25-Hydroxyvitamin D and glycemic control: A cross-sectional study of children and adolescents with type 1 diabetes

Highlights

• To our knowledge this is the first study that has been adequately-powered to examine the association between 25-hydroxyvitamin D and HbA1c in children and adolescents with T1DM.

• The association between 25-hydroxyvitamin D and HbA1c was not positive, calling for longitudinal studies to confirm these findings.

• This study demonstrated the high prevalence of patients with low levels of 25-hydroxyvitamin D specifically in healthy weight and Caucasian children and adolescents with T1DM.

• These data suggest the need for monitoring of 25-hydroxyvitamin D in all youth with T1DM.

Abstract

Aim

The objective of this study was to describe the vitamin D status of children and adolescents with type 1 diabetes and to evaluate whether levels of 25-hydroxyvitamin D are significantly associated with HbA1c in this population.

Methods

197 children and adolescents from a diabetes center in a children's hospital were recruited during regular follow up visit. Non-fasting blood samples were collected to measure 25-hydroxyvitamin D and blood glucose levels. HbA1c and other key variables were abstracted from patients’ medical records.

Results

Of the 197 children and adolescents, more than half were adolescents, males, and Caucasian. 23% were overweight, while 13% were obese. Mean HbA1c was 8.6 ± 1.4% (70 ± 15.3 mmol/mol). 40.6% of patients had 25-hydroxyvitamin D levels ≤50 nmol/L; 49.2% had 25-hydroxyvitamin D levels between 51 and 75 nmol/L and 10.2% had 25-hydroxyvitamin D levels >75 nmol/L. The bivariate relationship between 25-hydroxyvitamin D and HbA1c almost reached statistical significance (P = 0.057), while no significance was established in the multivariate model.

Conclusions

To the best of our knowledge this is the first study that has been adequately-powered to examine the association between 25-hydroxyvitamin D and HbA1c in children and adolescents with T1DM. This study demonstrated the high prevalence of patients with low levels of 25-hydroxyvitamin D specifically in healthy weight and Caucasian children and adolescents with T1DM. These data suggest the need for monitoring of 25-hydroxyvitamin D in all youth with T1DM.

Introduction

During the past two decades vitamin D status, defined as serum concentration of 25-hydroxyvitamin D, has emerged as a predictor of key clinical outcomes including bone health, glucose metabolism, cardiovascular health, immune health and survival [1], [2], [3]. Past estimates of vitamin D status in the pediatric U.S. population have shown a high prevalence of children and adolescents (∼70%) with 25-hydroxyvitamin D <75 nmol/L [4]. More recent data from the National Health and Nutrition Examination Survey (NHANES) confirmed these estimates and demonstrated even higher prevalence of 25-hydroxyvitamin D <75 nmol/L in non-Hispanic Black (94%) and Mexican American (80%) children and in overweight (74%) and obese (81%) children [5]. These national findings of vitamin D inadequacy in the healthy U.S. pediatric population have triggered questions about the status of vitamin D in pediatric subgroups with chronic illnesses and its associated risk of morbidity and survival [6], [7].

From previous ecological, animal and human studies, it was established that low 25-hydroxyvitamin D level is a significant risk factor for the development of impaired glucose control and diabetes over time [8], [9], [10], [11]. Low levels of 25-hydroxyvitamin D have been associated with the increased risk of developing T1DM where the immune modulatory role of 25-hydroxyvitamin D has been suggested as the underlying mechanism explaining this relationship [8], [12], [13], [14], [15], [16], [17]. Furthermore, studies have demonstrated that low levels of 25-hydroxyvitamin D increase the risk of type 2 diabetes through its effect on glucose metabolism, insulin secretion and insulin sensitivity [11], [18], [19], [20], [21]. Studies investigating the association between 25-hydroxyvitamin D and diabetes control in children have shown no association [22], that those with poor diabetes control were more likely to have low levels of 25-hydroxyvitamin D [23], and that administration of Vitamin D3 improves diabetes control [24].

Many of the previous studies evaluating 25-hydroxyvitamin D in diabetes have focused on understanding the longitudinal risk of low levels of 25-hydroxyvitamin D in developing diabetes over time. Furthermore, to our knowledge, none of the cross-sectional studies previously published were sufficiently powered to evaluate the relationship between 25-hydroxyvitamin D and glycemic control in T1DM. In this study, we used a cross-sectional approach to assess 25-hydroxyvitamin D levels in a sample of children and adolescents with type 1 diabetes. Further, we sought to examine the relationship between 25-hydroxyvitamin D level and glycemic control as measured by HbA1c in an adequately powered sample.