tuberculosis and diabetes

T H E IRISH J O U R N A L OF M E D I C A L S C I E N C E THE OFFICIAL JOURNAL OF THE ROYAL ACADEMY OF MEDICINE IN IRELAND

SEVENTH SERIES. No. 6 JUNE, 1930

TUBERCULOSIS AND DIABETES. ~ By PROF. L~O~ BERNARD.

(Clinique de la T~berculose de la Facult~ de M~decine de Paris.)

frequent T H E conception of the association of classical pulmonary tuberculosis with diabetes is so fixed that phthisis is generally considered to be one of the most

frequent, as it is one of the most serious, complications of diabetes. Of recent years, however, there has taken place a certain re-orientation of our ideas in regard, to both these diseases, of such nature as to lead to a change in our views on the relations which exist between the two diseases. In practice, the remarkable improvements in our anti-diabetic therapy, tha~fi~s to Lhe development of the insulin treatment, in addition to the success obtained with newer methods of treatment in tuberculosis, have terrded rather to lessen our conception of the gravity of tuberculous infection in diabetic subjects; the frequency of association of the two diseases seems capable of reduction by an increase in the knowledge of prophylactic measures amongst patients. We are accordingly perhaps on the eve of a revision of the classical notion alluded to in our openin, g statement. But it ,is indispensable that we should first of all make a rapid r&um~ of the more recent developments in our krrowledge and treatment of both diabetes and tuberaulosis.

Turning first to the subject of the diabetic, the outstanding fact remains that if etiological and anatomo-pathological in- vestigations have thrown but little light on the problem, studies in pathological physiology have succeeded in finding the guiding thread through its many aspects, and have permitted us to formulate a scale of gravity by the division of our diabetic patients into two classes. Henceforth, from this time forward, it will be possible to " draw up a balance sheet " for the diabetie and from it to forecast the evolution of his ease. With Marcel Labbfi, we now distinguish two types :

1. Diabetes without denutritian. Here we have to deal with a simple alteration in carbohydrate metabolism, due to a disturbance of the sugar-regulating mechanism. IIyperglyeaemia and glyeosuria result; incidentally, we recollect that the normal propor$ion of sugar in the blood varies between 1 and 1.5 grammes per litre. In this relatively simple type of diabetes the patient

[By kind permission of the Editors, La Presse M~dica~e, Paris.]

230 IRISH JOURNAL OF MEDICAL SCIENCE

preserves a certain degree of tolerance for carbohydrates, and as this index of tolerance varies between individuals, the essential problem in practice comes down to the determination of the personal coefficient.

2. Diabetes with denutrition. Here we have added to a disturbed carbohydrate metabolism a disturbance of the protein metabolism. The carbohydrate tolerance has disappeared: even on a diet from which all carbohydrate has been eliminated, we find no diminution of the glycosuria. Sugar is formed by the destruction of protein material (and doubtless also of fats), and as has been well said, these patients " manufacture sugar from everything that they ingest."

The disturbance of protein metabolism is revealed by the alterations in the urinary an, alyses, by the appearance of abnormal proteins in the urine, and above all by the disturbed normal acid'-base equilibrium and the ,appearance of acidosis, due to the presence of b-oxybutyric acid, diacetic acid and acetone.

Our better knowledge of the diabetic process would have served us but little if we had remained as poorly armed against it as of old. but dietetic cures in themselves have become a waluable therapeutic aid since the day when, under the guidance of these physio-pathological concepts, it became possible to adjust the diet to each individual case.

In diabetes without denutrition, a reduced carbohydrate regime will cause the disappearance of glycosuria; from this point, by progressive and judicious adjustment of the diet, we can arrive at the estimation of the patient 's threshold of carbohydrate tolerance; there remains nothing then but the fixation of the regime of tolerance.

The serious difficulties arise in diabetes with denutrition; these cases call for a reduction of carbohydrates and also of proteins in the diet, although the actual protein wastage requires an increased protein intake; furthermore, the proteins are the main source of the ketone bodies. In such cases, we should rely chiefly on the fats in the diet, which will act as " sparers " of the proteins.

