of diabetes mellitus978-3-642-73583...of diabetes mellitus with 61 figures and 36 tables...
TRANSCRIPT
W. Creutzfeldt (Ed.)
Acarbose for the Treatment of Diabetes Mellitus
With 61 Figures and 36 Tables
Springer-Verlag Berlin Heidelberg New York London Paris Tokyo
W. Creutzfeldt, Prof. Dr. med. Dr. h. c. Abteilung Gastroenterologie und Endokrinologie Zentrum Innere Medizin Georg-August-UniversWit G6ttingen Robert-Koch-Str. 40
3400 G6ttingen
Library of Congress Cataloging-in-Publication Data
Acarbose for the treatment of diabetes mellitus / W. Creutzfeldt (ed.). p. cm. Includes index.
ISBN-13: 978-3-540-19145-2 e-ISBN-13: 978-3-642-73583-7 DOl: 10.1007/978-3-642-73583-7 1. Acarbose--Therapeutic use--Testing--Congresses. 2. Diabetes-Chemotherapy--Congresses. I. Creutzfeldt, W. (Werner), 1924-. [DNLM: 1. Diabetes Mellitus--drug therapy. 2. Hypoglycemic Agents--therapeutic use. 3. Trisaccharides--therapeutic use. WK 825 A168j RC661.A33A27 1988 616.4'62061--dc 19 DNLMlDLC for Library of Congress
88-30819 CIP
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© Springer-Verlag Berlin Heidelberg 1988
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Contents
Introduction
w. CREUTZFELDT
Experimental Data on Acarbose I
Toxicology of Acarbose, with Special Reference to Long-Term Carcinogenicity Studies
G.SCHLOTER
Discussion
The Disposition and Pharmacokinetics of Acarbose in Man
F. O. MOLLER, H. K. L. HUNDT, H. G. Luus, M. VAN DYK, G. GROENEWOUD, and!. HILLEBRAND ........... .
Discussion
Experimental Data on Acarbose II
The Pharmacological Rationale of Diabetes Mellitus Therapy with Acarbose
W. PULS, andH. BISCHOFF
Discussion
Pharmacodynamics of Acarbose: Clinical Investigations
B.LEMBCKE
Discussion
1
5
15
17
25
29
39
41
53
VI Contents
Posters
Comparative Effects of Acarbose on Glycemia, Weight Gain, and Serum Lipids in Adult Male and Female Diabetic Wistar Fatty Rats
O. L. TULP, C. STEVENS, O. BARBEE, M. L. APOSTOLOU, and O. E. MICHAELIS . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Effects of Low-Dose Acarbose on Glycemia, Adiposity, and Cholesterolemia in Obese and Obese Non-Insulin-Dependent Diabetic Corpulant Rats
O. E. TULP, S. P. DEBoLT, L. PIETRANGELO, R. SCHNITZER-POLOKOFF, A. ABDOLLAHI, M. E. HESS, and N. HAUGARD .............. 58
A Preclinical Study on the Effects of Acarbose on Mice Rendered Obese with Gold Thioglucose
I. MAROT, and Y. LEMARcHAND-BRUSTEL
Enhancement of Insulin Binding and Glucose Transport by Acarbose in Adipocytes of Zucker Rats
J. R. VASSELLI, T. FLORY, andS. K. FRIED ........ .
Treatment of Streptozotocin-Diabetic Rats with Acarbose: Influence on Metabolism and Heart Function
P.ROSEN ......... " ................ .
Effects of Acarbose on Cardiac and Hepatic Metabolism in Diabetic Rats
M. E. HESS, N. HAUGARD, A. TORBATI, A. RASTOGI, and O. L. TULP
Effects of Acarbose on Experimental Diabetic Nephropathy, Metabolic Control, and Intestinal Glycosidase Activity in Normal and Genetically Diabetic Mice
S.M.LEE ............................ .
The Effectiveness of Acarbose in the Reduction of Diabetic Symptoms and Neuropathic Complications in an NIDDM Animal Model
R. G. PETERSON, M. A. NEEL, L. A. LITTLE, J. C. KINCAID, andN. S. FINEBERG ..................... .
Effects of Acarbose on the Hormonal and Metabolic Response to the Simultaneous Ingestion of Sucrose and Ethanol
B.JANDRAIN,J. GERARD,E. VERDIN,andP.J.LEFEBVRE ...
