Continuous Glucose Monitoring Roadmap for 21st century diabetes therapy DAVID C. KLONOFF, MD, FACP C ontinuous glucose monitoring pro- vides maximal information about shifting blood glucose levels throughout the day and facilitates the making of optimal treatment decisions for the diabetic patient. This report discusses continuous glucose monitoring in terms of its purposes, technologies, target pop- ulations, accuracy, clinical indications, outcomes, and problems. In this context, the medical literature on continuous glu- cose monitoring available through the end of 2004 is reviewed. PURPOSES — Continuous glucose monitoring provides information about the direction, magnitude, duration, fre- quency, and causes of fluctuations in blood glucose levels. Compared with con- ventional intensified glucose monitoring, defined as three to four blood glucose measurements per day, continuous mon- itoring provides much greater insight into glucose levels throughout the day. Con- tinuous glucose readings that supply trend information can help identify and prevent unwanted periods of hypo- and hyperglycemia. The difference between an intermit- tent and a continuous monitor for moni- toring blood glucose is similar to that between a regular camera and a continu- ous security camera for monitoring an im- portant situation. A regular camera takes discrete, accurate snapshots; its pictures do not predict the future; it produces a small set of pictures that can all be care- fully studied; and effort is required to take each picture. A continuous security cam- era, on the other hand, takes multiple, poorly focused frames; displays a sequen- tial array of frames whose trend predicts the future; produces too much informa- tion for each frame to be studied carefully; and operates automatically after it is turned on. The two types of blood glucose monitors differ in much the same way: 1) an intermittent blood glucose monitor measures discrete glucose levels ex- tremely accurately, whereas a continuous monitor provides multiple glucose levels of fair accuracy; 2) with an intermittent monitor, current blood glucose levels do not predict future glucose levels, but with a continuous monitor, trends in glucose levels do have this predictive capability; 3) with an intermittent monitor, it is easy to study every measured blood glucose value over most time periods, but with a continuous monitor, too many data are generated to study all data points; and 4) an intermittent blood glucose monitor re- quires effort to operate, whereas a contin- uous monitor does not. Returning to the camera analogy, just as the best tool for closely monitoring a situation when the outcome is important often may be a con- tinuous security camera rather than a reg- ular camera, likewise the best way to monitor diabetes often may be a continu- ous glucose monitor (CGM) rather than an intermittent monitor. TECHNOLOGIES — Five CGMs have been approved by the U.S. Food and Drug Administration (FDA) for use in the U.S. or carry CE marking for use in Europe. They are the Continuous Glucose Moni- toring System Gold (CGMS Gold; Medtronic MiniMed, Northridge, CA) (1), the GlucoWatch G2 Biographer (GW2B; Cygnus, Redwood City, CA) (2), the Guardian Telemetered Glucose Mon- itoring System (Medtronic MiniMed) (3), the GlucoDay (A. Menarini Diagnostics, Florence, Italy) (4), and the Pendra (Pen- dragon Medical, Zurich, Switzerland) (5). A sixth monitor, whose premarket ap- proval application has been submitted to the FDA, is the FreeStyle Navigator Con- tinuous Glucose Monitor (Abbott Labora- tories, Alameda, CA) (6). The currently available CGMs mea- sure blood glucose either with minimal invasiveness through continuous mea- surement of interstitial fluid (ISF) or with the noninvasive method of applying elec- tromagnetic radiation through the skin to blood vessels in the body. The technolo- gies for bringing a sensor into contact with ISF include inserting an indwelling sensor subcutaneously (into the abdomi- nal wall or arm) to measure ISF in situ or harvesting this fluid by various mecha- nisms that compromise the skin barrier and delivering the fluid to an external sen- sor (7). These ISF measurement technol- ogies are defined as minimally invasive because they compromise the skin barrier but do not puncture any blood vessels. After a warm-up period of up to 2 h and a device-specific calibration process, each device’s sensor will provide a blood glu- cose reading every 1–10 min for up to 72 h with the minimally invasive technol- ogy and up to 3 months with the nonin- vasive technology. Results are available to the patient in real time or retrospectively. Every manufacturer of a CGM produces at least one model that sounds an alarm if the glucose level falls outside of a preset euglycemic range. The available and likely soon-to-be-available CGMs are compared in Table 1. Based on their mechanisms, specifica- tions, and performance records, each CGM offers a particular set of features that are attractive for patients and clinicians. Table 2 presents three of these features for each available and likely soon-to-be- available CGM. ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From the Mills-Peninsula Health Services Diabetes Research Institute, San Mateo, California. Address correspondence and reprint requests to David C. Klonoff, MD, Mills-Peninsula Health Services Diabetes Research Institute, 100 S. San Mateo Dr., Rm. 3124, San Mateo, CA 94401. E-mail: klonoff@itsa. ucsf.edu. Received for publication 15 December 2004 and accepted in revised form 31 January 2005. Abbreviations: CGM, continuous glucose monitor; CGMS, continuous glucose monitoring system; EGA, error grid analysis; FDA, U.S. Food and Drug Administration; GW2B, GlucoWatch G2 Biographer; ISF, interstitial fluid; ISO, International Organization for Standardization; RAD, relative absolute difference. A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. © 2005 by the American Diabetes Association. Reviews/Commentaries/ADA Statements R E V I E W A R T I C L E DIABETES CARE, VOLUME 28, NUMBER 5, MAY 2005 1231 Downloaded from http://diabetesjournals.org/care/article-pdf/28/5/1231/566184/zdc00505001231.pdf by guest on 11 December 2022