In this fashion, we have come to the meticulous regulation in practice of the ,appropriate dietary in each individual case of diabetes, and even to its suitable variation as we follow the fluctuations of the carbohydrate and protein metabolism in the same patient.

But if we have thus acquired a definite improvement on older methods, the discovery of insulin has endowed us with a weapon of inaalculable value. This pancreatic derivative, isolated at Toronto by Banting and Best in 1922, has changed the entire outlook in severe forms of diabetes. Insulin, we know, acts at the same time on carbohydrate metabolism and on the ketogenic bodies and ketones: on the other hand, it so ~ar diminishes hyperglycaemia as even to suppress it completely (this action, however, is merely temporary, rarely lasting for more than 8 to 1~ hours), and, on the other hand, it reduces or abolishes aceto-

TUBERCULOSIS AND DIABETES 231

nuria, while at the same time it raises the thres~hold of the alkaline reserve; its action here ought to be of the same duration, but the point is not yet definitely determined.

We have seen that dietetic treatment may suffice in diabetes without denutrition, but in diabetes with denutrition, i.e., in the grave forms of which coma is the natural outcome, the indicatiol] for the administration of insulin is formal.

We have thought it 'well briefly to put together these ideas relative to diabetes and its treatment, so markedly have they modified the prognosis in tMs disease. So, too, more recent - -and equally important~knowledge has upset many notions con- cerning human tuberculosis and has increased our weapons against it. Let us recollect that we know to-day how relatively rare is contagion between adults. The course of events is one rather of a reactivation in the adult of old-standing tuberculous loci dating back to the days of childhood, which had remained latent, only to burst into activity in states of lowered resistance. We may even go so far as to say that our present-day conception of pulmonary tuberculosis in the adult is based entirely upon this foundation. Amongst the various activating factors we must consider states of denutrition; we can see here how important this condition can be in conjunction with diabetes. Finally, we know how favou~ably sugar-bearing media influence the growth of Koch's bacillus.

In the domain of therapeutics we have equally new acquisitions to record. Artificial pneumothorax has revolutionised the treatment of pulmonary tuberculosis. I t is universally employed for all progressive unilateral lesions, and at the moment promising attempts are being made by some investigators to extend the application of this method to bilateral cases.

For these bilateral cases, to which pneumothorax is not strictly applicable, we possess a new form of drug treatment in sanocrysin. We have shown elsewhere what favourable results have been obtained by its employment in many cases. While it is not actually a specific drug treatment, at least it carries with it the hope of an improvement in precisely those cases for which, previous to its discovery, we had no method of treatment. Beyond doubt this chemo-therapeutic method, applied to tuberculous patients who are diabetics, will materially improve their future.

How far has our increased knowledge modified our outlook on the relations between tuberculosis and diabetes ? First of all, how are we to regard at present the etiological connection between the two diseases, and, in particular, what incidence are we to attribute to tuberculosis as a complication of diabetes ?

Earlier writers (e.g., Bardley, Copland, Nicolas, Gucudeville) have gone so far as to consider tuberculosis as almost the pre- dominant cause of death amongst diabetics. ,Statistical reports from various sources have been productive of contradictory or


discordant evidence, but the most reliable statistics all furnish results of much the same order. Thus Griessinger has reported a mortality rate of 43 %, all due to tuberculous infection. The tables published by Frerichs, by Seegen, by Williamson, all show the same figure of 43 %, but we should remember that these figures have all been derived from hospital post-mortem ex.aminations. Marcel Labb~ has shown that in diabetes, as in many other maladies, due allowance must be made for the milieu in which the disease has evolved and in which the final account of the disease must be reckoned; he arrives at the following memerical proportions: of hospital cases, 35 % to 40 % develop tuberculous infection, but in private practice the proportion is appreciably lower; he gives it as 1 in 10. Similar estimates have been put forward by Bouchardat, by Durand-Pardel, Griessinger, Mandl, and yon Noorden. Labbfi attributes the difference of incidence in hospital and in private practice to contagion in the hospital wards. I confess that his explanation is to me unsatis- factory, for infection from adult to adult in well-kept hospital services should be infinitesimal. I believe rather that treatment, being more easily carried out in private practice, is there more efficacious than in hospital; the hospital patient has much less opportunity to benefit by the regime which is necessary, and as a result we see fewer instances of advanced diabetes in private than in hospital practice.

