IDDM and Early Infant Feeding - Diabetes Care

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RESEARCH DESIGN AND METHODS— We have carried out a case-control study in the area of Sassari (northern Sardinia, Italy), which is characterized by an ...
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A R T I C L E

IDDM and Early Infant Feeding Sardinian case-control study TULLIO MELONI, MD ANNA MARIA MARINARO, MD MARIA CHIARA MANNAZZU, MD AUGUSTO OGANA, MD

CARLO LA VECCHIA, MD EVA NEGRI, PHD CARLA COLOMBO, MD

OBJECTIVE — To further investigate the association between the type of feeding in infancy and the development of IDDM. RESEARCH DESIGN A N D M E T H O D S — We have carried out a case-control study in the area of Sassari (northern Sardinia, Italy), which is characterized by an ethnically homogenous population at high risk of IDDM. The study subjects comprised 100 IDDM patients and 100 control subjects, matched for sex and age and selected from children admitted at the Department of Pediatrics of the University of Sassari. Diabetic children (53 boys, 47 girls) had been diagnosed between 1983 and 1994, and their age at diagnosis ranged between 1 and 15 years. Information on feeding patterns during the 1st year of life was collected through questionnaires administered to the mothers. The questionnaire was designed to evaluate the duration of complete or partial breast-feeding and the age at which dietary products containing cow's milk were introduced into the diet. RESULTS — A larger proportion of the diabetic children rather than the control children had been breast-fed, and the risk of IDDM among children who had not been breast-fed was below unity (odds ratio [OR] 0.41; 95% CI 0.19-0.91). No clear difference was observed between diabetic and control subjects in the duration of breast-feeding (medians: 3 and 2 months, respectively), even if, overall, the data suggested a slight increase in the risk of IDDM with longer duration of breast-feeding (OR 1.10; 95% CI 0.99-1.22 per month). Although a larger proportion of control children rather than diabetic children had been given cow's milk-derived formula and solid food before the age of 3 months, there was no time-risk relationship. CONCLUSIONS — Our data do not support the existence of a protective effect of breastfeeding on the risk of IDDM, nor do the data indicate that early exposure to cow's milk and dairy products has any influence on the development of IDDM in a high-risk population.

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here is convincing evidence that both genetic susceptibility and the environment play a role in the etiology of IDDM. The autoimmune destruction of insulin-producing (3-cells of the pancreas in genetically susceptible individuals may in fact result from exposure to environmental factors, including infectious agents (mostly viruses), chemical toxins, emotional stress, and diet (1,2). In consideration of the significant burden to diabetic patients and society,

research aimed at the prevention of IDDM through elimination of possible causative agents is a clear priority. After the experimental observation of the diabetogenic effect of cow's milk and dairy proteins in genetically susceptible animals (biobreeding rat and nonobese diabetic mouse) (3,4), specific efforts have been addressed to establish the existence of a relationship between feeding patterns in early life and later development of the disease (5). Evidence of a protective influence of breast-

feeding was first derived from ecological studies, which reported a negative correlation between incidence rates of breast-feeding and childhood IDDM (6); these studies also suggested that cow's milk proteins may be involved in its pathogenesis, since the incidence of IDDM was found to be directly correlated with a population's daily milk protein consumption (7,8). More recently, a cow's milk diabetes hypothesis has been formulated that assumes dietary exposure to cows milk early in life may be of major importance (9,10). Serological evidence has been obtained that the autoimmune destruction of pancreatic (3-cells may be triggered by early exposure to a protein present in cow's milk (11). A 17-amino-acid fragment of bovine serum albumin has been identified that cross-reacts immunologically with an islet antigen called p69. IDDM may thus occur through molecular mimicry between the antigen p69 and bovine serum albumin in cow's milk. These observations, however, have not been confirmed by other investigators (12). In addition, while a few case-control studies have shown that patients with IDDM are more likely to have a history of neonatal cow's milk exposure or a short/negative history of breast-feeding as compared with nondiabetic control subjects, other studies with similar design have failed to demonstrate such a relationship (13). Case-control studies in populations at high risk of IDDM may be particularly relevant in establishing environmental determinants of IDDM. Sardinia has the second highest incidence rate of IDDM in Europe after Finland (14). To further investigate the role of early infant feeding in the development of IDDM, we carried out a case-control study in the area of Sassari, which is characterized by an ethnically homogenous population at high risk of IDDM.

