Challenges of diagnosis and management for Infants Diabetes
Infants who are at genetic risk of developing type 1 diabetes and who were given probiotics before 3 months of age had a 33% reduction in the risk of pancreatic beta-cell islet autoimmunity, according to new results from an ongoing international study in over 7000 children.
Ulla Uusitalo, PhD, a nutritionist at the University of South Florida, Tampa, and a member of The Environmental Determinants of Diabetes in the Young (TEDDY) study, presented the results here at the European Association for the Study of Diabetes 2014 Meeting.
She was cautiously optimistic in her conclusions and noted that the results show a definite trend that strongly suggests a positive effect of probiotics in infants with diabetes under the age of 3 months.
“Our data show that the early introduction of probiotics may decrease the risk of islet autoimmunity. We found a one-third reduction in the incidence of islet autoimmunity, and this is high,” she said. “However, this association requires confirmation by other studies,” she stressed.
In particular, she emphasized that the link was strongest in infants who had received probiotics at a very young age, at less than 1 month old.
Asked to comment on the data, Outi Vaarala, MD, research director at the Institute of Clinical Medicine, University of Helsinki, Finland, said: “The results of the study by Dr. Uusitalo, if reproduced in another observational study, suggest that an intervention with probiotics could be reasonable for the prevention of beta-cell autoimmunity.
“A pilot study we conducted in 2003 in Linköping, Sweden, tested the feasibility of probiotics in the prevention of beta-cell autoimmunity, and the results showed that there were no adverse effects and it was a safe intervention,” she told Medscape Medical News.
TEDDY Study Details
The TEDDY study is an ongoing prospective birth-cohort study of 8676 children carrying type 1 diabetes–associated HLA-DR-DQ alleles. It started in 2004 in Finland, Sweden, the United States (Colorado, Georgia, and Washington State), and Germany.
Data are collected from the families every 3 months, including information on maternal dietary supplements, fermented-/sour-milk consumption, medications during pregnancy, and smoking; and for the child, illnesses, medications, use of probiotic supplements or infant formula, and breastfeeding information are logged.
In the investigation led by Dr. Uusitalo, the researchers wanted to test the hypothesis that early probiotic exposure might be associated with reduced risk for islet-cell autoimmunity. Blood samples taken every 3 months were used to test for the appearance of 1 or more of the islet autoantibodies GADA, IAA, or IA-2A, as markers for islet autoimmunity.
First exposure to probiotics was monitored and categorized as before 1 month of age, 1 to 3 months, and between 3 and 12 months. Exposure after 12 months or no exposure was considered a reference group. The researchers then stratified the findings by country and adjusted for influencing factors, including HLA genotype, having a first-degree relative with type 1 diabetes, gender, mode of delivery, and exclusive breastfeeding for over 3 months. A total of 7468 infants were assessed.
Findings Differ by Country: Risk Halved in Sweden
Islet-cell autoimmunity was found in 575 infants, 7.7% of the total. When stratified by country, 6.3% of subjects in the United States developed islet autoimmunity; in Sweden this figure was 8.6%, in Finland 8.7%, and in Germany 9.1%.
The results showed the biggest effect in infants under 1 month of age (hazard ratio [HR], 0.63; P = .022) when compared with those given probiotics over the age of 12 months or not at all. Those aged 1 to 3 months also had a reduction in the development of beta cell autoimmunity (HR, 0.73; P = .097).
When these 2 age groups were combined, there was a 33% reduction in autoimmunity (HR, 0.67; P = .005)
Dr. Uusitalo explained some of the background that may account for the intercountry differences observed. “In Germany, the selection of infants was different, because we initially included only subjects with a first-degree relative with type 1 diabetes. German babies also have a high genetic risk,” she noted.
“We also know from previous studies that the incidence of islet autoimmunity is higher in Finland and Sweden compared with the US. In fact, Finland has the highest incidence in the world for type 1 diabetes.”
She also drew attention to the halving of incidence of islet autoimmunity with use of probiotics found in Sweden.
“It is a striking result, but we don’t know why at the moment. The finding here is statistically significant [HR, 0.5; P = .026]. Finland also demonstrated a good result, although just outside of statistical significance [HR, 0.75].”
Newborn Gut Very Vulnerable: May Explain Early Benefit
Asked why she believed the probiotics had such a marked effect in very young infants, Dr. Uusitalo said that during the first 3 months of life, the infant gut is vulnerable, and leakage can occur through the gut wall.
“One theory is that the probiotics enhance the maturity of the gut barrier to help defend the body against environmental exposure…[to] viruses and foreign proteins,” she explained. “[With probiotics], the infant is better prepared to process these, and in this way they may not trigger an adverse autoimmune response.”
She added that after around 3 months of age there is usually a natural maturation of the gut wall. This may explain why they did not see any association between the provision of probiotics and islet-cell autoimmunity in infants between the ages of 3 and 12 months (HR, 1.14; P = .4).
“This is when mothers introduce supplemental foods to the child, and this modifies the gut microbiota. It is difficult to separate the effect of probiotics from other triggers like foods. We can’t say that there is no association after 3 months; we have yet to determine whether this is the case.”
Probiotic Use by Country Varies
Another interesting observation included the amount of probiotic use, again stratified by country, which differed markedly.
For example, in Finland, 36% of infants had started probiotics by 3 months, whereas in the United States, only 2% had. In Germany, 24% had started by 3 months.
“I know in Finland there is a lot of media coverage of probiotic use. In Germany, probiotics are usually added into infant formula,” remarked Dr. Uusitalo.
“We also found that mothers who don’t smoke, who don’t exclusively breastfeed for long, or who are older tend to be the ones who give probiotics.”
But after Dr. Uusitalo’s presentation, an audience member pointed out that the data should be checked for other confounding factors — for example, allergies that might have been a reason for giving the probiotics. This might affect seroconversion.
“We still need to be cautious with interpretation at this stage,” she agreed.
Dr. Vaarala concurred that care is still needed because of the possibility of confounding factors.
“Probiotics are often started at early infancy if there are symptoms of colic or family risk of allergy. Thus, the infants who have received probiotics may be different from the infants who have not received probiotics, and they may have a lower risk of autoimmunity due to this.”
The study was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, JDRF, and Centers for Disease Control and Prevention. Drs. Uusitalo and Vaarala have reported no relevant financial relationships.
European Association for the Study of Diabetes; September 18, 2014; Vienna, Austria. Abstract 170