Be this as it may, it is a noteworthy fact that recent statistics give much lower figures than those of former days. Joslin, of America, in 1923 could find only 6 % of diabetics who died of tuberculosis. Another American .observer, Montgomery, had in 1912 observed that tuberculosis was of no more frequent incidence amongst diabetics than amongst the rest of the population. And recerrtly, Abraham, in Germany, in 1927 published statistics with a death rate but little higher: in his table, not more than 10 to 15 % of diabetics acquired tuberculous disease. These tables make no mention .of any differentiation in the social scale to which the cases quoted belong.

Can the statement be made that tuberculosis claims fewer victims amongst diabetics to-day than formerly obtained ? Labb6 attributes the diminution of incidence recorded by Ameri- can observers to the effect of the intensive anti-tuberculosis campaign in the United States. But we can scarcely accept this interpretation: so far back as 1912, prophylactic measures can scarcely have produced an already considerable result; further. more, this explanation is entirely based or~ the idea of contagion between adults, and our knowledge of infection to-day is rather an argument against than for this etiological factor. And against it, too, as Labb~ has correctly observed, since the introduction of insulin it would seem that the deaths due to tuberculosis are apparently more common among diabetics than those due to other eauses; this, however, is only apparently so: in reality, it is the diminution in the number of deaths from coma which is respon-


sible for the proportional increase of tuberculosis as a lethal factor in diabetes.

To sum up, we are of opinion that fewer diabetic subjects die to-day from tuberculosis than in former years. The cause would appear to lie in the fact that to-day the diabetic is better cared. In subjects whose dietary is well regulated, in whom all denutrition is steadily avoided, from whom all risk of acidosis is removed 'by insulin, how can they but avoid the pathological tendency, obscure though it be, which under the earlier regime so frequently made itself manifest by the sudden lighting-up of a rapidly progressive tuberculous infection?

The proof is that although tuberculosis may appear as a complication of any form or type of diabetes, it is to-day an excep- tional occurrence in the benign forms, those without denutrition; it is in the grave forms, with well marked denutritior~, that we meet the greatest incidence of tuberculous infectious.

I t was formerly believed that diabetes in the young subject was never complicated by tuberculosis; this view is inaccurate, and the two cases which I cite later are those of young people.

I have stated that the pathogenesis of tuberculous infection in the diabetic subject is still an obscure process; in strict fact, we are reduced to hypothesis to explain its occurrence. :Contact infection, upheld as the method .of origin by certain observers, can account for only a very small number of cases indeed. De- nutrition is apparently a more potent causal factor; tuberculous infection, however, is observed in cases of diabetes without denutrition, so that this explanation will hold for only certain cases. A humoral pathology has also been invoked to account for the origin of tuberculosis in the course of diabetes. The tubercle bacillus has a definite predilection for saccharine media; this observation, which has been verified experimentally, deserves to be kept in mind'. The existence of a definite weakness of the body defences in diabetes has also been alleged, and Labb4 and Boulin have considered the possibility of such anergic mechanism. In this connection, it would be of interest to undertake the syste. matic study of the skin reaction in diabetics.

The clinical picture of tuberculosis as it affects the diabetic is more exact in its description. 'The infection appears un~ler various forms, but all have in common a caseous evolution, from the pneumonic or broncho-pneumonic type to the usual ulcero- caseating form. In all cases its progress is rapid and serious, so that in the absence of treatment it is definitely fatal, which, indeed, it often is despite all our therapeutic efforts.