59
60
61
62
63
64
66
Contents VII
Effects of Acarbose on Serum Lipids and Lipoproteins in Healthy Individuals During Prolonged Administration of a Fiber-Free Diet
I. WALTER-SACK, P. KRANz-RIBs, G. WOLFRAM, andN. ZOLLNER .
Lower Triglyceride Production with Carbohydrate-Rich Diets During Treatment with Acarbose
P.J.NESTEL
Long-Term Metabolic Effects of Acarbose in Healthy Young Men
C. COUET, M. ULMER, M.liAMDAOUI, and G. DERBY . . . . . . .
Mode of Action of the a-Glucosidase Inhibitor Acarbose in the Small Bowel: A Perfusion Study in Man
H.-J. HAGEL, H. RUPPIN, J. PICHL, W. FEUERBACH, S. BLOOM, and W. DOMSCHKE . . . . . . . . . . . . . . . . . . . . . . . .
Effect of Acarbose in Fecal Short-Chain Fatty Acid Excretion in Man
W. SCHEPPACH, C. FABIAN, M. SACHS, M. SPENGLER, andH. KASPER
Effect of Acarbose on Colonic Nitrogen Metabolism in Man
C. FABIAN, W. SCHEPPACH, M. SPENGLER, andH. KASPER
The Influence of Acarbose Dosage Scheme on Intestinal Symptoms and Intestinal Transit Time in Healthy Volunteers
H. J. WILDGRUBE, M. SPENGLER, and K. BOEHME . . . . . . . .
The Development of a Method for Measuring Starch Absorption and its Alteration by a-Glucosidase Inhibitors
S. PYE, andJ. RAoZIUK ..................... .
Acarbose in NIDDM
Acarbose in Non-Insulin-Dependent Diabetes Mellitus: Short-Term Studies in Combination with Oral Agents
B. WILLMS
Acarbose in Non-Insulin-Dependent Diabetes - Long-Term Studies in Combination with Oral Agents
G.SACHSE
Discussion
67
68
69
70
71
73
74
75
79
92
102
VIII Contents
Acarbose Monotherapy in the Treatment of Non-Insulin-Dependent Diabetes Mellitus
J. TUOMILEHTO
Discussion
Posters
Acarbose Treatment of NIDDM: Multiclinic Trial for Dose Finding
Y. GOTO, S. NAKAGAWA, N. HOSOYA, H. ORIMO, Y. IKEDA, N. SAKAMOTO,
104
117
I. FUKUI, S.TARUI, S. BABA, T. KANEKO, and G. MIMURA . . . . . . . . .. 121
Metabolic Effects of Acarbose in Normal and NIDDM Subjects
P.-H. GROOP, L. GROOP, K. J. TOTTERMANN, andF. FYHRQUIST
Efficacy and Tolerability of a 3-Month Treatment with Acarbose in Type II Diabetic Outpatients Treated with a High Dose of Sulfonylurea
122
B.MAY,andD.HOPPE . . . . . . . . . . . . . . . . . . . . . . . . . . .. 124
Metabolic Control in Type II Diabetes with Long-Term Acarbose Therapy: A Double-Blind Study
M. RODIER, J. L. RICHARD, L. MONNIER, and J. MIROUZE . . . . . . . . .. 125
Clinical Trial to Investigate the Efficacy and Tolerability of Acarbose in Type II Diabetic Patients Treated with Diet Alone
R. PORTEN, J. R. BAUER, and K. BOEHME .................. 126
Comparison of the Action of an a-Glucosidase Inhibitor (Acarbose) and a Sulfonylurea Preparation (Glisoexpide) in Non-Insulin-Dependent Diabetics
J. FABIAN-KRAUSE . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 127
Efficacy of the Glucosidase Inhibitor Acarbose Compared to the Sylfonylurea Glisoexpide on Metabolic Control in Diet-Treated Type II Diabetics
R. MIES, M. SPENGLER, U. HENKE, and K. BOEHME . . . . . . . . . . . 128
Multicenter Clinical Trial Up to 15 Months: Efficacy and Tolerability of Acarbose in Glibenclamide-Treated Type II Diabetics with Secondary Sulfonylurea Failure Versus Glibenclamide Therapy Alone
M. SPENGLER, K. BOEHME, and R. AUBELL ................ 129
Contents IX
Acarbose Does not Affect Glibenclamide Pharmacokinetics in Type II Diabetic Patients
