500 DIABETES CARE, VOLUME 23, NUMBER 4, APRIL 2000 D iabetic ketoacidosis (DKA) is a serious complication of diabetes that is associ- ated with considerable mortality and m o rb id ity. Although the mortality rate diminished from 44% in the 1930s (1) to 16% in the 1970s (2) and to 3–5% in the 1980s (3,4), little improvement in these rates has been evident in recent years, and the incidence of DKA remains 20% in patients 65 years of age (5). Delays in the diagnosis and treatment of DKA are associ- ated with an increase in morbidity and mor- tality (6). The diagnosis of DKA is not always ea sy. Between 1 and 8% of patients are ketoacidotic without significant hypergly- cemia (6,7). Ketostix (Bayer Diagnostics, Stoke Poges, Slough, U.K.) measure urinary acetoacetate but not - hyd ro xyb ut yra t e ( -HBA), which is the predominant ketone body in DKA, and Ketostix may give false- negative results even if blood is tested. Lab- o ra to ry measurement of -HBA is not routinely available and takes too long to be of practical use in the emergency diagnosis and management of DKA. A combined glu- cose and ketone sensor that produces an electrical current pro p o rtional to blood -HBA concentration has been developed (MediSense/Abbott Laboratories, Abingdon, U.K.) (Fig. 1). By using a 10-μl capillary blood sample, this hand-held sensor pro- duces -HBA results within 30 s. The aim of this study was to compare the accuracy and precision of the ketone sensor against an established laboratory enzymatic ref erence method (Pro c ed ure No. 310-UV 1994; Sigma Diagnostics, St. Louis, MO). RESEARCH DESIGN AND M E TH O D S — Two groups of patients who were suspected of having abnorma li- ties of ketone metabolism were studied: patients with suspected DKA (group D) and patients treated with a very-lo w-ca lo r ie diet who attend a weight management clinic (group W). All subjects gave their info rmed consent, and the local ethics committee approved the study. For group D, 500-μl capillary blood or 2-ml venous whole blood samples were col- lected during routine management. For group W, a single 500-μl capillary blood sample was obtained during the clinic visit. Sensor measurements were made in dupli- cate within 20 min for capillary samples and at the earliest opportunity (always within 12 h) for venous samples. Veno us samples were refrigerated at 4°C before test- ing. One res ea rcher (K.L.T.) perfo rmed all mea s urements. An electrochemical strip was ins erted into the sensor to which 10 μl of whole blood were applied (Fig. 1). The -HBA, in the presence of hydro xybut yr a t e dehydrogenase, was oxidized to acetoacetate with the concomitant reduction of NAD t o NADH. The NADH was reoxidized to NAD by a redox mediator, and the current generated was directly pro po rtional to the -HBA concentration. After 30 s, the -HB A concentrations (mmol/l) were displayed. Hemoglobin was measured using a HemoCue AB analyzer (Angelholm, Swe- den); room temperature and humidity were rec o rded using a Vaisala meter (Va isa la , S uffolk, U.K.). After initial testing with the ketone sensor, the samples were cen- trifuged, and the plasma was stored at 20°C pending analysis with an enzymatic la b o ra to ry method (Cobas Fara; Roche Diagnostics, Welwyn Garden City, U.K.). To evaluate the precision of the ketone s ens o r, three venous whole blood samples with -HBA concentrations of 1, 1.1–3.0, and 3.1–6.0 mmol/l as determined by the la bo r a t o ry method were tested 20 times each within a 30-min period. Accuracy was assessed by comparing the sensor res ult with the reference method. F rom the Departments of Diabetes and Endocrinology (H.A.B., T.L.D., J.P.N.), and Clinical Biochemistry ( K .L .T.), Hope Hospital, Salford; and the Medical Statistics Unit (S.H.), Department of Mathematics and Sta- tistics, Lancaster University, Lancaster, U.K. Ad d ress correspondence and reprint requests to J.P . New, Department of Diabetes and Endocrinology, Hope Hospital, Stott Ln., Salford M6 8HD, U.K. Received for publication 28 June 1999 and accepted in revised form 7 December 1999. H.A.B. and K.L.T. are employed through an educational grant from MediSense; H.A.B., K.L.T., T.L.D., and J .P .N. have received resea rch grant funding from MediSense; and T.L.D. and J.P .N. have received consulting fees from MediSense, which manufactures the sensor discussed in this article. Abbreviatio ns : -HBA, - hyd roxybutyrate; CV, coefficient of variation; DKA, diabetic ketoacidosis. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Evaluation of an Electrochemical Sensor for M easuring Blood Ketones O R I G I N A L A R T I C L E O BJE C TI V E — To evaluate the perf ormance of a hand-held ketone sensor that is able to measu re blood -h ydroxybutyrate ( -HBA) concentrations within 30 s in patients with diabetic ketoacidosis (DKA) and patients who attend a weight management clinic. RESEARCH DESIGN AND M ETHODS — Two groups of patients were studied: 19 patients admitted with DKA and 156 patients attending a weight management clinic. Paired capillary and venous whole blood samples were measured using the ketone sensor and also using an enzymatic laboratory ref erence method. RE SU LTS — The ketone sensor accurately measured -HBA concentrations in patients with DKA (limits of agreement 0.9 to 1.0 mmol/l) or starvation-induced ketonemia (limits of agreement 0.5 to 0.5 mmol/l). C O N C L U SI O N S — This ketone sensor accurately measures whole blood -HBA concen- trations within 30 s. Diabetes Care 23:500–503, 2000 HILARY A. BYRNE, MRCP KENNETH L. TIESZEN, PHD SALLY HOLLIS, MSC TIM L. DORNAN, FRCP J OHN P. N EW , MRCP Emerging Treatm ents a nd T e c h n o l o g i e s