598
A given level of basal hyperglycaemia (e.g., 10 mmol/1)could be obtained from several different combinations ofinsulin resistance and insulin deficiency due to beta-celldysfunction (fig. 2A). It might be possible to obtaininformation on the relative contributions of these factorsfrom the associated basal plasma insulin concentrations.9 9Diabetes can be associated with low, normal, or raised basalplasma insulin concentrations, depending on the relativecontributions of beta-cell dysfunction and insulin resistance(fig. 2B).
.
Hyperglycaemia per se induces post-receptor insulin
resistance, 13 and an increase in plasma glucose concentrationsfrom 5 to 10 mmol/1 doubles the resistance.14 Thus, if
hyperglycaemia occurs, the insulin resistance would be
greater than that expected from the degree of obesity alone.Since fig. 2A is calculated from resistance, this value, ratherthan obesity, should be read off the axis. Thus, a non-obesediabetic patient with a basal plasma glucose concentration of10 mmol/1 would have an insulin resistance of 2.
DISCUSSION
This approach indicates the independent effects of beta-celldeficiency and insulin resistance and the manner in whichthey combine to produce hyperglycaemia. The response ofthe feedback loop to beta-cell dysfunction maintains near-normal basal plasma insulin levels by means of basalhyperglycaemia.5,8 Similarly, in response to insulin
resistance, the basal plasma insulin levels are increased tomaintain a near-normal insulin effect on hepatic glucoserelease. In the computer model, the basal glucose turnoverremained normal over wide ranges of beta-cell dysfunctionand insulin resistance. The maintenance of effective basalinsulin concentrations at the liver and adipose tissue bymeans of basal hyperglycaemia probably accounts for the lackof ketosis in maturity-onset diabetes. However, even grosshyperglycaemia cannot maintain effective basal insulin levelsif beta-cell function is extremely deficient, particularly ifaccompanied by insulin resistance, and ketosis would thenensued The finding that juvenile ketotic diabetics have lessthan 5% of the normal number of beta-cells accords with themodel. 15The results of this analysis are only semi-quantitative
because accurate data on the functions of the various control
points are not available, and the model is a simplification of acomplex homoeostatic system. Nevertheless, the generalrelations arising from the mathematical model are probablycorrect. For instance, if non-glucose, as well as glucose,stimuli control basal insulin secretion,16 this could be
allowed for mathematically by altering the function
describing the beta-cell secretion in relation to glucose. Asmore accurate mathematical descriptions of the control
points become available the predictions of the model willbecome more exact and thus might enable assessment of thedegree of insulin resistance and beta-cell dysfunction fromthe basal plasma insulin and glucose concentrations. ç
However, allowance would need to be made both for th{pulsatile nature of basal insulin secretion 17 and for the effect*of slight stress increasing the basal plasma glucose and insulirconcentrations of diabetic patients.18 Evaluation of tht
degree to which beta-cell deficiency and insulin resistanccontribute to a particular patient’s basal hyperglycaemiamight permit selection of the most appropriate therapy.We thank Leora Hoffman for drawing fig 2, Prof. T. Brooke Benjamin for
helpful discussions, and the Charles Wolfson Charitable Trust, the
Clothworkers Foundation, and Novo Research Institute for grants. D. R. M.is a Nuffield Research Fellow.
Correspondence should be addressed to R. C. T.
1. Reaven GM, Bernstein R, Davis B, et al. Non-ketotic diabetes mellitus: insulin
deficiency or insulin resistance. Am J Med 1976; 60: 80-88.2. Fajans SS. Heterogeneity of plasma IRI responses in patients with IGT and diabetes
Diabetologia 1980; 19: 250.3. McCarthy ST, Harris E, Turner RC. Glucose control of basal insulin secretion in
diabetes. Diabetologia 1977; 13: 93-97.4. Turner RC, McCarthy ST, Holman RR, Harris E. Beta cell function improved by
supplementing basal insulin secetion in mild diabetes. Br Med J 1976; i: 1252-54.5. Holman RR, Turner RC. Maintenance of basal plasma glucose and insulin
concentration in maturity-onset diabetes. Diabetes 1979; 3: 227-30.6. Felig P, Wahren J. Influence of endogenous insulin secretion on splanchnic glucose and
ammo acid metabolism in man. J Clin Invest 1971; 50: 1702-11.7. Brown PM, Tompkins CV, Juul S, et al. Mechanism of action of insulin in diabetic
patients: a dose-related effect on glucose production and utilisation. Br Med J 1978;i: 1239-42.
