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Vol. 54, No. 3, 2009
Issue release date: August 2009
Free Access
Ann Nutr Metab 2009;54:208–217
(DOI:10.1159/000220416)

Influence of Early Nutritional Components on the Development of Murine Autoimmune Diabetes

Mueller D.B.a · Koczwara K.a · Mueller A.S.c, d · Pallauf J.c · Ziegler A.-G.a, b · Bonifacio E.e
aInstitut für Diabetesforschung der Forschergruppe Diabetes e.V. am Helmholtz Zentrum München and bKlinik für Endokrinologie, Diabetologie und Suchtmedizin, Klinikum Schwabing, Städt. Klinikum München GmbH, München, cInstitute of Animal Nutrition and Nutritional Physiology, University Giessen, Giessen, dInstitute of Agricultural and Nutritional Sciences, Preventive Nutrition Group, University Halle, Halle/Saale, and eCenter for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany
email Corresponding Author

Abstract

Background/Aims: Infant diet is suggested to modify autoimmune diabetes risk. The aim of this study was to determine whether infant food components affect diabetes development in the nonobese autoimmune diabetes (NOD) mouse. Methods: A basal low-diabetogenic diet was identified by feeding litter-matched female NOD mice standardized diets with and without casein and wheat proteins after weaning. In subsequent trials, basal diet with supplements of wheat (5, 10 and 30%), gluten, wheat globulin/albumin, corn (5%), potato (5%), apple (5%) or carrot (5%) was fed to litter-matched female NOD mice after weaning. Mice were followed for diabetes development and insulin autoantibodies. Results: A casein- and wheat-free diet was associated with the lowest rate of diabetes development (37% by age 25 weeks). Increased diabetes rates were observed when the basal diet was supplemented with 5% wheat (71% by age 25 weeks; p = 0.023) and 5% corn (57% by age 25 weeks; p = 0.05). Increasing wheat concentrations returned diabetes development to that in basal diet-fed mice. Other food supplements had no or minimal effects on diabetes development. Conclusions: Early supplementation of a basal low-diabetogenic diet with low concentrations of the cereals wheat or corn is associated with a moderate increase in the rate of diabetes. Removal of cereals, however, does not abrogate diabetes development in NOD mice.


 goto top of outline Key Words

  • Type 1 diabetes
  • Autoimmunity
  • NOD mice
  • Diet
  • Prevention
  • Gluten
  • Casein

 goto top of outline Abstract

Background/Aims: Infant diet is suggested to modify autoimmune diabetes risk. The aim of this study was to determine whether infant food components affect diabetes development in the nonobese autoimmune diabetes (NOD) mouse. Methods: A basal low-diabetogenic diet was identified by feeding litter-matched female NOD mice standardized diets with and without casein and wheat proteins after weaning. In subsequent trials, basal diet with supplements of wheat (5, 10 and 30%), gluten, wheat globulin/albumin, corn (5%), potato (5%), apple (5%) or carrot (5%) was fed to litter-matched female NOD mice after weaning. Mice were followed for diabetes development and insulin autoantibodies. Results: A casein- and wheat-free diet was associated with the lowest rate of diabetes development (37% by age 25 weeks). Increased diabetes rates were observed when the basal diet was supplemented with 5% wheat (71% by age 25 weeks; p = 0.023) and 5% corn (57% by age 25 weeks; p = 0.05). Increasing wheat concentrations returned diabetes development to that in basal diet-fed mice. Other food supplements had no or minimal effects on diabetes development. Conclusions: Early supplementation of a basal low-diabetogenic diet with low concentrations of the cereals wheat or corn is associated with a moderate increase in the rate of diabetes. Removal of cereals, however, does not abrogate diabetes development in NOD mice.

