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

Josefin E Löfvenborg; Sofia Carlsson; Tomas Andersson; Christiane S Hampe; Albert Koulman; María Dolores Chirlaque Lopez; Paula Jakszyn; Verena A Katzke; Tilman Kühn; Cecilie Kyrø; Giovanna Masala; Peter M Nilsson; Kim Overvad; Salvatore Panico; Maria-Jose Sánchez; Yvonne van der Schouw; Matthias B Schulze; Anne Tjønneland; Elisabete Weiderpass; Elio Riboli; Nita G Forouhi; Stephen J Sharp; Olov Rolandsson; Nicholas J Wareham

doi:10.2337/dc20-1463

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

Josefin E Löfvenborg, Sofia Carlsson, Tomas Andersson, Christiane S Hampe, Albert Koulman, María Dolores Chirlaque Lopez, Paula Jakszyn, Verena A Katzke, Tilman Kühn, Cecilie Kyrø, Giovanna Masala, Peter M Nilsson, Kim Overvad, Salvatore Panico, Maria-Jose Sánchez, Yvonne van der Schouw, Matthias B Schulze, Anne Tjønneland, Elisabete Weiderpass, Elio RiboliNita G Forouhi, Stephen J Sharp, Olov Rolandsson, Nicholas J Wareham

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Abstract

OBJECTIVE: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.

RESEARCH DESIGN AND METHODS: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.

RESULTS: The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs.

CONCLUSIONS: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.

Original language	English
Journal	Diabetes Care
Early online date	10 Dec 2020
DOIs	https://doi.org/10.2337/dc20-1463
Publication status	Early online date - 10 Dec 2020
Externally published	Yes

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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
Copyright 2020 American Diabetes Association. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 299 KBLicence: Unspecified

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Löfvenborg, J. E., Carlsson, S., Andersson, T., Hampe, C. S., Koulman, A., Chirlaque Lopez, M. D., Jakszyn, P., Katzke, V. A., Kühn, T., Kyrø, C., Masala, G., Nilsson, P. M., Overvad, K., Panico, S., Sánchez, M.-J., van der Schouw, Y., Schulze, M. B., Tjønneland, A., Weiderpass, E., ... Wareham, N. J. (2020). 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. Diabetes Care. Advance online publication. https://doi.org/10.2337/dc20-1463

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title = "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",

abstract = "OBJECTIVE: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.RESEARCH DESIGN AND METHODS: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.RESULTS: The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs.CONCLUSIONS: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.",

author = "L{\"o}fvenborg, {Josefin E} and Sofia Carlsson and Tomas Andersson and Hampe, {Christiane S} and Albert Koulman and {Chirlaque Lopez}, {Mar{\'i}a Dolores} and Paula Jakszyn and Katzke, {Verena A} and Tilman K{\"u}hn and Cecilie Kyr{\o} and Giovanna Masala and Nilsson, {Peter M} and Kim Overvad and Salvatore Panico and Maria-Jose S{\'a}nchez and {van der Schouw}, Yvonne and Schulze, {Matthias B} and Anne Tj{\o}nneland and Elisabete Weiderpass and Elio Riboli and Forouhi, {Nita G} and Sharp, {Stephen J} and Olov Rolandsson and Wareham, {Nicholas J}",

note = "{\textcopyright} 2020 by the American Diabetes Association.",

year = "2020",

month = dec,

day = "10",

doi = "10.2337/dc20-1463",

language = "English",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association Inc.",

}

Löfvenborg, JE, Carlsson, S, Andersson, T, Hampe, CS, Koulman, A, Chirlaque Lopez, MD, Jakszyn, P, Katzke, VA, Kühn, T, Kyrø, C, Masala, G, Nilsson, PM, Overvad, K, Panico, S, Sánchez, M-J, van der Schouw, Y, Schulze, MB, Tjønneland, A, Weiderpass, E, Riboli, E, Forouhi, NG, Sharp, SJ, Rolandsson, O & Wareham, NJ 2020, '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', Diabetes Care. https://doi.org/10.2337/dc20-1463

TY - JOUR

T1 - 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

AU - Löfvenborg, Josefin E

AU - Carlsson, Sofia

AU - Andersson, Tomas

AU - Hampe, Christiane S

AU - Koulman, Albert

AU - Chirlaque Lopez, María Dolores

AU - Jakszyn, Paula

AU - Katzke, Verena A

AU - Kühn, Tilman

AU - Kyrø, Cecilie

AU - Masala, Giovanna

AU - Nilsson, Peter M

AU - Overvad, Kim

AU - Panico, Salvatore

AU - Sánchez, Maria-Jose

AU - van der Schouw, Yvonne

AU - Schulze, Matthias B

AU - Tjønneland, Anne

AU - Weiderpass, Elisabete

AU - Riboli, Elio

AU - Forouhi, Nita G

AU - Sharp, Stephen J

AU - Rolandsson, Olov

AU - Wareham, Nicholas J

PY - 2020/12/10

Y1 - 2020/12/10

N2 - OBJECTIVE: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.RESEARCH DESIGN AND METHODS: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.RESULTS: The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs.CONCLUSIONS: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.

AB - OBJECTIVE: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.RESEARCH DESIGN AND METHODS: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.RESULTS: The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs.CONCLUSIONS: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.

U2 - 10.2337/dc20-1463

DO - 10.2337/dc20-1463

M3 - Article

C2 - 33303636

SN - 0149-5992

JO - Diabetes Care

JF - Diabetes Care

ER -

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

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