8. Turner RC, Holman RR. Insulin rather than glucose homoeostasis in the
pathophysiology of diabetes. Lancet 1976; i: 1272-74.9. Turner RC, Holman RR, Matthews D, Hockaday TDR, Peto J. Insulin deficiency and
insulin resistance interaction in diabetes: estimation of their relative contribution byfeedback analysis from basal plasma insulin and glucose concentrations. Metabolism1979; 28: 1086-96.
10. Turner RC, Harris EA, Ounsted M, Ponsford C. Two abnormalities of glucose-induced insulin secretion: dose-response characteristics and insulin sensitivity. ActaEndocrinol 1979; 92: 148-65.
11. Albano JDM, Ekins RP, Maritz G, Turner RC. A sensitive and precise radio-
immunoassay of insulin relying on charcoal separation of bound and free moietiesActa Endocrinol 1972; 70: 487-509.
12. Olefsky JM. Insulin resistance and insulin action. An in vitro and in vivo perspective.Diabetes 1981; 30: 148-62.
13. Kolterman OG, Gray RS, Griffin J, Burstein P, Insel J. Receptor and post-receptordefects contribute to insulin resistance in non-insulin-dependent diabetes mellitus.J Clin Invest 1981; 68: 957-69.
14. Ginsberg H, Rayfield EJ. Effect of insulin therapy on insulin resistance in Type IIdiabetic subjects. Evidence for heterogeneity. Diabetes 1981; 30: 739-45.
15. Gepts W. Pathological anatomy of the pancreas in juvenile diabetes mellitus. Diabetes1965; 14: 619-33.
16. Halter JB, Graf RJ, Porte D. Potentiation of insulin secretory responses by plasmaglucose levels in man: evidence that hyperglycaemia in diabetes compensates forimpaired glucose potentiation. J Clin Endocrinol Metab 1979; 48: 946-54.
17. Lang DA, Matthews DR, Peto J, Turner RC Cyclic oscillations of basal plasmaglucose and insulin concentrations in human beings. N Engl J Med 1979; 301:1023-27.
18. Holman RR, Turner RC. The basal plasma glucose: a simple, relevant index ofmaturity-onset diabetes. Clin Endocrinol 1980; 14: 279-86.
Reviews of Books
Preterm Labor
Obstetrics and Gynecology 1, Butterworths International Medical Reviews.Edited by M. G. Elder, Hammersmith Hospital, London, and Charles H.Hendrick, North Carolina Memorial Hospital, Chapel Hill, NorthCarolina. London and Boston: Butterworths. 1981. Pp. 329. NorthCarolina. London and Boston: Butterworths. 1981. Pp. 329. £13.50(subscription price )E10.50).
PRETERM and low-birth-weight babies are heavily over-
represented amongst perinatal deaths and the handicapped. Theymay be the result of (a) low birth-weight at term, (b) birth inducedpreterm because of recognised pathology, or (c) spontaneouspreterm labour (complicated or uncomplicated). This new bookdeals with all of the above conditions and so Preterm Labor is amisnomer. However, there is a great deal to be learnt from it aboutpreterm labour, and most of the authors do define their subjectclearly. Eminent epidemiologists, paediatricians, and obstetriciansfrom both sides of the Atlantic and the North Sea give a mostinteresting and scholarly account of the prediction, diagnosis, treat-ment, mode of delivery, and outcome for both mother and baby.The chapter on epidemiology, by L. S. Bakketeig, makes
fascinating reading for an obstetrician; his longitudinal analysiscasts doubt upon some firmly held convictions such as the supposedincreased risk of preterm birth with parity. The size and
completeness of the Norwegian birth registration data make up foroccasional problems such as the lack of precision about whetherlabour was induced or not and the use of "positional anomaly"(breech) as a predictive factor for preterm labour rather than as theconsequence of preterm birth. A. C. Turnbull and M. D. Mitchell
provide a concise account of the endocrine aspects which is anexcellent introduction to the discussion of controversial subjectssuch as the use of tocolytics and corticosteroids; both sides of thecontroversy are well ventilated by having one author arguing for and
599
one against. The protagonists of drug therapy are very restrainedand realistic, and readers may find more support for theconservative standpoint, which is powerfully advocated. Theexcellent results from major centres for the preterm infant are putinto perspective by Rosamund Jones and Pamela Davies coveringthe vexed question of whether handicap rates per 1000 births (notsurvivors) have been reduced.There is inevitably a good deal of repetition in the references
(Liggins and Howie appear at least five times), but the book will beenjoyed by all those interested in one of the most complex problemsin reproduction.
