Hemoglobin A1c to Diagnose Diabetes: Why the Controversy over Adding a New Tool?

Abstract

Perhaps diabetes is a bit like obscenity: We know it when we see obvious cases, but it is difficult to develop one definition that encompasses the entire spectrum of disease. Hyperglycemia exists on a continuum, and persons destined to develop type 2 diabetes progress along this continuum over time, from having blood glucose concentrations that are physiologic, to those in some intermediate but asymptomatic range, to glucose concentrations that are frankly increased and often associated with acute symptoms and chronic complications of the disease. But at what point does an individual have blood glucose concentrations, or other measures of glycemia, that cross the line from no diabetes to diabetes? Several decades ago, the National Diabetes Data Group (NDDG)2 developed consensus diagnostic criteria for diabetes that were based on population distributions of glucose concentrations (even though for most populations there is not a bimodal distribution for glucose clearly dividing diseased from nondiseased individuals) and based on the relative risk of decompensation to overt or symptomatic diabetes. These criteria, including a fasting plasma glucose (FPG) concentration of 140 mg/dL (7.8 mmol/L) or greater and a 2-h plasma glucose concentration during a 75-g oral glucose tolerance test (OGTT) of 200 mg/dL (11.1 mmol/L) or greater, became the worldwide standard for diagnosing diabetes. Even in 1979, however, the NDDG noted that “there is no clear division between [those with diabetes] and [those without diabetes] in the FPG concentration or their response to an oral glucose load” and acknowledged that the cutpoints chosen were arbitrary (1). In 1997, the Expert Committee on Diagnosis and Classification of Diabetes Mellitus was convened to revisit the criteria for diagnosing diabetes. This group examined population data for retinopathy in 3 distinct populations and noted that for FPG, 2-h postload glucose (PG), and hemoglobin A1c (Hb A …