Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-05T22:23:58.544Z Has data issue: false hasContentIssue false
  • English
  • Français

Cow’s milk and immune-mediated diabetes

Published online by Cambridge University Press:  28 February 2007

Hermann E. Wasmuth  and
Hubert Kolb
Hermann E. Wasmuth
Affiliation:
German Diabetes Research Institute at the University of Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany
Hubert Kolb*
Affiliation:
German Diabetes Research Institute at the University of Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany
*
Corresponding Author: Dr Hubert Kolb, fax +49 211 3382 606, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Cow’s milk-based infant formulas and cow’s milk consumption in childhood have been suggested to promote the development of type 1 diabetes mellitus and other immune-mediated or neurological diseases. Epidemiological studies in man have led to the hypothesis that introduction of cow’s milk-based infant formula within the first 3 months of life is associated with increased risk of type 1 diabetes mellitus. Furthermore, in animal models of type 1 diabetes mellitus, cow’s milk proteins have been proven to be ‘diabetogenic’. However, the issue seems far from being resolved. Several epidemiological studies and, more importantly, the first prospective trials did not show an association between early exposure to cow’s milk and type 1 diabetes mellitus. In animal models, cow’s milk proteins are modestly and variably diabetogenic, wheat or soyabean proteins in the diet cause higher rates of autoimmune diabetes. In both man and rodents there is increasing evidence that the gut-associated immune system plays a major role in disease development, probably because of disturbed oral tolerance mechanisms. Oral tolerance depends on immunological homeostasis and normal maturation of the gut. These factors are influenced by growth factors and cytokines from breast milk, normal bacterial colonization, infections and diet. All these factors have been proposed as risk factors for type 1 diabetes mellitus. Hence, cow’s milk proteins may provide mimicry epitopes relevant in autoimmunity, as well as destabilizing oral tolerance mechanisms by biologically active peptides. The concept of dietary regulation of autoimmunity does not apply only to cow’s milk protein, but also to other dietary proteins.

Keywords

Cow’s milk proteinType 1-diabetes mellitusGut-associated immune system
Type
Meeting Report
Information
Proceedings of the Nutrition Society , Volume 59 , Issue 4 , November 2000 , pp. 573 - 579
Copyright
Copyright © The Nutrition Society 2000

References

Akerblom, HK & Knip, M (1998) Putative environmental factors of type 1 diabetes. Diabetes Metabolism Reviews 14, 31–67.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
Akerblom, HK, Savilahti, E, Saukkonen, TT, Paganus, A, Virtanen, SM, Teramo, K, Knip, M, Reijonen, H, Karjalainen, J, Vaarala, O & Reunanen, A (1993) The case for elimination of cow's milk in early infancy in the prevention of type 1 diabetes: The Finnish experience. Diabetes Metabolism Reviews 9, 269–278.CrossRefGoogle ScholarPubMed
Akerblom, HK, Virtanen, SM, Hamalainen, A, Ilonen, J, Savilahti, E, Vaarala, O, Reunannen, A, Teramo, K & Knip, M (1999) Emergence of diabetes associated autoantibodies in the nutritional prevention of IDDM (TRIGR) project. Diabetes 48, Suppl. 1, A45.Google Scholar
Atkinson, MA, Bowman, MA, Kao, KJ, Campbell, L, Dush, PJ, Shar, SC, Simell, O & Maclaren, NK (1993) Lack of immune responsiveness to bovine serum albumin in insulin-dependent diabetes. New England Journal of Medicine 329, 1853–1858.CrossRefGoogle ScholarPubMed
Borch-Johnsen, K, Joner, G, Mandrup-Poulsen, T, Christy, M, Zachau-Christiansen, B, Kastrup, K & Nerup, J (1984) Relation between breast-feeding and incidence rates of insulin-dependent diabetes mellitus. Lancet ii, 1083–1086.CrossRefGoogle Scholar
