June 1976

TheJournalofPEDIATRICS

943

Good diabetic c o n t r o l - a study in mass delusion The terms "diabetic control" and "diabetic management" are not synonymous. Diabetic control implies normal glucose metabolism, typically monitored by periodic determinations of plasma glucose and urine redueing sugar concentrations. A group of 220 diabetic children attending a camp complied 74% o f the time with the request to collect and test their urine for URS. Fifty percent of random URS values determined by the children varied from those obtained on the same specimens of urine by laboratory technicians. Good diabetic control defined as URS < 25 gin~24 hours was found in 18 o f 54 children. "'Good control" as indicated by the fasting plasma glucose concentration was found in 11 o f 18 children with URS < 25 gm/24 hours. However, seven of those 11 had poor control applying the same criteria to a second PG on the same day. Unreliable testing of urine by patients, inconsistent correlations between the 24-hour excretion of reducing sugar and PG, plus variability in an individual's control as defined by conflicting same-day test results indicate that these measures o f diabetic control do not refleet the true metabolic state. Consequently, they are not adequate criteria to define the degree of diabetic control. These observations, however, do not negate the usefulness of URS and PG in the management o f diabetes mellitas.

John I. Malone, M.D.,* John M. Hellrung, M.D., Edward W. Malphus, M.D., T a m p a , Fla.,

Arian L. Rosenbloom, M.D., Ante Grgic, M.D., and

F. T h o m a s W e b e r , M . D . , Gainesville, Fla.

" D i A B E T I C C O N T R O L " is a r e c u r r e n t topic of c o n c e r n and interest of patients who have diabetes, their families, physicians, and medical investigators. The objective of diabetic control is to restore normal metabolic homeostasis in patients with diabetes by using carbohydrate metabolism as the index? Interest in this subject relates to its possible importance in the prevention of the vascular complications of diabetes. Conflicting reports have suggested that good diabetic control minimizes or prevents diabetic complications, ~-5 whereas others indicate that control apparently makes no difference. 6-8 The confusion surrounding the importance o f diabetic control has led to divergent philosophies of diabetic management2 Is the best management of diabetes in children the

From the Division of Metabolism, Department of Pediatrics, University of South Florida, College of Medicine, and the Division of Genetics, Endocrinology and Metabolism, Department of Pediatrics, University of Florida. *Reprint address: Department of Pediatrics, College of Medicine, Universityof South Florida, Tampa, Fla. 33620.

achievement of good diabetic control as presently defined? The determinants of diabetic control traditionally have been: (1) the blood glucose concentration (fasting and postprandial) and (2) the degree of glucosuria, as determined in the physician's office as well as that recorded in

See related article, p. 1074. Abbreviations used PG: p!asma glucose concentration URS: urine reducing sugar concentration FPG: fasting plasma glucose concentration the patient's record of urine tests performed at home. 9 The control criteria in common use are listed in Table I. The question that has not been critically evaluated is whether the carbohydrate metabolism in individuals with good diabetic control as defined by these criteria is different from that in individuals said to have poor control. This question was examined by measuring PG and URS in a

Vol. 88, No. 6, pp 943-947

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Malone et al.

The Journal of Pediatrics June 1976

Table I. Criteria of diabetic control (modified from data

of others*)

Excellent[ Good I Fair Fasting blood glucose < I10 mg/dl (% of blood tests) 2 hr postprandial < 150 mg/dl (% of blood tests) Urine glucose (gm/ 24 hr) Urine specimenst" free of sugar (% of urines tested) Urine acetone~ (mg/ dl)

Poor

100

85%

70%

< 70%

100

85%

70%

< 70%

0

0-25

25-50

> 100

100

75%

50%

< 50%

0

0-10

> 30

0

*References 1, 2, 13, 17. ~Five-drop Clinitest method. ~Acetest method.

