Diabetes Mellitus and Autoimmunity

Diabetes Mellitus and Autoimmunity

1124 duction of neutralising antibody is the essential for failure of viral elimination in HBsAgpositive chronic active hepatitis. Although no dramat...

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duction of neutralising antibody is the essential for failure of viral elimination in HBsAgpositive chronic active hepatitis. Although no dramatic clinical effects have been observed in the studies reported so far-perhaps because the dose of interferon was too small or the period of treatment too short-there are clearly other areas of interest in relation to hepatitis-B virus infection. An immediate practical benefit may be the reduction in infectivity which should parallel the fall in production of Dane particles. reason

Diabetes Mellitus and Autoimmunity FOR several years circumstantial evidence has been accumulating that insulin-dependent diabetes is associated with disorders of the immune mechanisms. A statistical association between insulindependent diabetes and the organ-specific "autoimmune" diseases, Hashimoto’s disease, pernicious anaemia, and idiopathic adrenal atrophy, has been detected,I-4 and serological work has revealed high prevalence of humoral, organ-specific autoantibodies in insulin-dependent diabetes. These include antibodies to thyroid and gastric parietal-cell cytoplasm, to intrinsic factor, and to adrenal cortical tissue.2-4 Schmidt’s syndrome, a combination of adrenalitis and thyroiditis, has been reported associated with insulin-dependent diabetes in nearly 200 cases.5 There are also accounts of families with multiple disorders affecting the immune mechanisms and associated with insulin-dependent diabetes.6 Insulitis, described by SCHMIDT in 1902,’ has been reported several times in acute, rapidly fatal cases of juvenile diabetes.8 The intensity and distribution of the insulitis is variable and the islets are infiltrated predominantly with lymphocytes. This insulitis has been invoked to support the autoimmune concept of diabetes, by analogy with thyroiditis and adrenalitis; but, as DoNIACH pointed out,9 plasma cells are absent from the islet infiltrate and there is no lymphoid-follicle formation, these being features of the accepted organspecific disorders. Cell-mediated immunity to pancreatic elements other than insulin has been

the leucocyte-migration technique in third of diabetics-mainly, but not enabout tirely, those with insulin-dependent diabetes.10 11 Earlier reports of humoral antibodies in diabetics were discounted as artefacts. In 1974, however, two groups reported the occurrence of isletcell antibodies (I.C.A.) in insulin-dependent diabetics with coexistent autoimmune disease."13 Both groups felt it necessary to state that I.C.A. were likely to be uncommon in diabetics, occurring only in patients with overt autoimmunity. But this view was soon overtaken by events. i.c.A. are now known to be common in newly diagnosed juvenile diabetics,14 15 their prevalence and titre falling with duration of the disease.15 Indeed, on p. 1097 this week, Dr IRVINE and his colleagues claim that I.C.A. can be detected in 05% of the general population. Like LENDRUM et aI.,15 the Edinburgh workers find that I.C.A. may precede the onset of diabetes by several years. Whether the I.C.A. are concerned in the genesis of the diabetes and whether they can be regarded as a marker for the condition, remains speculative at present. The I.C.A. reported to date are non-specific and may react with any or all of the islet-cell types-not just the insulin-producing -cells. BoTTAZzo and LENDRUM16 have lately reported specific islet antibodies, so more precise answers may be in the offing. Meanwhile, BoTTAZZo and DONIACH17 have presented an attractive hypothesis. Adopting the terminology suggested by CUDWORTH18 of types I and II diabetes (I=juvenile-onset or dent diabetes; Immaturity-onset diabetes) they have divided type I into IA, associated with temporary I.C.A. positivity perhaps secondary to viral disease of the islets, and IB associated with greater permanence of I.C.A. and with other, organ-specific autoimmune disorders. The discovery of the relationship between insuand certain histocompatibilin-dependent diabetes 20 lity antigens,19 together with the possibility of viral21 and immunological factors in the setioiogy, has stimulated a great deal of interest and research. In the excitement we must not forget the 3-cell itself and its apparent vulnerability. As GEPTS and his colleagues22 have shown, at a time when the

