EDITOR'S C O L U M N

The control of diabetes mellitus: Is it achievable? Is it desirable?

DIABETES MELLITUS is a major health problem, ranking fifth as a cause of death in our society? The fact that diabetes occurs uncommonly in children (the prevalence lies between one in 600 and one in 1,200 children under 16 years of age) in no way negates or minimizes the importance to the pediatric community. The ',vascular complications" of diabetes take their toll at much greater frequency with early-onset diabetes than in those with maturity-onset disease. The devastation of the disease lies not only in the loss of life but also in blindness, renal failure, peripheral vascular insufficiency, and neurologic darriage, all of which characterize the course of insulindeficiency diabetes. All of us who care for children with diabetes are united in our desire to provide optimal care, both in terms of day-to-day management and long-term health. Why, then, are there major differences in therapeutic approaches among the various "diabetic experts"? The differences are derived primarily from interpretation of studies attempting to relate metabolic control and the development of vascular complications. Until recently, the evidence linking the two was controversial at best. Within the past five years several studies in experimental animals and humans have appeared which substantially strengthen the argument that the metabolic derangements are major causative factors in the development of the vascular alterations. 2-7 Based on the accumulated evidence, the American Diabetes Association has adopted a policy statement on the control of diabetes? It states in part, "These data place the burden of proof upon those who deny diabetes control is without effect. The goals of appropriate therapy for those with diabetes should include a serious effort to achieve levels of blood glucose as close to those in the non-diabetic as feasible . . . . The weight of evidence places certain complications of diabetes, particularly the nephropathy and retinopathy, into the same category as acidosis, severe hypoglycemia, decreased growth and development and prenatal morbidity; namely that these long-term specific complications of diabetes may be minimized and presently result from our-

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The Journal o f P E D I A T R I C S I1ol. 88, No. 6, pp. 1074-1076

inability to correct metabolic abnormalities by conventional insulin therapy." A recent report by Goodkin 9 provides mortality statistics on 10,000 diabetics followed prospectively over 20 years by the Metropolitan Life Insurance Company. He confirms the findings of many others that the mortality statistics of those with diabetes having its onset in childhood or young adult life is exceedingly high, approximately 11 times that of age-matched controls. Further, classifying insurance applicants on the basis of urine and blood glucose concentrations as either poorly controlled or well controlled, they report a 250% increase in mortality statistics in those in the poorly controlled category. This finding held true whether or not the juvenile-onset diabetics were included or excluded from the analysis. See related article, p. 943.

Abbreviation used ADA: American Diabetes Association These findings provide further evidence of the controlcomplication relationship and are challenged to us to improve the care of our patients. An awareness that normalization of energy metabolism is not achievable in the patient with insulin deficiency, however, is reflected in the final statement from the ADA position paper. It is highly important in terms of the physician's therapeutic approach. It is not difficult to accept accumulating evidence that the multitude of metabolic and endocrine alterations associated with insulin deficiency are intimately related to the progression of microangiopathic disease. What is dearly missing is evidence that there is a linear relationshil~ between the severity of the metabolic alterations and the frequency and rate of progression of vascular disease. Stated another way, evidence is lacking that if we could move patients from "fair" to "good" metabolic control substantial benefits would necessarily follow.

Volume 88 Number 6

In my opinion, one of the most difficult tasks we have is the scientific assessment of metabolic control in children with diabetes mellitus. In recent extensive in-patient studies, we have documented wide swings in metabolic homeostasis throughout the day in many patients, with poor correlation between the concentration of glucose in blood and urine. The majority of patients we have had the opportunity to evaluate on an in-patient basis have had periods of good, fair, and poor control within each 24 hour period. Further, we have abandoned the classification of diabetic control for scientific purposes, based on patient-produced urine reduction records because of the high degree of unreliability and variability over time. Our experience would appear to confirm that of Malone and associates TM appearing elsewhere in this issue. There are, however, some major interpretive differences. It is not surprising that there is little correlation between excretion of glucose over 24 hours and the concentration of glucose in blood in the fasting and postprandial states. Although we are not so informed, it is likely that most of the children in this study received a single injection of NPH insulin once daily. In many children, the effect of a single injection of NPH will "wane" during the early morning hours, resulting in an increase in the concentration of glucose from euglycemic, or even hypoglycemic levels, to hyperglycemic concentrations prior to breakfast. In addition, postprandial hyperglycemia characterizes the insulin-deficient diabetic, regardless of the therapeutic modality. Increasing doses of regular insulin will impede the increase in glucose concentrations following meals, but w i l l rarely normalize the response without creating later hypoglycemia. The authors provide an important service in pointing out the problems inherent in utilizing blood and urine glucose testing in the management of the child with diabetes, but leave the reader with a sense of futility which, I think, is inappropriate. Therapy of the child with diabetes mellitus should, and can, in the great majority of cases, achieve the following therapeutic objectives: 1. Control of the symptoms of diabetes. This includes elimination of polyuria, polydypsia, and polyphagia and the avoidance of hypoglycemia. 2. Maintenance of normal growth and maturation. This is one of the best indicators of the adequacy of energy homeostasis. The declining growth rate, whether above or below the third percentile, must be viewed as inadequate management of diabetes until proved otherwise. Similarly, delay in sexual maturation in the child with diabetes can usually be corrected by improved insulin administration and nutrition. 3. Maintenance of normal blood lipids. The serum

