Robert J. Heine

OBJECTIVE: The A1C assay, expressed as the percent of hemoglobin that is glycated, measures chronic glycemia and is widely used to judge the adequacy of diabetes treatment and adjust therapy. Day-to-day management is guided by self-monitoring of capillary glucose concentrations (milligrams per deciliter or millimoles per liter). We sought to define the mathematical relationship between A1C and average glucose (AG) levels and determine whether A1C could be expressed and reported as AG in the same units as used in self-monitoring. RESEARCH DESIGN AND METHODS: A total of 507 subjects, including 268 patients with type 1 diabetes, 159 with type 2 diabetes, and 80 nondiabetic subjects from 10 international centers, was included in the analyses. A1C levels obtained at the end of 3 months and measured in a central laboratory were compared with the AG levels during the previous 3 months. AG was calculated by combining weighted results from at least 2 days of continuous glucose monitoring performed four times, with seven-point daily self-monitoring of capillary (fingerstick) glucose performed at least 3 days per week. RESULTS: Approximately 2,700 glucose values were obtained by each subject during 3 months. Linear regression analysis between the A1C and AG values provided the tightest correlations (AG(mg/dl) = 28.7 x A1C - 46.7, R(2) = 0.84, P < 0.0001), allowing calculation of an estimated average glucose (eAG) for A1C values. The linear regression equations did not differ significantly across subgroups based on age, sex, diabetes type, race/ethnicity, or smoking status. CONCLUSIONS: A1C levels can be expressed as eAG for most patients with type 1 and type 2 diabetes.

Type 2 diabetes is now epidemic. In the U.S., there has been a 61% increase in incidence between 1990 and 2001 (1). There are currently 1.5 million new cases per year, and the prevalence in 2005 was almost 21 million (2). The epidemic has affected developed and developing countries alike, and the worldwide prevalence of diabetes is projected to increase dramatically by 2025 (3). The increase in type 2 diabetes is related to lifestyle changes that have resulted in overweight, obesity, and decreased physical activity levels. These environmental changes, superimposed on genetic predisposition, increase insulin resistance, which, in concert with progressive β-cell failure, results in rising glycemia in the nondiabetic range. In addition to the risk for diabetes, insulin resistance and impaired insulin secretion are accompanied by a host of major cardiovascular disease (CVD) risk factors including hypertension and dyslipidemia. Further reduction in insulin secretion over time results in increasing glycemia and the development of diabetes, which in turn is associated with the development of microvascular and cardiovascular complications. The transition from the early metabolic abnormalities that precede diabetes, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), to diabetes may take many years; however, current estimates indicate that most individuals (perhaps up to 70%) with these pre-diabetic states eventually develop diabetes (4–10). During the pre-diabetic state, the risk of a CVD event is modestly increased (11–22). With the development of diabetes, however, there is a large increase in risk for CVD, as well as for long-term complications affecting the eyes, kidneys, and nervous system. The complications of diabetes, which are the cause of major morbidity and mortality, are related to its duration, chronic level of glycemia, and other risk factors. Although clinical trials have demonstrated the effectiveness of intensive glycemic and blood pressure control to …

The epidemic of type 2 diabetes in the latter part of the 20th and in the early 21st century, and the recognition that achieving specific glycemic goals can substantially reduce morbidity, have made the effective treatment of hyperglycemia a top priority (1–3). While the management of hyperglycemia, the hallmark metabolic abnormality associated with type 2 diabetes, has historically had center stage in the treatment of diabetes, therapies directed at other coincident features, such as dyslipidemia, hypertension, hypercoagulability, obesity, and insulin resistance, have also been a major focus of research and therapy. Maintaining glycemic levels as close to the nondiabetic range as possible has been demonstrated to have a powerful beneficial impact on diabetes-specific complications, including retinopathy, nephropathy, and neuropathy in the setting of type 1 diabetes (4,5); in type 2 diabetes, more intensive treatment strategies have likewise been demonstrated to reduce complications (6–8). Intensive glycemic management resulting in lower HbA1c (A1C) levels has also been shown to have a beneficial effect on cardiovascular disease (CVD) complications in type 1 diabetes (9,10); however, the role of intensive diabetes therapy on CVD in type 2 diabetes remains under active investigation (11,12). Some therapies directed at lowering glucose levels have additional benefits with regard to CVD risk factors, while others lower glucose without additional benefits. The development of new classes of blood glucose–lowering medications to supplement the older therapies, such as lifestyle-directed interventions, insulin, sulfonylureas, and metformin, has increased the treatment options for type 2 diabetes. Whether used alone or in combination with other blood glucose–lowering interventions, the availability of the newer agents has provided an increased number of choices for practitioners and patients and heightened uncertainty regarding the most appropriate means of treating this widespread disease. Although numerous reviews on the …