Either high fish intake or relative plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration may work to counteract the increased diabetes risk associated with 65-kDa isoform of GAD (GAD65) positivity, according to research results published in Diabetes Care.

Using data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, investigators sought to examine potential interactions between GAD65 antibody positivity, dietary fish intake, and relative n-3 PUFA plasma phospholipid concentrations in relation to incident adult-onset diabetes.

The EPIC-InterAct study included 340,234 participants who were followed for 3.99 million person-years. The current study sample included a total of 25,535 participants, including 11,247 with incident adult-onset diabetes and 14,981 in the subcohort that included 693 of the cases by design. Dietary data and standardized data on health and lifestyle factors were all collected through questionnaires; and height, weight, and waist circumference measures were taken during baseline health exams.

Within the cohort, baseline prevalence of GAD65 antibodies was 2% in the subcohort and 3.6% among those with incident diabetes. No major differences in baseline characteristics by GAD65 antibody status were noted, although those with GAD65 antibody positivity were more likely to have a lower body mass index.


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Plasma phospholipid n-3 PUFAs had small positive correlations with total fish intake, fatty fish intake, and lean fish intake (r=0.26, 0.26, and 0.15, respectively). The positive correlation with total fish was highest for docosahexaenoic acid or DHA and eicosapentaenoic acid or EPA (r=0.35 and 0.15, respectively), while docosapentaenoic acid or DPA was negatively correlated (r=-0.17).

GAD65 antibody positivity was associated with higher diabetes incidence (hazard ratio [HR], 1.81; 95% CI, 1.49-2.20); a stronger association for high GAD65 antibody levels vs GAD65 antibody negativity was noted (HR, 2.93; 95% CI, 2.27-3.79). Neither fish intake nor plasma phospholipid n-3 PUFA was associated with incident diabetes, although an exception for plasma phospholipid EPA was identified.

Investigators also identified a positive association with incident diabetes for the combination of GAD65 antibody positivity and low total fish intake or fatty fish intake (HR, 2.52; 95% CI, 1.76-3.63 and HR, 2.48; 95% CI, 1.79-3.45, respectively). In sensitivity analyses, the joint effects of GAD65 antibody positivity and low total plasma phospholipid n-3 PUFAs or total fish intake were largely unchanged, with exception of sensitivity to adjustments for family history of type 2 diabetes.

Study limitations include the use of baseline blood samples collected before diabetes diagnosis, an inability to account for participants later diagnosed with type 1 diabetes or latent autoimmune diabetes in adults during follow-up, and the potential for unmeasured or residual confounding.

“Our results suggest that dietary fish intake and plasma phospholipid n-3 PUFAs may modify the association between GAD65 antibody positivity and adult-onset diabetes and that the excess risk of diabetes conferred by GAD65 antibody positivity is amplified in individuals with low n-3 PUFA status,” the researchers concluded. “This study contributes to the limited body of knowledge about factors that influence the progression from islet autoimmunity to diabetes in adults.”

Reference

Löfvenborg JE, Carlsson S, Andersson T, et al. Interaction between GAD65 antibodies and dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acids on incident adult-onset diabetes: the EPIC-InterAct study. Published online December 10, 2020. Diabetes Care. doi:10.2337/dc20-1463