Effect of Docosahexaenoic Acid Supplementation on Inflammatory Cytokine Levels in Infants at High Genetic Risk for Type 1 Diabetes

Overview

Journal Pediatr Diabetes

Publisher Wiley

Specialties Endocrinology
Pediatrics

Date 2014 Jul 22

PMID 25039804

Citations 18

Authors

H Peter Chase

David Boulware

Henry Rodriguez

David Donaldson

Sonia Chritton

Lisa Rafkin-Mervis

Jeffrey Krischer

Jay S Skyler

Michael Clare-Salzler

Affiliations

Soon will be listed here.

Abstract

Objective: Type 1 diabetes (T1D) results from the inflammatory destruction of pancreatic β-cells. In this study, we investigated the effect of docosahexaenoic acid (DHA) supplementation on stimulated inflammatory cytokine production in white blood cells (WBC) from infants with a high genetic risk for T1D.

Research Design And Methods: This was a multicenter, two-arm, randomized, double-blind pilot trial of DHA supplementation, beginning either in the last trimester of pregnancy (41 infants) or in the first 5 months after birth (57 infants). Levels of DHA in infant and maternal red blood cell (RBC) membranes and in breast milk were analyzed by gas chromatography/mass spectrometry. Inflammatory cytokines were assayed from whole blood culture supernatants using the Luminex multiplex assay after stimulation with high dose lipopolysaccharide (LPS), 1 µg/mL.

Results: The levels of RBC DHA were increased by 61-100% in treated compared to control infants at ages 6-36 months. There were no statistically significant reductions in production of the inflammatory cytokines, IL-1β, TNFα, or IL-12p40 at any of the six timepoints measured. The inflammatory marker, high-sensitivity C-reactive protein (hsCRP), was significantly lower in breast-fed DHA-treated infants compared to all formula-fed infants at the age of 12 months. Three infants (two received DHA) were removed from the study as a result of developing ≥two persistently positive biochemical islet autoantibodies.

Conclusions: This pilot trial showed that supplementation of infant diets with DHA is safe and fulfilled the pre-study goal of increasing infant RBC DHA levels by at least 20%. Inflammatory cytokine production was not consistently reduced.

Citing Articles

Prevention of Type 1 Diabetes in Children: A Worthy Challenge?.

Ingrosso D, Quarta M, Quarta A, Chiarelli F Int J Environ Res Public Health. 2023; 20(11).

PMID: 37297566 PMC: 10252671. DOI: 10.3390/ijerph20115962.

Dietary fatty acid intake in childhood and the risk of islet autoimmunity and type 1 diabetes: the DIPP birth cohort study.

Hakola L, Vuorinen A, Takkinen H, Niinisto S, Ahonen S, Rautanen J Eur J Nutr. 2022; 62(2):847-856.

PMID: 36284022 PMC: 9941262. DOI: 10.1007/s00394-022-03035-2.

Lipid metabolism in type 1 diabetes mellitus: Pathogenetic and therapeutic implications.

Zhang J, Xiao Y, Hu J, Liu S, Zhou Z, Xie L Front Immunol. 2022; 13:999108.

PMID: 36275658 PMC: 9583919. DOI: 10.3389/fimmu.2022.999108.

Associations Between Serum Fatty Acids and Immunological Markers in Children Developing Islet Autoimmunity-The TRIGR Nested Case-Control Study.

Niinisto S, Miettinen M, Cuthbertson D, Honkanen J, Hakola L, Autio R Front Immunol. 2022; 13:858875.

PMID: 35693790 PMC: 9175567. DOI: 10.3389/fimmu.2022.858875.

Long-Chain Polyunsaturated Fatty Acid Status at Birth and Development of Childhood Allergy: A Systematic Review.

Decsi T, Marosvolgyi T, Muszil E, Body B, Szabo E Life (Basel). 2022; 12(4).

PMID: 35455017 PMC: 9030843. DOI: 10.3390/life12040526.

References

Onkamo P, Vaananen S, Karvonen M, Tuomilehto J . Worldwide increase in incidence of Type I diabetes--the analysis of the data on published incidence trends. Diabetologia. 2000; 42(12):1395-403. DOI: 10.1007/s001250051309. View

FIDLER N, Sauerwald T, Pohl A, Demmelmair H, Koletzko B . Docosahexaenoic acid transfer into human milk after dietary supplementation: a randomized clinical trial. J Lipid Res. 2000; 41(9):1376-83. View

Skyler J, Greenbaum C, Lachin J, Leschek E, Rafkin-Mervis L, Savage P . Type 1 Diabetes TrialNet--an international collaborative clinical trials network. Ann N Y Acad Sci. 2009; 1150:14-24. PMC: 2918900. DOI: 10.1196/annals.1447.054. View

