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PARTIAL PRESERVATION OF PANCREATIC BETA-CELL FUNCTION IN CHILDREN WITH DIABETES

A. H. BARNETT

Princess Margaret Hospital,Department of Endocrinology,Christchurch 2, New Zealand

SIR,-There are some worrying aspects to the study reported byProfessor Elliott and colleagues (July 4, p. 1), especially since it hasreceived extensive coverage by the New Zealand media. Elliott et al.indicate that they used only a small dose of prednisone (0 - 25 mg/kgbody weight daily): this is equivalent to about 18 mg/day for anaverage adult, and the 1-2 mg used for the first two weeks in somechildren is equivalent to 70-140 mg/day. How were the childrenwho were to receive the higher doses selected. It is especiallyworrying that one child became hypertensive and had a

retrolenticular cataract.Since there was no significant difference in insulin requirements

or diabetic control between the treated and untreated groups, theincreased output of urinary C-peptide suggests that the treatedchildren were merely showing an increased insulin resistance whichhas continued for a year after stopping the prednisone. The findingsdo not justify any serious claims as to the usefulness of steroidtherapy in the management of early insulin-dependent diabetes.

SIR,-Professor Elliott and colleagues found that administrationof prednisone (0-25 mg/kg daily) to newly diagnosed insulin-dependent diabetic (IDD) children for the first 12 months afterdiagnosis resulted in significantly higher urinary C-peptide levels incomparison with control values, both during and for a year aftercorticosteroid therapy. Reduction in exogenous insulin

requirement was not as great as might have been expected, however,and Elliott et al. suggest that the low dose given may have had ananti-inflammatory rather than an immunosuppressive effect.We have studied’ the effects of doses of cortisone up to 48 times

as high as that used by Elliott et al. administered for 2 weeks afterdiagnosis of diabetes, in a prospective trial which also investigated

Results as mean SD; glucose values are mean blood glucose (1 mmol/1 = 18 mg/dl).

the effects of insulin infusion therapy in newly manifested IDD (age18±6 years). Twelve patients were treated during the first few weeksafter diagnosis with continuous insulin infusion, using the artificialendocrine pancreas to pre-programme an externally worn open-loopinfusion device. The aim was to achieve normoglycaemic control toavoid overstimulation of the (3-cells by raised blood glucoseconcentrations. Twelve age and sex-matched controls were

conventionally treated with s.c. insulin from the time of diagnosis.Six of the infusion-treated patients were randomly allocated to

additional treatment with an oral daily dose of prednisone, 12 mg/kgdaily. After 2 weeks all patients were switched to sc. injectiontherapy. In no case was insulin omitted.Total remission did not occur in any patient (see table). Partial

remission, defined as a reduction in insulin requirement to less than

1 Najemnik CM, Kritz H, Kaspar L, Irsigler K. Remission phase: Prospective study toinduce or prolong remission (REM) with closed and open loop treatment (effect ofadditional cortisone treatment). Diabetologia 1980; 19: 251-327.

Najemnik CM, Kritz H, Kaspar L, Irsigler K. Prospective study of remission in newlymanifest JOD with closed and open loop treatment. In: Irsigler K, Kunz K, OwensD. Regal H, eds. New approaches to insulin therapy. Lancaster: MTP Press, 1981:159-68

0’ 4 IU/kg daily, while maintaining near normoglycaemic control,occurred in 20 of the 24 cases, with no differences between groups.Neither the administration of prednisone nor the level of glucagon-stimulated serum C-peptide was related to duration of the partialremission phase. Thus, we conclude that even high doses ofcortisone, when given for short periods immediately after diabetesmanifestation do not produce a sufficient immunosuppressiveeffect.

All new methods of immunosuppressive therapy, 3 includingadministration of cortisone, cyclosporin, selective irradiation,5 ormonoclonal antibody subsets, must finally be judged by theirability to reduce insulin requirement while maintaining goodmetabolic control. In our opinion, increase in C-peptide valueswithout concomitant reduction in insulin need is not a sufficient

proof of improvement of&bgr;-cell function. Not only was the reductionin insulin dose in Elliott’s study modest but also the degree ofmetabolic control achieved was only fair. This study is also

hampered by the fact that treatment allocation was not randomised,and the drop-out rates for the two groups differed substantially, sothat selection factors may have played a role.While reserving judgment on the value of cortisone therapy, we

did note that strict metabolic control in the weeks immediately afterdiagnosis has long-lasting beneficial effects on the patient’smotivation and ability to manage his diabetes.

HARALD KRITZCLAUDIA NAJEMNIKKARL IRSIGLER

3rd Medical Department (Metabolic Unit),and Ludwig Boltzmann Research Institutefor Metabolism and Nutrition

City Hospital Vienna-Lainz,A-1130 Vienna, Austria

INACCURACIES IN TWO LANCET ARTICLES

PATRICK S. PARFREY

Department of Medicine,Charing Cross Hospital Medical School,Fulham Palace Road,London W6 8RF

J. M. LEDINGHAMF. J. GOODWINS. J. W. EVANSM. J. VANDENBURGJ. M. P. HOLLY

Medical Unit,The London Hospital,Whitechapel, London E1 1BB

Sir,- wish to report to your readers that inaccuracies for which Iwas solely responsible have been recently discovered in two paperspublished by The Lancet (Jan. 11 and 18):(1) Blood pressure and hormonal changes following alteration in dietarysodium and potassium in mild essential hypertension. Parfrey PS,Vandenburg MJ, Wright P, Holly JMP, Goodwm FJ, Evans SJW, LedinghamJM. Lancet 1981; i: 59-63.(2) Blood pressure and hormonal changes following alteration in dietarysodium and potassium in young men with and without a familial

predisposition to hypertension. Parfrey PS, Condon K, Wright P,Vandenburg MJ, Holly JMP, Goodwin FJ, Evans SJW, Ledingham JM.Lancet 1981; i: 113-17.

My coauthors unanimously agree that this statement should bemade and that at the present time the conclusions arising from thesestudies cannot be fully substantiated.

SIR,-We wish to express our profound regret to readers of TheLancet that inaccuracies have been discovered in the two papersreferred to in the above letter from Dr Parfrey. We are currentlyundertaking a complete reanalysis of the data and hope to informyou of the results as soon as possible.

3. Leslie RDG, Pyke DA. Immunosuppression of acute insulin-independent diabetics.In- Irvine WJ, ed. Immunology of diabetes. Edinburgh- Teviot Scientific

Publications, 1980 345-47.4. Calne RY, Rolles K, White DJG, et al. Cyclosporin A initially as the only

immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases,and 2 livers. Lancet 1979; ii: 1033-40.

5. Strober S, Slavin S, Gottlieb M et al. Allograft tolerance after total lymphoid irradiation(TLI). Immunol Rev 1979; 46: 87-112.

6. Reinherz EL, Schlossman SF Regulation of the immune response-inducer andsuppressor T-lymphocyte subsets in human beings N Engl J Med 1980; 303:370-73