Editor's column

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concentrations of cholesterol and triglyceride are regularly elevated in diabetic patients who are grossly undertreated with insulin. In our experience, the great majority of children who are symptomatically controlled have lipid concentrations within the limits of normal. 4. Minimization of urinary glucose loss. For clinical purposes the 2-drop Clinitest method, testing three to four urine specimens daily, provides useful information on which to make decisions regarding insulin and diet. Few children can be maintained aglucosuric. Indeed, because of the danger of hypoglycemia, it is questionable whether this is a desirable objective. A more reasonable objective is the achievement of a urinary glucose pattern that is below 1% ( 3 + ) most of the time. The occasional quantitative determination of 24 hour urinary glucose loss can be extremely useful under certain circumstances. The loss of less than 7% of the dietary intake of carbohydrate is a reasonable indication of good control. For the average teen-ager this approximates 25 gm of glucose or a concentration of 2.5% ( 4 + ) when placed in a liter of urine. Stated differently, a consistent 4 + spill may be entirely compatible with "good control" if the urine volume is not excessive. 5. Because of the extreme variability of blood glucose concentration in the child with diabetes, well documented by the study of Malone and associates, I do not feel that euglycemia is a reasonable objective nor do I recommend routine determination of blood glucose. The practicing physician and the diabetic investigator share the dilemma of therapy in the patient with diabetes. We are informed that (1) complete normalization of energy metabolism is not achievable with currently available modes of therapy, (2) "poor" control is associated with an increased likelihood of cardiovascular complications, and (3) the routine methods used to evaluate the level of control are scientifically unacceptable. I feel that it is appropriate for the physician to attempt to achieve the best possible level of metabolic balance in his patients, always keeping in mind the psychologic hazarcls of overly restrictive regimens and the very real dangers of recurrent hypoglycemia. The first four objectives listed above can be achieved in most children, some of whom may require multiple injections of insulin and highly restrictive dietary and exercise programs. In our experience the latter children represent the exception rather than the rule. Much remains to be learned about the complex relationship between the biochemical and hormonal alterations associated with insulin deficiency and the vascular complications of diabetes. We await a definitive explanation of this relation, reliable methods for monitoring

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Editor's column

b i o c h e m i c a l control, and, m o s t i m p o r t a n t o f all, i m p r o v e d m o d e s o f t h e r a p y t h a t will place " g o o d c o n t r o l " within the grasp o f every p a t i e n t with diabetes.

Allan Drash, M.D. University o f Pittsburgh School o f Medicine Childrens Hospital 125 DeSoto St. Pittsburgh, Pa. 15213 REFERENCES

1. Crofford O, et al: Reports to Congress of the National Commission on Diabetes, U.S. Government Printing Office, 1976. 2. Spiro RG: Biochemistry of renal glomerular basement membrane and its alterations in diabetes mellitus, N Engl J Med 228:1337, 1973. 3. Trivelli LA, Ranney HM, and Lai HT: Hemoglobin components in patients with diabetes mellitus, N Engl J Med 284:353, 1971.

The Journal of Pediatrics June 1976

4. Koenig RJ, and Cerami A: Glycosylation of hemoglobin in the diabetic mouse, Fed Proc 34:335, 1975. 5. Osterby R: Morphometric studies of the peripheral glomerular basement in early juvenile diabetes mellitus. I. Development of initial basement membrane thickening, Diabetologia 8:84, 1972. 6. Kilo C, Vogler N, and Williamson JR: Muscle capillary basement membrane changes related to aging and diabetes mellitus, Diabetes 21:881, 1972. 7. Job D, Eschweg E, Guyot C, and Tchobroutsky G: Effect of multiple daily insulin injections on the course of diabetic retinopathy, Diabetes 24 (Suppl 2):397, 1975. 8. Cahill GF, Etzwiler D, and Freinkel N: Blood glucose control in diabetes, Diabetes 25: 1976. 9. Goodkin G: Mortality factors in diabetes: A 20 year mortality study, J Oceup Med 17:716, 1975. 10. Malone JI, Hellrung JM, Malphus EW, Rosenbloom AL, Grgic A, and Weber FT: Good diabetic control-a study in mass delusion, J PEDIATR 88:943, 1976.

Erratum. In the April, 1976, issue of THE JOURNAL OF PEDIATRICS (8~8:584, 1976), in the article "Joint contracturecommon manifestation of childhood diabetes mellitus" by Ante Grgic, Arian L. Rosenbloom, F. Thomas Weber, Beverly Giordano, John I. Malone, and Jonathan J. Shuster, the second sentence of the legend for Fig. 1 on page 585 should have read, "The numbers above the bars indicate~ the total number of campers examined in the duration group." Errata: In the "Report of the Committee for a Study for Evaluation of Testing for Cystic Fibrosis" published as Part 2 of the April issue of TrIE JOURNAL OF PEDIATRICS, on page 731, recommendation No. 3 under Setting should read, "Practitioners should not attempt either to screen or to test for cystic fibrosis in their offices." On page 745 in the "Circuit diagram for Farrall Instrument and H. Schwachman and Kopito sweat test kit," the symbol labeled "RHEO" is that for a variable inductor: it should be shown as a variable resistor (or potentiometer).

The control of diabetes mellitus: is it achievable? Is it desirable?

EDITOR'S C O L U M N The control of diabetes mellitus: Is it achievable? Is it desirable? DIABETES MELLITUS is a major health problem, ranking fifth...
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