Department of Obstetrics andGynaecology,
University of Aberdeen MARION H. HALL
latrogenic Diseases
Update 1981. Edited by P. F. D’Arcy, University of Belfast, and J. P.Gnffin, Medicines Division, Department of Health and Social Security.Oxford: Oxford University Press. 1981. Pp. 262. ;C25.
NOWHERE in medicine in recent times has there been greateractivity than in the area of adverse reactions to drug therapy: in 1952Meyler was able to cover the subject adequately in 268 small pageswith single columns; by 1975 his successors needed 1132 large,double-columned pages to do the same thing. Since then, theamount of information on adverse drug reactions has continued togrow apace, and books on the subject are inevitably obsolescent onthe day they are published. This problem is unlikely to be solvedcompletely by’conventional publishing methods, and the best thatcan be done is either to publish new editions fairly often or to bringout supplements at even shorter intervals.Professor D’Arcy and Dr Griffin have opted for a supplement, or
"update", to the most recent edition of their important work. Theyhave done a very good job, as might be expected from two authorswhose first edition was a tour de force in that they wrote almost all ofit themselves. That they did not repeat the duet in their secondedition or in its update, but chose instead to lead a small orchestra ofcontributors, shows that the repertoire has become too large and toocomplex for a two-man band.In this excellent supplementary volume the information in the
earlier volumes has been carefully revised and, in many instances,considerably amplified. Two chapters are new, and one of these, onadverse reactions to herbal preparations, is probably unique-andquite fascinating. The first and second editions ofiatrogenic Diseaseswere notable for the thorough way in which published reports ofadverse reactions were critically discussed and evaluated, and thisupdate volume upholds this tradition.Everyone who uses drugs ought to be familiar with Iatrogenic
Diseases and its Update, and no medical library should be withoutcopies.
Department of Medicine,Shotley Bridge General Hospital,Consett D. M. DAVIES
Clinical Use of Mechanical Ventilation
Edited by Christen C. Rattenborg and Enrique Via-Reque, University ofChicago. Chicago and London: Year Book Medical Publishers. 1981. Pp.363. t4.75.
THIS book is addressed to physicians, medical students, nurses,respiratory therapists, and all others taking care of ventilatorpatients. Professor Rattenborg is one of the thirty-two contributors,of whom all except the two Danish ones are American. He was ahouse physician to Professor H. C. A. Lassen in Copenhagen duringthe famous polio epidemic of 1952. Lassen, whose interest andexperience in the management of respiratory failure dates from thattime, describes in a most interesting manner the events andoutcome of that epidemic.The book’s coverage of current knowledge of mechanical
venntatory assistance includes the use of negative-pressure "tanks"and cuirasse ventilation and the science upon which suchtreatments are based. The relative merits and complications of
endotracheal intubation and tracheostomy and the effects ofintermittent positive pressure ventilation (IPPV) on renal andcardiac function are discussed.The section that reviews the surgical and medical conditions
leading to the necessity for IPPV also discusses the administrativemanagement of mechanical ventilation facilities. The conditions
for, and care of patients during, withdrawal ofIPPV are particularlywell described, and the ethics of the termination of IPPV when apatient’s condition seems to offer little hope of a return to
consciousness are considered; so are the support of long-termpatients’ and relatives’ morale and these patients’ reintegration intothe family.For those preparing for the F.F.A. R.C.S. examination this book
gives a sound basis of the knowledge relating to mechanicalventilation, and the references help to give a historical perspectiveof developments in intensive care. The book should also well satisfythose others whom its authors set out to address.
My only criticism of the book is that the first two chapters (onairway pressure patterns, blood gas measurement, and the
importance of abnormal values of gases, pH, and buffers) are hardgoing enough to deter readers who are keen and able to benefit fromthe rich clinical experience recorded in the rest of the text fromproceeding any further. The information in these two chapterswould have been better included in an appendix.Intensive-Care Unit,Royal Berkshire Hospital, Reading D. G. PRICE
Clinical DermatologyAn Illustrated Textbook. Rona MacKie, University of Glasgow. Oxford:Oxford University Press. 1981. Pp. 301. 8.95.
