EARLY PROGRAMMING OF DIABETES RISK – AN INTRODUCTION
H.K.Åkerblom
Biomedicum Helsinki and Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
1. INTRODUCTION
The importance of perinatal nutrition is well recognized with regard to later growth and the risk of type 2 diabetes in adult life. However, nutrition in very early life has also implications with regard to the risk of type 1 diabetes in childhood. This field was reviewed in the presentations in a session at the Workshop “Early Nutrition and Its Later Consequences: New Opportunities” in Paris, July 2-3, 2004. A review of the relation between early nutrition and later diabetes risk is presented in this supplement by Knip and Åkerblom.
2. HISTORY
The cow’s milk and type 1 diabetes hypothesis has been debated for some two decades. Experiments in BB rats (1) and NOD mice (2) have clearly demonstrated a deleterious effect of dietary proteins, such as cow’s milk proteins in the disease process. The classical report of Elliott and Martin (1) was followed by a report from the same group (3) of the effect of cow’s milk proteins appearing during a relatively narrow and early phase in the postnatal (weaning) period. Many ecological and epidemiological studies, but not all, in man have shown that exposure to
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140 H.K.Åkerblom cow’s milk proteins during the first months of life may be particularly important. The strongest indirect evidence in man comes from infant feeding studies, an inverse correlation being found between the duration of breast feeding and the incidence of type 1 diabetes in childhood (reviewed in ref. 4).
3. POSSIBLE MECHANISMS
The mechanism of the possible beta-cell lesion by cow’s milk protein remains to be clarified, and several proteins in cow’s milk have been suggested to be the diabetogenic compound.
In recent years much interest has been directed to the importance of the induction of immune tolerance in the gut. Several studies indicate that patients with type 1 diabetes have an enhanced humoral and cellular immunity to a series of cow’s milk proteins. The findings of altered immune responsiveness to dietary antigens in type 1 diabetes suggest that the regulation of mucosal immunity may be disturbed. Accordingly it is possible that none of these antigen-specific immune responses may be directly involved in the pathogenesis of the disease, but they are induced as a consequence of dysregulated oral tolerance (4). This regulatory defect of the gut immune system may actually have a fundamental role in the pathogenetic process leading to type 1 diabetes (5,6).
The possibility that bovine insulin could be the pathogenetic compound has gained attention in recent years, and is presented in more detail in the article by Vaarala. The possibility that lymphocytes sensitized to bovine insulin in early infancy will later mature toward autoreactive insulin-specific lymphocytes in some individuals and lead to the destruction of insulin producing beta-cells is a new hypothesis in the pathogenesis of type 1 diabetes (6).
Gluten is another dietary protein of great interest with regard to the pathogenesis of type 1 diabetes in relation to early feeding. In BB rats wheat gluten in the diet increased the incidence of diabetes (7), and a gluten-free diet prevented diabetes in NOD mice (8). Recently it was
EARLY PROGRAMMING OF DIABETES RISK 141 reported that gluten feeding in early infancy may lead to the appearance of autoimmune markers of type 1 diabetes (9,10).
4. CONCLUSIONS
Many important challenges remain for investigators in the field of early nutrition and the risk of type 1 diabetes, e.g. the mechanisms of the beta-cell lesion by foreign proteins, and the timing of exposure (9).
REFERENCES
1. ELLIOTT RB, MARTIN JM. Dietary protein: a trigger of insulin-dependent diabetes in the BB rat ? Diabetologia 26:297-299, 1984.
2. ELLIOTT RB, REDDY SN, BIBBY NJ, KIDA K. Dietary prevention of diabetes in the non-obese diabetic mouse. Diabetologia 31:62-64, 1988.
3. DANEMAN D, FISHMAN L, CLARSON C, MARTIN JM. Dietary triggers of insulin-dependent diabetes in the BB rat. Diabetes Res 5:93-97, 1987.
4. ÅKERBLOM HK, KNIP M. Putative environmental factors in Type 1 diabetes.
Diabetes Metab Rev 14:31-67, 1998.
5. HARRISON LC, HONEYMAN MC. Cow’s milk and type 1 diabetes. The real debate is about mucosal immune function. Diabetes 48:1501-1507, 1999.
6. VAARALA O. Gut and the induction of immune tolerance in Type 1 diabetes.
Diabetes Metab Res Rev 15:353-361, 1999.
7. HOORFAR J, SCOTT FW, CLOUTIER HE. Dietary plant materials and development of diabetes in the BB rat. J Nutr 121:908-916, 1991.
8, FUNDA DP, KAAS A, BOCK T, TLASKALOVA-HOGENOVA H, BUSCHARD K.
Gluten-free diet prevents diabetes in NOD mice. Diabetes Metab Rev Res 15:323- 327, 1999.
9. NORRIS JM, BARRIGA K, KLINGENSMITH G et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA 290:1713-1720, 2003.
10. ZIEGLER A-G, SCHMID S, HUBER D, HUMMEL M, BONIFACIO E. Early infant feeding and risk of developing Type 1 diabetes-associated autoantibodies. JAMA 290:1721-1728, 2003.
