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Slide 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
Slide 2 - Overview Health effects of Vitamin D Type 1 diabetes Vitamin D and type 1 diabetes Public health importance
Slide 3 - Health effects of vitamin D Traditionally: regulation of calcium homeostasis and bone metabolism More recently suggested to affect a wide-range of diseases, including autoimmune disorders, cancer, metabolic syndrome Vitamin D is known to modulate immune function in humans suppresses (overaggressive) reactions
Slide 4 - Etiology of type 1 diabetes Destruction of beta cells by autoimmune process Length of latency period varies, often very long Disease develops in a genetically susceptible individual after (series of) environmental insults Viral infections and several dietary factors suggested to be involved in the pathogenic process
Slide 5 - Vitamin D & Type 1 diabetes - Seasonal and geographical variation Some evidence for north-south gradient exceptions (e.g. Sardinia) association diluted by variations in genetic susceptibility? Little evidence for seasonal variation by time of birth in diabetic cases or according to season of the onset of the disease multifactorial disease, latency may be long confounded by use of vitamin D supplements, recommended during the dark seasons of the year
Slide 6 - Vitamin D & Type 1 diabetes -Studies in animals and humans Type 1 diabetes prevented by 1,25-(OH)2D in animal models Some evidence for protective effect in humans only a few studies published to date
Slide 7 - Vitamin D & Type 1 diabetes - Relevant time window? Pregnancy mothers cod liver oil consumption  diabetes risk  Infancy any vitamin D supplementation  diabetes risk  dose of supplementation   diabetes risk  vitamin D deficiency  diabetes risk  Childhood ? Adolescence? Adulthood?
Slide 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
Slide 9 - Northern Finland 1966 Cohort Study All 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 Information on vitamin D intake/status collected at 1 year of age (n=10, 366) Follow-up for type 1 diabetes up to December 1997 Hyppönen et al. Lancet 2001;358:1500-1503
Slide 10 - Hyppönen et al. Lancet 2001;358:1500-1503 Incidence of type 1 diabetes by use of vitamin D supplements in infancy * Adjusted for neonatal, social and anthropometric factors.
Slide 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.
Slide 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.
Slide 13 - Associated temporal changes ? (in Finland) Increasing incidence of type 1 diabetes Dose reduction in infant vitamin D recommendations 1956: 4000-5000 IU 1964: -> 2000 IU 1975: -> 1000 IU 1992: -> 400 IU Changes in the compliance of giving vitamin D ? Increase in the incidence of rickets during 1980s AND
Slide 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...