Diabetic Renal-Retinal Syndrome: Pathogenesis and Management Update 2002

252 Pages·2002·6.1 MB·English

by  Clinton D. Brown M.D., Zhong Zhao, Loraine Thomas (auth.), Eli A. Friedman M.D., Francis A. L’Esperance Jr. M.D. (eds.)

DIABETIC RENAL-RETINAL SYNDROME
DIABETIC RENAL-RETINAL
SYNDROME
Pathogenesis and Management Update 2002
Edited by
Eli A. Friedman, M.D.
State University 01 New York,
Downstate Medical Center, New York, U.S.A.
and
Francis A. L'Esperance, Jr. M.D.
Colombia University,
New York, U.S.A.
SPRINGER-SCIENCE+BUSINESS MEDIA,B.V.
A C.I.P. Catalogue record for this book is available from the Library of Congress.
ISBN 978-94-010-3930-7 ISBN 978-94-010-0614-9 (eBook)
DOI 10.1007/978-94-010-0614-9
Printed on acid-free paper
All Rights Reserved
© 2002 Springer Science+Business Media Dordrecht
Originally published by Kluwer Academic Publishers in 2002
Softcover reprint ofthe hardcover 1st edition 2002
No part of this work may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming, recording
or otherwise, without written permission from the Publisher, with the exception
of any material supplied specifically for the purpose of being entered
and executed on a computer system, for exclusive use by the purchaser of the work.
Table of Contents
Dedication Vll
Foreword IX- Xlii
Con ference Participant s XV- XVlII
I . Effect of Aminoguanidine on Induced-d iabetic Rabbits and Diabetic
Patient s with ESRD 1-5
C D. Brown. Z H. Zhao. L.L. Thomas and E.A. Friedman
2. Impact of Nutr ition in Uremic Diabetics 7- 21
M.M. Avram
3. New Insights into the Molecular Mechanisms of Vasc ular Permeabil ity
in Diabetes 23-33
D.A. Antonetti and the Penn State Retina Research Group
4. Apop tosis and Neurodegeneration in Diabetes: Lessons From the Retina 35-45
A.J. Barber. M. Nakamura and the Penn State Retina Research Group
5. Diabetic Macular Edema 47-58
F.L. Ferris III
6. Diabetic Vitrec tomy Update 59-65
S.T. Charles
7. Medica l App roaches to Preventing Vision Loss from Diabetic
Retin opathy 67-74
R.I. Klein and B.E.K. Klein
8. Ocular Findings at Onset of Uremia 75-88
D.H. Berman
9. Prolife rative Diabetic Retinopathy: Current Treatment Strategies for
Progression 89-104
J.A. Sheindlin
v
vi TABLE OF CONTENTS
10. Microalbuminuria in Perspectives 105-120
C.E. Mogensen
II. Which Comes First: Renal Injury or Microalbuminuria? 121-128
S.M. Mauer, M.L.A. Carumori and P. Fioretto
12. Prevention, Diagnosis and Management of Heart Disease in Patients
with Renal Failure 129-145
L.T. Clark and O. Abe
13. Reducing Mortality for Diabetes Patients on Hemodialysis 147-154
Y. Worerdekal
14. Long-Term Perspective on Utility of Peritoneal Dialysis in Diabetes 155-172
P.S. Passadakis and D.G. Oreopoulos
15. Complications of Post-transplant Diabetes 173-181
M.S. Markell
16. Prevalent US Transplant Center Policies Towards Pancreas
Transplantation for Patients with Type 2 Diabetes Mellitus 183-189
A.L. Friedman and E.A. Friedman
17. Pancreas Transplantation: Does It Have a Future? 191-195
1.S. Najarian
18. Novel Applications for Recombinant Human Erythropoietin 197-206
A. Cerami, M. Brines, C. Cerami, P. Ghezzi and L. ltri
19. Lesson s Learned Since the Last Renal-Retinal Conference 207-242
E.A. Friedman
Index 243
Dedication
From their inception in 1976, these Symposia devoted to the Diabetic Renal-Retinal
Syndrome derived their energy from clinicians deliverin g care to diabetic indi vidual s
in the seemingly unyielding grasp of progressive co-morb id compl icat ions. A quarter-
century ago, efforts to attain reasonable rehab ilitation afte r onset of urem ia and severe
vision loss attributed to diabetes uniformly resulted in marginal short-term benefit with
minimal life extension. Gradu ally and inexorably the prognosis has improved with an
increasing cohort of patients returning to employment, education, or home respon si-
bilities.