displayed by a


Nerup, J., Andersen, O. O., Bendixen, G., Egeberg, J., Gunnarsson, R., Kromann, H., Poulsen, J. Proc. R. Soc. Med. 1974, 67, 506. 11. MacCuish, A. C., Jordan, J., Campbell, C. J., Duncan, L J. P., Irvine. W. J. Diabetes, 1974, 23, 693. 12. Bottazzo, G. F., Florin-Christensen, A., Doniach, D. Lancet, 1974, ii, 1279 13. MacCuish, A. C., Barnes, E. W., Irvine, W. J., Duncan, L. J. P. ibid. p. 1529. 14. Lendrum, R., Walker, G., Gamble, D. R. ibid. 1975, i, 880. 15. Lendrum, R., Nelson, P. G., Pyke, D. A., Walker, G., Gamble, D R Br. med. J. 1976, i, 553. 16. Bottazzo, G. F., Lendrum, R. Lancet, Oct. 23, 1976, p. 873. 17. Bottazzo, G F., Doniach, D. ibid. Oct. 9,1976, p. 800. 18. Cudworth, A. G. Br. J. Hosp. Med. 1976, 16, 207. 19. Nerup, J., Platz, P., Andersen, O. O., Christy, M., Lyngsoe, J. Poulsen J. E., Ryder, L. P., Staub Nielsen, L., Thomsen, M., Svejgaard. A. Lancet, 1974, ii, 864. 20. Cudworth, A. G., Woodrow, J. C. Diabetes, 1975, 24, 345. 21. Steinke, J., Taylor, K. W. ibid. 1974, 23, 631. 22. Gepts, W., de Mey, J., Marichal-Pipeleers, M. Diabetologia (in the press).

10. 1. 2.

Ungar, B., Stocks, A. E., Martin, F. I. R., Whittingham, S., MacKay, Lancet, 1968, ii, 415. Irvine, W J., Clarke, B. F., Scarth, L., Cullen, D. R., Duncan, L. J. P.

I. R. ibid.

1970, ii, 163. 3. Whittingham, S., Mathews, J. D., MacKay, I. R., Stocks, A. E., Ungar, B., Martin, F. I. R. ibid. 1971, i, 763. 4. Nerup, J. in Immunity and Autoimmunity in Diabetes Mellitus (edited by P. A. Basteme and W. Gepts); p. 149. Amsterdam, 1974. 5. Carpenter, C. C. J., Solomon, N., Silverberg, S. G., Bledsoe, T., Northcutt, R. C., Klinenberg, J. R., Bennett, I. L., Harvey, A. M. Medicine, 1964, 43, 153 6. Blizzard, R. M. in Textbook of Immunopathology (edited by P. A. Miescher and H. J. Müller-Eberhard), p. 547 New York, 1969. 7. Schmidt, M. B. Munch. med. Wschr. 1902, 49, 51. 8 Gepts, W. Diabetes, 1965, 14, 619. 9 Doniach, I. in Immunity and Autoimmunity in Diabetes Mellitus (edited by P. A. Bastenie and W. Gepts); p. 175. Amsterdam, 1974.


other endocrine cells in the islets are flourishing. We may need to know more about the &bgr;-cell to make sense of the disorders of the immune system.

;,-ceUs have atrophied,


fibreoptic endoscopy of the upper aliendoscopists usually sedate the patient with incremental doses of diazepam. The amount of diazepam is kept to a minimum to avoid serious respiratory depression and loss of consciousness-complications which would require the presence of an anaesthetist. Successful management of these patients, most of whom are outpatients, requires an agent which produces the following conditions after intravenous injection : rapid, flexible sedation and analgesia without loss of consciousness or agitation; stable cardiovascular system; little respiratory depression; no nausea or vomiting; and a rapid uncomplicated recovery. Diazepam fulfils most of these requirements but it is not ideal. Le Brun’ reports his dissatisfaction with the analgesia provided by diazepam and he finds that the discomfort of gastroduodenoscopy can be reduced by employing neuroleptic drugs along with this agent. He advocates premedication with droperidol 5 mg and fentanyl 0.1 mg by intravenous injection half an hour before endoscopy. In elderly and infirm patients this dosage is reduced by half. In the endoscopy room droperidol 10 mg and fentanyl 0.11 mg are given intravenously through an indwelling needle in the forearm. Again dosage is reduced in the frail and elderly. Next, the pharynx is sprayed with 4% topical lignocaine. Diazepam is then given incrementally (about 1 mg per minute) until the patient is moderately drowsy. At this stage the patient is asked to turn onto his left side and endoscopy is begun. In only a few cases is further injection of diazepam required during the procedure. Outpatients are allowed to leave hospital, accompanied by a responsible person, within two to four hours of endosTo facilitate mentary tract,