Whatever be the clinical cause of the infection, a certain number of signs are common to all forms. The rapidity of ex- tension of the lesion is one of its most characteristic trai ts; although the hyperacute forms are rare the duration of the disease rarely exceeds a few months as a general rule. The apparently latent nature of these lesions, notwithstanding their gravity and their extent, is likewise peculiar to this form of

234 I R I S H JOURNAL OF MEDICAL SCIENCE

tuberculosis. P idoux used to teach tha t there were no physical signs which revealed the presence of tuberculosis in diabetic subjects. Actual ly, we must not expect to find the character is t ic ~igns of a general infect ion: loss of weight is present , but it is as much to be a t t r ibu ted to the diabetes as to the tuberculous process, nor is a diabetic who is losing weight necessari ly tuberculous. The t empera tu re of ten remains normal, or at least shows but sl ight elevation. Few funct ional signs are present : cough and expectora t ion are of ten missing; a still more curious fac t is the abs6nce of Koch ' s bacillus f rom the sputum, or at least its presence in scanty numbers, or its in te rmi t ten t appearance only. The local signs, however, are more obvious. Auscul ta t ion will often reveal widespread evidence of an unexpec ted nature . Radiological examinat ion will invar iably furnish us with the surest p roof of the existence and the extent of the tuberculous lesion, as well as of its p rogress ; it may disclose the existence of extensive damage to the lungs, involving the loss of a sub- stantial amount of lung tissue, which would have remained un- suspected in a diabetic subject who was present ing an apparen t ly sa t is factory condit ion of health.

I t is a common err.or tha t tuberculosis gives rise to v e ry l i t t le h~moptys is in diabetic subjects ; this idea needs revis~ion; as we shall see, in one of our pat ients the actual cause of death was a profuse hmmoptysis.

I f the diabetes leaves its special impr in t on the charac ter of the tuberculous process, does the evolutio~ of the tuberculosis in tu rn produce any effect on the course of the diabetes ? I t is a classical observat ion that towards the close of the tuberculous evolution the diabetes to a cer ta in ex ten t becomes effaced. The glycos.uria diminishes, and will even completely disappear ; the disapI~earance of sugar f rom the urine will be la rge ly due to the considerably reduced intake of food. ~Coming nearer to our own day, Lundbe rg maintains tha t tuberculous tissues contain a sugar- reducing substance, to which he gives the name o~ " para- insu l in ." Labb~, who has subjected the observations recorded by Lundbe rg in suppor t of his theory to a .most r igorous analysis, has demons t ra ted thei r f au l ty founda t ion : the diminut ion in the glyeosuria and acetonuria, as also the increased tolerance to carbohydrates in Lundberg ' s cases are solely due to the effects of the combined insulin and dietetic t rea tment .

On the contrary , it seems as if there were an aggrava t ion of the diabetic process fol lowing on the development of the tuberculous infection. This la t te r commences like a diabetic crisis, but is amenable to t rea tment . Our own observations tend to confirm those of Labb~.

A boy of 19 years, recently under my care at hospital, demonstrated the r course of a case of advanced diabetes complicated by tuberculosis of rapidly fatal evolution. J~or two years his diabetic condition had escaped recognition, and after this period of time the diabetes became complicated by an ulcero-caseous form of pulmonary tuberculosis of low virulence but of singularly wide extent. In his 17th year he had shown


t h e f irst signs of d iabetes , which remained nnrecognised; i~ was only dur ing our re t rospec t ive enqui ry into .his case-history t h a t we were in a posit~on to ident i fy t h e ear l ier condit ion. For two years he had been to r tu red by a n excessive th i r s t , which obliged him to get ou t of bed several t imes each n i g h t to ge t some th ing to dr ink . There was, however, no sign of any general de te r io ra t ion in his hea l th , and especially no evidence of wast ing As ~o examina t ion of the ur ine ~ad been made, the diabetes was not diagnosed.

I n Augus t , 1928, the fir,st signs of pu lmonary involvement made the i r appearance , a t t e n t i o n being d rawn to t hem by the progressive loss of weight , which was in m a r k e d c o n t r a s t wi th his excellent , no t to say ex- cew a p p e t i t e ; t he re la t ive absence of resp i ra to ry physical signs failed as' ye t to draw a t t e n t i o n to the side involved.

~One m o n t h la ter , the s imul taneous discovery was made of bo th the d iabetes and the tuberculosis ; ~ollowing the usual rule,, an exacerbat ion of t h e :~uberculous process had promoted a .diabetic crisis, wi th bulemia, sudden 'increa,se in loss of weight , and an excessive polyuria, amoun t ing to 6 and 7 litre,s ~n • 24 hours.