WHETHER we really want another textbook of clinical derma-tology, time and the sales statistics of this one will tell us. I hope itwill do well despite what may seem a lot to pay for a paperback. Butit contains many excellent colour photographs, so for most readersthe additional purchase of a dermatological atlas will be
unnecessary.This book is written with undergraduates, postgraduate students,
and general practitioners in mind and, as with anything that is
"multipurpose", it is too much to expect that it will please all of thepeople for whom it is intended all of the time. It is tightly packedwith information about all the common and many of the lesscommon skin diseases and, although it gives what is inevitably aGlasgow view of the subject, there is little with which dermatol-ogists in other places are likely to disagree. The book aims tointroduce modern clinical dermatology in a stimulating manner,and helpful features in this respect are the "growth points" whichindicate the areas of current research and thinking at the end of eachchapter.Small "niggles" are the unattractive blacking-out of the eyes to
preserve anonymity in some of the clinical photographs, the use ofthe term linear macule to describe the white reaction in atopicdermatitis, and the somewhat obvious remarks about history takingand examination-for example, that a good light and reasonablypleasant surroundings are necessary.To whom then should the book be recommended? Undergrad-
uates will like it for its pictures and its dogmatic approach; but itcontains much that they will not need to know and they may not,without guidance, be able to select what is essential reading fromwhat they should regard as "small print" material. For M.R.c.P.examination candidates it provides a good account of the
background knowledge every well-educated doctor should haveabout "pure" dermatology: it also contains much that is
immediately relevant to other branches of medicine, though spacedoes not permit more than a brief mention for some of the importantsyndromes. Interested general practitioners will find the bookuseful for reference, and dermatologists-in-training, as well as thosewho regard themselves as trained, could do worse than buy a copyand learn from it.
Department of Dermatology,Royal Victoria Infirmary,Newcastle upon Tyne JANET MARKS
600
A Practice of Vascular SurgeryR. C. Kester and S. H. Leveson, St James’s University Hospital, Leeds.Tunbridge Wells: Pitman Medical. 1981. Pp. 373. ;E25.
IN their preface the authors state that their book is aimed
primarily at medical students and young surgeons. Although it isdoubtful if many medical students will read such a specialist book, itis clearly written and the two authors have covered concisely a largearea, including microsurgery in different systems, varicose veins,venous thrombosis, and the surgery of portal hypertension andhaemodialysis. In an area of surgery where much is still contro-versial the authors manage to present a clear and reasonable accountof the current consensus of opinion. As such this book is ideal forparamedical staff involved in the management of vascular surgicalpatients, or possibly as an introduction for junior doctors. Theselected references at the end of each chapter are appropriate for thisreadership. The book is not comprehensive or detailed enough to bevery useful to the surgeon specialising in this area. There are somequite important omissions; for instance, there is no mention ofhaematological disorders in the differential diagnosis ofatherosclerotic intermittent claudication. The discussion of thedifficulties associated with interpreting arteriograms points out thatthese pictures provide no information about the compliance of thevessel wall, but does not mention the much more practical andserious problem of failure to demonstrate a patent artery because ofmistiming of the films. The other deficiency of this book is the poorquality and choice of illustrations-for example, there are twophotographs of an ultrasonic imaging system but no reproduction ofthe kind of display which such units are capable of. No doubt theseimbalances and omissions will be corrected in subsequent editionswhich may well prove to be a useful basic introduction to vascular
surgery.
Department of Surgery,St James’ Hospital,London JOHN A. DORMANDY
Endocrine Physiology
Physiological Principles in Medicine Series. Richard N. Hardy, University ofCambridge. London: Edward Arnold. 1981. Pp. 179. jE4.95.
Clinical EndocrinologyPhysiological Principles in Medicine Series. Peter Daggett, MiddlesexHospital, London. London: Edward Arnold. 1981. Pp. 179. 4.95.
THESE two books are companion volumes in a new series of textsdesigned to cater for the preclinical student (Endocrine Physiology)and the clinical student (Clinical Endocrinology). It is immediatelyapparent that the student is expected to cope with about 360 pageson endocrinology alone-a somewhat daunting prospect.My overall impression of the two volumes is that they are
frustratingly uneven in style-for example, inconsistencies ofabbreviations abound, and the illustrations vary greatly in quality.Although it is difficult to make the books complement oneanother and yet stand alone, the extent of overlap is considerable,and there are some curious inclusions, especially in Clinical
Endocrinology, where the value of including the anatomy of thehypothalamus and pituitary gland and a description of stereo-isomerism of steroids escapes me.In both cases the text is readable and generally accurate, though it
should be pointed out (Endocrine Physiology) that in vitamin Dmetabolism the liver 25-hydroxylase enzyme is micrososmal in
origin and not mitochondrial as stated. In the same volume the useof the word "parathormone" for parathyroid hormone is to bedeplored; it is a trade name for a parathyroid gland extract and notthe native product. In Clinical Endocrinology surely the outmodedT3 resin uptake test no longer merits a diagram? And most peoplewould not think administration of bromocriptine in acromegaly orintramuscular insulin in diabetic ketoacidosis sound advice. In
addition, the statements concerning localisation studies in the neckin hyperparathyroid patients imply that these should be used beforeinitial surgery, whereas neck localisation should be reserved for
problem patients who are to undergo re-operation.
