Gluten-free diet during pregnancy alleviates signs of diabetes and celiac disease in NOD mouse offspring

Diabetes Metab Res Rev. 2018 May;34(4):e2987. doi: 10.1002/dmrr.2987. Epub 2018 Mar 15.


Background: Gluten-free (GF) diet during pregnancy ameliorates autoimmune diabetes in nonobese diabetic (NOD) mouse offspring. Due to comorbidity of celiac disease in type 1 diabetes, we hypothesized that GF diet in utero alleviates the humoral and histopathological signs of celiac disease in NOD mice. We aimed to establish the mechanisms behind the diabetes-protective effect of GF diet in utero.

Methods: Breeding pairs of NOD mice were fed a GF or gluten-containing standard (STD) diet until parturition. The offspring were nursed by mothers on STD diet and continued on this diet until ages 4 and 13 weeks. Analyses of serum antitissue transglutaminase (anti-tTG) intestine and islet histology, islet transglutaminase (TG) activity, and cytokine expression in T cells from lymphoid organs were performed.

Results: GF versus STD diet in utero led to reduced serum anti-tTG titre and increased villus-to-crypt ratio at both ages. Insulitis along with systemic and local inflammation were decreased, but islet TG activity was unchanged in 13-week-old GF mice. These mice had unchanged beta-cell volumes, but increased islet numbers throughout the prediabetic period.

Conclusions: Collectively, GF diet administered during pregnancy improves signs of celiac disease and autoimmune diabetes in the offspring. The diabetes-ameliorative effect of GF diet in utero is followed by dampening of inflammation, unchanged beta-cell volume, but increased islet numbers.

Keywords: NOD mice; beta-cell; celiac disease; gluten-free diet; islet of Langerhans; type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers / analysis*
  • Celiac Disease / diet therapy*
  • Diabetes Mellitus, Experimental / diet therapy*
  • Diet, Gluten-Free*
  • Female
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects*
  • Mice
  • Mice, Inbred NOD
  • Pregnancy
  • Prognosis


  • Biomarkers