December 31, 2020
2 min read
Adults positive for glutamic acid decarboxylase antibodies are more than twice as likely to develop adult-onset diabetes with low fish intake compared with high fish intake, according to findings published in Diabetes Care.
Josefin E. Löfvenborg
“Fish intake may reduce the risk of developing diabetes among glutamic acid decarboxylase (GAD65) antibody-positive adults,” Josefin E. Löfvenborg, PhD, MSc, a postdoctoral researcher and nutritionist at the Institute of Environmental Medicine at the Karolinska Institutet in Stockholm, told Healio. “These findings are of interest since they increase our understanding about factors influencing the progression from islet autoimmunity to clinical diabetes in adults. Such knowledge may also be useful for screening programs for diabetes-related antibodies.”
In a prospective study, Löfvenborg and colleagues analyzed data from 11,247 incident cases of adult-onset diabetes and 14,288 controls from the EPIC-InterAct case-cohort study conducted in eight European countries. Researchers assessed baseline plasma samples for GAD65 antibodies and phospholipid omega-3 PUFAs, and collected dietary data at baseline with validated questionnaires, and used data on lean fish, fatty fish and total fish consumption. Researchers calculated adjusted HRs for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid omega-3 PUFA or fish consumption, estimated using Prentice-weighted Cox regression analysis. The findings were published in Diabetes Care.
Researchers found that, compared with adults who were GAD65 antibody-negative with high fish intake, adults who were GAD65 antibody-positive and had a low intake of total and fatty fish were more than twice as likely to develop diabetes, with HRs of 2.52 (95% CI, 1.76-3.63) and 2.48 (95% CI, 1.79-3.45), respectively, with evidence of both additive and multiplicative interactions.
Additionally, adults with high GAD65 antibody levels, defined as at least 167.5 U/mL, and low total plasma phospholipid omega-3 PUFAs, had a more than fourfold higher risk for developing diabetes, with an HR of 4.26 (95% CI, 2.7-6.72) compared with adults who were antibody-negative with high omega-3 PUFAs, with evidence of additive interaction but not multiplicative interaction.
In sensitivity analyses restricted to adults with available information on family history, the HR associated with GAD65 antibody positivity combined with low total fish consumption was 3.54 after adjustment (95% CI, 2.24-5.58).
“Analyses restricted to GAD65 antibody-positive individuals were hampered by small numbers but indicated a lower HR of diabetes among those with high compared with low fatty fish intake,” the researchers wrote.
The researchers noted that fish consumption or elevated omega-3 PUFA levels may delay the progression from islet autoimmunity to onset of diabetes, especially among those with more pronounced autoimmunity as indicated by high levels of GAD65 antibodies.
“In this study, we identified evidence of an interaction between GAD65 antibody positivity and dietary fish intake or plasma phospholipid omega-3 PUFAs on incident adult-onset diabetes,” the researchers wrote. “This means that the incidence is increased among antibody-positive individuals who have low dietary fish intake and that this increase may be higher than expected from the sum or product of the two individual exposures. Thus, our findings suggest that fish intake or the relative plasma phospholipid omega-3 PUFA concentration may partly counteract the increased incidence of adult-onset diabetes in individuals who are GAD65 antibody positive.”
For more information:
Josefin E. Löfvenborg, PhD, can be reached at Josefin.lofvenborg@ki.se.
Perspective
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Diabetes is a complex disease with a heterogeneous etiology that we are just beginning to unravel. There are many unknown pathways that influence disease onset. Unraveling these will help in pointing to more specific and efficient prevention and treatment strategies. The interplay between environment and lifestyle against a genetic background contributes to diabetes risk.
Among adults, GAD65 autoantibodies are associated with a slower, progressing form of diabetes. This work is exciting, as it identifies a link between GAD65 titers and fish intake (n-3 PUFAs), modifying the risk for progression to diabetes. Although there are many unknowns in this study — only two observation time points, further development of autoantibodies, n-3 PUFA exposure over time — these findings are encouraging and should be replicated in other populations, with research expanded to assess serial measures at shorter intervals.
Ultimately, this work may lead to specific prevention protocols based on autoantibody profile through early dietary modifications to reduce or delay the risk for diabetes.
Kendra Vehik, PhD, MPH
Professor, Health informatics Institute
University of South Florida
Tampa, Florida
Disclosures: Vehik reports no relevant financial disclosures.
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December 31, 2020 at 09:17PM
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