Copyright © 2009 S. Karger AG, Basel


 goto top of outline References
  1. Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK: Environmental triggers and determinants of type 1 diabetes. Diabetes 2005;54(suppl 2):S125–S136.
  2. Lefebvre DE, Powell KL, Strom A, Scott FW: Dietary proteins as environmental modifiers of type 1 diabetes mellitus. Annu Rev Nutr 2006;26:175–202.
  3. Turley SJ, Lee JW, Dutton-Swain N, Mathis D, Benoist C: Endocrine self and gut non-self intersect in the pancreatic lymph nodes. Proc Natl Acad Sci USA 2005;102:17729–17733.
  4. Elliott RB, Reddy SN, Bibby NJ, Kida K: Dietary prevention of diabetes in the non-obese diabetic mouse. Diabetologia 1988;31:62–64.
  5. Coleman DL, Kuzava JE, Leiter EH: Effect of diet on incidence of diabetes in nonobese diabetic mice. Diabetes 1990;39:432–436.
  6. Karges W, Hammond-McKibben D, Cheung RK, Visconti M, Shibuya N, Kemp D, Dosch HM: Immunological aspects of nutritional diabetes prevention in NOD mice: a pilot study for the cow’s milk-based IDDM prevention trial. Diabetes 1997;46:557–564.
  7. Funda DP, Kaas A, Bock T, Tlaskalova-Hogenova H, Buschard K: Gluten-free diet prevents diabetes in NOD mice. Diabetes Metab Res Rev 1999;15:323–327.
  8. Schmid S, Koczwara K, Schwinghammer S, Lampasona V, Ziegler AG, Bonifacio E: Delayed exposure to wheat and barley proteins reduces diabetes incidence in non-obese diabetic mice. Clin Immunol 2004;111:108–118.
  9. Maurano F, Mazzarella G, Luongo D, Stefanile R, D’Arienzo R, Rossi M, Auricchio S, Troncone R: Small intestinal enteropathy in nonobese diabetic mice fed a diet containing wheat. Diabetologia 2005;48:931–937.
  10. Agostoni C, Decsi T, Fewtrell M, Goulet O, Kolacek S, Koletzko B, Michaelsen KF, Moreno L, Puntis J, Rigo J, Shamir R, Szajewska H, Turck D, van Goudoever J, ESPGHAN Committee on Nutrition: Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 2008;46:99–110.
  11. Hannan JM, Ali L, Rokeya B, Khaleque J, Akhter M, Flatt PR, Abdel-Wahab YH: Soluble dietary fibre fraction of Trigonella foenum-graecum (fenugreek) seed improves glucose homeostasis in animal models of type 1 and type 2 diabetes by delaying carbohydrate digestion and absorption, and enhancing insulin action. Br J Nutr 2007;97:514–521.
  12. National Research Council (NRC): Nutrient Requirements of Laboratory Animals, ed 4 (rev). Washington, National Academies Press, 1995.
  13. Osborne TB (ed): The Proteins of the Wheat Kernel. Washington, Carnegie Institute Publishers, 1907, vol 84.
  14. Mimouni B, Robin JM, Azanza JL, Raymond J: Wheat flour proteins: Isolation and functionality of gliadin and HMW-glutenin enriched fractions. J Sci Food Agric 1998;78:423–428.
  15. Nicolas Y, Martinant JP, Denery-Papini S, Popineau Y: Analysis of wheat storage proteins by exhaustive sequential extraction followed by RP-HPLC and nitrogen determination. J Sci Food Agric 1998;77:96–102.
  16. Koczwara K, Schenker M, Schmid S, Kredel K, Ziegler AG, Bonifacio E: Characterization of antibody responses to endogenous and exogenous antigen in the nonobese diabetic mouse. Clin Immunol 2003;106:155–162.
  17. Bonifacio E, Atkinson M, Eisenbarth G, Serreze D, Kay T W, Lee-Chan E, Singh B: International workshop on lessons from animal models for human type 1 diabetes: identification of insulin but not glutamic acid decarboxylase or IA-2 as specific autoantigens of humoral autoimmunity in nonobese diabetic mice. Diabetes 2001;50:2451–2458.
  18. Hoorfar J, Buschard K, Dagnaes-Hansen F: Prophylactic nutritional modification of the incidence of diabetes in autoimmune non-obese diabetic (NOD) mice. Br J Nutr 1993;69:597–607.
  19. Beales PE, Elliott RB, Flohé S, Hill JP, Kolb H, Pozzilli P, Wang GS, Wasmuth H, Scott FW: A multi-centre, blinded international trial of the effect of A1 and A2 β-casein variants on diabetes incidence in two rodent models of spontaneous type I diabetes. Diabetologia 2002;45:1240–1246.
  20. Flohé SB, Wasmuth HE, Kerad JB, Beales PE, Pozzilli P, Elliott RB, Hill JP, Scott FW, Kolb H: A wheat-based, diabetes-promoting diet induces a Th1-type cytokine bias in the gut of NOD mice. Cytokine 2003;21:149–154.
  21. Funda DP, Kaas A, Tlaskalová-Hogenová H, Buschard K: Gluten-free but also gluten-enriched (gluten+) diet prevent diabetes in NOD mice; the gluten enigma in type 1 diabetes. Diabetes Metab Res Rev 2008;24:59–63.
  22. Pomeranz Y: Wheat: Chemistry and Technology, ed 3. St. Paul, American Association of Cereal Chemists Monograph Series, 1988.
  23. Hyppönen E: Micronutrients and the risk of type 1 diabetes: vitamin D, vitamin E, and nicotinamide. Nutr Rev 2004;62:340–347.