Knip M, Virtanen S, Akerblom H . Infant feeding and the risk of type 1 diabetes. Am J Clin Nutr. 2010; 91(5):1506S-1513S. PMC: 6443298. DOI: 10.3945/ajcn.2010.28701C. View

Peter Chase H, Cooper S, Osberg I, Stene L, Barriga K, Norris J . Elevated C-reactive protein levels in the development of type 1 diabetes. Diabetes. 2004; 53(10):2569-73. DOI: 10.2337/diabetes.53.10.2569. View

Vehik K, Hamman R, Lezotte D, Norris J, Klingensmith G, Rewers M . Trends in high-risk HLA susceptibility genes among Colorado youth with type 1 diabetes. Diabetes Care. 2008; 31(7):1392-6. PMC: 2453682. DOI: 10.2337/dc07-2210. View

Stene L, Ulriksen J, Magnus P, Joner G . Use of cod liver oil during pregnancy associated with lower risk of Type I diabetes in the offspring. Diabetologia. 2000; 43(9):1093-8. DOI: 10.1007/s001250051499. View

Miller M, Yin X, Seifert J, Clare-Salzler M, Eisenbarth G, Rewers M . Erythrocyte membrane omega-3 fatty acid levels and omega-3 fatty acid intake are not associated with conversion to type 1 diabetes in children with islet autoimmunity: the Diabetes Autoimmunity Study in the Young (DAISY). Pediatr Diabetes. 2011; 12(8):669-75. PMC: 3475955. DOI: 10.1111/j.1399-5448.2011.00760.x. View

Green A, Patterson C . Trends in the incidence of childhood-onset diabetes in Europe 1989-1998. Diabetologia. 2001; 44 Suppl 3:B3-8. DOI: 10.1007/pl00002950. View

10.

Mayer-Davis E, Dabelea D, Crandell J, Crume T, DAgostino Jr R, Dolan L . Nutritional factors and preservation of C-peptide in youth with recently diagnosed type 1 diabetes: SEARCH Nutrition Ancillary Study. Diabetes Care. 2013; 36(7):1842-50. PMC: 3687285. DOI: 10.2337/dc12-2084. View

11.

Norris J, Yin X, Lamb M, Barriga K, Seifert J, Hoffman M . Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes. JAMA. 2007; 298(12):1420-8. DOI: 10.1001/jama.298.12.1420. View

12.

TerreBlanche G, Van der Walt M, Bergh J, Mienie L . Treatment of an adrenomyeloneuropathy patient with Lorenzo's oil and supplementation with docosahexaenoic acid--a case report. Lipids Health Dis. 2011; 10:152. PMC: 3177782. DOI: 10.1186/1476-511X-10-152. View

13.

Verge C, Gianani R, Kawasaki E, Yu L, Pietropaolo M, Jackson R . Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes. 1996; 45(7):926-33. DOI: 10.2337/diab.45.7.926. View

14.

Stene L, Joner G . Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. Am J Clin Nutr. 2003; 78(6):1128-34. DOI: 10.1093/ajcn/78.6.1128. View

15.

Endres S, Ghorbani R, Kelley V, Georgilis K, Lonnemann G, van der Meer J . The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med. 1989; 320(5):265-71. DOI: 10.1056/NEJM198902023200501. View

16.

Bonifacio E, Yu L, Williams A, Eisenbarth G, Bingley P, Marcovina S . Harmonization of glutamic acid decarboxylase and islet antigen-2 autoantibody assays for national institute of diabetes and digestive and kidney diseases consortia. J Clin Endocrinol Metab. 2010; 95(7):3360-7. PMC: 2928900. DOI: 10.1210/jc.2010-0293. View

17.

Berger A, Mutch D, German J, Roberts M . Dietary effects of arachidonate-rich fungal oil and fish oil on murine hepatic and hippocampal gene expression. Lipids Health Dis. 2003; 1:2. PMC: 139963. DOI: 10.1186/1476-511x-1-2. View

18.

van Houwelingen A, Sorensen J, Hornstra G, Simonis M, Boris J, Olsen S . Essential fatty acid status in neonates after fish-oil supplementation during late pregnancy. Br J Nutr. 1995; 74(5):723-31. DOI: 10.1079/bjn19950175. View

19.

Wei D, Li J, Shen M, Jia W, Chen N, Chen T . Cellular production of n-3 PUFAs and reduction of n-6-to-n-3 ratios in the pancreatic beta-cells and islets enhance insulin secretion and confer protection against cytokine-induced cell death. Diabetes. 2009; 59(2):471-8. PMC: 2809969. DOI: 10.2337/db09-0284. View

20.

Hummel K, McFann K, Realsen J, Messer L, Klingensmith G, Peter Chase H . The increasing onset of type 1 diabetes in children. J Pediatr. 2012; 161(4):652-7.e1. DOI: 10.1016/j.jpeds.2012.03.061. View