Buckley, RH & Dees, SC (1969) Correlation of milk precipitins with IgA deficiency. New England Journal of Medicine 281, 465–469.CrossRefGoogle ScholarPubMed
Carratu, R, Secundulfo, M, de Magistris, L, Iafusco, D, Urio, A, Carbone, MG, Pontoni, G, Carteni, M & Prisco, F (1999) Altered intestinal permeability to mannitol in diabetes mellitus type 1. Journal of Pediatric Gastroenterology and Nutrition 28, 264–269.Google Scholar
Catino, M, Tumini, S, Mezzetti, A & Chiarelli, F (1998) Coeliac disease and diabetes mellitus in children: a non casual association. Diabetes Nutrition and Metabolism 11, 296–302.Google Scholar
Cavallo, MG, Fava, SD, Monetini, L, Barone, F & Pozzilli, P (1996) Cell-mediated immune response to β-casein in recent-onset insulin-dependent diabetes: implications for disease pathogenesis. Lancet 348, 926–928.CrossRefGoogle Scholar
Cronin, CC & Shanahan, F (1997) Insulin-dependent diabetes mellitus and coeliac disease. Lancet 349, 1096–1097.CrossRefGoogle ScholarPubMed
Cheung, R, Karjalainen, J, Van der Meulem, J, Signal, DP & Dosch, H-M (1994) T cells from children with IDDM are sensitized to bovine serum albumin. Scandinavian Journal of Immunology 40, 623–628.CrossRefGoogle ScholarPubMed
Couper, J, Steele, C, Beresford, S, Powell, T, McCaul, K, Pollard, A, Gellert, S, Janulovski, C, Harrison, L & Colman, P (1998) Lack of association between breast-feeding or introduction of cow's milk protein and the development of anti-islet autoimmunity. In Proceedings of the 41st Annual Scientific Meeting of The Endocrine Society of Australia Perth 1998, p. 120 [Coulter, CL editor]. Melbourne, Australia: The Endocrine Society of Australia.Google Scholar
Dahl-Jorgensen, K, Joner, G & Hanssen, KF (1991) Relationship between cows' milk consumption and incidence of IDDM in childhood. Diabetes Care 14, 1081–1083.CrossRefGoogle Scholar
Dahlquist, G, Savilahti, E & Landin-Olsson, M (1992) An increased level of antibodies to β-lactoglobulin is a risk determinant for early onset type 1 (insulin-dependent) diabetes mellitus independent of islet cell antibodies and early introduction of cow's milk. Diabetologia 35, 980–984.CrossRefGoogle ScholarPubMed
Di Mario, U, Dotta, F, Crisa, L, Anastasi, E, Andreani, D, Dib, SA & Eisenbarth, GS (1988) Circulating anti-immunoglobulin antibodies in recent-onset type 1 diabetic patients. Diabetes 37, 462–466.CrossRefGoogle Scholar
Elitsur, Y & Luk, GD (1991) Beta-casomorphin (BCM) and human lamina propria lymphocyte proliferation. Clinical and Experimental Immunology 85, 493–497.CrossRefGoogle ScholarPubMed
Elliott, RB, Harris, DP, Hill, JP, Bibby, NJ & Wasmuth, HE (1999) Type 1 (insulin-dependent) diabetes mellitus and cow's milk: casein variant consumption. Diabetologia 42, 292–296.CrossRefGoogle Scholar
Elliott, RB & Martin, JM (1984) Dietary protein: a trigger of insulin dependent diabetes in the BB rat? Diabetologia 26, 297–299.CrossRefGoogle Scholar
Elliott, RB, Reddy, SN, Bibby, NJ & Kida, K (1988) Dietary prevention of diabetes in the non-obese diabetic mouse. Diabetologia 31, 62–64.CrossRefGoogle ScholarPubMed
Elliott, RB, Wasmuth, H, Hill, J, Songini, M & Bottazzo, GF for the Sardinian, IDDM Study, Groups (1996) Diabetes and cow's milk. Lancet 348, 1657.CrossRefGoogle Scholar
Ellis, TM, Ottendorfer, E, Jodoin, E, Salisbury, PJ, She, JX, Schatz, DA & Atkinson, MA (1998) Cellular immune responses to β-casein: elevated but not specific for individuals with type 1 diabetes mellitus. Diabetologia 41, 731–735.CrossRefGoogle ScholarPubMed
Fava, D, Leslie, RDG & Pozzilli, P (1994) Relationship between dairy product consumption and incidence of IDDM in childhood in Italy. Diabetes Care 17, 1488–1490.CrossRefGoogle ScholarPubMed
