The need for separate performance goals for glucose sensors in the hypoglycemic, normoglycemic, and hyperglycemic ranges.

Goals for Glucose Sensors in the Hypoglycemic, Normoglycemic, and Hyperglycemic Ranges B lood glucose monitors are an important tool for people with diabetes to assess their physiological status and allow them to properly dose themselves with medication or food. The need to adjust the amount of treatment is greatest when the blood glucose level is in the hypoglycemic range because of the risk of acute brain damage if the condition is not quickly treated. A variety of technologies are available to assist patients with detecting hypoglycemia. How accurate are the various types of technologies at detecting hypoglycemia? Are the new continuous glucose monitoring technologies as accurate as current performance guidelines for home blood glucose monitors specify? In this issue of Diabetes Care, the Diabetes Research in Children Network (DirecNet) collaborative study group concludes (1) that the GlucoWatch G2 Biographer (GW2B) and continuous glucose monitoring systems (CGMSs) do not reliably detect hypoglycemia in children and adolescents. They noted that as few as 31% of GW2B values and as few as 42% of CGMSs (including both firstand secondgeneration sensors) were within 15 mg/dl of reference serum values. When a hypoglycemia alarm value was set at 60 mg/dl, the GW2B demonstrated that the sensitivity to detect hypoglycemia was 23%, the specificity to detect hypoglycemia was 49%, and the false-alarm incidence was 51%. The two continuous glucose monitors probably performed less accurately in this DirecNet study than many clinicians would expect of new technology that has been approved by the U.S. Food and Drug Administration within the past few years. The performance statistics for glucose monitoring systems that are frequently quoted from the literature or from the package inserts of manufacturers mostly derive from studies that measure patients whose blood glucose levels can be low, normal, or high. Because most patients spend little time in a state of hypoglycemia, the majority of data points in these studies derive from the normoglycemic or hyperglycemic ranges. Data from the DirecNet study (1) and from older studies (2,3) suggest that the performance of blood glucose monitoring systems would be best evaluated if separate performance goals for hypoglycemic, normoglycemic, and hyperglycemic ranges were established. Current glucose monitoring systems, including home blood glucose monitors and continuous glucose monitors, such as the GW2B and CGMS, do not perform as accurately in the hypoglycemic range as they do in higher ranges. Five sets of criteria for blood glucose monitor performance are frequently referred to in the medical literature. They are each identified by the professional or regulatory agency that proposed them. Criteria proposed by the National Committee for Clinical Laboratory Standards (4), the American Diabetes Association (ADA) in 1987 (5) and again in 1996 (6), and the U.S. Food and Drug Administration (7) are stratified into two parts according to whether the blood glucose level is either 100 or 100 mg/dl. Criteria proposed by the International Organization for Standardization (ISO) (8) are stratified for blood glucose levels 75 or 75 mg/dl. These criteria were all developed before any continuous glucose monitors became available on the market, and it is possible that eventually alternate performance standards for glucose monitors may become developed (9). None of these agencies’ criteria, however, are stratified for the performance of blood glucose monitors during hypoglycemia, which is usually defined as a blood glucose level 50–70 mg/dl (10,11). Consumers and health care professionals need to know the performance of their blood glucose monitors, and performance information is especially important for a patient to trust that their monitor will detect hypoglycemia. It is necessary to understand the likelihood that hypoglycemia will be identified when this condition occurs as well as the likelihood that a hypoglycemic reading truly reflects a physiological state of glucose depletion in the blood, as opposed to the low number being a “false-alarm” low reading. Diagnosing hypoglycemia is the most important function of home blood glucose monitoring because this problem, if detected, can be immediately and effectively treated, preventing acute catastrophic end-organ damage. Specific performance goals for blood glucose monitors during hypoglycemia are needed because blood glucose monitors do not perform consistently over the physiological range of blood glucose levels. Evidence demonstrating the different performance of blood glucose monitors in the hypoglycemic, normoglycemic, and hyperglycemic ranges comes from studies on three different types of monitoring systems. The three types of monitors that provide virtually all currently measured home blood glucose values are 1) episodic home blood glucose monitors (multiple manufacturers), 2) the GW2B (Cygnus, Redwood City, CA), and 3) the CGMS (Medtronic MiniMed, Northridge, CA). For all three types of monitoring systems, performance is the worst in the hypoglycemic range. Thus, even when acceptable global standards are achieved by a monitoring system, the distribution of readings from the three glycemic categories can affect the overall percentage of readings that are within the target range. This diluting effect on global performance occurs because hypoglycemic readings are less often within target ranges than are readings from the euglycemic and hyperglycemic ranges. A set of data that is poor in hypoglycemic readings is more likely to achieve global performance standards than a set that is rich in hypoglycemic readings. Home blood glucose monitors, identical or similar to currently available monitors, have been recently evaluated according to their performance during hypoglycemia compared with normoglycemia or hyperglycemia, in four reports E D I T O R I A L ( S E E D I R E C N E T S T U D Y G R O U P , P . 7 2 2 )