Table II. The meaning_ o f tests for urine reducing

substance

Camper Compliance* Agreet LowerS Highert

656/880 336 271 49

[

% 74 51.2 41.3 7.5

*The number of children who complied with the request to collect and test a specimen of urine. t A comparison of urine test results done by the campers and the technicians.

group of children with diabetes taking part in an unmodified camping program. .1~ This allowed the evaluation of the diabetic control criteria in a setting more typical of life outside of a hospital. MATERIALS

AND

METHODS

Two-hundred-twenty boys and girls ranging in age from seven to 18 years were studied. These children had insulin-dependent diabetes varying in duration from three months to 18 years (mean 4.5 years). Fifty-four of these children cooperated completely with the study, so that their diabetic control could be evaluated more closely. Six of these 54 children had heights that were more than 2 ~D below the mean for their age? 1 Three of these were rated by the criteria described in this report as having good and three were rated as having poor control while at camp. Hypertension as defined by the Committee on Arteriosclerosis and Hypertension in Childhood of the American *The Florida Camp for Children and Youth with Diabetes; at C a m p Swan Lake, Melrose, Fla.

Heart Association1~ was not present in the study group: Only one of the 54 children studied had proteinuria (530 mg/24 hr). This same individual had growth failure and microaneurysms. Interestingly, his degree of diabetic control at camp was rated as good. All of the children took part in an active unmodified camping program and consumed self-selected portions of a nutritionally balanced diet offered as three meals and three snacks each day. '~ The insulin administration and urine testing were supervised by the medical personnel of the camp. The children routinely collected urine specimens and tested them for URS three times a day and recorded the results. They were also asked to save the first voided morning urine specimen tested and the late afternoon (2hour postprandial) specimen tested on two separate days. These specimens were then examined for URS by laboratory technicians. The degree of glucosuria was measured by both the children and the technicians in grams percent (0 to 10%) using the 1- and 2-drop Clinitest method14. I5 Each child collected urine for a single 24-hour period in individual polyethylene bottles stored on ice, The total volume was recorded and the URS determined by the Clinitest method, The completeness of the urine collection was estimated in terms of the 24-hour excretion of creatinine.10 Blood specimens were withdrawn into heparinized tubes before breakfast and two hours after eating in the afternoon. The blood samples were centrifuged immediately and the plasma analyzed f o r glucose using a Beckman glucose analyzer. All of the tests were done in duplicate at the camp immediately after collection. RESULTS A comparison of the URS recorded by the campers with those determined by the laboratory technicians is seen in Table II. Camper compliance with the request to determine the URS was 74%. The test results obtained by the children agreed with those of the laboratory technicians in 51% of the urines tested. The children reported URS that were lower than those reported by the technicians in 41% of the urines tested. These results varied by 2 g m / ~ or more in 80% of the comparative tests. The technicians, on the other hand, reported values lower than the children's in 8% of the tests with 75% of tl'/ese being a difference of 2 gm/dl or more. A complete 24-hour collection of urine was accomplished for only 54 of the 220 campers. Although the request Was strengthened by peer and medical staff coercion and supervision, only 24% of the children fully complied, as judged by the excretion of more than 15 mg of creatinine/kg body weight? ~ The 24-hour excretion of

Volume 88 Number 6

Good diabetic control

945

Table IlL Indicators of diabetic control in 54 children PG (mg/dl) 'him

Age

G.A. R.B. K.B. C.B. D.B. J.B. H.B. V.B. L.B. L.C. K.C. D.C. S.C. C.C. N.C. H.C. O.D. K.D. D.D. D.Dk. C.F. S.F. U.F: S.G. M.G. C.H. T.H. T.J. B.J. E.J. M.J. J.L. S.L. C.M. J.M. D.M. F.O. M.P. E.R. D.R. J.R. R.S. C.S. R.Sh. J.S. S.S. K.S. G.T. B.V. J.W. O.W. S.W. A.W. J.Y.

