BACKGROUND:Bovine beta-casein is a cow's milk protein that targets both humoral and cellular immune responses in patients with Type 1 diabetes and, to a lesser degree, also in normal subjects. In this study we aimed to determine whether the avoidance of cow's milk consumption early in life could prevent the development of antibody response to bovine beta-casein despite the mother being exposed on a daily basis to cow's milk consumption.

MATERIALS AND METHODS:We measured the antibody response to bovine beta-casein using an ELISA method in 28 healthy infants under 4 months of age, of whom 16 were exclusively breast-fed and 12 were bottle-fed with cow's milk. In addition, beta-casein antibodies were measured in 37 prepubertal children with Type 1 diabetes and in 31 healthy children who were exposed to cow's milk or dairy products to see whether differences in antibody titers exist in this young age group. Antibodies binding to beta-casein were also evaluated by immunoblotting analysis.

RESULTS:Elevated levels of beta-casein antibodies were found in bottle-fed infants compared to breast-fed infants (p<0.0001). Antibody levels to bovine beta-casein were also significantly higher in children with Type 1 diabetes compared to age-matched controls (p=0.03). By western blot analysis we confirmed specific binding to bovine beta-casein in bottle-fed infants, in children with Type 1 diabetes and in controls exposed to cow's milk, but not in infants who were exclusively breast-fed.

CONCLUSIONS:The results of this study indicate that breastfeeding within the first 4 months of life prevents the generation of antibody response to bovine beta-casein despite the mothers' consumption of cow's milk during the breastfeeding period. These findings may have relevance for disease prevention.

OBJECTIVE: There is evidence of gut barrier and immune system dysfunction in some patients with type 1 diabetes, possibly linked with exposure to dietary wheat polypeptides (WP). However, questions arise regarding the frequency of abnormal immune responses to wheat and their nature, and it remains unclear whether such responses are diabetes specific.

RESEARCH DESIGN AND METHODS: In type 1 diabetic patients and healthy control subjects, the immune response of peripheral CD3(+) T-cells to WPs, ovalbumin, gliadin, alpha-gliadin 33-mer peptide, tetanus toxoid, and phytohemagglutinin was measured using a carboxyfluorescein diacetate succinimidyl ester (CFSE) proliferation assay. T-helper cell type 1 (Th1), Th2, and Th17 cytokines were analyzed in WP-stimulated peripheral blood mononuclear cell (PBMNC) supernatants, and HLA was analyzed by PCR.

RESULTS: Of 42 patients, 20 displayed increased CD3(+) T-cell proliferation to WPs and were classified as responders; proliferative responses to other dietary antigens were less pronounced. WP-stimulated PBMNCs from patients showed a mixed proinflammatory cytokine response with large amounts of IFN-gamma, IL-17A, and increased TNF. HLA-DQ2, the major celiac disease risk gene, was not significantly different. Nearly all responders carried the diabetes risk gene HLA-DR4. Anti-DR antibodies blocked the WP response and inhibited secretion of Th1 and Th17 cytokines. High amounts of WP-stimulated IL-6 were not blocked.

CONCLUSIONS: T-cell reactivity to WPs was frequently present in type 1 diabetic patients and associated with HLA-DR4 but not HLA-DQ2. The presence of an HLA-DR-restricted Th1 and Th17 response to WPs in a subset of patients indicates a diabetes-related inflammatory state in the gut immune tissues associated with defective oral tolerance and possibly gut barrier dysfunction.

The low calorie juice Aronia melanocarpa (sugar free, with artificial sweeteners) could be a valuable adjunct to the complex therapy of patients with diabetes mellitus. In this study no increased blood glucose levels were established 60 min. following ingestion of 200 ml Aronia juice. On the contrary, lower fasting blood glucose concentrations were measured in 16 patients with insulin dependent diabetes and in 25 patients with non-insulin dependent diabetes (25 women and 16 men, 3 to 62 years of age, median age 38.8 +/- 4.7) with duration of the disease from 1 month to 13 years. Serial blood glucose measurements showed: 14.23 +/- 1.32 mmol/l at baseline and 11.4 +/- 0.89 mmol/l blood glucose level after 60 min., the difference being statistically significant (p<0.05). The ingestion of 200 ml Aronia juice combined with a standard breakfast produced similar results (the basal concentration of glucose was 13.43 +/- 1.12 mmol/l; it decreased to 11.94 +/- 1.02 mmol/l at 60 min., the difference did not reach statistical significance. The daily intake of 200 ml Aronia juice over a period of 3 months was effective in lowering fasting blood glucose levels from 13.28 +/- 4.55 mmol/l to 9.10 +/- 3.05 mmol/l (p<0.001) in 21 patients with non-insulin dependent diabetes--13 women and 8 men aged from 42 to 62 (median age 53.6 +/- 3.65) with disease duration from 6 to 17 years. Aronia had a beneficial effect on HbA1c, total cholesterol and lipid levels. They dropped from 9.39 +/- 2.16% to 7.49 +/- 1.33% (p<0.001), from 6.45 +/- 1.59 mmol/l to 5.05 +/- 0.96 mmol/l (p<0.001) and from 2.92 +/- 2.15 mmol/l to 1.7 +/- 1.07 mmol/l (p<0.001), respectively. Results were compared with those obtained in 23 patients with non-insulin dependent diabetes (15 women and 8 men aged from 48 to 67 years, median age 54.9 +/- 3.34) with disease duration from 6 to 17 years. The above mentioned parameters remained unchanged in these patients. Accumulated data illustrated the hypoglycemic potential of Aronia juice. The precise mechanism of its action is unknown but its beneficial effects and good taste make it a valuable adjunct to the dietary treatment of patients with diabetes mellitus.