On hi~s admission to hospital , t he re was an a lmost en t i re absence of cough or s p u t u m ; physical examina t ion disclosed widespread symmetr ica l cavi ty fo rma t ion ; rad iograms revealed the presence of two enormous para- h i la r areas of ,ins made up of i r regular , non-homogeneous patches speckled wi th definite cavit ies on bo th sides. The diabetes was mani fes ted by a polyuria exceeding 3 l i t res in t he 24 hour s ; .by marked glycosuria, a m o u n t i n g to 76 gins. of glucose per l i tre, and t he excret ion of 251 gms. in the 24 ,houus ; acetone and acetylacet ic acid were p re sen t in the propor- t ions of 0.199 per l i t re and 0.656 gins. in the 24 hour~. The blood-sugar amounted to 1.79 gms. per l i t re .

I n view of t he e x t e n t of the tuberculous lesions and the severi ty of the diabet ic crisis, t h e following l ine of t r e a t m e n t waa i n s t i t u t e d : a careful r egu la t ion af the dmt was suppor ted by the admin i s t r a t i on of 60 un i t s o~ in,sulin per day, and a series of in t rave inous iniect ions of sanocrysin. This t r e a t m e n t , howev.er, did no t appear to exer t much influence upon the course of t he tuberculosis . The phy.sical signs remained unc]~anged, and rad iograms showed t h a t w i t hou t any f u r t he r wide extens ion of the process t h e cavity fo rmat ion was increasing. Up to th i s t ime the t empe ra tu r e had remained about normal , a n d of ten subnormal , b u t ~ow fever set in, wi th marked ~s~illations. The p a t i e n t ' s phy,sical condi t ion rapidly d~simproved, while he h imsel f r emained optmlis t ic and cheerful, wi thout p resen t ing ~he common and l amentab le chain of symptoms which are general ly evinced by tuberculous pa t i en t s in a s t a t e of advanced cachexia.

The t r e a t m e n t of the diabetes was .more effective. T~he polyuria became markedly diminished, reducing steadily t rom the ini t ia l 3 l i t res to 2, t h e n to 1.5 and tinally to 1.2 l i t res in the 24 hours. A t t he same t ime, the glycosuria decrea.sed from 77 gins. to 72, t h e n to 52, and finally to 44 or 45 gins. per litre. The daily excret ion of sugar fell ~rom 200 gins. to 53 or 54, .but the blood sugar remained as h igh as before. The ke tone bodies, a l t hough cont inuously present , were none the less reduced in amount , and one found only 0.15 gin. acetone per l i t re and 0.199 gin. in t h e 24 hours ins tead ,of the figures 0.27 and 0.656 of the earl ier es t imat ions .

Under these condit ions, despi te the a p p a r e n t improvement of the d iabetes , t h e prognosis could not be otherwis~ t h a n ext remely grave. The pa t i en t had wasted to the proport ions of a skeleton, and our young p a t i e n t succumbed to his maladies one m o n t h and a half a f te r his en t ry ~ t o hospi ta l w i thou t hav ing a t any t ime mani fes ted any of t~le usual ,signs of a progressive and fa ta l pu lmonary lesion.

:In a second case, t h a t of a voung m an of 24 years, who died recent ly while unde r our care, we wa tch~ l a similar evolut{on of the combinat ion of d iabetes and pu lmonary tuberculosis . In th i s pa t i en t , the diabetes would appear to have had a sudden o n s e t : marked th i r s t , lass i tude and was t ing .set in ab rup t ly in December, 1927. Three mon ths la ter~ on his f irst medical e x a m i n a t m n , were found the signs of a simple diabetes , w i thou t acidosi.s ; careful regu la t ion of the diet , wi~h the daily admin i s t r a t ion of 30 un i t s ot msuhn , was sufficient to produce the complete d~sappearance of suga r from the urine. I t is i m p o r t a n t to note t h a t in t lds ins tance a complete and careful physical e~am~nation was made, on which occasion t he re were no signs of any pu lmonary lesion.