Feighery, C (1999) Coeliac disease. British Medical Journal 319, 236–239.CrossRefGoogle ScholarPubMed
Ferguson, A (1977) Immunogenicity of cows' milk in man: influence of age and of disease on serum antibodies to cows' milk proteins. Ricerca in Clinica e in Laboratorio 7, 211–219.CrossRefGoogle ScholarPubMed
Füchtenbusch, M, Karges, W, Standl, E, Dosch, H-M, & Ziegler, AG (1997) Antibodies to bovine serum albumin (BSA) in type 1 diabetes and other autoimmune disorders. Experimental and Clinical Endocrinology Diabetes 105, 86–91.CrossRefGoogle ScholarPubMed
Fukudome, S, Jinsmaa, Y, Matsukawa, T, Sasaki, R & Yoshikawa, M (1997) Release of opioid peptides, gluten exorphins by the action of pancreatic elastase. FEBS Letters 412, 475–479.CrossRefGoogle Scholar
Fukudome, S & Yoshikawa, M (1992) Opioid peptides derived from wheat gluten: their isolation and characterization. FEBS Letters 296, 107–111.CrossRefGoogle ScholarPubMed
Garside, P, Khoruts, A & Mowat, AM (1999) Oral tolerance in disease. Gut 44, 137–142.CrossRefGoogle ScholarPubMed
Gerstein, H (1994) Cow's milk exposure and type 1 diabetes mellitus. Diabetes Care 17, 13–19.CrossRefGoogle Scholar
Goebel, C, Kirchhoff, K, Wasmuth, H, Flohé, S, Elliott, RB & Kolb, H (1999) The gut cytokine balance as a target of lead toxicity. Life Sciences 64, 2207–2214.CrossRefGoogle ScholarPubMed
Graves, PM, Norris, JM, Pallansch, MA, Gerling, IC & Rewers, M (1997) The role of enteroviral infections in the development of IDDM: limitations of current approaches. Diabetes 46, 161–168.CrossRefGoogle ScholarPubMed
Hammarstrom, L & Smith, CIE (1983) HLA-A, B, C and DR antigens in IgA deficiency. Tissue Antigens 21, 75–79.CrossRefGoogle Scholar
Hanglow, AC, Welsh, CJ, Conn, P & Coombs, RR (1985) Early rheumatoid-like synovial lesions in rabbits drinking cow's milk. II. Antibody responses to bovine serum proteins. International Archives of Allergy and Applied Immunology 78, 152–160.CrossRefGoogle ScholarPubMed
Hänninen, A, Jaakköla, I & Jalkanen, S (1998) Mucosal addressin is required for the development of diabetes in the nonobese diabetic mice. Journal of Immunology 160, 6018–6025.CrossRefGoogle ScholarPubMed
Hänninen, A, Salmi, M, Simell, O & Jalkanen, S (1993 a) Endothelial cell-binding properties of lymphocytes infiltrated into human diabetic pancreas. Diabetes 42, 1656–1662.CrossRefGoogle Scholar
Hänninen, A, Taylor, C, Streeter, PR, Stark, LS, Sarte, JM, Shiruzu, JA, Simell, O & Michie, SA (1993 b) Vascular addressins are induced on islet vessels during insulitis in non-obese diabetic mice and are involved in lymphoid cell binding to islet endothelium. Journal of Clinical Investigation 92, 2509–2515.CrossRefGoogle ScholarPubMed
Harrison, LC & Honeyman, MC (1999) Cow's milk and type 1 diabetes. The real debate is about mucosal immune function. Diabetes 48, 1501–1507.CrossRefGoogle ScholarPubMed
Honeyman, MC, Stone, NL & Harrison, LC (1998) T-cell epitopes in the type 1 diabetes autoantigen IA-2: potential for mimicry with rotavirus and other environmental agents. Molecular Medicine 4, 231–239.CrossRefGoogle ScholarPubMed
Hummel, M, Schenker, M, Ziegler, AG and the BABY-DIAB Study Group (1998) Appearance of diabetes-associated antibodies in offspring of parents with type 1 diabetes is independent from environmental factors. Diabetologia 41, Suppl. 1, A 91 Abstr.Google Scholar
Issa-Chergui, B, Guttmann, RD, Seemayer, TA, Kelley, VE & Colle, E (1988) The effect of diet on the spontaneous insulin dependent diabetes syndrome in the rat. Diabetes Research 9, 81–86.Google ScholarPubMed
Jinsmaa, Y & Yoshikawa, M (1999) Enzymatic release of neocasomorphin and β-casomorphin from bovine β-casein. Peptides 20, 957–962.CrossRefGoogle ScholarPubMed