    External Resources

  24. Dilworth LL, Omoruyi FO, Simon OR, Morrison EY, Asemota HN: The effect of phytic acid on the levels of blood glucose and some enzymes of carbohydrate and lipid metabolism. West Indian Med J 2005;54:102–106.
  25. Lee S, Park H, Chun H, Cho S, Cho S, Lillehoj HS: Dietary phytic acid lowers the blood glucose level in diabetic KK mice. Nutr Res 2006;26:474–479.
  26. Panlasigui LN, Thompson LU: Blood glucose lowering effects of brown rice in normal and diabetic subjects..Int J Food Sci Nutr 2006;57:151–158.
  27. MacFarlane AJ, Burghardt KM, Kelly J, Simell T, Simell O, Altosaar I, Scott FW: A type 1 diabetes-related protein from wheat (Triticum aestivum). cDNA clone of a wheat storage globulin, Glb1, linked to islet damage. J Biol Chem 2003;278:54–63.
  28. Myers MA, Hettiarachchi KD, Ludeman JP, Wilson AJ, Wilson CR, Zimmet PZ: Dietary microbial toxins and type 1 diabetes. Ann NY Acad Sci 2003;1005:418–422.

 goto top of outline Author Contacts

Dr. Kerstin Koczwara
Institut für Diabetesforschung am Helmholtz Zentrum München
Ingolstädter Landstrasse 1, DE–85764 Neuherberg (Germany)
Tel. +49 89 31 87 39 06, Fax +49 89 30 81 733
E-Mail Kerstin.Koczwara@lrz.uni-muenchen.de


 goto top of outline Article Information

Received: August 26, 2008
Accepted after revision: March 17, 2009
Published online: May 27, 2009
Number of Print Pages : 10
Number of Figures : 4, Number of Tables : 3, Number of References : 28


 goto top of outline Publication Details

Annals of Nutrition and Metabolism (Journal of Nutrition, Metabolic Diseases and Dietetics)

Vol. 54, No. 3, Year 2009 (Cover Date: August 2009)

Journal Editor: Elmadfa I. (Vienna)
ISSN: 0250-6807 (Print), eISSN: 1421-9697 (Online)

For additional information: http://www.karger.com/ANM


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background/Aims: Infant diet is suggested to modify autoimmune diabetes risk. The aim of this study was to determine whether infant food components affect diabetes development in the nonobese autoimmune diabetes (NOD) mouse. Methods: A basal low-diabetogenic diet was identified by feeding litter-matched female NOD mice standardized diets with and without casein and wheat proteins after weaning. In subsequent trials, basal diet with supplements of wheat (5, 10 and 30%), gluten, wheat globulin/albumin, corn (5%), potato (5%), apple (5%) or carrot (5%) was fed to litter-matched female NOD mice after weaning. Mice were followed for diabetes development and insulin autoantibodies. Results: A casein- and wheat-free diet was associated with the lowest rate of diabetes development (37% by age 25 weeks). Increased diabetes rates were observed when the basal diet was supplemented with 5% wheat (71% by age 25 weeks; p = 0.023) and 5% corn (57% by age 25 weeks; p = 0.05). Increasing wheat concentrations returned diabetes development to that in basal diet-fed mice. Other food supplements had no or minimal effects on diabetes development. Conclusions: Early supplementation of a basal low-diabetogenic diet with low concentrations of the cereals wheat or corn is associated with a moderate increase in the rate of diabetes. Removal of cereals, however, does not abrogate diabetes development in NOD mice.



