Background
In the recent years, controversy has emerged regarding the relationship between vitamin D deficiency and the potential effects it could have on glycemic control in patients with type 1 diabetes mellitus (T1D). This study investigates the prevalence of vitamin D insufficiency/deficiency in pediatric patients with T1D from a single, large volume practice.
Methods
This was a retrospective chart review that collected clinical/demographic data as well as serum 25(OH) D levels from medical records of 395 children between the ages of 3 and 18 years with T1D followed at Nemours Children’s Hospital. This data was compared to the National Health and Nutrition Examination Survey (NHANES) database. A Pearson’s Chi-square test was used between group associations. All statistical tests were two-sided and p < 0.05 was used for statistical significance.
Results
Of the 395 children included in these analyses, 4% were vitamin D deficient and 60% were vitamin D insufficient. There were no significant associations of vitamin D deficiency based on sex and age. Vitamin D deficiency was more common among White children when compared to Hispanic children and African American children (42% vs 29%; p < 0.001). Of those that were vitamin D insufficient (n = 235), most were Hispanic (51%), 36% White and 13% African American. There was a significant association between vitamin D deficiency and body mass index (BMI) (p = 0.035). In the summer, children were less likely to be vitamin D deficient (3% vs 6% in winter) and less likely to be vitamin D insufficient (55% vs 71% in winter) (p = 0.007).
Conclusions
Vitamin D insufficiency is highly prevalent among pediatric type 1 diabetics of Central Florida and statistically significant correlation was found between vitamin D status and ethnicity, BMI as well as seasonal variation.
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Vitamin D deficiency is prevalent in both developed and developing countries. The presence of high affinity vitamin D receptors (VDR) in a variety of cell types has led researchers to believe that vitamin D deficiency could contribute to environmentally driven pathogenesis of many diseases, including type 1 diabetes mellitus (T1D) [
A link between autoimmune conditions and vitamin D deficiency/insufficiency has been implicated. A longitudinal study in Western Australia found both geographical and seasonal variations in incidence of T1D in children [
A prospective study in Finland followed over 10,000 children for up to 31 years and concluded that those who received a daily dose of 2000 IU of vitamin D during infancy had a 78% risk reduction in developing T1D [
Diabetes is one of the fastest-growing chronic diseases worldwide. The number of U.S. children living with type 1 diabetes has increased by almost 60 percent since 2002, and experts are unsure of the cause. Using a national database, researchers found that the prevalence of type 1 diabetes stood at just under 1.5 cases per 1,000 children and teenagers in 2002. By 2013, that figure had risen to 2.3 per 1,000. This rise has also been accompanied by an increase in diabetes comorbidities [
Our study estimates the prevalence of vitamin D deficiency/insufficiency in pediatric patients followed in our practice with type 1 diabetes mellitus and its association, if any with sociodemographic factors, BMI and diabetes control.
A retrospective chart review of children with T1D treated at the Nemours Children’s Hospital outpatient endocrine clinic between January 2016 and December 2018 (N = 395) was conducted utilizing electronic medical records. Sample was identified via ICD-10 codes (E10.9 and E10.65) and lab orders for serum 25 (OH) vitamin D. Children between the ages of 3 and 18 were included. Children with severe pathological risk factors associated with vitamin D deficiency, such as osteogenesis imperfecta, kidney disease or cystic fibrosis were excluded. Only those not already on vitamin D supplementation were included. Children younger than 3 were excluded to minimize the influence of extended breastfeeding on their initial vitamin D status. Additionally, there are very few children under the age of 3 with T1D in our practice. Including ages 3-18 enhanced the data homogeneity of our study population. This study was reviewed and approved by the Institutional Review Board at Nemours Children’s Hospital (IRB# 762598).
