Which of the two different regimens of vitamin D supplementation, in addition to lifestyle modification, would improve glucose tolerance in vitamin D-deficient Sri Lankan adults?

Study setting – Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura

Study population – Adults residing in Anuradhapura district Sri Lanka. Adults with impaired glucose tolerance (IGT) as per the WHO criteria (fasting plasma glucose (< 126 mg/dL, 7 mmol/L) and 2-hour plasma glucose after a 75g of glucose load between 140 – 199 mg/dL (7.8 – 11.1 mmol/L)

Intervention Group 1 - 2,000 IU daily cholecalciferol (vitamin D3) for 24 weeks+ lifestyle modifications* Group 2 - 60,000 IU per week cholecalciferol (vitamin D3) for 8 weeks, followed by 2,000 IU/day cholecalciferol (vitamin D3) for 16 weeks + lifestyle modifications* *-lifestyle modifications include sun exposure, diet and level of physical activities

Sun exposure -Exposing at least 25-30% of body surface area (face, arms and legs) for direct sunlight without sunscreen daily for 30-35 minutes between 10.00 am to 3.00 pm,

Diet - The dietary pattern of the participants will be assessed based on the data obtained at the baseline assessment through 3-day food diary. Accordingly necessary dietary modification advices will be given based on food based dietary guidelines developed by Ministry of Health, Sri Lanka

Level of Physical activities - The advices will be provided based on the 2024 Guideline for the Primary Prevention of Stroke: A Guideline from the American Heart Association/American Stroke Association. Accordingly, the participants will be advised to engage in at least 150 minutes of moderate-intensity physical activity, 75 minutes of vigorous-intensity physical activity, or an equivalent combination per week and to avoid excessive time spent in sedentary behaviour (characterized by low energy expenditure while sitting, reclining, or lying while awake)

Randomization – block randomization Block randomization will be performed after recruitment of the required sample size. Initially, participants will be ranked in descending order based on baseline serum vitamin D levels to ensure comparable baseline distribution between groups. Subsequently, participants will be divided into 10 blocks, each comprising four individuals. Within each block, two participants will be assigned to each group. Allocation within each block will be determined using randomly selected sequences. All possible allocation arrangements (e.g., 1-1-2-2, 1-2-1-2, 2-2-1-1, 1-2-2-1, 2-1-1-2) will be written on paper chits. For each block, one chit will be randomly selected to determine the allocation sequence. After each selection, the chit will be returned to the pool to allow for random reuse in subsequent blocks.

Adults (both males and females) aged 30-50 years Normal body mass index 18.5 – 22.9 kg/m² as per the South Asian cutoffs Vitamin D deficient (<20 ng/mL) or insufficient (21-29 ng/mL) Impaired glucose tolerance as of the results of oral glucose tolerance test (fasting plasma glucose (< 126 mg/dL) and 2- hour plasma glucose 140 – 199 mg/dL), Adults who can understand written and verbal communications in Sinhala or English languages

Adults who have any acute or chronic illnesses and, on any medication, or supplementation (including vitamin D and calcium), Adults who have present or past history of nephrolithiasis, Pregnant and lactating mothers (though empiric vitamin D supplementation during pregnancy is recommended by the 2024 guidelines of American endocrine society this group will be excluded considering the significant effect of pregnancy related hormones on glucose homeostasis and the physical parameters measured in the study), Adults who consume alcohol or smoking, Menopaused females, Adults who will be detected to have hypercalcaemia, elevated liver enzymes (ALT, AST) and serum creatinine and parathyroid hormone levels at baseline investigations