RESEARCH DESIGN AND From the Istituto di Clinica Pediatrica e Neonatologica, University of Sassari (T.M., A.M.M., M.C.M., A.O., C.C.), Sassari; Istituto di Ricerche Farmacologiche "Mario Negri" (C.L.V, E.N.); Istituto di Statistica Medica e Biometria (C.L.V), University of Milan, Milan, Italy. Address correspondence and reprint requests to Carla Colombo, MD, Department of Pediatrics and Neonatology, University of Sassari, Viale San Pietro 12, 01700 Sassari, Italy. Received for publication 26 July 1996 and accepted in revised form 18 October 1996. OR, odds ratio.

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M E T H O D S — All diabetic subjects followed up at the Department of Pediatrics of the University of Sassari were considered for enrollment into the study. Inclusion criteria were as follows: 1) age was younger than 17 years at diagnosis of IDDM, 2) diagnosis of IDDM was achieved between

DIABETES CARE, VOLUME 20, NIMBER 3, MARCH

1997

Meloni and Associates

RESULTS — The characteristics of the CONCLUSIONS — There is a variabilstudy population are reported in Table 1. ity in the results of case-control studies Cases and control subjects were similar designed to evaluate the cows milk diawith reference to mother's education and betes hypothesis, and it has been recently Diabetic Control number of siblings. Influences of feeding suggested that inconsistencies in the availpatients patients habits in the 1st year of life on the risk of able data may be at least in part due to inac53:47 53:47 Sex (M:F) IDDM are reported in Table 2. curacies in long-term dietary recall, lower Age at interview (years) A larger proportion of the diabetic chil- response rate in control subjects vs. cases, 6 6 15 16 anything, was below unity (OR 0.41; 95% few studies carried out in both high-risk 6 (1-15) CI 0.19-0.91). No clear difference was (Finnish) (17) and low-risk (Hungarian) Age at diagnosis (years) observed between diabetic and control sub- (18) populations. Mother's education jects in the duration of breast-feeding 72 67 Primary However, this issue is still controver(medians: 3 and 2 months, respectively); sial, despite the fact that two recently pubI ligh school or college 28 33 Number of siblings when the duration of breast-feeding was lished meta-analyses of the more rigorous divided into three categories (1-2 months, case-control studies are consistent with a 6 months), the data sug- modest increase in theriskof IDDM in sub>2 29 29 gested a slight increase in the risk of IDDM jects with a history of early cow's milk Data are n and median (range). with duration of breast-feeding (Table 2). exposure and breast-feeding for < 3 Compared with those children who had months' duration (13,16). 1983 and 1994, and 3) patient's mother been breast-fed for 6 months or longer, the The idea that IDDM might be dietwas currently living, which was consid- OR of diabetes was 1.18 for those breast- induced discloses important perspectives ered necessary to obtain accurate infant fed for 3-5 months, 0.48 for those breast- concerning its prevention. Accordingly, the fed for 1-2 months, and 0.36 for those who Work Group on Cows Milk Protein and diet information. According to these criteria, 100IDDM were not breast-fed. Diabetes Mellitus of the American Academy patients (of the 115 eligible) were included. Although a larger proportion of control of Pediatrics has recommended "breast Also, 100 control subjects were selected children rather than diabetic children had feeding and avoidance of commercially from children admitted at the Department been given cow's milk-derived formula and available cows milk and products containof Pediatrics of the University of Sassari, so solid food before the age of 3 months, there ing intact cows milk protein during the 1st that each diabetic subject could be was no evidence of a dose-response effect year of life in families with a strong history matched for sex and age to a control sub- in the risk of IDDM. of IDDM" (5). The group has also encourject. None of the control subjects had a family history of IDDM. Information on feeding patterns during the 1st year of life was collected through Table 2—Influence offeeding habits on the risk of IDDM questionnaires administered by two of us to the mothers of diabetic children and conCase subjects Control subjects OR (95% CI) trol subjects. The questionnaire was designed to evaluate, through long-term Breast-feeding maternal recall, the duration of complete or Yes 84 70 1* partial breast-feeding and the age at which No 16 30 0.41 (0.19-0.91) dietary products containing cow's milk Duration of breast-feeding (months) were introduced into the diet. Replies to the >6 25 19 1* questionnaires were obtained from all cases 3-5 41 25 1.18(0.52-2.68) and control subjects. 1-2 18 26 0.48(0.19-1.24) 0 16 30 0.36(0.14-0.94) Statistical analysis Continuous coefficient 1.10(0.99-1.22) Together with the corresponding 95% CI, Age at introduction of cow's milkthe odds ratio (OR) of diabetes according to derived formula (months) >6 30 23 1* breast-feeding, the duration of breast-feed3-5 37 24 1.45 (0.60-3.51) ing, the age at introduction of dietary prod