236 I R I S H J O U R N A L O F M E D I C A L ~ C I E N C E

~During the following month the patient 's condition became so satisfac- tory that on his own initiative the insulin injections were dispeased with. Immediately, the glycosuria re-appeared. But i t was only 4 months ~later tha t the first ~igns of lung trouble made their appearance : a few shivering fits, stitch in the side, a little cough, and finally a slight haemoptysis.

The patient was re-admitted to hospital, where examination revealed the presence of a bilateral pulmonary tuberenlosis, and the diagnosis was con- firmed ~by the discovery of Kooh's bacillus in the sputum.

gmmediately afterwards, we watched the patient pass through a positive diabetic crisis, in which the glycosuria rose to 120 gms. per litre, the blood- sugar to 2.89%, and acidosis developed.

With the cough, the sputum was tinged with blood. But his general condition remained good, even though, as in the fi~st case, the physical signs were well marked. Moist tales were found over both putmonary areas, most marked at the left apex. Radiography conilrmed the inv.olve- ment of .both lungs; both sides were literally sown with patches of a non- homogeneous nature, more marked and more numerous on the left side.

,An energetic t reatment was instituted, ~but neither a rigorous dieting, nor the daily administration of 180 units of insulin, aor yet the intra- veinous injection of crysalbin afforded any check to the onward maroh of either the diabetes or the tuberculosis. The acidosis persisted, and the cry~aLbin seemed (as in the preceding observation) only to increase the febrile reaction. One month after his entry into hospital the patient died suddenly from an abundant haemoptysis.

O u r p r e d o m i n a n t r eco l l ec t ion of these tw o cases is the associa- t i o n of the onse t of the t u b e r c u l o u s i n f e c t i o n w i t h a d i a b e t i c cr is is of the u t m o s t s eve r i ty , e h a r a c t e r i s e d b y the d e v e l o p m e n t of a n a c e t o n u r i a wh ich r e s i s t ed a l l i n s u l i n t r e a t m e n t . F u r t h e r - more , t he t u b e r c u l o u s process was in no w a y in f luenced b y c h e m o - t h e r a p e u t i c m e a s u r e s ; on the c o n t r a r y , t he a d m i n i s t r a t i o n of go ld p r e p a r a t i o n s w o u l d seem on ly to have g i ve n r ise to a m a r k e d febr i l e reac t ion .

H a p p i l y , however , a l l cases of t ube rcu lo s i s i n d iabe t i c s a r e n o t of such sever i ty . T r e a t m e n t can, i n c e r t a i n cases, p r ove efficacious, a n d we m a y f ind a good exampl e of such in a case which I p r e s e n t e d in 1924 ( in c o l l a b o r a t i o n w i th M. Sa lomon) to the Soci~tg m~dicale des H~pitau:c d~ Paris.

I t was that of a woman aged 41 years, who had for several years exhibited a moderately large goi tre , which had appeared suddenly, accom- panied by signs of mild toxicity. The basal metabolic rate (increased by 51%) demonstrated the toxic nature of the goitre. But while our patient had up to the time of the development of the goitre ,been of a certain oorpulen% and florid ~spect, in April, 1923, she commenced to cough, to expectorate, and to lose weight. For a period of 18 months she ran a feverish course, suffered from malaise and lost some 44 l~bs. in weight.

At the time of her admission to hospital, there were definite signs of cavity formation a t the apex of the left upper lobe. A radiogram showed a cavity about 10 cms. in diameter in the left pulmonary field. The rest of the field was of diminished transparency; the retraction of the media- stinum was such that the right margin of the heart was situated between the line of the spinous processes and the left border of the vertebral column. The right pulmonary area, on the other hand, was of perfectly normal appearance. The cavity formation in the left lung was associated with the presence of Koch's bacillus in the sputum.

T,hese tu,berculous lesions had developed in a diabetic subject. For at least two months previously, the patient had been aware that she had glycosuria. The appetite was enormou.sly increased, while thirst was only moderate. The polyuria did not exceed 2 litres in the 24 hours. The glycosurla, which had at one time reached 49 gms. in the 24 hours, was reduced by dietary treatment to 17 gms. No acetonuria developed, but the blood-sugar reached t,he figure of 2.1, and even 2.4, gms. per litre.