12 9 16 13 13 13 14 15 18 14 14 8 10 12 15 15 11 14 17 16 14 7 7 11 10 12 10 8 9 18 9 13 9 18 10 10 11 9 10 13 17 10 10 8 9 11 15 13 15 17 8 16 12

Control

Duration of diabetes

UG gin~24 hr

FPG

PPG

24 hr/UG

FPG

PPG

1 yr 1 yr 4yr 2mo 4 yr 7mo 4yr 4 yr 7 yr 5 yr 9 yr 9mo 2yr 8yr 2 yr 7 yr 13 yr 15 yr 5 yr 1 yr 3 yr 5 yr -9 yr 2 yr 7 yr 8 yr 7 yr l mo 8 yr 5 yr 6yr 7 yr 9 yr 3 yr 2 mo 1 yr 4 yr 1 yr 3 yr 2 yr 1 yr 6 yr 1 yr 4 yr 4 yr 3yr 7 yr 5 yr 2 yr 5 yr 5 yr

29.4 7.8 276.0 164.2 0 22.0 304.2 91.4 178.4 22.0 114.0 12.9 110.2 92.0 105.8 229.6 112.0 69.9 5.0 32.3 35.2 31.1 4.4 71.8 39.0 24.9 43.8 27.6 66.4 .2 119.5 8.8 20.6 127.0 61.5 8.7 6.0 52.8 5.6 4.2 102.0 20.4 29.4 96.0 4.2 5.5 87.0 108.8 136.0 212.7 133.9 64.0 320.0 49.5

224/155 103/145 271/242 250/150 113/51 309/287 120/171 336/398 318/138 230/324 57/242 206/270 263/269 128/124 106/192 215/141 204/57 213/305 63/50 60/154 58/68 332/312 84/171 106/260/280 238/275 130/100 63/283 89/228 87/85 237/266 182/249 64/69 337/192 192/259 244/179 93/89 74/118 46/126 69/202 291/376 317/303 314/259 251/289 197/165 217/217 305/297 83/106 100/98 233/307 290/278 140/80 323/296 94/-

256/210 104/170 251/458 393/467 84/54 149/419 486/323 249/360 373/406 343/420 96/263 443/406 478/404 416/438 83/334 480/287 545/374 432/285 183/256 42/52 47/328 392/294 202/371 314/318 582/482 447/455 160/194 30/159 458/388 109/75 106/309 420/438 165/127 447/544 419/411 207/484 57/263 151/371 68/52 122/316 339/334 365/618 451/382 239/483 289/56 275/385 261/387 259/130 369/286 544/760 319/186 466/291 217/529 190/83

F* G P P E G P P P G P G P P P P P P G F F F G P F G F F P G P G G P P G G P G G P G F P G G P P P P P P P F

P/P G/P P/P P/P E/E P/P G/P P/P P/P P/P G/P P/P P/P P/P G/P P/P P/G P/P G/G G/P G/G P/P G/P P/P P/P p/P P/G G/P G/P G/G P/P P/P G/G P/P P/P P/P G/G G/G G/P G/P P/P P/P P/P P/P P/P P/P P/P G/G G/G P/P P/P P/G P/P G/-

P/P G/P P/P P/P E/E G/P P/P P/P P/P P/P G/P P/P P/P P/P G/P P/P P/P P/P P/P G/G G/P P/P P/P P/P P/P P/P G/P G/G P/P G/G G/P P/P P/G P/P P/P P/P G/P G/P G/G G/P P/P P/P P/P P/P P/G P/P P/P P/G P/P P/P P/P P/P P/P P/G

PG = Plasma glucose; UG = urine glucose; FPG = fasting plasma glucose (two separate determinations); PPG = postprandial glucose (two separate determinations); E = excellent; F = fair; G = good; P = poor.

946

M a l o n e et al.

