Dilemmas in Diabetes

175 Pages·1975·9.468 MB·English

by  Stewart Wolf, Beatrice Bishop Berle (auth.), Stewart Wolf, Beatrice Bishop Berle (eds.)

DILEMMAS IN DIABETES
ADVA NCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
Nathan Back State University of New York at Buffalo
N. R. Di Luzio Tulane University School of Medicine
Bernard Halpern College de France and Institute of Immuno.Biology
Ephraim Katchalski The Weizmann Institute of Science
David Kritchevsky Wistar Institute
Abel Lajtha New York State Research Institute for Neurochemistry and Drug Addiction
Rodolfo Paoletti University of Milan
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Volume 65
DILEMMAS IN DIABETES
Edited by Stewart Wolf and Beatrice Bishop Berle • 1975
DILEMMAS IN DIABETES
Edited by
Stewart Wolf
The Marine Biomedical Institute
The University of Texas Medical Branch at Galveston
and
Beatrice Bishop Berle
Albert Einstein CoIIe!(e of Medicine
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Totts Gap Colloquium on Diabetes Mellitus, 1974.
Dilemmas in diabetes.
(Advances in experimental medicine and biology; v. 65)
Bibliography: p.
Includes index.
1. Diabetes-Congresses. I. Wolf, Stewart George, 1914- II. Berle, Beatrice
Bishop, 1902 III. Title. IV. Series.
RC660.AIT67 1974 616.4'62 75-33729
ISBN-13: 978-1-4684-0954-3 e-ISBN-13: 978-1-4684-0952-9
DOl: 10.1007/978-1-4684-0952-9
Proceedings of the Totts Gap Colloquium on Diabetes Mellitus,
held in Totts Gap, Pennsylvania, May 9-11, 1974
Officers and Directors
John G. Bruhn, Ph.D., President and Director
Beatrice B. Berle, M.D., Vic~President and Director
Stewart Wolf, M.D., Secretary Treasurer and Director
Mr. George Plush, Director
Board of Trustees
Mark D. Altschule, M.D. Robert C. Page, M.D.
William B. Bean, M.D. Edmund D. Pellegrino, M.D.
Andre Cournand, M.D. Eliot Stellar, Ph. D.
William C. Gibson, M.D. Mr. Oscar Swarth
Miss Helen Goodell Joseph M. White, M.D.
Franz J. Ingelfmger, M.D.
Advisory Council to Totts Gap Colloquia:
Mark D. Altschule, M.D. Franz J. Ingelfmger, M.D.
Andre Cournand, M.D. Mr. Oscar Swarth
Martin M. Cummings, M.D. N. T. Werthessen, Ph.D.
© 1975 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1975
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
United Kingdom edition published by Plenum Press, London
A Division of Plenum Publishing Company, Ltd.
Davis House (4th Floor), 8 Scrubs Lane, Harlesden, London, NWI0 6SE, England
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical, photocopying, microfllming,
recording, or otherwise, without written permission from the Publisher
This volume is dedicated to the memory of
I. Arthur Mirsky
who died at the age of 67, several weeks after the Colloquium in
which he was to have participated. Dr. Mirsky, a physician, scientist,
and scholar of rare quality, contributed richly to our present-day
understanding of diabetes. His remarkable capacity for synthesis
sprang from a mind both quick and judicious. His personal warmth,
his fairness and dogged pursuit of truth endeared him to all who
knew him well.
Preface
This volume contains the edited proceedings of the Totts Gap
Colloquium on Diabetes Mellitus, DILEMMAS IN DIABETES. The Collo
quium, lasting two and a half days, was organized mainly as a dia
logue among experts in the field with different disciplinary back
grounds and, to some extent, differing points of view. The effort
was to synthesize existing knowledge, reconciling disparate data and
interpretation, and pointing up important areas of ignorance. Thus,
the book should serve not only as a summary of recent information
on diabetes, but as a reliable guide to the practicing physician as
he wades through often conflicting etiologic dogmas and therapeutic
practices.
The Colloquium was made possible through the generous support
of the Geigy Pharmaceutical Company and the conscientious and expert
coordination of Mr. Oscar Swarth.
The participants were:
Dr. George F. Cahill, Boston, Massachusetts
Dr. Harvey C. Knowles, Cincinnati, Ohio
Dr. Rachmiel Levine, Duarte, California
Dr. Lelio Orci, Geneva, Switzerland
Dr. Norton Spritz, New York, New York
Dr. Roger Unger, Dallas, Texas
Dr. Robert Williams, Seattle, Washington
Dr. Stewart Wolf, Galveston, Texas
Dr. Arnold Lazarow and Dr. I. Arthur Mirsky were to have partici
pated, but unfortunately were ill at the time of the meeting.
Others in attendance included five medical students, especially
selected from medical schools in the Philadelphia/New York area.
They were:
Mr. Louis Green, Univ. of Pennsylvania School of Medicine
Dr. Steven Peiken, Jefferson Medical College
vii
PREFACE
Dr. Alan Ropper, Cornell Univ. Medical College
Dr. Allan Schwartz, Columbia Univ. School of Medicine
Dr. Charles Rost, Temple Univ. School of Medicine
Four members of the Board of Trustees of the Totts Gap Institute
(Dr. Beatrice B. Berle, Miss Helen Goodell, Dr. Robert C. Page, and
Mr. Oscar Swarth) were present, as well as Miss Barbara Ramm and