T U B E R C U L O S I S AND D I A B E T E S 237

In this patient's case, presenting as she did a goitre, fever, definite tuberculosis in full activity and a diabetes without denutrition, we were to register a remarkable therapeutic success. As the pulmonary lesion was unilateral, we were abIe to employ artificial pneumothorax, at the same time effecting a marked reduction in her carbohydrate intake. The fever rapidly came down, the cough and expectoration diminished, and the bacilli ~l~sappeared from the sputum. The diabetes showed a similar improvement~ sugar was no longer .demonstrable in the urine, and the blood-sugar fell to 1.9 gins. .In addition, her general condition showed an extra- erdi~ari~y rapid improvement. Sev.en months after the establishment of the pneumotherax, she had regained the lost 44 lbs., and, without adhering to a very ,strict dietary, no further sugar appeared in the urine.

To .sum up, in this patient the onset of the tuberculous lesion had set alight a diabetic crisis. This aggr~v.ation of the diabetic state, iS is true, was of a moderate type, and we had not here the clinical picture of grave ~tiabet~ with acidosis observed ~n ,the two other patients. But the prog- noses appeared serious in the extreme owing to the febrile state and rapid cavity formation. Despite this fact, the establishment of an artificial pneumothorax brought the tuberculous lesion to a complete standstill, and in conjunction with a dietetic regime favourably influenced the restoration of the paVient to her former appearance of florid good health.

There are thus, as we see, cases of widely different behaviour in the ca tegory which we have been studying. A rat ional thera- peusis is necessary for all. F i r s t and foremost, we must cast aside t radi t ional errors, of which the most prevalent is that of t reat ing tuberculous diabetics by super-alimentation. The only tar~gible result of this course is to increase the blood-sugar and to aggrava te the diabetes. I t is agreed that there is an absolute necessity for careful regula t ion of the diet, following the same principles as obtain in non-tuberculous diabetics. Marcel Labb~ has r igh t ly insisted on the f requency with which dietetic treatment alone will reduce the glyc~emia with excellent effect on the tuberculous process, in thus render ing the tissue fluids less favourable to the g rowth of the tubercle bacillus.

Are we to use insulin, and what m ay we expect f rom its use ? Some years ago, it was mainta ined that insulin had an nn-

favourable effect upon the tuberculous lesions. Two cases of Blum, others repor ted by Chabrol and by S~zary, appeared to lend suppor t to this opinion. Our better acquaintance with the course of the tuberculous process in diabetic subjects, and the improved dosage of insulin, no longer permit us to believe in such an unfavourable action. The observations of Sausum, H a r t and Creele, Peco, and Labbd prove that a diabetic patient, even though tuberculous, should receive as much benefit f rom insulin as any other. At the same time, Blum has again recent ly put fo rward the hypothesis tha t injection of insulin can at t imes provoke the lighting-up of a tuberculous lesion. These alleged aggravat ions occur, as we believe, only in cases where the insulin remains inact ive; in them, the tuberculous process but follows its inevitable and inexorable course. There are, on the contrary, numerous observations to show that very f requent ly insulin modifies in the happiest manner the evolution of the diabetes and the tuberculosis alike. I t may happen, of course, as in our first two cases above, tha t the insulin exerts a beneficial effect upon


the diabetes without in any way influencing the rapid progress of the active tuberculous lesion.

Against the tuberculous lesion itself, we possess an excellent we~.pon in artificial pneumothorax, when the presence of a unilateral lesion permits of its employment under conditions favourable to success.

Lucherini, an Italian observer, has put forward the objection that the establishment of a pneumothorax increases the blood sugar. The injection of air will occasionally produce slight febrile reactions ; such instances are to be seen apart from diabetic eases. The reactions are of no importance. In practice, we should establish an artificial pneumothorax in every instance where we can be sure that the lesion is unilateral. Unilateral lesions are none too common. Tuberculous infection in the diabetic subject is so often latent in character that very frequently they are already bilateral when revealed for the first time. The attempt has been recently made to establish a bilateral pneumothorax in such cases; the results, however, are most un- certain, as demonstrated by two recently published cases ,~f Labb6's.