sugar as a measure of diabetic control was then compared with the F P G in the morning and two hours postprandial in the afternoon (Table II1). The excretion of < 25 gm of sugar in 24 hours has been proposed as an indicator of good control? Using that definition, 18 of the 54 children had good control; only two of those 18 children, however, consistently had random PG that would be categorized as good controlY DISCUSSION The most practical indicator of day-to-day diabetic management has been the home record of urine testing? In a camp situation that should produce maximal patient compliance in urine testing, only 3/4 of the children's urine tests were performed. In a home situation without peer pressure and general acceptibility of the task, one would expect a smaller degree of compliance. If, on the other hand, the urine specimens were collected and tested, only 51% of the results were accurate (Table II). This error might reflect bias induced by stressing the importance of low urine sugar concentrations to patients with diabetes in general and to children with diabetes in particular. The explanation that the children purposely lowered the test results for approval overlooks, however, the possibility that genuine technical errors in urine testing occurred. The fact that approximately 20% of the results of the urine tests were discrepant by a single color change on the Clinitest color chart suggests that some difficulty exists in discriminating between the color standards. It is also conceivable that larger errors may be the result of other testing difficulties. If so, these were present in spite of daily instruction and frequent medical staff supervision in the techniques of urine testing. Thus, the great probability of noncompliance, together with reporting inaccuracies, make the results of random urine tests performed at home highly suspect as an indicator of metabolic control in children with diabetes. Even if these inaccuracies could be overcome in a rigidly controlled environment such as a hospital, it should be recognized that the application of urine sugar concentration for diabetic management is limited by the fact that it is not a precise reflection o f the plasma glucose. 18 Since random URS do not accurately reflect glucose homeostasis for an entire day, the 24-hour excretion of glucose, or aliquots thereof, has been recommended as a more reliable technique. 19 The major difficulty with this technique in our study was that only 54 of the 220 children (24%) fully complied with the request to collect the urine. Eighteen of the 54 (33%) had good control on the basis of the 24-hour excretion of glucose. 13 Since the reference standard of diabetic control has not been established it

The Journal o f Pediatrics June 1976

seemed appropriate to compare the results of measured 24-hour excretion of glucose with another measure of control, the PG concentration. The plasma specimens collected following an overnight fast were evaluated by using 120 mg/dl of glucose as the upper limit of normal.* The postprandial specimens were evaluated using a PG of 160 mg/dl as the upper limit of normal.* The 54 children who had their diabetic control rated on the basis of the 24hour excretion of glucose were then evaluated in terms of two fasting and two postprandial P G values. Fasting plasma glucose < 120 m g / d l was found in 23 of the 54 children (43%). Of that group, nine or 18% h a d a normal F P G on a different day. Fourteen of the children with good control as judged by the F P G had poor control on the basis of the 24-hour excretion of glucose. The 2hour postprandial PG was < 160 m g / d l in 19 of 54 of the children (35%); of these 14 (26%) were found in the same children who had normal fasting plasma glucose values. Only five (9%) of the children, however, had normal postprandial concentrations of plasma glucose on both determinations. Thirty-three of the 54 children had good diabetic control on the basis of at least one of the five determinations. If one looks at all five, however, only two of the 54 children had good control. In addition, those children with good control on the basis of the 24-hour excretion of glucose had good control in 11 of 18 instances, as determined by one or more random PG determinations and poor control as defined by the same criteria when applied to other specimens in 15 of the same 18 examinations. Random plasma glucose determinations in this group of children are thus seen to have wide variability. This type of variability has been described by otherslS. 21 and is characteristic of insulin-deficient diabetes. Thus, intermittent plasma glucose determinations in ketosis-prone diabetic patients do not relate sufficiently to overall glucose homeostasis to be used as an indicator of diabetic control. Approximately 50% of t h e children had control that varied between good and poor on the same day. This same day variability indicates that the most significant factor for defining diabetic control by PG values is the time of drawing the blood specimen. The intent of this paper is not to say that the measurements o f URS and PG are not useful for the management of children with diabetes. Instead it is to point out that when using these criteria the terms diabetic management and diabetic control are not synonymous. Testing urine for reducing sugar at home should continue as a cornerstone of diabetic management. It can serve the patient with objective evidence of chronic hyperglycemia, *These valueswere arrivedat by adding 10 mg/dl to the blood glucose norms~~to correct for the plasma glucose determinations used in this study.

Volume 88 Number 6

impending ketoacidosis, a n d / o r impending hypoglycemia. Periodic PG determinations may be helpful for evaluating symptoms thought to result from hypoglycemia and for correlation with U R S tested at the same time. The collection of urine for 24 hours or in aliquots thereof, can be useful for the evaluation of the 24-hour effectiveness o f diabetic therapy. Thus U R S and PG determinations can be useful m a n a g e m e n t guidelines for the physician and the patient with diabetes. It is important, however, for those who care for diabetic patients to realize that the degree o f glucose homeostasis in two or more patients judged to be significantly different by the criteria evaluated in this study may in fact be very similar. Likewise the opposite may also be true. Strict diabetic control as defined by these indicators may all be delusions in the mind of the observer. Therefore, physicians should discontinue using these nondiscriminating criteria as prognostic indices to compare the effectiveness of diabetic therapy for the prevention o f the associated vascular complications.

