Vitamin D Supplementation and Glycemic Control Improvement Among Type 1 Diabetic Children
Condition: Type 1 Diabetes Mellitus; Vitamin D Deficiency
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Vitamin D Deficiency
Study type: Interventional

Summary: 
      Type 1 diabetes mellitus (T1DM) is an immune-mediated disease characterized by diminished
      insulin secretion due to damage to islets of Langerhans in the pancreas, which eventually
      results in high levels of glucose in the blood. According to World Diabetes Foundation, in
      Palestine, 4.4% of diabetic patients are diagnosed with T1DM, while 95.3% are diagnosed with
      type 2 diabetes (T2DM) (World Diabetes Foundation, 2020).

      Observational studies have reliably provided evidence that T1DM patients with acceptable
      glycemic control have higher 25(OH)D levels than T1DM with lesser glycemic control.
      Additionally, it has been specified by some of the research-based studies that there is a
      strong connection between the deficiency of vitamin D and the incidence of T1DM.

      In interventional studies of T1DM children and adults, repletion of vitamin D in deficient
      individuals improved HbA1c in a period of 12 weeks. Participants were more likely to achieve
      HbA1c < 7.8% if they had higher 25(OH)D levels on week 12 than on baseline, especially if
      25(OH)D levels were exceeded 51 nmol/l.

      According to the Food and Drug Administration (FDA), The Institute of Medicine's (IOM)
      recommended Upper Limit (UL) for chronic Vitamin D intake for infants (children less than 1
      year of age) is 25 mcg/day (1,000 IU/d), and for children age 1 year and older the
      recommended UL is 50 mcg/day (2,000 IU/d) (Institute of Medicine Standing Committee on the
      Scientific Evaluation of Dietary Reference Intakes, 1997).

      Despite a large amount of evidence from observational and experimental studies supporting the
      effects of vitamin D on glucose metabolism and the immune system, results from clinical
      studies remain inconsistent, which makes it impossible to recommend vitamin D supplementation
      for the treatment of T1DM. Therefore, this study aimed to investigate the status of vitamin D
      among T1DM children for vitamin and to examine the effects of vitamin D supplementation on
      glycemic control in children with T1DM. This is the first randomized controlled trial that
      studied the effects of vitamin D supplementation on glycemic control among T1DM children in
      the Gaza Strip, Palestine.
    

Detailed description: 
      2.1 Study design The study design was experimental, A randomized controlled trial. 2.2 Study
      setting The study was conducted at the endocrinology outpatients' clinic at AL-RANTISI
      PEDIATRIC HOSPITAL in Gaza Strip.

      2.3 Study Sample After getting the ethical approval, data were collected throughout 3 months,
      starting from October 2017 to January 2018. In this period, 80 children who were less than 14
      years old were diagnosed with T1DM which was indicated through fasting blood glucose level
      greater than 126 mg/dl or HbA1c cut point of ≥6.5% (American Diabetes Association, 2010), and
      had vitamin D deficiency which indicated by its levels of less than 12 ng/ml (Sullivan,
      2019), were recruited from endocrinology outpatients' clinic at AL-RANTISI PEDIATRIC HOSPITAL
      in Gaza Strip.

      2.4 Sampling

      A stratified random sampling technique was applied to assign children with the previously
      mentioned criteria into two groups. The first group is the interventional (experimental)
      group that received vitamin D supplements (2000 IU/day) and the second group is the control
      group that did not receive any supplements. Both groups were on their regular diet and
      treatment, but one group was put on vitamin D supplement and the other group received a
      placebo instead. According to previous studies and after the direct supervision from the
      treating pediatrician and endocrinologist, the best preparation and dosage of vitamin D was
      used (According to FDA the recommended dose for children age 1 year and older is 2,000
      IU/day). The two groups were defined as follows:

      Group A: is the control group, that received a placebo as a supplement. Group B: is the
      interventional group that supplemented with vitamin D tablets containing 2000 IU once time
      daily with a meal, for 3 months of intervention.

      Concerning the laboratory investigations; vitamin D status was assessed by measuring the
      concentration of 25-hydroxyvitamin D (25(OH)D) in the children's serum. Levels of 25(OH)D
      were interpreted as deficiency (≤20 ng/ml or ≤50 nmol/L), insufficiency (21-29 ng/ml or
      52.5-72.5 nmol/L), and sufficiency (30-100 ng/ml ng/ml or 75-250 nmol/L). The glycated
      hemoglobin levels are defined based on the control of diabetes, as good control (HbA1c<7.8%),
      moderate control (HbA1c:7.8%-9.9%), and poor control (HbA1c>9.9%).

      2.5 Tools of Data Collection

      Children's health assessment structure interview sheet was used to collect data. It was
      constructed by the researchers based upon relevant literature. The questionnaire consisted of
      three parts:

      Part I: Children's socio-demographic characteristics This part was aimed to collect
      socio-demographic characteristics for both interventions, and control groups before the
      intervention such as age, gender, number of family members, and level of education.

      Part II: Children's current health history It covered the history of the discovery of
      diabetes, duration of diabetes, type of insulin, family history of diabetes, and periodic
      test for diabetes. This part had been used before the intervention for both the intervention
      and control groups.

      Part III: Children's laboratory investigations This part addressed HbA1c that was
      investigated and recorded before and after the interference for both interventions, and
      control groups. Additionally, vitamin D status was assessed and recorded before the
      intervention for both interventions, and control groups.

      2.6 Statistical analysis Data was entered and statistically analyzed using a statistical
      package for social sciences (SPSS) version 26 database for windows 10. Descriptive statistics
      were used to summarize the socio-demographic characteristics of subjects. Numerical data like
      25-(OH)D levels, and HbA1c, were presented as mean (SD) or median (IQR) based on their
      normality distribution. Categorical data were presented as frequency (percentage). The
      chi-square test was used for categorical data comparison. Analysis of quantitative data
      between two groups was done using unpaired t-test. Pearson correlation coefficients between
      continuous variables were used as a measure of association. A p-value <0.05 was considered
      statistically significant.
    

Intervention name(s): vitamin D supplements (2000 IU/day)
Intervention type(s): Dietary Supplement
Intervention description(s): The interventional (experimental) group received vitamin D supplements (2000 IU/day). According to previous studies and after the direct supervision from the treating pediatrician and endocrinologist, the best preparation and dosage of vitamin D was used (According to FDA the recommended dose for children age 1 year and older is 2,000 IU/day).
Intervention MeSH terms: Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Screening
Keywords: Vitamin D Supplementation; Glycemic Control; Type 1 Diabetes Mellitus; Gaza Strip; Randomized Controlled Trial.