The reagent-strip method for estimating blood glucose concentration
Herman Kaplan, MD, DDS, San Francisco
By use of a new rapid stick method, Dextrostix, for estimating blood glucose, 100 selected patients were screened for diabetes. There were ten positive responses, and seven of the subjects were confirmed as diabetic and are receiving treatment. Dextrostix is a method that should be incorporated in the armamen tarium of the dental student, the dental col lege, and the practicing dentist.
In 1964, Dextrostix* was introduced as a rapid method to estimate blood glucose. Dextrostix are reagent strips of cellulose impregnated with glu cose oxidase and a chromogen-indicator system and covered by a semipermeable membrane. A drop of blood may be obtained from the finger tip or earlobe or heel, or venous blood may be used. The semipermeable membrane acts to pro-
duce a filtrate of the blood that reacts with the glucose oxidase. Glucose in the filtrate is oxidized to gluconic acid and hydrogen peroxide. The amount of hydrogen peroxide evolved is propor tional to the glucose concentration. The peroxide oxidizes the indicator system to produce a color that is compared with a standardized color chart. This chart comprises seven color blocks ranging from shades of gray to blue-purple, which cor respond to a glucose concentration of 40 to 250 mg./100 ml. of blood. The enzyme system is specific for glucose. Technic The technic is uncomplicated. A drop of capillary or venous blood is applied to the reagent area on the printed side of the strip, an area 11 to 12 mm. in length. The strip is then set aside for exactly 60 seconds. After the blood is washed off by use of a jet of tap water from a wash bottle, the resulting color is compared with the standards on the side of the reagent stick container, and the blood glucose concentration is estimated. The values for in-between colors can be interpolated. One should use a large drop of blood, wait 1 minute, wash off the blood completely, and then 1261
compare the color with the chart immediately. Failure to follow these precautions may cause variances in color and inaccurate interpretation. Repeated use of the strips results in greater ease of handling and color interpretation.
History of technics After the introduction of this method of measur ing blood glucose, many investigators began to compare results of the stick method with quan titative chemical methods by use of the same blood sample. Some observers agreed that there was good correlation but that the level of corre lation varied. Cohen1 thought that with further ex perience the Dextrostix method would take the place of laboratory methods as urine clinitest had done in the management of some diabetics and screening surveys. Beckett and Cook2 and MacKay, Gordon, and Neilson3 were not so enthu siastic. Alberti, Middleton, and Caird4 thought that Dextrostix underestimated blood glucose in all parts of the range from 16 to 33 percent. They thought that the color blocks should be narrowed to three to encompass the low, middle, and high ranges. Beckett and Cook2 came to the same con clusion. Strip estimates were most accurate at the high and low concentration of blood sugar in all surveys. A survey of many of the reports on this new method are probably best summarized by Joyner.5 After comparing the results with a quan titative laboratory method, he thought that the test was suitable for application in an occupa tional health program. He concluded that the test was not designed to replace conventionl precise methods and should not replace them. The advantages of the stick method indicated that it might be of value in dentistry. Three pos sibilities suggested for its use were as follows: ■ Screening of patients at the dental college to diagnose diabetes. ■ Checking the status of controlled diabetics to determine the relation to dental disease and to encourage revisits to their physicians if necessary. ■ Research into abnormalities of glucose con centration and oral disease. In the past, a sample of urine was brought to the examination by the patient and tested if dia betes was suspected. This method is still in use. Urine-testing is a cumbersome and unreliable 1 262 ■ JADA, Vol. 74, M ay
1967
method of detecting disease. Diabetes may be present in persons without, glycosuria and may be absent in persons with glycosuria. In a recent study of 392 people without gly cosuria, diabetes was detected in 15 percent after appropriate blood studies. Conversely, after study324 people with glycosuria, 29.9 percent were found not to have the disease.6 The latter figure represents the difficulties in equating glycosuria with diabetes mellitus. Hyperglycemia and glyco suria occur in patients with many conditions and do not necessarily signify diabetes. Alimentary glycosuria, renal glycosuria, adrenal tumors, brain injuries, infections, and tumors are only a few of the pathologic conditions that may be implicated. Many clinicians and investigators and the American Diabetes Association think that urine tests are unreliable for screening: “A negative urine test even after a full meal does not rule out diabetes. A blood test two hours after a heavy carbohydrate meal or ingestion of 75 to 100 grams of glucose provides the greatest reliability. In suspected cases, a glucose tolerance test is used to confirm the diagnosis.”8 Because of the information available, it was felt that the Dextrostix test provided a low-cost, quick method with reasonable accuracy and pa tient comfort. It could easily be done by the dental student in the examining room. A small pilot project was started at the dental college to evaluate the usefulness of the method. The com mercial product was used. An unprepared patient was to have a Dextro stix test by use of fingertip blood if he fulfilled any of the requirements that follow: 1. Family history of diabetes. 2. Overt symptoms of diabetes. 3. Over 45 years of age. 4. Obesity. It was thought that these criteria would pro duce the greatest yield. In a later study, a true mass screening would test every patient that reg istered at the clinic. Persons in the aforementioned categories were asked when and what they had eaten. If it was morning and the patient had not eaten since evening, he was classified as fasting. If the patient had eaten a fairly heavy carbo hydrate meal, he was classified as postprandial. If the patient had eaten at 8 a . m . and was tested at 10 a . m . , he was classified as 2-hour postpran dial. If the patient had eaten a small meal, he was
Toble ■ Result of screening
100 patients
(patients with
positive results)
P a tie n t
A ge
Sex
D e xtro stix reading
Reason fo r te s t
L ab o ra to ry te s t
Disposition
39
F
2 -h o u r postp ran d ia l blood sugar, 140 mg.