Serum 25 (OH) D and HbA1c
Serum 25 (OH) D assays were processed by a local laboratory utilizing liquid chromatography tandem mass spectrometry assay (LC-MS/MS). In order to control for effects of vitamin D supplementation, the 25 (OH) D levels before supplementation were used. A point of care (POC) hemoglobin A1C (HbA1C) level closest in time to the 25 (OH) D test was used. The POC HbA1C system, while providing immediate test results and quick therapy judgments, is subject to the same competency requirements as laboratory HbA1c methods and therefore provides comparable analytical presentation of bias, reliability, and error.
Statistical analysis and data management
In accordance with the national population represented in the NHANES 2001-2004 study (National Health and Nutrition Examination Survey), vitamin D levels were stratified into three groups: vitamin D deficiency (<15 ng/mL), vitamin D insufficiency (15-29 ng/mL), and vitamin D sufficiency (≥30 ng/mL) [
Gender, race/ethnicity, HbA1c status and BMI are reported as frequency (n) and percentage (%). In this study, race/ethnicity was defined as follows: Hispanics (Hispanic/Latin American descent), African Americans (non-Hispanic Blacks or African-Americans) and Caucasian (non-Hispanic Whites).
HbA1c and BMI were dichotomized as follows: HbA1c (adequate and suboptimal), where <9% is adequate and ≥9% suboptimal. BMI (obese and not obese) where obese ≥95th percentile and not obese <95th percentile. Age at which serum 25 (OH) D was obtained is reported as mean (SD) and median (min-max); to test for mean age differences a one-way ANOVA was used.
A Pearson’s Chi-square was used between group associations: First, associations of vitamin D levels (deficient, insufficient and sufficient) and sociodemographic factors (gender, race/ethnicity and age) were conducted. As a second step, associations of vitamin D levels and HbA1c and BMI were conducted. As a final step, the same associations, separately for children that had serum drawn in the summer months (March-October) and the winter months (November-February) were conducted. All statistical tests were two-sided and p < 0.05 was used for statistical significance.
Association of vitamin D deficiency and sociodemographic factors
There were 395 children included in these analyses: Four percent of children were vitamin D deficient, 60% of children were insufficient, and 36% were sufficient (Table
When percentages do not add to 100%, it is due to rounding.
HbA1c: Hemoglobin A1c; BMI: Body mass index.
Vitamin D deficient <15 ng/mL (n = 17) | Vitamin D insufficient 15-29 ng/mL (n = 235) | Vitamin D sufficient ≥30 ng/mL (n = 143) | Total | P value | |
Sex | |||||
Female | 8 (47) | 117 (50) | 68 (48) | 193 (49) | 0.904 |
Male | 9 (53) | 118 (50) | 75 (52) | 202 (202) | |
Race/Ethnicity | |||||
African American | 5 (29) | 30 (13) | 10 (7) | 45 | <0.001 |
Hispanic | 5 (29) | 120 (51) | 46 (32) | 171 | |
White | 7 (42) | 85 (36) | 87 (61) | 179 | |
Age | |||||
Mean (SD) | 14.60 (2.42) | 12.96 (3.1) | 12.64 (3.42) | 12.91 (3.23) | 0.057 |
Median (Min-Max) | 14.72 (8-18) | 13.06 (3-18) | 13.04 (3-18) | 13.17 (3-18) | |
HbA1C Status | |||||
Adequate | 6 (35) | 117 (50) | 83 (58) | 206 (52) | 0.108 |
Suboptimal | 11 (65) | 118 (50) | 42 (143) | 189 (48) | |
BMI Status | |||||
Obese | 5 (29) | 24 (10) | 13 (9) | 42 (11) | 0.035 |
Non-Obese | 12 (71) | 211 (90) | 130 (91) | 353 (90) |
There were no significant associations of vitamin D deficiency based on sex and age. There was a significant association between race/ethnicity and vitamin D levels. Specifically, vitamin D deficiency was more common among White children as compared to Hispanic children (42% vs 29%, respectively) and African American children (42% vs 29%). African American and Hispanic children were vitamin D deficient at the same rate (29%). Of those that were vitamin D insufficient (n = 235), most were Hispanic (51%), 36% White and 13% African American (see Table
Vitamin D deficiency: HbA1c and BMI
There was no significant association between vitamin D deficiency and HbA1c levels (p = 0.108; see Table
Vitamin D deficiency: seasonal changes
Two hundred and eighty-six children (73%) had serum vitamin D levels collected in the summer months and 109 (25%) in the winter months. There was a significant and weak association between vitamin D status and season. In the summer, children were less likely to be vitamin D deficient (3% vs 6% in winter), less likely to be vitamin D insufficient (55% vs 71% in winter) and more likely to be vitamin D sufficient (55% vs 71% in winter), X2 (2) = 9.99, V = .16, p = 0.007.
