Omega-3 Fatty Acids Protective for Children at Risk for Type 1 Diabetes

DENVER, Sept 25-A higher intake of omega-3 fatty acids found in fish was linked to a lower risk of pancreatic islet autoimmunity in children at genetic risk for type 1 diabetes, according to a preliminary study.

This association was further strengthened by the finding that a high level of omega-3 fatty acids in erythrocyte membranes was associated with a decreased risk of islet autoimmunity in a subset of this population, Jill M. Norris, MPH, PhD, of the University of Colorado here, and colleagues reported in the September 26 issue of the Journal of the American Medical Association.

A case-control study from Norway had reported that children with diabetes were less likely to have been given cod liver oil during infancy than those without diabetes.

Given that cod liver oil contains both vitamin D and the marine omega-3 fatty acids, it was not clear whether the protective factor was the vitamin D, the fatty acids, or both, the researchers wrote.

To examine the role of omega-3 and omega-6 fatty acids in the etiology of diabetes, the researchers undertook a longitudinal, observational study, the Diabetes Autoimmunity Study in the Young (DAISY).

The study was conducted in Denver, from January 1994 through November 2006 and included 1770 children at increased risk for type 1 diabetes, defined as either possession of HLA genotype for a high diabetes risk or having a sibling or parent with type 1 diabetes. The mean age at follow-up was 6.2 years.

Islet autoimmunity was assessed in association with dietary intake reported on a food frequency questionnaire, starting when the children were a year old.

A commonly used unit or portion size was specified for each food on the questionnaire and parents were asked how often, on average, during the previous year the child had consumed that amount. Possible responses ranged from never to 6 or more times a day.

The questionnaire asked specifically about how often the child consumed canned tuna, dark-meat fish (mackerel, salmon, sardines, bluefish, and swordfish), and shellfish, and the kind of fat usually used for cooking (vegetable oil, solid vegetable shortening, oil, butter, margarine, lard, or none).

The risk of islet autoimmunity was defined as being positive for insulin, glutamic acid decarboxylase, or insulinoma-associated antigen-2 autoantibodies on 2 consecutive visits and still autoantibody positive or having diabetes at the last follow-up visit.

The researchers found that 58 children developed islet autoimmunity during follow-up. Adjusting for HLA genotype, family history of type 1 diabetes, caloric intake, and omega-6 fatty acid intake, omega-3 fatty acid intake was associated with a 55% reduced risk of islet autoimmunity (hazard ratio [HR] = 0.45; 95% confidence interval [CI], 0.21-0.96; P=.04).

The association reached a 77% decreased risk when the definition of the outcome was limited to those positive for 2 or more autoantibodies (HR = 0.23; 95% CI, 0.09-0.58; P=.002).

A second part of the study, using 244 children in the same cohort, examined the association between the fatty-acid content of erythrocyte membranes, a biomarker for the status of polyunsaturated fatty acids, and the appearance of islet autoantibodies.

The researchers found that the omega-3 fatty acid content of erythrocyte membranes was associated with a 37% decreased risk of islet autoimmunity (HR = 0.63; 95% CI, 0.41-0.96; P=.03).

Although total omega-6 fatty acid intake was not associated with a risk of islet cell autoimmunity, it was retained in the model because among other reasons, its inclusion strengthened the omega-3 fatty acid association, the researchers said.

Because fish is also a source of vitamin D, the researchers did a further analysis and found that vitamin D was neither a covariate nor a confounder in the association between the polyunsaturated fat intake and islet autoimmunity.

They suggested that increased levels of omega-3 fatty acids may lead to increased membrane concentration of these fatty acids, limiting production of prostaglandins while promoting the generation of anti-inflammatory eicosanoids, known as resolvins and protectins.

Acknowledging that the use of food-frequency surveys to measure intake of polyunsaturated fatty acids is subject to reporting errors, the researchers noted that the biomarker of erythrocyte-membrane fatty acid content used in this study has been shown to be a good indicator of polyunsaturated fatty acids in children younger than 2.

Overall, these data suggest that ingestion of omega-3 fatty acids throughout childhood may decrease the risk of islet autoimmunity, Dr Norris and colleagues wrote.

A new nutritional intervention clinical trial will address the hypothesis that both in the womb and in infancy dietary supplementation with anti-inflammatory doses of docosahexanoic acid (DHA), one of the marine omega-3 fatty acids, will block early islet inflammatory events, the researchers said.

Theoretically, they noted, this would prevent development of early islet autoimmunity in infants with a high genetic risk.

If that trial confirms the hypothesis, dietary supplementation with omega-3 fatty acids could become a mainstay for early intervention to safely prevent the development of type 1 diabetes, the researchers said.