The books are cheap, but I remain to be convinced that a studentrequires such extensive knowledge or that paired texts are the bestway of presenting the information.
Endocrine Unit,Hammersmith Hospital, London IMOGEN M. A. EVANS
Pathology of Congenital Heart Disease
Postgraduate Pathology Series. AntonE. Becker, Cardiology Institute, TheNetherlands, and R. H. Anderson, Brompton Hospital, London. London:Butterworths. 1981. Pp. 497. .45.
THE diversity of congenital heart disease and the inherent
complexity of many of the defects have led to the study of thesedefects becoming the prerogative of a small minority of
pathologists. The subject has become obscured by endless reclassifi-cation, complex terminology, and disagreement over the
embryological basis: many pathologists have come to believe thesubject is beyond them. This book by Becker and Anderson willdispel this view and enable everyone to make valid examinations ofall congenitally abnormal hearts.The first step of any examination is to identify the chambers of the
heart and the book starts by describing the characteristic
morphological features of each chamber. Photographs of actualspecimens aid understanding of this vital first step, which will allowprogression to the next step of ascertaining how the variouschambers communicate one with another. The possiblecombinations are illustrated by clear line-drawings. The final step isto define how each chamber is related to the position of the heart.This logical sequential approach, coupled with a simplifieddescriptive terminology, should enable every heart to be accuratelycategorised. Practical advice on the technique of dissection is given.The second section of the book consists of chapters dealing with
the detailed morphology of each major group of abnormalities.Hearts with normal chamber relations such as atrial septal defectsare discussed first, then those with abnormally connected chambers,as in transposition, and finally malformations of the aortic andpulmonary trunks. There are short sections on the congenitalanomalies of the coronary arteries and conduction system. Becauseof its brevity the section on myocardial disorders, includinghypertrophic cardiomyopathy, is less authoritative but still a usefulguide. The cataloguing of syndromes associating cardiac defectswith other genetic abnormalities is helpful, but again exhaustivedetail is not given for each entity. The last chapter is a masterlyreview of the changes seen in the pulmonary vasculature in
congenital heart disease.The book provides a practical approach to congenital heart
disease and is free of confusing jargon. It should be read by everypathologist-in-training for its philosophical approach and be inevery laboratory as a reference work. I hope that paediatric
. cardiologists and surgeons will recognise the value of this book and
.
not be inhibited from reading it simply because of its inclusion in a.
pathology series.
Department of Histopathology,St George’s Hospital Medical School,London M. J. DAVIES
New Editions
Year Book of Cardiology. -Edited by W. Proctor Harvey, Walter Ni
Kirkendall, John W. Kirklin, Alexander S. Nadas, Leon Resnekov, EdmundH. Sonnenblick. London: Y.B. Medical Publishers. 1981. Pp. 407. f24.50Medical Pharmacology.-l0th ed. By Andres Goth. London: Y.B. Medical
Publishers. 1981. Pp. 815. f17.50.The Visual Fzelds.-5th ed. By David O. Harnngton. London: Y.B. Medical
Publishers. 1981. Pp. 437. 27.Integrated Obstetrics and Gynaecology for Postgraduates.-3rd ed. Edited bv
Sir John Dewhurst. Oxford: Blackwell Scientific Publications. 1981. Pp 81047.50.
Respzratory Physiology.-4th ed. By N. Balfour Slonim and Lyle HHamilton. London: Y.B. Medical Publishers. 1981. Pp. 301. f14.25.Ocular TherapeutIcs and Pharmacology. -6th ed. By Philip P. Ellis. London
Y.B. Medical Publishers. 1981. Pp. 320. £ 22.25.The Hamet Lane Handbook.-9th ed. Edited by J. A. Biller and A .’II
Yeager. London: Y.B. Medical Publishers. 1981. Pp. 328. f9 50.