 goto top of outline Author Contacts

Dr. Kerstin Koczwara
Institut für Diabetesforschung am Helmholtz Zentrum München
Ingolstädter Landstrasse 1, DE–85764 Neuherberg (Germany)
Tel. +49 89 31 87 39 06, Fax +49 89 30 81 733
E-Mail Kerstin.Koczwara@lrz.uni-muenchen.de


 goto top of outline Article Information

Received: August 26, 2008
Accepted after revision: March 17, 2009
Published online: May 27, 2009
Number of Print Pages : 10
Number of Figures : 4, Number of Tables : 3, Number of References : 28


 goto top of outline Publication Details

Annals of Nutrition and Metabolism (Journal of Nutrition, Metabolic Diseases and Dietetics)

Vol. 54, No. 3, Year 2009 (Cover Date: August 2009)

Journal Editor: Elmadfa I. (Vienna)
ISSN: 0250-6807 (Print), eISSN: 1421-9697 (Online)

For additional information: http://www.karger.com/ANM


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK: Environmental triggers and determinants of type 1 diabetes. Diabetes 2005;54(suppl 2):S125–S136.
  2. Lefebvre DE, Powell KL, Strom A, Scott FW: Dietary proteins as environmental modifiers of type 1 diabetes mellitus. Annu Rev Nutr 2006;26:175–202.
  3. Turley SJ, Lee JW, Dutton-Swain N, Mathis D, Benoist C: Endocrine self and gut non-self intersect in the pancreatic lymph nodes. Proc Natl Acad Sci USA 2005;102:17729–17733.
  4. Elliott RB, Reddy SN, Bibby NJ, Kida K: Dietary prevention of diabetes in the non-obese diabetic mouse. Diabetologia 1988;31:62–64.
  5. Coleman DL, Kuzava JE, Leiter EH: Effect of diet on incidence of diabetes in nonobese diabetic mice. Diabetes 1990;39:432–436.
  6. Karges W, Hammond-McKibben D, Cheung RK, Visconti M, Shibuya N, Kemp D, Dosch HM: Immunological aspects of nutritional diabetes prevention in NOD mice: a pilot study for the cow’s milk-based IDDM prevention trial. Diabetes 1997;46:557–564.
  7. Funda DP, Kaas A, Bock T, Tlaskalova-Hogenova H, Buschard K: Gluten-free diet prevents diabetes in NOD mice. Diabetes Metab Res Rev 1999;15:323–327.
  8. Schmid S, Koczwara K, Schwinghammer S, Lampasona V, Ziegler AG, Bonifacio E: Delayed exposure to wheat and barley proteins reduces diabetes incidence in non-obese diabetic mice. Clin Immunol 2004;111:108–118.
  9. Maurano F, Mazzarella G, Luongo D, Stefanile R, D’Arienzo R, Rossi M, Auricchio S, Troncone R: Small intestinal enteropathy in nonobese diabetic mice fed a diet containing wheat. Diabetologia 2005;48:931–937.
  10. Agostoni C, Decsi T, Fewtrell M, Goulet O, Kolacek S, Koletzko B, Michaelsen KF, Moreno L, Puntis J, Rigo J, Shamir R, Szajewska H, Turck D, van Goudoever J, ESPGHAN Committee on Nutrition: Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 2008;46:99–110.
  11. Hannan JM, Ali L, Rokeya B, Khaleque J, Akhter M, Flatt PR, Abdel-Wahab YH: Soluble dietary fibre fraction of Trigonella foenum-graecum (fenugreek) seed improves glucose homeostasis in animal models of type 1 and type 2 diabetes by delaying carbohydrate digestion and absorption, and enhancing insulin action. Br J Nutr 2007;97:514–521.
  12. National Research Council (NRC): Nutrient Requirements of Laboratory Animals, ed 4 (rev). Washington, National Academies Press, 1995.