We salute our brave, intrepid , and trusting patients who have followed the difficult
course we prescribe to preserve sight while substituting for vision loss. In so many
instance s, it has been the life force of our patients that has prompted the medical,
surgi cal, and pharmacologic adva nces detailed in this volume. By permitting us to
address their threatened existence and need for remedy, our patient s gave us the stimulus
and motivation to join the strugg le against a disease about to yield to the wonders of
molecular medicine. With exceptional optimism for a near term conquest of its subject,
we ded icate these proceedings to our patients.
Eli A. Friedman
Francis A. L 'Esperance, Jr.
VII
Foreword
Diabetic Renal-Retinal Syndrome Proactive not
Reactive Intervention
Conference held March 23, 2001
In the thirty years since this series of symposia on the Diabetic Renal-Retinal syndrome
were begun, there has been an epidemiologic explosion in the incidence and preva-
lence of end-stage renal disease (ESRD) attributed to diabetes. Furthermore, according
to the most current estimates by the world health organization, the growth rate of
diabetes world-wide is accelerating resulting in a pandemic of ESRD [I]. Whereas in
1995 there were an estimated 133,286,000 diabetic persons throughout the world, by
2,025 there will be a minimum of 299,974,000 with diagnosed diabetes, an increase of
210% [2).
James V. Neel in 1962 proposed that the basic defect in type 2 diabetes was a quick
insulin trigger meaning that the pancreas secretes insulin too quickly in response to
elevated blood sugar assisting our tribal, hunter-gatherer ancestors through intermittent,
sometimes feast-or-famine food availability, minimizing renal loss of glucose [3] .
Analogous to the advantage afforded by the sickle hemoglobin mutation against malarial
parasites in the wild, the so called thrifty gene that is beneficial during food depriva-
tion converts to a disease promoter when food is abundent. Under genetic control, a
too quick insulin trigger might be disadvantageous and might take the form of a balanced
polymorphism. By the end of the last century, it was evident that at least 95% of newly
diagnosed people with diabetes had type 2 diabetes reflecting emergence and domi-
nance of the thrifty gene [4).
The basic premise underlying the thrifty gene hypothesis is that genes that determine
increased fat storage, which in times of famine represent a survival advantage, in a
plentiful food environment result in obesity and type 2 diabetes. The peroxisome pro-
liferator-activated receptor gamma (PPARgamma) has over the last decade been shown
to have a key role in adipogenesis and may be a master controller of the 'thrifty gene
response' leading to efficient energy storage. Its synthetic ligands, the thiazolidine-
diones, are insulin sensitizing drugs, currently utilized in treating type 2 diabetes mellitus
[5]. High rates of type 2 diabetes are repeatedly detected in historically undernourished,
recently urbanized peoples characterized by Nelson as 'transitional and disadvantaged
populations [6) .'
Extrarenal comorbidity, especially heart disease and blindness has accompanied the
kidney failure in pandemic type 2 diabetes. For example, among the aboriginal Oji-Cree
ix
x E.A. FRIEDMAN AND EA. L'EsPERANCE, JR.