Good diabetic control

8.

9.

10.

11.

12. 13. 14.

15. REFERENCES

I. White P: The child with diabetes, Med Clin North Am 49:1069, 1965. 2. Jackson RL, Hardin RC, Walker GL, Hendricks AB, and Kelly HG: Degenerative changes in young diabetic patients in relationship to level of control, Pediatrics 5:959, 1950. 3. Hardin RC, Jackson RL, Johnston TL, and Kelly HG: The development of diabetic retinopathy: Effects of duration and control of diabetes, Diabetes 5:397, 1956. 4. Marble A: Relation of control of diabetes to vascular sequelae, Med Clin North Am 49:1137, 1965. 5. Kilo C, Vogler N, and Williams JR: Muscle capillarybasement membrane changes related to aging and to diabetes mellitus, Diabetes 21:881, 1972. 6. Knowles HC Jr, Guest GM, Lampe J, Kessler M, and Stillmen TG: The course of juvenile diabetes treated with unmeasured diet, Diabetes 14:239, I965. 7. Siperstein MD, Unger RH, and Madison LL: Studies .of muscle capillary basement membranes in normal subjects,

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diabetic and prediabetic patients, J Clin Invest 47:1973, 1968. Siperstein MD: The relationship of carbohydrate derangements to the microangiopathy of diabetes, in Cerasi E, and Luft R, editors: Proceedings of the Noble Symposium XIII on the pathogenesis of diabetes mellitus, New York, 1970, Wiley Interscience Division, p 81-122. Krall LP: Clinical evaluation of prognosis in Marble A, White P, Bradley RF, and Krall LP, editors: Joslin's diabetes mellitus, Philadelphia, 1971, Lea and Febiger, Publishers, p 214. Rosenbloom AL, Grossman MS, and Malone JI: Florida's camps for children and youth with diabetes, J Fla Med Assoc 61:228, 1974. Kohler E: A single sheet pediatric growth chart; A convenient device for following the physical growth patterns of both boys and girls, Clin Pediatr 12:497, 1973. Mitchell SC, Blount SG, Jr, Blumenthal S, et al: The Pediatrician and hypertension, Pediatrics 56:3, 1975. Traisman HS: Management of juvenile diabetes mellitus, St. Louis, 1971, The C.V. Mosby Company, p 54. Belmonte MM, Sarkozy E, and Harpur ER: Urine sugar determination by the two drop Clinitest method, Diabetes 16:557, 1967. Rosenbloom AL, Londono JH, Nickerson D, Jordon J, and Rosenbloom E: Stability and control of diabetes mellitus in children, South Med J 6:727, 1971. Cook RE, and Levin S, editors: The biologic basis of pediatric practice, New York, 1968, The Blakiston Division of McGraw-Hill Book Company, Inc, p 1694. Lukens FDW, and Franklin SN: Long-term diabetes without vascular disease, Med Clin North Am 50:1385, 1966. Service FJ, Molnar GD, and Taylor WF: Urine glucose analysis during continuous blood glucose monitoring, JAMA 222:294, 1972. Forman BH, Goldstein PS, and Genel M, Management of juvenile diabetes mellitus: Usefulness of 24-hour fractional quantitative urine glucose, Pediatrics 53:257, 1974. Cervantes-Ansezcua A, Naldjian S, Camerine-Davalus R, and Marble A: Long-term use of chlorpropamide in diabetes, JAMA 193-759, 1965. Molnar GD, Taylor WF, and Ho MM: Day-to-day variation of continuously monitored glycemia: A further measure of diabetic instability, Diabetologia 8:342, 1972.

Good diabetic control - a study in mass delusion.

The terms "diabetic control" and "diabetic management" are not synonymous. Diabetic control implies normal glucose metabolism, typically monitored by ...
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