Kallmann, B, Hüther, M, Tubes, M, Feldkamp, J, Bertrams, J, Gries, FA, Lampeter, EF & Kolb, H (1997) Systemic bias of cytokine production towards cell-mediated immune regulation in IDDM and towards humoral immunity in Graves' disease. Diabetes 46, 237–243.CrossRefGoogle Scholar
Karjalainen, J, Martin, JM, Knip, M, Ilonen, J, Robinson, BH, Savilathi, E, Akerblom, HK & Dosch, HM (1992) A bovine albumine peptide as a possible trigger of insulin-dependent diabetes mellitus. New England Journal of Medicine 327, 302–307.CrossRefGoogle ScholarPubMed
Kolb, H & Elliott, RB (1994) Increasing incidence of IDDM: a consequence of improved hygiene? Diabetologia 37, 729.CrossRefGoogle ScholarPubMed
Kolb, H & Pozzilli, P (1999) Cow's milk and type 1 diabetes: the gut immune system deserves attention. Immunology Today 20, 108–110.CrossRefGoogle Scholar
Kostraba, JN, Cruikshanks, KJ, Lawler-Heavner, J, Jobim, LF, Rewers, MJ, Gay, EC, Chase, HP, Klingensmith, G & Hamman, RF (1993) Early exposure to cow's milk and solid foods in infancy, genetic predisposition, and risk of IDDM. Diabetes 42, 288–295.CrossRefGoogle ScholarPubMed
Krokowski, M, Caillat-Zucman, S, Timsit, J, Larger, E, Pehuet-Figoni, M, Bach, JF & Boitard, C (1995) Anti-bovine serum albumin antibodies: genetic heterogeneity and clinical relevance in adult-onset IDDM. Diabetes Care 18, 170–173.CrossRefGoogle ScholarPubMed
Lucarelli, S, Frediani, T, Zingoni, AM, Ferruzzi, F, Giardini, O, Quintieri, F, Barbato, M, Déufemia, P & Cardi, E (1995) Food allergy and infantile autism. Panminerva Medicine 37, 137–141.Google ScholarPubMed
Lühder, F, Schlosser, M, Michaelis, D, Ziegler, B, Kohnert, K-D, & Ziegler, M (1994) No association between anti-bovine serum albumin antibodies and islet cell reactive antibodies in newly diagnosed type 1 diabetic patients. Diabetes Research and Clinical Practice 26, 35–41.CrossRefGoogle Scholar
Mäki, M & Collin, P (1997) Coeliac disease. Lancet 349, 1755–1759.CrossRefGoogle Scholar
Malkani, S, Nommpleggi, D, Hansen, JW, Greiner, DL, Mordes, JP & Rossini, AA (1997) Dietary cow's milk protein does not alter the frequency of diabetes in the BB rat. Diabetes 46, 1133–1140.CrossRefGoogle Scholar
Malosse, D, Perron, H, Sasco, A & Seigneurin, JM (1992) Correlation between milk and dairy product consumption and multiple sclerosis prevalence: a worldwide study. Neuroepidemiology 11, 304–312.CrossRefGoogle Scholar
Norris, JM & Scott, FW (1996) A meta analysis of infant diet and insulin-dependent diabetes mellitus: do biases play a role? Epidemiology 7, 87–92.CrossRefGoogle ScholarPubMed
Paronen, J, Klemetti, P, Kantele, JM, Savilathi, E, Perheentupa, J, Akerblom, HK & Vaarala, O (1997) Glutamate decarboxylase-reactive peripheral blood lymphocytes from patients with IDDM express gut-specific homing receptor α4β7-integrin. Diabetes 46, 583–588.CrossRefGoogle ScholarPubMed
Paxson, JA, Weber, JG & Kulczycki, A (1997) Cow's milk free diet does not prevent diabetes in NOD mice. Diabetes 46, 1711–1717.CrossRefGoogle Scholar
Perez-Bravo, F, Cassasco, E, Gutierrez-Lopez, MD, Martinez, MT, Lopez, G & Garcia de los Rios, M (1996) Genetic predisposition and environmental factors leading to the development of insulin-dependent diabetes in Chilean children. Journal of Molecular Medicine 74, 105–109.CrossRefGoogle Scholar
Petrovsky, N & Harrison, LC (1995) HLA-matched control subjects are essential in studies of susceptibility to IDDM. Diabetologia 38, 125–126.CrossRefGoogle ScholarPubMed
Saukkonen, T, Savilathi, E, Reijonen, H, Ilonen, J, Tuomiletho-Wolf, E & Akerblom, HK (1996) Coeliac disease: frequent occurrence after clinical onset of insulin-dependent diabetes mellitus. Childhood in Finland Study Group. Diabetic Medicine 13, 464–470.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