D iabetic sister
No la b o ra to ry test
Lost to fo llo w -u p
68
F
Fasting blood sugar, 130 mg.
Over 45 years o f age
Fasting blood sugar, 142 mg.
Referred to physician, oral m edica tio n, d ie t
70
M
3 -h o u r postprandial blood sugar, 150 mg.
Over 45 years o f age
2 -h o u r p ostp ran d ia l blood sugar, 150 mg.
Referred to physician, d ie t
49
M
2 -h o u r postp ran d ia l blood sugar, 250 mg.
Over 45 years o f age, obese
2 -h o u r p ostp ran d ia l blood sugar, 330 mg.
A tte n d in g d ia b e tic c lin ic
63
F
4 -h o u r postp ran d ia l blood sugar, 150 mg.
Over 45 years o f age, obese
Fasting blood sugar, 133 mg.
Referred to physician, d ie t
82
M
1.5 -h o ur postp ran d ia l blood sugar, 175 mg.
Over 45 years o f age
No la b o ra to ry test
Did n ot w an t fu rth e r testing
75
F
2 -h o u r postp ran d ia l blood sugar, 175 mg.
Over 45 years o f age, hype rten sion *
2 -h o u r p ostp ran d ia l blood sugar, 353 mg.
Referred to physician, o ral m edica tio n, d ie t
54
F
Fasting blood sugar, 150 mg.
Over 45 years o f age
2 -h o u r p ostp ran d ia l blood sugar, 283 mg.
Referred to physician, oral m edica tio n, d ie t
58
F
Fasting blood sugar, 140 mg.
Over 45 years o f age
2 -ho u r p ostp ran d ia l blood sugar, 145 mg.
Referred to physician, d ie t
53
F
1-hour p ostprandial blood sugar, 160 mg. (d o u b tfu l)
Over 45 years o f age (sent as check)
2 -h o u r p ostp ran d ia l blood sugar, 81 mg.
N eg a tive
*T h is p a tie n t had a p ostoperative den tal in fe c tio n a t th e in itia l te s t, b u t the in fe c tio n cleared a fte r co ntro l.
not included in the test. If the fasting or the 2-hour (or greater) postprandial subject had blood sugar of 130 mg. or more, he was referred to a laboratory for further testing. In subjects classified between fasting and 2-hours postpran dial, 150 mg. was the limit. The results are shown in the table.
