Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice

Diabetologia. 2004 Mar;47(3):451-462. doi: 10.1007/s00125-004-1329-3. Epub 2004 Jan 31.


Aims/hypothesis: 1,25-dihydroxyvitamin D(3), the active form of vitamin D, prevents Type 1 diabetes in non-obese diabetic (NOD) mice. Epidemiological data show a threefold increase in human Type 1 diabetes when vitamin D deficiency was present in the first months of life. To evaluate whether a similar dietary deficiency affects diabetes incidence in NOD mice, we generated NOD mice with vitamin D deficiency in early life.

Methods: Breeding pairs of NOD mice, as well as their offspring (test mice), were kept in surroundings devoid of ultraviolet light and were fed a vitamin D-depleted diet for 100 days. Mice were followed for 250 days.

Results: At 250 days, 35% (12/35) male and 66% (22/33) female vitamin D-deficient mice were diabetic compared to 15% (6/40, p=0.05) and 45% (13/29, p<0.01) of the control mice. At 100 days no difference in insulitis was seen, but more vitamin D-deficient mice were glucose intolerant. Higher IL1 expression was detected in islets of vitamin D-deficient mice and their peritoneal macrophages had an aberrant cytokine profile (low IL1 and IL6, high IL15). Thymus and lymph nodes of vitamin D-deficient mice contained less CD4(+)CD62L(+) cells.

Conclusion/interpretation: Vitamin D status increases the expression of Type 1 diabetes in NOD mice. Our data in NOD mice, as well as human epidemiological data, point to the importance of preventing vitamin D deficiency in early childhood. Controlling this dietary factor could be an easy and safe way to reduce the incidence of Type 1 diabetes in subjects who are genetically at risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Calcitriol / blood
  • Calcium / blood
  • Calcium / metabolism
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Female
  • Male
  • Mice
  • Mice, Inbred NOD
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / immunology
  • Vitamin D Deficiency / pathology


  • Calcitriol
  • Calcium