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Page 1: Diabetic Micro-angiopathy


recommending intracardiac surgery. CAMPBELL

suggests that the indications for operation include,in addition to the electrocardiographic pattern,a jugular " a


wave, severe symptoms, or muchcardiac enlargement. Cyanosis with clubbing of thefingers always means severe stenosis, with risingpressure on the right side causing a shunt, usuallythrough the foramen ovale or an atrial septal defect.It seems that patients with moderate or severe

stenosis, but without any of these signs, should beseen regularly and, if there is any hint thattheir condition is deteriorating, should be examinedby cardiac catheterisation. Angiocardiography is

unlikely to help, for the experienced operator candetect with the catheter whether the stenosis isvalvular or infundibular, besides recording pressuresin each chamber. CAMPBELL believes that operationshould not be be long delayed if the patient’s condi-tion is deteriorating and the right-ventricular pressureis 100 mm. Hg or more, while DIMOND and LiN

suggest a figure of 75 mm. Certainly the risk ofoperation increases alarmingly as the patient becomesmore severely disabled, 8 The results of pulmonaryvalvotomy to be published by CAMPBELL may givefurther information on these problems.

1. Lundbaek, K. Lancet, 1954, i, 377.2. Ditzel, J. New Engl. J. Med. 1954, 250, 541.3. Ditzel, J., Sagild, U. Ibid. p. 587.

Diabetic Micro-angiopathyINCREASING success in the treatment of primary

diabetic symptoms, and the consequent greaterlongevity of diabetics, accentuate the importance ofwork on the mechanism of diabetic complications.These involve mainly the vascular and nervous

systems, eyes, and kidneys, and it would be satisfyingto find explanations that were common to such variedmanifestations. The most obvious common factor isthe vascular supply, which might be particularlyprone to involvement in certain organs because of

special local conditions. In advanced vascular diseaseof diabetics all types of blood-vessel are involved, 1but careful study indicates that capillary lesions mayprecede sclerosis in other parts of the vascular system.2In this sense are the capillary changes primary ;and those tissues in which the capillary bed formsthe only vascular component, such as the innernuclear layer of the retina, the glomeruli of the kidney,and the pancreatic islets of Langerhans, are the veryones particularly prone to degenerative change indiabetes. Detailed study of the capillary changesin diabetics thus promises to increase our under-

standing of the pathogenesis of the complicationsof diabetes.

In two sites of the living body-the conjunctivasand the nail beds-capillaries can be examined withrelative ease under normal conditions, using a cornealmicroscope which can give a magnification of from16 to 150. It may be assumed that the conjunctivaland nail-bed capillaries fairly represent all the capill-aries of the subcutaneous layer, but they may well beless affected by diabetes than those in the particularorgans subject to the common complications. DITZELand SAGILD 3 studied the conjunctival vessels of 150diabetics and 90 normal controls. In the diabetics the

capillaries were more numerous and elongated, par-

ticularly in their venous parts, forming an irregularnetwork. It was also noted that the blood withinthem was often in large aggregates which tended

seriously to obstruct the rate of flow. The distensionof the venules, sometimes to two or more times theirnormal diameter, contributed further to the sluggishflow. It is said that aggregation of red blood-cellsor


sludging " does not occur to any significant

degree in healthy people, although it is common in

many diseases 4 ; and such gross distension of thevenules was not seen in the 90 controls. Capillarymicro-aneurysms, so characteristic of diabetic retino-pathy, were no more common in diabetic conjunctivaethan in the normals. These studies of the living arereinforced by a formidable number of examinations ofdead tissues. 5-8 Thus, the elongation and angularcourse of capillaries has been noted in diabetic retinze, 5 8where in addition BALLANTYNE and LOWENSTEIN 9

described the micro-aneurysms in the venous segmentsof the capillaries. It is from these micro-aneurysmsthat red cells may escape to produce haemorrhages,1Oand their subsequent hyalinisation and fusion producesthe typical waxy exudates of diabetic retinopathy. Inthe glomeruli of the kidney, too, there is proliferationand hyalinisation of the capillary walls." Parts ofthe capillaries may be dilated,12 and, with the eye offaith, micro-aneurysms may be made out.13 Patientswith these capillary changes in the fundi are extremelylikely to have them in the kidneys as well, althoughthey probably occur rather later there.l0 Hyalinisationof the islets of Langerhans, a common finding in olderdiabetics,14 may represent a similar process. Thereare conflicting accounts of the presence