copy. Whilst relief of the discomfort of endoscopy is a worthy aim, there are potential hazards when potent agents are given intravenously by the unaided physician. His attention is going to be focused on the instrument rather than on the patient. Darkening of the endoscopy room will make observation of the patient more difficult for assistants. A sensible precaution is to carry out endoscopies in the operating area, where the help of an anaesthetist is available should an emergency arise. Though Le Brun concluded, after a trial lasting a year during which 250 patients were investigated, that the intravenous-sedation technique was suitable for use by the endoscopist working without an anxsthetist, he does not dispel doubts about giving droperidol to outpatients. The action of droperidol can last for many hours and the manufacturer warns that patients who have been given this agent for minor surgery should not drive or operate machinery for 48 hours.2 Two undesirable effects of droperidol are extrapyramidal movements and psychic disturbances, both of which are usually eli1 Le Brun, H. I. Gut, 1976, 17, 655. 2 AGuide to Anæsthesia with Droleptan ceuticals Ltd. Marlow, Bucks.


p. 10.

Janssen Pharma-

by concomitant administration of fentanyl and diazepam. However, because the action of droperidol considerably outlasts that of the other two drugs, the pa-


tient’s muscle coordination and mental state may be compromised later, perhaps the next day. Even after diazepam alone, recovery is not uncomplicated. If the patient is kept lying down after intravenous sedation with diazepam, the drug may briefly be remobilised when the patient first becomes ambulant, as shown by Hannington-Kiff3 in dental patients. He advocates giving patients a short period of activity before they are due for discharge so that any recrudescence of drowsiness will take place under supervision. Patients may seem to have recovered well about two hours after intravenous diazepam only to become drowsy again several hours later-possibly owing to intestinal resorption of diazepam secreted in the bile. Clearly, the single-handed endoscopist must make himself familiar with the risks of intravenous anæsthesia. The person escorting the patient home should be told about necessary precautions and given a sealed envelope containing a standard form detailing the drugs administered and what has been done. This can be handed to the general practitioner should a complication arise after discharge from hospital; or, if all goes well, it can later be transmitted to the family doctor for information. The endoscopist/anxsthetist would be well advised to adhere to the routine evolved in his hospital for the management of surgical day-cases.


THIS year is the twenty-fifth anniversary of the opening of the medical faculty of the University of Natal. Established at King Edward VIII Hospital in Durban to train Black doctors, it is now active in teaching, patient care, and research. Still the main teaching hospital, this must be one of the busiest in the world. It has 2100 beds and for convalescent patients uses another 1300 at an auxiliary hospital a few miles away. Despite this accommodation, it is always full and often overcrowded. Its main task is to serve the African and Indian communities of a metropolitan area which has more than a million people. Among them, primary health care is almost non-existent, so between two and three thousand sick and injured come to the outpatient and casualty departments each day. Apart from this function, King Edward VIII Hospital provides specialist care for much of the population of southern Natal. For this purpose it uses its own stretched facilities and those at Wentworth Hospital (built by the Royal Navy in World War II) where there are cardiac, thoracic-surgery, and neurosurgical units. Although heavily burdened with patients, these hospitals are properly staffed and are equipped with modern facilities for diagnosis and treatment. The abundant clinical material and the gross disease encountered would have been familiar to Osler and Horder in their hospital work; they set the stage 25 years ago for a thriving medical school in Durban. And this indeed is what it is. The South African Medical journal recently commemorated the school’s foundation in a special issue (Sept. 25). In 3. Hannington-Kiff, J. G. SAAD Digest, 1972, 1, 235. 4. Baird, E. S., Hailey, D. M. Br. J. Anœsth. 1972, 44, 803.