No association of vitamin D intake or 25-hydroxyvitamin D levels in childhood with risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY)

Abstract

Aims/hypothesis: The aim of the study was to investigate the association between vitamin D intake and status and the risk of islet autoimmunity (IA) and subsequent type 1 diabetes in children at increased risk of type 1 diabetes.

Methods: The Diabetes Autoimmunity Study in the Young (DAISY) in Denver, CO, USA, has been following children at increased risk of diabetes since 1993. As of February 2011, 198 children developed IA during follow-up of 2,644 DAISY children. Vitamin D intake and plasma 25-hydroxyvitamin D [25(OH)D] were measured longitudinally. Proportional hazards regression analyses of time to IA, or type 1 diabetes in IA-positive children, were conducted, with vitamin D intake and 25(OH)D as time-varying covariates. HRs were calculated for a standard deviation difference in exposure, with adjustment for confounders.

Results: Intake of vitamin D was not associated with the risk of IA (adjusted HR 1.13; 95% CI 0.95, 1.35; p = 0.18) nor progression to diabetes in IA-positive children (adjusted HR 1.30; 95% CI 0.91, 1.86; p = 0.15). Moreover, 25(OH)D level was not associated with the risk of IA (adjusted HR 1.12; 95% CI 0.88, 1.43; p = 0.36), nor progression to diabetes in IA-positive children (adjusted HR 0.91; 95% CI 0.68, 1.22; p = 0.54). In the 128 children in whom we measured 25(OH)D at 9 months of age, 25(OH)D was not associated with risk of IA (n = 30 IA-positive children) (adjusted HR 1.02; 95% CI 0.96, 1.07; p = 0.58).

Conclusions/interpretation: Neither vitamin D intake nor 25(OH)D levels throughout childhood were associated with the risk of IA or progression to type 1 diabetes in our population.

Fig. 1

Flow chart illustrating the formation of the cohorts for the vitamin D studies from the DAISY population. T1D, type 1 diabetes

Fig. 2

Unadjusted plasma 25(OH)D levels and percentage of children with inadequate 25(OH)D by age, in a representative cohort of 373 DAISY children. Mean 25(OH)D (nmol/l) of children at each age are represented by a black circle, and the line is intended to connect these points. The right-hand axis lists the values for mean 25(OH)D. The grey bars represent the percentage of children with inadequate plasma 25(OH)D (≤50 nmol/l) at each age. The actual percents are listed on the left-hand axis. The values in parentheses on the x-axis represent the number of children included in each age group. As children had multiple measurements of vitamin D over time, they may be in more than one age group

Fig. 3

Plasma 25(OH)D levels by age in children who subsequently developed IA (n=85) and those who remained autoantibody negative (n=316), using data from 2,207 visits. The symbols represent adjusted mean 25(OH)D levels (in nmol/l); black symbols are mean 25(OH)D in children who subsequently became IA positive; white symbols are mean 25(OH)D in children who remained IA negative. The solid line is the predicted mean 25(OH)D in IA-positive children, and the dotted line is the predicted mean 25(OH)D in IA negative children by age, with adjustment for month and year of the blood draw, ethnicity and dietary intake of vitamin D. The grey shaded areas surrounding each line represent the 95% CIs of the predicted line. The shading of the 95% CI of the IA positive line is lighter than the shading of that of the IA negative line in order to differentiate the two intervals when they overlap. The regression equation used to generate these predicted lines is: 69.23+1.71×month+1.99× month² −0.38×month³+0.017×month⁴−1.03×year of blood draw −0.69×age (years)+2.11×non-Hispanic white+1.54×vitamin D intake (SD of IU/day)+1.08× IA positivity status. The p values for each covariate are: month (0.62), month² (0.05), month³ (0.001), month⁴ (0.0002), year (0.0001), age (0.004), non-Hispanic white ethnicity (0.18), vitamin D intake (0.0002) and IA positivity status (0.54)