Summer Months
For children that had vitamin D serum drawn in the summer, there were no significant associations of vitamin D deficiency based on sex. There was a significant association between vitamin D levels and age and race/ethnicity: Children in the deficient group were older (see Table
N = 286; when percentages do not add to 100%, it is due to rounding.
HbA1c: Hemoglobin A1c; BMI: Body mass index.
Vitamin D deficient <15 ng/mL (n = 11) | Vitamin D insufficient 15-29 ng/mL (n = 158) | Vitamin D sufficient ≥30 ng/mL (n = 117) | P value | |
Sex | ||||
Female | 3 (27) | 73 (46) | 58 (49) | 0.356 |
Male | 8 (73) | 85 (54) | 59 (51) | |
Age, years | ||||
Mean (SD) | 15.30 (1.83) | 12.87 (3.20) | 12.66 (3.32) | 0.035 |
Median (Min-Max) | 15.23 (12-18) | 12.93 (3-18) | 13.01 (3-18) | |
Race | ||||
African American | 4 (36) | 23 (15) | 7 (6) | <0.001 |
Hispanic | 2 (18) | 79 (50) | 37 (32) | |
White | 5 (46) | 56 (35) | 73 (62) | |
HbA1C Status | ||||
Adequate | 5 (46) | 76 (48) | 74 (63) | 0.038 |
Suboptimal | 6 (54) | 82 (52) | 43 (37) | |
BMI Status | ||||
Obese | 3 (27) | 19 (12) | 10 (9) | 0.15 |
Non-Obese | 8 (72) | 139 (88) | 107 (91) |
White children were more likely to be deficient than Hispanic children (46% vs 18%, respectively) and African American children (46% vs 36%). Moreover, African American children were more likely than Hispanic children to be vitamin D deficient (36% vs 18%, respectively). Of those that were vitamin D insufficient (n = 158), most were Hispanic (50%), 35% White and 15% African American (see Table
In regards to the association between vitamin D deficiency and diabetes control, i.e. HbA1c levels, we found a significant association between vitamin D levels and HbA1c (p = 0.038). Additionally, a non-significant relationship between vitamin D levels and BMI was found (p = 0.038) (Table
Winter Months
For children that had a serum vitamin D level drawn in the winter, there were no significant associations of vitamin D deficiency based sociodemographic factors. Additionally, no significant association was found between vitamin D deficiency and HbA1c levels (p = 0.081) or BMI (p = 0.080) in this subset (Table
N = 109; when percentages do not add to 100%, it is due to rounding.
HbA1c: Hemoglobin A1c; BMI: Body mass index.