OBJECTIVE:Our aim was to study the relation between the duration of full and any breastfeeding and risk of type 1 diabetes.

RESEARCH DESIGN AND METHODS:We included two population-based cohorts of children followed from birth (1996-2009) to 2014 (Denmark) or 2015 (Norway). We analyzed data from a total of 155,392 children participating in the Norwegian Mother and Child Cohort Study (MoBa) and the Danish National Birth Cohort (DNBC). Parents reported infant dietary practices when their child was 6 and 18 months old. The outcome was clinical type 1 diabetes, ascertained from nationwide childhood diabetes registries. Hazard ratios (HRs) were estimated using Cox regression.

RESULTS:Type 1 diabetes was identified in 504 children during follow-up, and the incidence of type 1 diabetes per 100,000 person-years was 30.5 in the Norwegian cohort and 23.5 in the Danish cohort. Children who were never breastfed had a twofold increased risk of type 1 diabetes compared with those who were breastfed (HR 2.29 [95% CI 1.14-4.61] for no breastfeeding vs. any breastfeeding for≥12 months). Among those who were breastfed, however, the incidence of type 1 diabetes was independent of duration of both full breastfeeding (HR per month 0.99 [95% CI 0.97-1.01]) and any breastfeeding (0.97 [0.92-1.03]).

CONCLUSIONS:Suggestive evidence supports the contention that breastfeeding reduces the risk of type 1 diabetes. Among those who were breastfed, however, no evidence indicated that prolonging full or any breastfeeding was associated with a reduced risk of type 1 diabetes.

Experiments in rodent models of insulin-dependent diabetes mellitus (IDDM) suggest that destruction of pancreatic beta cells can be both initiated and inhibited by certain environmental factors such as dietary constituents. We studied nutritional impact of certain protein sources of natural-ingredient, non-purified (NP) rodent diet on diabetes incidence and insulitis severity in the spontaneous diabetic, non-obese diabetic (NOD) mouse. Long-term ad lib. feeding of diets containing wheat flour (800 g/kg), and to a lesser extent soya-bean meal (400 g/kg), were associated with relatively high diabetes incidence (65 and 45% respectively), whereas a diet based on hydrolysed casein (HC; 200 g/kg) as the only source of protein significantly (compared with the wheat-flour diet) inhibited expression of diabetes (22%). Feeding a hypo-allergenic soya-bean-protein hydrolysate resulted in diabetes incidence and insulitis severity similar to that of the soya-bean-meal-fed group. This may indicate that protein hydrolysis per se may not be necessary for dietary modification of diabetes in the NOD mouse. The window of vulnerability to diabetogenic diets was found to be between weaning and about 70 d of age. In the diabetic mice insulitis was less frequent in the HC-fed group when compared with those fed NP (P = 0.04), soybean meal (P = 0.03), soya-bean-protein hydrolysate (P = 0.012) or wheat flour (P = 0.0002). In the non-diabetic mice the wheat-flour diet was associated with a high insulitis severity in comparison with the HC group (P = 0.004). Early avoidance of NP diet was associated with lower degree of insulitis in both diabetic (P = 0.00003) and non-diabetic mice (P = 0.001) when compared with the mice fed on the HC diet later in life. These findings are contributing to further clarification of diabetes-promoting dietary constituents, which may have some nutritional implications for IDDM-susceptible children.

A 5-year and 10-month old boy was diagnosed with classical type 1 diabetes mellitus (T1DM) without celiac disease. He started on a gluten-free diet after 2-3 week without need of insulin treatment. At the initiation of gluten-free diet, HbA1c was 7.8% and was stabilised at 5.8%-6.0% without insulin therapy. Fasting blood glucose was maintained at 4.0-5.0 mmol/l. At 16 months after diagnosis the fasting blood glucose was 4.1 mmol/l and after 20 months he is still without daily insulin therapy. There was no alteration in glutamic acid decarboxylase positivity. The gluten-free diet was safe and without side effects. The authors propose that the gluten-free diet has prolonged remission in this patient with T1DM and that further trials are indicated.

In most developed countries, gluten is currently most commonly introduced between 4 and 6 months of age, in spite of little evidence to support this practice. As for infants at risk of developing food allergies, there is clear evidence that introducing solid foods before the end of the 3rd month is detrimental and should be avoided. A recent growing body of evidence however challenges the notion that solids (and among them, gluten-containing foods) should be introduced beyond the 6th month of life. Another important aspect of gluten introduction into the diet has to do with its possible role in causing type-1 diabetes (IDDM). Recently, a large epidemiological investigation in a cohort of children at risk for IDDM found that exposure to cereals (rice, wheat, oats, barley, rye) that occurred early (< or = 3 months) as well as late (> or = 7 months) resulted in a significantly higher risk of the appearance of islet cell autoimmunity compared to the introduction between 4 and 6 months. As for celiac disease, the protective role of breastfeeding can be considered ascertained, especially the protection offered by having gluten introduced while breastfeeding is continued. Evidence is emerging that early (< or = 3 months) and perhaps even late (7 months or after) first exposure to gluten may favor the onset of celiac disease in predisposed individuals. Additionally, large amounts of gluten at weaning are associated with an increased risk of developing celiac disease, as documented in studies from Scandinavian countries. In celiac children observed in our center, we could show that breastfeeding at the time of gluten introduction delays the appearance of celiac disease and makes it less likely that its presentation is predominantly gastrointestinal. Based on current evidence, it appears reasonable to recommend that gluten be introduced in small amounts in the diet between 4 and 6 months, while the infant is breastfed, and that breastfeeding is continued for at least a further 2-3 months.