1. Vitamin D and risk of Type 1 diabetes Dr Elina Hyppönen MSc, MSc, MPH, PhD Centre for Pediatric Epidemiology and Biostatistics Institute of Child Health London, UK email: e.hypponen@ich.ucl.ac.uk

2. Overview zHealth effects of Vitamin D zType 1 diabetes zVitamin D and type 1 diabetes zPublic health importance

3. Health effects of vitamin D zTraditionally: regulation of calcium homeostasis and bone metabolism zMore recently suggested to affect a wide-range of diseases, including autoimmune disorders, cancer, metabolic syndrome zVitamin D is known to modulate immune function in humans ysuppresses (overaggressive) reactions

4. Etiology of type 1 diabetes zDestruction of beta cells by autoimmune process zLength of latency period varies, often very long zDisease develops in a genetically susceptible individual after (series of) environmental insults zViral infections and several dietary factors suggested to be involved in the pathogenic process

5. Vitamin D & Type 1 diabetes - Seasonal and geographical variation ySome evidence for north-south gradient xexceptions (e.g. Sardinia) xassociation diluted by variations in genetic susceptibility? yLittle evidence for seasonal variation by time of birth in diabetic cases or according to season of the onset of the disease xmultifactorial disease, latency may be long xconfounded by use of vitamin D supplements, recommended during the dark seasons of the year

6. Vitamin D & Type 1 diabetes - Studies in animals and humans zType 1 diabetes prevented by 1,25-(OH) 2 D in animal models zSome evidence for protective effect in humans yonly a few studies published to date

7. Vitamin D & Type 1 diabetes - Relevant time window? zPregnancy xmothers cod liver oil consumption  diabetes risk  zInfancy xany vitamin D supplementation  diabetes risk  xdose of supplementation   diabetes risk  xvitamin D deficiency  diabetes risk  zChildhood ? Adolescence? Adulthood?

8. Intake of vitamin D and risk of type 1 diabetes: a birth cohort study Elina Hyppönen, Esa Läärä, Antti Reunanen, Marjo-Riitta Järvelin, Suvi Virtanen Lancet 2001;358:1500-1503

9. Northern Finland 1966 Cohort Study zAll pregnant mothers in the two northernmost provinces of Finland (Oulu and Lapland) with expected date of delivery in 1966 invited to participate -> 12,058 live births zInformation on vitamin D intake/status collected at 1 year of age (n=10, 366) zFollow-up for type 1 diabetes up to December 1997 Hyppönen et al. Lancet 2001;358:1500-1503

10. Incidence of type 1 diabetes by use of vitamin D supplements in infancy * Adjusted for neonatal, social and anthropometric factors.

11. † Dose has been presented for infants receiving vitamin D regularly Hyppönen et al. Lancet 2001;358:1500-1503 Incidence of type 1 diabetes by dose of vitamin D supplementation * Adjusted for neonatal, social and anthropometric factors.

12. Hyppönen et al. Lancet 2001;358:1500-1503 Incidence of type 1 diabetes by suspected rickets in infancy * Adjusted for neonatal, social and anthropometric factors.

13. Associated temporal changes ? (in Finland) zIncreasing incidence of type 1 diabetes zDose reduction in infant vitamin D recommendations y1956: 4000-5000 IU y1964:-> 2000 IU y1975: -> 1000 IU y1992: -> 400 IU zChanges in the compliance of giving vitamin D ? zIncrease in the incidence of rickets during 1980s AND

14. The BIG public health question...the intake is too low only to prevent the destructive autoimmune reaction in susceptible individuals ?...the intake is too low to prevent human immune system from developing/working optimally ? OR IF the association between vitamin D and type 1 diabetes is shown to be causal, is it because...