The Diagnosis of Diabetes Is Changing: How Implementation of Hemoglobin A1c Will Impact Clinical Laboratories

Abstract

The earliest known description of diabetes mellitus is in the Papyrus of Ebers by Hesy-Ra in 1552 BC. Since then, we have learned that diabetes consists of a group of metabolic disorders, all of which produce hyperglycemia. The relatively specific complications of diabetes (affecting the eyes, kidneys, and nervous system) and the high prevalence (estimated at approximately 40 × 106 in the US and approximately 250 × 106 worldwide) combine to make it a substantial public health problem. Our comprehension of the pathophysiology of the disease is limited, however, and no biological marker is known to be unique to diabetes. Diagnosis has been based exclusively on the demonstration of increased glucose concentrations, initially in urine and subsequently in the blood. Therefore, the recent publication of the International Expert Committee report on the diagnosis of diabetes (1), which recommends the use of hemoglobin A1c (Hb A1c)1 rather than glucose for the diagnosis of diabetes, represents a dramatic change that deserves reflection. Hyperglycemia has been the sole diagnostic criterion for diabetes since the development of blood glucose assays 100 years ago. Measurement of the response to a metabolic challenge in the form of the oral glucose tolerance test (OGTT) was initially used. The cutoff was 2 SDs above the mean glucose concentration in healthy individuals. This strategy was limited by a lack of standardization in both the performance and the interpretation of the test and its poor reproducibility. In 1979, the National Diabetes Data Group proposed criteria that were derived from the distribution of glucose concentrations in populations with a high prevalence of diabetes (2). The diagnostic criteria were ( a ) classic symptoms of diabetes with an unequivocal increase in plasma glucose, ( b ) a venous fasting plasma glucose (FPG) concentration ≥7.8 mmol/L (140 mg/dL), or ( c ) a …