Saukkonen, T, Virtanen, SM, Karppinen, M, Reijonen, H, Ilonen, J, Räsänen, L, Akerblom, HK, Savilahti, E and the Childhood Diabetes in Finland Study Group (1998) Significance of cow's milk protein antibodies as risk factors for childhood IDDM: interactions with dietary cow's milk intake and HLA-DQB1 genotype. Diabetologia 41, 72–78.CrossRefGoogle ScholarPubMed
Savilahti, E, Akerblom, HK, Tainio, VM & Koskimies, S (1988) Children with newly-diagnosed insulin-dependent diabetes mellitus have increased levels of cow's milk antibodies. Diabetes Research 7, 137–140.Google ScholarPubMed
Savilahti, E, Ormala, T, Saukkonen, T, Sandini-Pohjavuori, U, Kantele, JM, Arato, A, Ilonen, J & Akerblom, HK (1999) Jejuna of patients with insulin-dependent diabetes mellitus (IDDM) show signs of immune activation. Clinical and Experimental Immunology 116, 70–77.CrossRefGoogle ScholarPubMed
Savilahti, E, Saukkonen, TT, Virtala, ET, Tuomiletho, J, Akerblom, HK and the Childhood in Diabetes in Finland Study Group (1993) Increased levels of cow's milk and β-lactoglobulin antibodies in young children with newly diagnosed IDDM. Diabetes Care 16, 137–140.CrossRefGoogle ScholarPubMed
Scott, FW (1990) Cow's milk and insulin-dependent diabetes: is there a relationship? American Journal of Clinical Nutrition 51, 489–491.CrossRefGoogle ScholarPubMed
Scott, FW (1996) Food-induced type 1 diabetes in the BB rat. Diabetes Metabolism Reviews 12, 341–359.3.0.CO;2-O>CrossRefGoogle ScholarPubMed
Scott, FW, Mongeau, R, Kardish, M, Hatina, G, Trick, KD & Wojcinski, Z (1985) Diet can prevent diabetes in the BB rat. Diabetes 34, 1059–1062.CrossRefGoogle ScholarPubMed
Scott, FW, Norris, JM & Kolb, H (1996) Milk and type 1 diabetes: examining the evidence and broadening the focus. Diabetes Care 19, 379–383.CrossRefGoogle Scholar
Srivastava, MD, Srivastava, A, Brouhard, B, Saneto, R, Groh-Wargo, S & Kubit, J (1996) Cytokines in human milk. Research Communications in Molecular Pathology and Pharmacology 93, 263–287.Google ScholarPubMed
Strobel, S & Mowat, AM (1998) Immune response to dietary antigens: oral tolerance. Immunology Today 19, 173–181.CrossRefGoogle ScholarPubMed
Teschemacher, H, Hock, G & Brantl, V (1997) Milk protein-derived opioid receptor ligands. Biopolymers 43, 99–117.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
Vaarala, O, Klemetti, P, Savilathi, E, Reijonen, H, Ilonen, J & Akerblom, HK (1996) Cellular immune response to cow's milk β-lactoglobulin in patients with newly diagnosed IDDM. Diabetes 45, 178–182.CrossRefGoogle ScholarPubMed
Vaarala, O, Knip, M, Paronen, J, Hämäläinen, AM, Muona, P, Väätäinen, M, Ilonen, J, Simell, O & Akerblom, HK (1999) Cow's milk formula feeding induces primary immunization to insulin in infants at genetic risk for type 1 diabetes. Diabetes 48, 1389–1394.CrossRefGoogle ScholarPubMed
Vaarala, O, Paronen, J, Otonkoski, T & Akerblom, HK (1998) Cow milk formula feeding induces antibodies to insulin in children – a link between cow milk and insulin-dependent diabetes mellitus? Scandinavian Journal of Immunology 47, 131–135.CrossRefGoogle ScholarPubMed
Virtanen, SM, Hypponen, E, Laara, E, Vahasalo, P, Kulmala, P, Savola, K, Rasanen, L, Aro, A, Knip, M & Akerblom, HK (1998) Cow's milk consumption, disease-associated autoantibodies and type 1 diabetes mellitus: a follow-up study in siblings of diabetic children. Childhood Diabetes in Finland Study Group. Diabetic Medicine 15, 730–738.3.0.CO;2-C>CrossRefGoogle ScholarPubMed
Wasmuth, HE, Becker, F, Seebaum, S, Elliott, RB & Federlin, K (1995) Association of antibodies to β casein with type 1 diabetes. Autoimmunity 21, A328.Google Scholar
Weiner, HL, Friedman, A & Miller, A (1994) Oral tolerance: immunologic mechanism and treatment of animal and human organ-specific autoimmune disease by oral administration of autoantigens. Annual Reviews of Immunology 12, 809–837.CrossRefGoogle ScholarPubMed