Vitamin D deficient <15 ng/mL (n = 6) | Vitamin D insufficient 15-29 ng/mL (n = 77) | Vitamin D sufficient ≥30 ng/mL (n = 26) | P value | |
Sex | ||||
Female | 5 (83) | 44 (57) | 10 (39) | 0.086 |
Male | 1 (17) | 33 (43) | 16 (61) | |
Age, years | ||||
Mean (SD) | 13.32 (3.0) | 13.13 (3.0) | 12.53 (3.93) | 0.691 |
Median (Min-Max) | 14.29 (8-16) | 13.33 (7-18) | 13.84 (4-18) | |
Race | ||||
African American | 1 (17) | 7 (9) | 3 (12) | 0.54 |
Hispanic | 3 (50) | 41 (53) | 9 (35) | |
White | 2 (33) | 29 (38) | 14 (54) | |
HbA1C Status | ||||
Adequate | 1 (17) | 41 (53) | 9 (35) | 0.081 |
Suboptimal | 5 (83) | 36 (47) | 17 (65) | |
BMI Status | ||||
Obese | 2 (33) | 5 (7) | 3 (12) | 0.08 |
Non-Obese | 4 (67) | 72 (94) | 23 (88) |
The data presented here shows that 64% of our pediatric patients with type 1 diabetes mellitus had a serum 25 (OH) vitamin D level below 30 ng/ml. These findings correlate with findings from other similar studies [
Interestingly, the patients evaluated in our study reside in Central Florida, a region with high-intensity sunlight, high annual UVB exposure and year-round hot temperatures. The high incidence of vitamin D insufficiency documented in our subjects demonstrates that residing in areas with easy access to sunlight does not guarantee protection against the development of vitamin D deficiency or insufficiency.
Furthermore, among ethnic groups, 42% of our White children with type 1 diabetes were found to have a low 25 (OH) vitamin level. In contrast, only 29% of the African-Americans screened had a low 25 (OH) vitamin D level. Such differences are surprising since darker skin allows less UVB skin penetration resulting in decreased production of vitamin D. The prevalence of vitamin D insufficiency in Hispanic children was not considerably different from the African-American children with T1D (29%). Significant vitamin D deficiency was rare among all studied subjects and only 5% were found to have a vitamin D level lower than 15 ng/ml.
The importance of our findings is substantiated by the significant relationship between type 1 diabetes mellitus and vitamin D status. There has been extensive evidence in the role of vitamin D in many autoimmune conditions including T1D, rheumatoid arthritis, scleroderma, psoriasis and multiple sclerosis [
The need for a better understanding of the risk factors associated with development of comorbidities in patients with type 1 diabetes becomes clear when one analyzes its financial implications. Individuals with diagnosed diabetes mellitus, on average, have medical expenditures approximately two times higher than their peers without diabetes mellitus [
Currently, screening for the most frequently associated autoimmune conditions (i.e., thyroid dysfunction and celiac disease) in patients with T1D is a common practice and recommendation by the American Diabetes Association. Hypothyroidism due to autoimmune thyroiditis occurs in approximately 3-8% of children and adolescents with T1D [
This is a retrospective study, thus it was not possible to match patients on important sociodemographic variables. Nonetheless, these data are a valuable contribution to the existing literature. Specifically, it is important to note that our sample is drawn from Central Florida. The Central Floridian population helps disregard the common belief that vitamin D deficiency/insufficiency is primarily due to patients residing in colder climates with low sunlight levels. Similar findings have been reported by other groups among patients living in a sun rich environment [
The data from our study indicates that 64% of children with T1D in our practice had low vitamin D levels, similar to the general US population. Interestingly, vitamin D deficiency is still quite prevalent in the sun rich environment of central Florida. We noted significant differences based on ethnicity, BMI and seasonal variation. Vitamin D deficiency was more common among White children as compared to Hispanic children (42% vs 29%, respectively) and African American children. When compared to obese children, non-obese children were less likely to be vitamin D deficient (71% vs 29%). In the summer, children were less likely to be vitamin D deficient or vitamin D insufficient.
A link between autoimmune conditions and vitamin D deficiency/insufficiency has been implicated. Considering the high incidence of vitamin D deficiency among children with T1D, its potential health implications and its ease of treatment, we argue that pediatric endocrinologists should consider regularly screening their patients with T1D for vitamin D insufficiency/deficiency.
The authors have declared that no competing interests exist.
Consent was obtained by all participants in this study. Nemours Children’s Hospital issued approval 762598