Abstract
Background: Gut dysbiosis and increased intestinal permeability have been reported to precede type 1 diabetes-related autoimmunity. The role of gut inflammation in autoimmunity is not understood. Objectives: This study aimed to assess whether gut inflammation markers are associated with risk of islet autoimmunity and whether diet is associated with gut inflammation markers. Methods: A nested case-control sample of 75 case children with islet autoimmunity and 88 control children was acquired from the Finnish Type 1 Diabetes Prediction and Prevention cohort. Diet was assessed with 3-d food records, and calprotectin and human β-defensin-2 (HBD-2) were analyzed from stool samples at 6 and 12 mo of age. Conditional logistic regression analysis was used in a matched case-control setting to assess risk of autoimmunity. Analysis of variance, independent samples t test, and a general linear model were used in secondary analyses to test associations of background characteristics and dietary factors with inflammation markers. Results: In unadjusted analyses, calprotectin was not associated with risk of islet autoimmunity, whereas HBD-2 in the middle (odds ratio [OR]: 3.23; 95% confidence interval [CI]: 1.03, 10.08) or highest tertile (OR: 3.02; 95% CI: 1.05, 8.69) in comparison to the lowest at 12 mo of age showed borderline association (P-trend = 0.063) with higher risk of islet autoimmunity. Excluding children with cow milk allergy in sensitivity analyses strengthened the association of HBD-2 with islet autoimmunity, whereas adjusting for dietary factors and maternal education weakened it. At age 12 mo, higher fat intake was associated with higher HBD-2 (β: 0.219; 95% CI: 0.110, 0.328) and higher intake of dietary fiber (β: −0.294; 95% CI: −0.510, −0.078), magnesium (β: −0.036; 95% CI: −0.059, −0.014), and potassium (β: −0.003; 95% CI: −0.005, −0.001) with lower HBD-2. Conclusions: Higher HBD-2 in infancy may be associated with higher risk of islet autoimmunity. Dietary factors play a role in gut inflammatory status.
| Original language | English |
|---|---|
| Pages (from-to) | 2244-2254 |
| Number of pages | 11 |
| Journal | Journal of Nutrition |
| Volume | 154 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2024 |
| Publication type | A1 Journal article-refereed |
Funding
Supported by: the Academy of Finland grants 63672, 79685, 79686, 80846, 201988, 210632, 129492, 126813, 276475 and 339922 (to S.M.V.); the Yrj\u00F6 Jahnsson Foundation (to S.M.V.); the Juho Vainio Foundation (to S.M.V.); the Competitive Research Funding of the Tampere University Hospital grants 9E082, 9F089, 9G087, 9H092, 9J147, 9K149, 9L035, 9L117, 9M029, 9M114, 9N086, 9P017, 9P057, 9R012, 9R055, 9S015, 9S074, 9T072, 9U016, 9U065, 9V012, 9V072, 9X062, 9AA084, 9AB083 and 9AC099 (to S.M.V); Medical Research Funds of Turku (to J.I., J.T.) and Oulu (to R.V.) University Hospitals; the European Foundation for the Study of Diabetes (supported by EFSD/JDRF/Lilly) (to S.M.V., H.H); the Juvenile Diabetes Research Foundation grants 197032, 4-1998-274, 4-1999-731, 4-2001-435, 1-SRA-2016-342-M-R, 1-41 SRA-2019-732-M-B (to J.T., M.K., R.V.), the Novo Nordisk Foundation and EU Biomed 2 grant BMH4-CT98-3314 (to J.T., M.K., R.V.); Sigrid Jus\u00E9lius Foundation (to J.I., J.T., M.K., R.V., H.H.) and Doctoral Programs for Public Health (to S.M.V.). The supporting sources were not involved in the study design, collection, analysis, and interpretation of data, writing of the report, or restrictions regarding publication. Supported by the Academy of Finland grants 63672, 79685, 79686, 80846, 201988, 210632, 129492, 126813, 276475, and 339922 (to SMV); the Yrj\u00F6 Jahnsson Foundation (to SMV); the Juho Vainio Foundation (to SMV); the Competitive Research Funding of the Tampere University Hospital grants 9E082, 9F089, 9G087, 9H092, 9J147, 9K149, 9L035, 9L117, 9M029, 9M114, 9N086, 9P017, 9P057, 9R012, 9R055, 9S015, 9S074, 9T072, 9U016, 9U065, 9V012, 9V072, 9X062, 9AA084, 9AB083, and 9AC099 (to SMV); Medical Research Funds of Turku (to JI and JT) and Oulu (to RV) University Hospitals; the European Foundation for the Study of Diabetes (supported by EFSD/JDRF/Lilly) (to SMV and HH); the Juvenile Diabetes Research Foundation grants 197032, 4-1998-274, 4-1999-731, 4-2001-435, 1-SRA-2016-342-M-R, and 1-41 SRA-2019-732-M-B (to JT, MK, RV), the Novo Nordisk Foundation and EU Biomed 2 grant BMH4-CT98-3314 (to JT, MK, and RV); Sigrid Jus\u00E9lius Foundation (to JI, JT, MK, RV, and HH), and Doctoral Programs for Public Health (to SMV). The supporting sources were not involved in the study design, collection, analysis, and interpretation of data, writing of the report, or restrictions regarding publication.
| Funders | Funder number |
|---|---|
| Eli Lilly and Company | |
| Medical Research Funds of Turku | |
| Juho Vainion Säätiö | |
| European Foundation for the Study of Diabetes | |
| Juvenile Diabetes Research Foundation United States of America | |
| Yrjö Jahnssonin säätiö | |
| Sigrid Juséliuksen Säätiö | |
| 9K149, 9L117, 9M029, 9G087, 9AA084, 9X062, 9S015, 9U016, 9S074, 9N086, 9AC099, 9V072, 9J147, 9M114, 9F089, 9AB083, 9R012, 9P057, 9P017, 9U065, 9L035, 9T072, 9E082, 9R055, 9H092, 9V012 | |
| Juvenile Diabetes Research Foundation International | 4-1999-731, 1-41 SRA-2019-732-M-B, 1-SRA-2016-342-M-R, 4-2001-435, 197032, 4-1998-274 |
| Strategic Research Council at the Research Council of Finland | 79685, 339922, 126813, 276475, 79686, 63672, 80846, 201988, 129492, 210632 |
| Novo Nordisk Fonden | BMH4-CT98-3314 |
Keywords
- calprotectin
- diet
- gut inflammation
- human β-defensin-2
- islet autoimmunity
Publication forum classification
- Publication forum level 2
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Nutrition and Dietetics
- Pediatrics, Perinatology, and Child Health
