal disease, 50% of all nontraumatic lower extremity amputations, >100 billion dollars annual cost); 5) it is well established that hyperglycemia is the proximate cause of the microvascular (retinopathy and nephropathy) and neuropathic complications of diabetes; and 6) early intervention (e.g., diet, exercise, medications) is helpful in reducing hyperglycemia. Knowler (2) discussed the general principles of screening and made the following points that are pertinent for diabetes. First, hyperglycemia is a continuum, and therefore the choice of cutoff values for diagnosis is somewhat arbitrary. Second, screening for diabetes is unusual because, depending on the test(s) chosen, the screening test may also be the diagnostic one. Third, as for all diseases, the screening test should have high test-performance characteristics, i.e., sensitivity, specificity, and predictive value. Finally, in a nonresearch setting, relatively stringent criteria should be selected to maximize the chance that detected subjects will benefit from therapy. Interestingly, Harris and Modan (1) concluded that the oral glucose tolerance test (OGTT) should be used as the primary screening (and diagnostic) method, whereas Knowler (2) concluded that a glycated hemoglobin level measurement should be the method of choice. BACKGROUND FOR DIAGNOSTIC CRITERIA — Before 1979, there were many different criteria for interpreting OGTT results (3) and no consensus existed regarding the best cutoff points for diagnosing diabetes. Studies performed in the 1970s and 1980s (4-7) evaluated the association between 2-h post-glucose load values (two studies [6,7] also assessed fasting plasma glucose [FPG] concentrations, and in one, glycated hemoglobin levels were also compared [7]) and the subsequent development of the microvascular complications of diabetes. These complications, especially diabetic retinopathy, are considered to be specific for diabetes. Two of these studies (4,5) evaluated patients who had abnormal 2-h capillary blood glucose values after administration of 50 g of oral glucose (fasting values were not considered). The patients were classified as either diabetic (2-h blood glucose ^200 mg/dl [11.1 mmol/1]) or "borderline" diabetic (2-h blood glucose 120-199 mg/dl [6.7-11 mmol/1]) and were followed for 5-8 years with ophthalmoscopic examination through dilated pupils to detect diabetic retinopathy. Diabetic retinopathy was defined in these studies as the presence of vascular lesions, such as microaneurysms alone (small red dots) or obvious hemorrhage with or without