Mr. Jerome Mattox from the Geigy Pharmaceutical Company.
Illustrations from the following publications have been repro
duced with permission:
Diabetes
Journal of Clinical Investigation
Metabolism
New England Journal of Medicine
The editors acknowledge the devoted help of Mrs. Joan Martin,
assisted by Miss Colleen Hogan and Mrs. Cindy Carter.
Contents
INTRODUCTION • • • • • • • • • • • • • • • • • • • • • • •• xi
Chapter I
HISTORICAL PERSPECTIVE 1
Chapter II
THE NATURE OF DIABETES 6
Chapter III
GLUCAGON AND OTHER HORMONES - A NEW PERSPECTIVE 26
Chapter IV
STRUCTURAL ASPECTS OF ISLET CELL MEMBRANES • • • • • • • •• 62
Chapter V
MICROVASCULAR LESIONS 87
Chapter VI
MACROVASCULAR DISEASE - ATHEROSCLEROSIS 106
Chapter VII
THERAPY 114
SUMMARY 145
BIBLIOGRAPHY • 147
INDEX • • • 159
ix
Introduction
"More things are shewed unto thee than men understand."
- Eccliasticus 3: 23
Knowledge of the diabetic state and the metabolic aberrations
associated with it has increased rapidly in the recent past. The
pieces of the puzzle have become so numerous, however, that to put
them together into a coherent picture has become more difficult
instead of less so. Instead of affording a clearer rationale for
therapy, the vast accumulation of information has brought into
question some of our most cherished therapeutic dogmas.
The concept of pre-diabetes, once widely accepted, is now
seriously challenged. No longer is lability of blood sugar regu
lation a reliable harbinger of clinical diabetes mellitus. Capil
lary basement membrane thickening, once confidently attributed to
sustained hyperglycemia has been found at times to precede the
hyperglycemic state by several years. The role of growth hormone
and the place of hypophysectomy in management are less certain than
they once were.
The value of oral hypoglycemic therapy and even the actions
of insulin are being examined. A variety of vexing problems con
cerning our understanding of diabetes has accumulated since the
seeming finality of the therapeutic preparation of insulin in 1927.
Therefore, in an effort to synthesize available knowledge and to
reconcile disparate data and interpretation, leading experts in the
field were brought together for informal dialogue.
xi
Chapter I - HISTORICAL PERSPECTIVE
DR. LEVINE: Before actually tackling the dilemma of the relat
ionship of pancreatic function to diabetes mellitus, I should point
out that early etiologic concepts did nat even take the pancreas in
to consideration.
Following the discovery by Thomas Willis that diabetic urine
was sweet (147) and after Dobson evaporated diabetic urine and saw
"candy" as a residue, (29) the natural inference was to implicate
a kidney disorder as the cause of diabetes. Cantharides, a kidney
poison, was therefore proposed as treatment. Perhaps the chronic
inflammation and scarring of glomeruli that resulted may have les
sened glycosuria, but surely it did not promote health or longevity.
Years later Rollo discovered the influence of diet on the degree of
severity of glycosuria (ll~. Observing the different effects of
carbohydrates, of proteins and of fats, he implicated the stomach
and gastro-intestinal tract as the primary organs affected in dia
betes. Despite his erroneous inference, Rollo must be credited with
taking the first practical steps toward the modern dietary treatment
of diabetes. About the same time as Rollo (in 1776), Cawley pub
lished the results of an autopsy of a patient who died with diabetes
( 19 ). He found that the pancreas was shriveled and full of calculi.
No contemporary paid any attention to this first mention of the pan
creas as possibly implicated in diabetes. The physiologist, Conrad
Bruner in Switzerland, came close to making the discovery Minkowski
made 150 years later (15). He did pancreatectomies in dogs, and
noted that they urinated very frequently, but he did not examine
their urine.
In the period from 1800 to 1889, the pancreatic lesions of
diabetes were rediscovered but their
The Pancreas as the inconsistent presence led to contro
Source of Diabetes versy as to whether diabetes had a pan
creatic etiology or not. Bouchardat,
Professor of Hygiene (Public Health) in the School of Public Health
at Paris, from the 1830's to the 1870's had an excellent background
in chemistry, imbibed from the French organic chemist, Chevreuil,
who was the first to determine that the sugar in diabetic urine is
glucose and differed from table sugar. He found at autopsy, damage
to the pancreas in 14 out of 19 wasted young people with heavy
glycosuria. On the basis of his findings, he divided diabetes in
to three etiological groups: Diab~te Maigre (lean diabetes) which
he considered to be due to a pancreatic disturbance; Diab~te Gras
(fat diabetes) in which the pancreas (he said) was not involved;
and a third group, Diab~te Nerveuse. The latter he modelled on
Claude Bernard's "Piqure" of the floor of the fourth ventricle,
which is followed by glycosuria (ll).