of northern Ontario coronary heart disease has tripled over the past 20 years and is
inextricably linked to the approximately 40% who manifest typical obesity-related type
2 diabetes [7]. Unacculturated Yanomama and Mambo of the Brazilian Amazon Basin
did not express the glucose intolerance of the highly acculturated and very obese adult
North American Pima . Validating Neel's findings, Valencia et al. compared the rate of
type 2 diabetes in Pima Indians of southern Arizona with the Pimas in the Sierra Madre
Mountains of northern Mexico. Both groups of Pima descended from the Hohokam
group that settled in the valleys of the Gila and Salt rivers in Arizona 2000 years ago
and separated about 700 years ago. Government assistance programs and a cash
economy replaced traditional farming activities for the Arizona Pima who have the
highest reported prevalence worldwide of type 2 diabetes, and are uniformly obese. By
contrast, the Mexican Pima who practice traditional , non-mechanized agriculture ,
lacking electricity and running water in their homes use no modern household devices
have a 5.6% rate of type 2 diabetes [8].
Based on the Pima diabetes story , there has been a quest for a single major locus
for type 2 diabetes. Mitchell reported that a (dominant) allele controls insulin levels
during insulin challenge tests in Mexican Americans and this allele accounts for 35%
of changes in 2-hour insulin levels . Recently a susceptibility locus on chromosome 2
was thought to account for 30% of type 2 diabetes in Mexican Americans [9].
Bearing on the explosion of incident type 2 diabetic people is the interest in
Syndrome X, the combination of type 2 diabetes, hypertension, and a truncal/abdom-
inal (android) obesity also called an insulin resistance syndrome. But in surveys
conducted by Neel and associates, obesity and hypertension were more closely corre-
lated than obesity and type 2 diabetes suggesting that Syndrome X may not be a true
syndrome governed by a common genetic pathogenesis [10] . Whatever the interrela-
tionships between Syndrome X and type 2 diabetes [II], it seems clear that the life style
changes that have made food abundant and exercise a sometime endeavor translate
into an era of increasing obesity coupled with hypertension and type 2 diabetes .
Projecting the expanded base of those with type 2 diabetes along side the pandemic of
obesity and hypertension defines a coming era of dominant metabolic disease leading
to the threat of multiple organ failure centering on the eyes, the, heart, kidneys, and
peripheral vasculature.
The American Diabetes Association 's most recent guidelines (2001) for blood
pressure regulation aim at a target of 135/85 mmHg and for glucose regulation a hemo-
globin AIc of < 7%. Additional components of contemporary care, not yet attaining
an 'affirmed by evidence' label include reduction of hyperlipidemia and aggressive
treatment of microalbuminuria even when blood pressure measurements are normal.
Indeed, the most aggre ssive strategists advocate treatment with an angiotensin con-
verting enzyme inhibitor for normalbuminuric normotensive people with diabetes [12] .
What is now clear is that strategic plann ing for 'long-term' care in diabetes should be
initiated as a component of the first contact with the health care team . By means of a
check list (Table 1), periodic and repetitive evaluations of the diabetic patient's most
vulnerable organ systems can be initiated along with a continuing education program.
Comprehensive management for the diabetic patient is a daunting undertaking demanding
large amounts of profes sional time, especially when enervating complications such as
impotence, vision loss, stroke residual, limb amputation, and the need for uremia therapy
threaten to interdict any forward motion in life planning. The American Diabetes
FOREWORD xi
Table I. Nephrologist's comprehensive diabetes care check list.
System Specialist Procedure
Eyes Ophthalmologist Fluorescein angiogram
Eye pressure
Cardiovascular Cardiologist Dobutamine stress test
Coronary angiography
Peripheral vascular Vascular surgeon Doppler vessel flow
MRI angiogram
Podiatry Podiatrist Prescription shoes, routine care
Neurologic Neurologist EEG, Carotid flow stroke
rehabilitation
Transplant Transplant Surgeon Consider kidney or kidney/
pancreas transplant
Gastroenterologic Gastroenterologist Endoscopy
Sonography for cholelithiasis
Endocrinologic Endocrinologist Pituitary-thyroid integrity
Bone density and maintenance
Genitourinary Urologist Urodynamics, sonography,
CT-scan, Penile prosthesis
Gynecologic Gynecolog ist Cytology, irregular bleeding
Overall health Nutritionist, Nurse Educator Weight adjustment diet prescription
Learn medications, instruction in
self-injection of insulin, erythropoietin
Social service Social worker Obtain benefits, restructure home
Total patient care Local and national organization Social interaction, facilitate proximity
to vital information
Assoc iation prep ares and upd ates a cli nical pract ice guide that is an im portant resource
when structuri ng a life plan for individu al diabet ic patien ts [13, 14].