J.GERARD,A.J.SCHEEN,andP.J.LEFEBVRE . . . . . . . . . . . . . 130
Effect of Acarbose in Type II Diabetics Treated with Diet Alone, with Diet, and with Sulfonylurea, Diet, and Insulin
V. PROFOZIC, M. KosEu, H. SCHULZ, M. GRANIC, I. HILLEBRAND, and Z. SKRABALO . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
The Long-Term Effects of Acarbose on Type II Diabetics on Diet or Oral Agents
S. RAPTIS, D. HAoJIDAKIS, A. RAPTIs, andE. DIAMANTOPOULOS . . 132
Long-Term Effects of Acarbose Treatment on Postprandial Glucose, Pancreatic and Gut Hormone Responses and Fasting Serum Lipids in Non-Insulin-Dependent Diabetics on Sulfonylureas
L. O. U'ITENTHAL, O. O. UKPONMWAN, M. GmGLIONE, S. M. WOOD, M. A. GHATEI, I. M. TRA YNER, and S. R. BLOOM ......... 133
Acarbose in the Treatment of NIDDM Patients with Hyperlipemia
H. BAR-ON, I. RAz, and M. KIDRON ............... .
Effectiveness and Tolerability of the a-Glucosidase Inhibitor Acarbose in NIDDM Patients with Elevated Liver Enzyme Activity
134
E. HAUPT, I. HILLEBRAND, andH. PFEFFER ................. 135
Effect of Acarbose on Blood Glucose and Insulin Response to a Sucrose Load in Subjects with Reactive Hypoglycemia
J. L. RICHARD, M. RODIER, L. MONNIER, and J. MIROUZE . . . . . . . . .. 136
Relapse-Reducing Effects of Acarbose After Weight Reduction in Severely Obese Subjects
L. SJOSTROM, and T. WILLIAM-OLSSON . . . . . . . . . . . . . . . . . . .. 137
Acarbose in IDDM
Acarbose Treatment in Insulin-Dependent (Type I) Diabetes Mellitus
S. RAPTIs, G. DIMITRIADIS, andD. HADJlDAKIS 141
Discussion 153
X Contents
Acarbose Treatment and Sulfonylurea Secondary Failure
C.ROSAK .
Discussion
Clinical Studies with Acarbose for the Control of Hyperglycemia which is the Major Pathogenetic Factor of the Complications of Diabetes Mellitus
H. E. ELIAHOU, P. SEGAL, I. HILLEBRAND, D. SACHS, B. HELLBERG,
156
162
A. BLAU, andE. TOPPER . . . . . . . . . . . . . . . . . . . . . . . . 163
Discussion
Posters
Inhibition of a-Glucosidase by Acarbose as an Additional tool for Glycemia Control in Insulin-Dependent Diabetics on Conventional Insulin Therapy
169
J. TAT6N .................................. 173
Acarbose in Insulin-Dependent Diabetes Mellitus: Efficacy and Tolerance
S. G. T.HuLST,P.F.J.M. SPOOREN,P.A. SMITH,andT.HuLK
Nonrandomized Follow-up Study with Acarbose Treatment and Pre- and Post-treatment with Placebo in Type I Diabetic Children
M. DAMJANOVA
Effects of Acarbose on Glycemic Control in IDDM under Feedback Control with Artificial Endocrine Pancreas
174
175
K. ITOH, and Y. IKEDA ............................ 176
Effects of Sucrose Meal on Insulin Requirement in IDDM and its Modulation by Acarbose
J.-L. CHIASSON . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177
Effect of Acarbose on Insulin Sensitivity and Liver Uptake in Patients with Type I Diabetes
P. POZZILLI, V. FIGHI, V. FIORE, M. CASANICA, A. GIACCARI, P. SBRACCIA, andG. TAMBURRANO . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 178
Contents XI
Comparative Metabolic Availability of Glucose and Sucrose and the Effect of Acarbose on Sucrose Utilization During Exercise in Type I Diabetic Patients
P. JANDRAIN, F. PIRNAY, A. SCREEN, M. LACROIX, F. MOSORA,
and P. J. LEFEBVRE . . . . . . . . . . . . . . . . . . . . . . . . .