Results and discussion In 100 unprepared clinic patients who were tested with Dextrostix, ten were over the set limits and were sent for a definitive laboratory test. Usually, a 2-hour postprandial classification was requested before further tests were ordered, but in some instances the physician ordered a fasting blood sugar determination. Two persons refused further testing and eight patients were tested. Of the eight persons tested, seven were not in the normal range, so they underwent fur ther study. All seven are receiving treatment. Be cause seven of the ten persons over the set limits were not found in the normal range after testing, we interpreted this result as a 7 percent dis covery rate, although we did not have the oppor tunity to test the two persons who refused. This result is also weighted because we did not test
everyone on a random basis. This sample is small, but the results were significant. A patient who was suspected after the Dextro stix test was informed but not alarmed about the implications. It was thought that further expla nation should be given by the patient’s physician after more definitive testing. Most of the patients were sent to a private laboratory unless someone objected. Estimates of the number of persons with un diagnosed diabetes in our population range from 1.4 to 2 million.8,9 In a study of 8,709 people, Kent and Leonards10 used a carbonated drink containing 75 Gm. of glucose. With a 2-hour postprandial blood analysis, a 4.5 percent inci dence of diabetes was found after confirmatory testing by glucose-tolerance examination. This result compares with the conclusion of Doctor McDonald, chief of the diabetes and arthritis program of the U.S. Public Health Service, that a 4.4 percent incidence of the population will be positive to screening. Examination of the litera ture indicates that the screening tests used are increasingly those that use blood glucose. Because of the number of people who might visit their dentists or a dental college, there would be an increase in the number of patients screened if testing were done by dentists.
Kaplan: REAGENT-STRIP M ETH O D FOR E S T IM A T IN G BLOOD GLUCOSE C O N C E N TR A TIO N
■ 1263
The value of early detection of diabetes has been emphasized in the literature. It is hoped that the late sequelae of the disease might be averted by early detection and well-controlled treatment. Diabetes discovered in the early phase might respond successfully to easy and simple treatment so that change of eating habits, insulin, or oral medication might not be necessary.11 There were other valuable aspects to the Dex trostix program. Persons who were known dia betics were also treated at the clinic. Some were taking therapy, whereas others were controlled by diet. It was simple to check on their status. Many patients who were confronted with results that indicated severe hyperglycemia admitted that they had not been back to their physicians and were remiss about checking their urine. At least six controlled patients were sent to their physicians with the results of their stick test. Dextrostix thus lends itself to patient education and persuasion. A patient at the examining room or one of the clinics could have what appears to be an attack of syncope. In those patients with a history of diabetes, it would help to know if they might be in a diabetic coma or insulin shock. The best and fastest test is the blood sugar test. The timely use of Dextrostix might diagnose the situation while a colleague examined the patient or called for assistance. The preceding material presents the advantages of incorporating a blood sugar estimating device in the armamentarium of the dental student, the dental college, and the practicing dentist. Research
1264 ■ JA D A , V o l. 74, M a y 1967
projects might also initiate the use of this method. In the public health field of screening and educa tion, the dentist may perform a valuable service as part of the health team.
Doctor Kaplan is an assistant professor o f oral sur gery, College o f Physicians and Surgeons, U niversity of the Pacific, School o f D e ntistry, San Francisco, 9 4 1 0 3 . *A m e s Co., Inc., E lkhart, Ind. 1 . Cohen, S. L.; Legg, S., and Bird, R. Bedside m eth od o f blood-glucose estim ation. Lancet 2 :8 8 3 Oct. 24, 1964. 2. Beckett, A . G., and Cook, I. J. Y . Letters to the e ditor. D e xtro stix estim ations o f blood-sugar. Lancet 2:5 91 Sept. 18, 1965. 3. M acK ay, N .; Gordon, A ., and Neilson, J. M . O b server error in d e xtro stix estim ations o f blood sugar. Lancet 2 :2 6 9 A u g . 7, 1965. 4 . A lb e rti, K. G.; M id d le to n , G. G., and Caird, F. I. The accuracy o f d e xtro stix in th e e stim ation o f blood sugar. Lancet 2 :3 1 9 A u g . 14, 1965. 5. Joyner, R. E. R eagent-strip m ethod o f bloodglucose d e term in a tion . J Occup M ed 7 :5 1 2 O ct., 1965. 6. Z a m m it M aem pel, J. V . Diabetes in M a lta . L an cet 2:1 197 Dec. 1 1, 1965. 7. D extrostix. Fed L e tt Drugs T he r 6 :9 3 Nov. 20, 1964. 8. Testing fo r diabetes. In From the note book. U.S. N aval M ed New L e tt 4 6 :1 5 Nov. 19, 1965. 9. Editorial. Diabetes week. J A M A 1 9 4 :6 6 4 Nov. 8, 1965. 10. Kent, G. T ., and Leonards, J. R. Mass screening fo r diabetes in a m etro p o lita n area using fin g e r blood glucose a fte r a carbohydrate load. Diabetes 1 4 :2 9 5 M ay, 1965. 1 1. Editorial. Diabetes and th a nksg iving . New Eng J M ed 2 7 3 :987 Oct. 2 8 , 1965.