Wh ile the specter of a potentiall y overwhe lmi ng 21st ce ntury burde n of type 2
diabe tes is frig htening, the progress of the past de cade in interdicti ng diabet ic compli-
ca tio ns provides reason to remai n hop eful th at medi cal progress wi ll prov e equa l to
the cha lle nge . Gr aduall y , almost un percepti vel y, the fo rmerly stark pr ogn osis for
combined diabe tic nephropath y and retinopathy has been tra nsformed from a tragedy
signaling near-term death to a clarion call for effective intervent ive measures. This
transit ion reflects the cum ula tive effect of multi ple small increments in und erstand ing
and therapy . Central to all current regimens for managing diabetes is the norm alization
of hypertensive blood pre ssure together with the bes t possib le approximation of nor-
mog lycemia.
If the ' diabetes wars' of 2002-2004 earn the label of detente or even truce because
the rate of complication s in properly treated patients can be slowed to that of aging
xii E.A. FRIEDMAN AND F.A. L'EsPERANCE, JR .
Table 2. Interdicting diabetes: Research initiatives.
Approach Strategy Authors
Pancreas transplants Improved results in diabetes types I and 2 Friedman A [161
Human islets repeated Sirolimus, tacrolimus, and daclizumab Shapiro et al. [17]
Intrahepatic islets Anti-CD 154 (hu5c8) Kenyon et al. [18]
Microencapsulated islets Purified alginate encapsulation Rayat et al. [19]
Bypass insulin receptor Demethylasterriquinone B-1 (DMAQ-B I) Salituro et aI. [20]
from endophytic fungus, Pseudomassaria sp
Inhale insulin Preprandial insulin given by inhalation Skyler et al. [21]
Beta cells Immortalize insulin secreting cells Andrikopoulos
et al. [22]
Bionic pancreas Implantable insulin secreting device Stotcum et aI. [23]
Gut stem cells Nurture regrowth of pancreas Silverstein and
Rosenbloom [24]
Genetic cell engineering Pancreatic and duodenal homebox genes-I Ferber S [25]
to liver by adenovirus
without the cloud of diabetes, then the years that follow should register unrestricted
triumph. While molecular biology will provide blocking and diverting techniques to
mute the panoply of tissue and organ complications the elusive goal of total preven-
tion of diabetes as a disease is within reach . The interdiction of diabetes has followed
a multi-front attack as shown in Table 2. Other promising approaches include: (I) insulin
sensitizers including protein tyrosine phosphatase-I B and glycogen synthase kinase 3,
(2) inhibitors of gluconeogenesis like pyruvate dehydrogenase kinase inhibitors, (3)
lipolysis inhibitors, (4) fat oxidation including carnitine palmitoyltransferase I and II
inhibitors, and (5) energy expenditure by means of beta 3-adrenoceptor agonists [15].
The pages of this brief volume recount a tale of adventure, high hopes, and pursuit of
enormous treasure - the main prize being elimination of a human scourge. What is clear
is that the hunt for a cure is the intoxicant that makes repetitive failures along the way
bearable. From the essays that follow, the reader perceives the message that 'it can be
done, and soon.'
Eli A. Friedman, M.D.
Francis A. L 'Esperance, Jr. M.D.
REFERENCES
l. Ritz E, Rychlik I. Locatelli F. Halimi S. End-stage renal failure in type 2 diabetes: a medical cata-
strophe of worldwide dimensions. Am J Kidney Dis 1999; 34: 795-808.
2. Httpllwww.who.int/ Revised 14 March 200l.
3. Diabetes mellitus: A 'thrifty' genotype rendered detrimental by 'progress"! Am J Hum Genet 1962; 14:
353-352.