Acarbose Treatment in Insulin-Dependent Diabetics
G. VIVIANI, L. CAMOGLIANO, M. G. BORGOGLIO, P. SALVINI, H. OHNMEISS,
180
andL. AoEZATI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 182
Panel Discussion: FutureAspects of a-Glucosidase Inhibition 183
SubjectIndex 195
Author Index 197
Presenting Authors
BAR-ON,H.
Hadassah Hospital, Jerusalem, Israel
CHIASSON, J.-L. IRCM, Montreal, Quebec, Canada
COUET, C.
Centre de Nutrition Humaine, Universite de Nancy I, 54000 Nancy, France
CREUTZFELDT, W. Abteilung Gastroenterologie und Endokrinologie, Medizinische Klinik und Poliklinik, Georg-August-Universitat Gottingen, Robert-Koch-StraBe 40, 3400 Gottingen, Federal Republic of Germany
DAMJANOVA, M. Research Institute of Pediatrics, G. Sofiiski str. I, Sofia 1431, Bulgaria
ELIAHOU, H. E.
Department of Nephrology, The Chaim Sheba Medical Center, Tel Aviv University, Sackler School of Medicine, Tel-Hashomer 52621, Israel
FABIAN, C.
Medizinische Klinik der Universitat Wiirzburg, Josef-Schneider-StraBe 2, 8700 Wiirzburg, Federal Republic of Germany
FABIAN-KRAUSE, J. Medizinische Klinik Schwenningen, 7730 VS-Schwenningen, Federal Republic of Germany
GERARD,J.
Division of Diabetes, Institute of Medicine, Hopital de Baviere, 66, Boulevard de la Constitution, 4020 Liege, Belgium
GOTO, Y. Acarbose Study Group, 3rd Department of Internal Medicine, Tohoku University School of Medicine, Seirvo-machi, Sendai, Mivagi Pref., Japan
GROOP, P.-H.
Fourth Department of Medicine, Helsinki University Central Hospital, Unioninkatu 38, 00170 Helsinki, Finland
XIV Presenting Authors
HAGEL, H.-J. WeiBenburger StraBe 4, 8540 Schwabach, Federal Republic of Germany
HAUPT, E. Klinikum Bad Kissingen der BfA, Saale-Klinik, KurhausstraBe 20, 8730 Bad Kissingen, Federal Republic of Germany
HEss, M. E. Department of Pharmacology, University of Pennsylvania, Philadelphia, P A, USA
HULST, S. G. T. Department of Internal Medicine, Biochemistry and Dietectics, Ziekenhuis "Ziekenzorg", Haaksbergerstraat 55, 7513 ER Enschede, The Netherlands
ITOH, K. Third Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, Japan
JANDRAIN, B. Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, University of Liege, 4020 Liege, Belgium
LEE, S. M.
Renal Section, Department of Medicine, University Medical Center, Tucson, AZ 85724, USA
LEMBCKE, B. Abteilung fUr Gastroenterologie, Zentrum der Inneren Medizin, Johann-Wolfgang-Goethe-Universitat, Theodor-Stern-Kai 7,6000 Frankfurt 70, Federal Republic of Germany
MAROT,1.