15 16 or

absence 7 10 of such changes in other tissues.Besides these morphological changes in the capill-

aries there is also evidence for abnormal capillaryfunction in diabetes. Some workers 17 18 have reportedincreased capillary fragility, measured usually bya tourniquet test; and FREHNER 15 noted increasedcapillary permeability using the method of fluoresceindiffusion.The descriptive stage of study of these changes

is well advanced, but there are many gaps inour understanding of how and why they occur. Is,for instance, the distension of the venules and capill.aries due to mechanical obstruction or to activedilatation ? GIBSON 19 believes that endothelial

proliferation causes the venous distension and thatthe capillary micro-aneurysms develop later. In thishe is supported by BECKER and POST,20 who foundcapillary changes, including micro-aneurysms, in theretinae of eyes with naturally occurring occlusion of4. Knisely, M. H., Bloch, E. H., Eliot, T. S., Warner, L. Science,

1947, 106, 431.5. Friedenwald, J. S. Amer. J. Ophthal. 1949, 32, 487.6. Ashton, N. Brit. J. Ophthal. 1950, 34, 38.7. Friedenwald, J. S. Amer. J. Ophthal. 1950, 33, 1187.8. Ashton, N. Postgrad. med. J. 1950, 26, 391.9. Ballantyne. A. J., Lowenstein, A. Trans. ophthal. Soc. U.K.

1944, 63, 95.10. Ashton, N. Brit. J. Ophthal. 1949, 33, 407.11. Kimmelstiel, P., Wilson, C. Amer. J. Path. 1936, 12, 83.12. Allen, A. C. Arch. Path. 1941, 32, 33.13. Friedenwald, J. S. Trans. Amer. Ass. Ophthal. 1948, 53, 73.14. Opie, E. L. Special Cytology. New York, 1928.15. Frehner, H. U. Thesis. University of Zürich, 1950.16. McCulloch, J. C., Pashby, T. J. Brit. J. Ophthal. 1950, 34, 49517. Hauum, S. Acta ophthal., Kbh. 1939, suppl. 16, p. 3.18. Barnes, R. H. Amer. J. med. Sci. 1950, 219, 368.19. Gibson, G. G. See Beetham, W. P. Trans. Amer. Ophthal. Soc.

1951, 48, 205.20. Becker, B., Post, L. T. jun. Amer. J. Ophthal. 1951, 34, 677.

Page 2: Diabetic Micro-angiopathy


the central retinal vein, and in cats in. which occlusionwas induced by electrocoagulation under direct

ophthalmoscopic vision. DITZEL and SAGILD,3 on theother hand, in their studies of diabetic conjunctivalvessels, noted that the early distension of the venuleswas not associated with constrictions and could nottherefore be attributed to endothelial proliferation :they ascribed the distension to active dilatation. Just

why the dilatation should occur is not known, butvague reference has been made to the possible role ofsuboxidation or subnutrition, and ELWYN 21 ascribedit simply to prolonged hyperglycsemia. DITZEL andSAGILD,3 however, have raised doubts about thecommon assumption that the metabolic changesassociated with diabetes are a cause of the vascular

degeneration. They noted extensive capillary changesin diabetics with only a few weeks’ symptoms ; and ofthe 6 supposedly non-diabetics who showed definiteelongation of the capillaries, 4 had diabetes in theirimmediate family. These suggestive observations needwider confirmation, for they sow suspicion of what isnow an apparently well-established precept-that theincidence of complications in diabetes bears a directrelation to the laxity of diabetic control.22 Such

apparent anomalies may assume undue importanceunless other possible mechanisms in the pathogenesisof diabetic complications are considered. From thesame series of observations,3 for instance, DITZEL andSAGILD suggest that " certain primary changes in themembrane function of the capillaries take place inthe diabetic condition." This view was based on the

surprising frequency of oedema, "

hyaline " infiltration,and punctate haemorrhages in the conjunctiva,associated with only slight haemodynamic changes.Another possibly important factor, not mentionedhitherto, is the disturbance of polysaccharide meta-bolism in diabetes, which, it has been suggested, mayaccount for the hyaline deposition in the eye, kidney,pancreas, and probably elsewhere.23 Much work is

being concentrated on this hypothesis, but it is stilltoo young to have a firm place in unravelling themechanism of these complications.

