Catch-22

In response to the article by Rohlfing et al.(1), in which HbA_lctesting was suggested as a suitable screening test for undiagnosed diabetes,Herman et al. (2) took issue by relying on the 2-h glucose value on the oral glucose tolerance test (OGTT) of 11.1 mmol/l (200 mg/dl) as the “gold standard” for the diagnosis of diabetes, as previously described by many other studies evaluating the fasting plasma glucose concentration as the diagnostic criterion. We need to look closely at how this gold standard was initially selected and to reveal its subsequent relationship to HbA_lc levels. A total of 1,213 subjects were given OGTTs and followed for the development of retinopathy over the next 3-8 years (3). Of these subjects, 77 developed retinopathy, and the gold standard for the diagnosis was based on their 2-h glucose values. Analyzing the Third National Health and Nutrition Examination Survey data set, my colleagues and I have shown that ∼70% of subjects with 2-h glucose values of 11.1-13.3 mmol/l(200-239 mg/dl) on the OGTT had normal HbA_lc levels(4). Because I believe that the diagnosis of diabetes is untenable in a person with a normal HbA_lclevel, this raises serious questions about the validity of the OGTT gold standard, which is based on the results of only 77 subjects. After all, a number of prospective studies have clearly demonstrated that the microvascular complications of diabetes are associated with elevated HbA_lc levels and that intervening to lower these values results in less complications, and as pointed out by Rolfing et al.(5), there are no data“suggesting that normoglycemic individuals are at significant risk for development of diabetic complications, as long as GHb levels remain within the nondiabetic range.” Are we not in a catch-22 situation by comparing diagnostic criteria for the diagnosis of diabetes with a glucose standard that is associated with a normal long-term index of glycemia in up to 70% of individuals?