INSERM U 145, Faculte de Medecine, Avenue de Valombrose, 06034 Nice Cedex, France
MAY,B. Abteilung fUr Gastroenterologie und Hepatologie der Universitatsklinik, Bergmannsheil, HundscheidtstraBe 1,4630 Bochum 1, Federal Republic of Germany
MIEs, R. Abteilung fUr Innere Medizin, St. Antonius Hospital, 5000 Koln 51, Federal Republic of Germany
MULLER, F. O. Department of Pharmacology, University of the Orange Free State, P. O. B. 339, ZA-Bloemfontein 9300, Republic of South Africa
NESTEL, P. J. CSIRO Division of Human Nutrition, Adelaide, Australia
PETERSON, R. G. Department of Anatomy, Indiana University School of Medicine, Indianapolis, Indiana 46223, USA
Presenting Authors XV
PYE,S. Division of Gastroenterology, Department of Medicine, Royal Victoria Hospital, Montreal, Canada
PORTEN,R.
Pforzheimer StraBe 318, 7000 Stuttgart 31, Federal Republic of Germany
POZZILLI, P.
Endocrinologia (I), II Clinica Medica, University of Rome, "La Sapienza", 00100 Rome, Italy
PROFOZIC, V. Vuk Yrhovac Institute of Diabetes, Endocrinology and Metabolic Disease, School of Medicine, University of Zagreb, Yugoslavia
PULS, W. Bayer AG, Pharma Forschungszentrum, Institut fiir Pharmakologie, Aprather Weg 18, 5600 Wuppertal1, Federal Republic of Germany
RAPTIs, S. II. Medizinische Universitatsklinik, Propadeutik, "Evangelismos" Hospital, P. O. Box 14127,11510 Athen, Griechenland
RICHARD, J. L. Service de Diabetologie, Centre Medico-Chirurgical, 30240 Le Grau du Roi, France
RODIER, M. Services des Maladies Metaboliques et Endocriniennes, Hopital Lapeyronie, 34059 Montpellier, France
ROSAK, C. Krankenhaus Sachsenhausen, Diabetologie, SchulstraBe 31, 6000 Frankfurt 70, Federal Republic of Germany
ROSEN, P. Diabetesforschungsinstitut an der Universitat Dusseldorf, Auf'm Hennekamp 65, 4000 Dusseldorf 1, Federal Republic of Germany
SACHSE, G. Deutsche Klinik fiir Diagnostik, Fachbereich Diabetologie, Aukammallee 33, 6200 Wiesbaden, Federal Republic of Germany
SCHEPPACH, W. Medizinische Klinik der UniversiHit Wurzburg, Josef-Schneider-StraBe 2, 8700 Wurzburg, Federal Republic of Germany
SCHLOTER,G. Bayer AG, Pharma Forschungszentrum, Institut fiir Toxikologie, Friedrich-Ebert-StraBe 217,5600 Wuppertal1, Federal Republic of Germany
XVI Presenting Authors
SJOSTROM, L. Department of Medicine I, Sahlgren's Hospital, University of Goteborg, Goteborg, Sweden
SPENGLER, M. Bayer AG, Pharma Forschungszentrum, Aprather Weg 18, 5600 Wuppertal1, Federal Republic of Germany
TAT6N,J.
Chair and Department of Internal Medicine and Diabetology, Warsaw Medical School, Warsaw, Poland
TULP, O. L. IV. Department of Nutrition and Food Sciences, Drexel University, Philadelphia, PA,USA
TUOMILEHTO, J.
National Public Health Institute, Department of Epidemiology, Mannerheimintie 166, 00280 Helsinki, Finland
UTTENTHAL, L. O. Department of Medicine, Royal Postgraduate Medical School, London W12 OHS, United Kingdom
V ASSELU, J. R. Obesity Research Center, St. Luke's-Roosevelt Hospital Center, New York, NY 10025, USA
VIVIANI, G. Istituto Scientifico Medicina Interna, Cattedra di Patologia Medica B, Universita di Genova, Genova, Italy
WALTER-SACK, I. Abteilung fiir Klinische Pharmakologie, Medizinische Universitatsklinik Heidelberg, Bergheimer StraBe 58, 6900 Heidelberg, Federal Republic of Germany
WILDGRUBE, H. J.
Institut fiir angewandte Diagnostik, 6450 Hanau, Federal Republic of Germany
WILLMS, B. Fachklinik fiir Diabetes und Stoffwechselkrankheiten, Kirchberg 21, 3422 Bad Lauterberg, Federal Republic of Germany