We have also been led to hope that good results would be obtained in these cases from the use of the gold salts, whieh for several years past have given remarkable results in the extensive ulcero-caseous forms of tuberculosis. Up to the present, we have to admit that the gold t reatment has been without effect ; we have even seen unfavourable results from its employment, for in two severe cases so treated by us the administration of crysalbin was followed by marked temperature reactions in subjects whose course had been hitherto afebrile, and without the slightest improvement in the tuberculous condition. In another patient whom I saw in private practice with M. Labb~ we observed a similar unfavourable result. Are we to believe that in such cases it is a question merely of dosage or of the drug chosen ? Will fresh trials prove any more hopeful ? We hope so; up to the present we have no authori ty for the conclusion that the gold therapy plays any useful par t in the treatment of thL special type of tuberculous lesion associated with diabetes.

To sum up, we need to employ a combination of the bess therapeutic methods in dealing with an associated diabetes and tuberculosis. Our results will depend on the severity of the twc associated diseases; they will be better in the cases of diabetes without denutrit ion; they will be easier to obtain where the tuberculous lesion is unilateral; and will depend largely on the stage at which the treatment is undertaken. Observations are now sufficiently numerous to allow of the statement that wc are better armed to-day for our combat against this formidable com. plication of diabetes.

To the observation published in collaboration with Salomon in 1924 we should add an old case of Forlanini 's, and a cure reported by Sklodowski and Konopnicki in 19~6; in all of these

T U B E R C U L O S I S AND D I A B E T E S 239

cases, either alone or in association with dietetic and insulb~ treatment, pneumothorax was successful. More recently, Labb~ has published even more favourable reports of the efficacy of the combination of dietetic t rea tment with insulin and pneumothorax. In 1928 Lenoir published a remarkable case of recovery in a yotmg subject entirely at t r ibutable to this triple line of treatment. Other similar results have been published in the past few months by Blum (Strasburg) and by Roques and Izzo (Buenos Ayres) , where this combined line of t reatment has been productive of a s t r ik ing success.

We have only to recall these improvements and cures to estimate the progress effected. The classical gloomy prognosis of tuberculous infection in diabetics is l ightened to-day, thanks to the combined use of modern me~hods in the t rea tment of the two diseases. One mus~ institute them, however, at the earliest possible moment, before the diabetes has become associated with denutr i t ion and while the tuberculous lesion is confined to one lung. The early diagnosis is admittedly difficult by reason of the long latent period of tuberculosis in diabetics; and owing to its rapid evolution once aroused, the f a w u r a b l e time for t rea tment is not of long duration. Hence we may say tha t this pathological association leawes no time for pro longed reflection on, the best course to adopt ; one must act without hesi tat ion; on the im- mediate establishment of a pneumothorax and the use of insulin depend the sole hope for cases hitherto considered to be of fatal prognosis.

T~E LATE ~IR JAMES MACKE,NZIE, M.D.

We .have received from :Masterpiece Engravings, ~bd. (Dunedin House, Basinghall Avenue, London, E.C.2) a beautifully execu~d proof in mezzo- tint of the portrait .of the la~ Sir Jame~ :Mackenzie by Herbert Sedcole. The plate h~s been engraved from a drawing by Sir James's daughter T~e proofs (signed by the artist) are obtainable at s 2s. 0d. ea~.h, in monochrome (no other state).

This portrait of an investigator of .singular courage, per.severance and optimism who, year in, year out, pursued his epoch-making researches into cardiac function amidst the hurly-burly of general practice in a busy Lancashire town, shows Mackenzie in ~is doctor's robes, at the summit of his career, the head of a great Institute for Research, Vhe Consulting Physician to .H.M. the King. ~he ,hair and beard are white, the face expresses a certain rugged serenity, but the lips tightly compressed beneath the short moustache and beard and the .slightly fro~wning brow.s lend a certain doggedne,ss to the facial expression, ~le native Scottish " dourness " doubtless accentuated by the long uphill fight of a lifetime to uphold and maintain his theories. There ~s little repose shown here, even in the evening of successful age. ~t is a striking portrait, and one handsomely fitted to adorn a doctor'.s study or library.

tuberculosis and diabetes

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