  13. Osborne TB (ed): The Proteins of the Wheat Kernel. Washington, Carnegie Institute Publishers, 1907, vol 84.
  14. Mimouni B, Robin JM, Azanza JL, Raymond J: Wheat flour proteins: Isolation and functionality of gliadin and HMW-glutenin enriched fractions. J Sci Food Agric 1998;78:423–428.
  15. Nicolas Y, Martinant JP, Denery-Papini S, Popineau Y: Analysis of wheat storage proteins by exhaustive sequential extraction followed by RP-HPLC and nitrogen determination. J Sci Food Agric 1998;77:96–102.
  16. Koczwara K, Schenker M, Schmid S, Kredel K, Ziegler AG, Bonifacio E: Characterization of antibody responses to endogenous and exogenous antigen in the nonobese diabetic mouse. Clin Immunol 2003;106:155–162.
  17. Bonifacio E, Atkinson M, Eisenbarth G, Serreze D, Kay T W, Lee-Chan E, Singh B: International workshop on lessons from animal models for human type 1 diabetes: identification of insulin but not glutamic acid decarboxylase or IA-2 as specific autoantigens of humoral autoimmunity in nonobese diabetic mice. Diabetes 2001;50:2451–2458.
  18. Hoorfar J, Buschard K, Dagnaes-Hansen F: Prophylactic nutritional modification of the incidence of diabetes in autoimmune non-obese diabetic (NOD) mice. Br J Nutr 1993;69:597–607.
  19. Beales PE, Elliott RB, Flohé S, Hill JP, Kolb H, Pozzilli P, Wang GS, Wasmuth H, Scott FW: A multi-centre, blinded international trial of the effect of A1 and A2 β-casein variants on diabetes incidence in two rodent models of spontaneous type I diabetes. Diabetologia 2002;45:1240–1246.
  20. Flohé SB, Wasmuth HE, Kerad JB, Beales PE, Pozzilli P, Elliott RB, Hill JP, Scott FW, Kolb H: A wheat-based, diabetes-promoting diet induces a Th1-type cytokine bias in the gut of NOD mice. Cytokine 2003;21:149–154.
  21. Funda DP, Kaas A, Tlaskalová-Hogenová H, Buschard K: Gluten-free but also gluten-enriched (gluten+) diet prevent diabetes in NOD mice; the gluten enigma in type 1 diabetes. Diabetes Metab Res Rev 2008;24:59–63.
  22. Pomeranz Y: Wheat: Chemistry and Technology, ed 3. St. Paul, American Association of Cereal Chemists Monograph Series, 1988.
  23. Hyppönen E: Micronutrients and the risk of type 1 diabetes: vitamin D, vitamin E, and nicotinamide. Nutr Rev 2004;62:340–347.

    External Resources

  24. Dilworth LL, Omoruyi FO, Simon OR, Morrison EY, Asemota HN: The effect of phytic acid on the levels of blood glucose and some enzymes of carbohydrate and lipid metabolism. West Indian Med J 2005;54:102–106.
  25. Lee S, Park H, Chun H, Cho S, Cho S, Lillehoj HS: Dietary phytic acid lowers the blood glucose level in diabetic KK mice. Nutr Res 2006;26:474–479.
  26. Panlasigui LN, Thompson LU: Blood glucose lowering effects of brown rice in normal and diabetic subjects..Int J Food Sci Nutr 2006;57:151–158.
  27. MacFarlane AJ, Burghardt KM, Kelly J, Simell T, Simell O, Altosaar I, Scott FW: A type 1 diabetes-related protein from wheat (Triticum aestivum). cDNA clone of a wheat storage globulin, Glb1, linked to islet damage. J Biol Chem 2003;278:54–63.
  28. Myers MA, Hettiarachchi KD, Ludeman JP, Wilson AJ, Wilson CR, Zimmet PZ: Dietary microbial toxins and type 1 diabetes. Ann NY Acad Sci 2003;1005:418–422.