21. Elwyn, H. Arch. Ophthal. 1944, 31, 376.22. Dunlop, D. M. Brit. med. J. Aug. 14, 1954, p. 383.23. Warren, S., LeCompte, P. M. Pathology of Diabetes Mellitus.

London, 1952.24. Kent and Sussex Courier, July 16, 1954.

The Incompetent Mother"I sentence you to three years’ imprisonment,"

pronounced the judge in one of CHESTERTON’S stories," under the firm and solemn and God-given convictionthat what you require is three months at the seaside."The case seems to offer a parallel to that of a mothersent to prison for six months by the Tonbridgemagistrates’ court,24 on July 13, for neglecting herchildren.The six children, ranging in age from 9 months to

13 years, were dirty and verminous, and so was theirhome ; but a doctor who visited them during May saidat the hearing : " I was surprised to find the generalhealth of the children so good in view of their surroundingsand the apparent lack of food in the hut." He thoughttheir good health must have been the result of outsidehelp, probably in the way of school dinners. An inspectorof the National Society for the Prevention of Cruelty toChildren had been visiting the house at intervals sinceMarch, and urging the mother to do better. On histhird visit she was clearly trying : the house was a

little tidier. and he saw her washing the children. But- since good mothers are not often created in a matterof weeks, or by the method of exhortation-there wererelapses. She did not feed the children very competently,it seems, and certainly there was never much in thelarder ; but on the other hand the larder never seemsto have been entirely empty, and there were alwaysbread and margarine, at least, in the house. As she wasgetting about jB7 a week in various allowances, and onlypaid 12s. 6d. in rent, she could, if she had been anaverage -rnanager, have fed them well ; but clearly shewas well below the average as a manager. Moreover shesmoked a packet of cigarettes in every two days, andwas paying off half a crown a week on a cheap wrist-watch-moderate extravagances which might surely havebeen evidence of a childish desire to console herselfrather than of wicked self-indulgence at the expense ofher children. She attributed her shortcomings as a

mother to her anxiety over her husband, who seems tohave been in hospital over the whole period ; and thishardly seems an unreasonable cause for anxiety, especiallyin a woman who may not be very bright, and who mayhave been much frightened by the responsibility whichhad fallen upon her.

Did anyone, we wonder, interrogate the childrenabout their views on the situation, or their feelingfor their mother, to whom they may well have beenwarmly attached ? The sentence of imprisonment hasnot only separated them from her but from eachother, two of them now being in one residential home,and three in another. They have thus been swept,in a moment, into that group of young people fromwhom we draw such a large proportion of our neuroticsand delinquents-the children deprived of a normalhome life.

During the last decade we have had to face somedisconcerting revisions of our views on what is badfor children. We have learnt, for instance, thatwhile it is bad to deprive a child of regular meals itis worse to deprive him of regular affection ; and thatthe clean inmate of a model children’s home maydevelop less successfully than the dirty member of afar-from-model family. The principle that the familyshould whenever possible be kept together has nowacquired the force of an axiom ; and it is disquietingto see that it can still be set aside as summarily as itwas in the case quoted. This incompetent motherwas given six months’ imprisonment, when what sheneeded was someone to teach her her job. There are

outstanding agencies which give such training-notably, the Family Service Units, and the threehomes in this country-Spofforth Hall near Harrogate,the Brentwood Home in Cheshire, and the MayflowerHome at Plymouthňwhich take incompetent mothers,with their children, into residence, and give them acourse in mothercraft and housekeeping. There arenow active Family Service Units in Liverpool, Man-chester, Salford, Oldham, Sheffield, York, Birming-ham, and London.25 The F.S.U. workers spend theirtime in the homes of families whose problems haveoverwhelmed them-helping with the cleaning andwashing, showing how broken furniture can bemended, decorating dingy rooms, and giving practicalencouragement. The worker accepts the familywithout criticism but with a clear -understanding oftheir limitations, and he makes friends with them,backing his friendship with a confidence in their

capacity to change and live like other people. Since

25. Family Service Units: Fifth Annual Report, 1952-53. Pp. 16.To be had from the secretary, F.S.U., 159, Westbourne Grove,London, W.11.

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