BackgroundIt is not known whether genetic variation in the vitamin D binding protein (DBP) influences 25-hydroxyvitamin D levels [25(OH)D] after vitamin D supplementation. We aimed to investigate the changes of total 25(OH)D, 25(OH)D3 and 25(OH)D2 in a Thai cohort, according to type of vitamin D supplement (vitamin D3 or D2) and DBP genotype, after receiving vitamin D3 or D2 for 3 months.MethodsThirty-nine healthy subjects completed the study. All subjects received 400 IU of either vitamin D3 or D2, plus a calcium supplement, every day for 3 months. Total serum 25(OH)D, 25(OH)D3 and 25(OH)D2 were measured by LC-MS/MS. Individual genotyping of rs4588 in the DBP gene was performed using real-time PCR.ResultsVitamin D3 supplementation of 400 IU/d increased 25(OH)D3 significantly (+16.2 ± 4.2 nmol/L, p <0.001). Vitamin D2 (400 IU/d) caused increased 25(OH)D2 levels (+22.0 ± 2.11 nmol/L, p <0.001), together with a decrease of 25(OH)D3 (−14.2 ± 2.0 nmol/L, p <0.001). At 3 month, subjects in vitamin D3 group tended to have higher total 25(OH)D levels than those in vitamin D2 (67.8 ± 3.9 vs. 61.0 ± 3.0 nmol/L; p = 0.08). Subjects were then classified into two subgroups: homozygous for the DBP rs4588 C allele (CC), and the rest (CA or AA). With D3 supplementation, subjects with CA or AA alleles had significantly less increase in 25(OH)D3 and total 25(OH)D when compared with those with the CC allele. However, no difference was found when the supplement was vitamin D2.ConclusionGenetic variation in DBP (rs4588 SNP) influences responsiveness to vitamin D3 but not vitamin D2.

Registry: ClinicalTrials.gov; Title: Obstructive Sleep Apnea and Gestational Diabetes: Incidence and Effects of Continuous Positive Airway Pressure Treatment on Glucose Metabolism; Identifier: NCT02108197; URL: https://clinicaltrials.gov/ct2/show/NCT02108197.

Summary Sleep disturbances have been linked to insulin resistance and poor glycaemic control in patients with type 2 diabetes. However, the data are limited in type 1 diabetes. Recently, varying day‐to‐day sleep schedules, i.e. sleep variability, have been associated with adverse metabolic profile in healthy individuals. This study explored whether sleep variability affects glycaemic control and insulin requirement in type 1 diabetes. Forty‐one adult patients with type 1 diabetes wore an actigraphy for 5 nights. Standard deviation of sleep duration, efficiency and mid‐sleep time were sleep variability parameters. Sleep apnoea risk and self‐reported sleep quality were assessed by the Berlin questionnaire and Pittsburgh Sleep Quality Index. Haemoglobin A1c, diabetes complications and insulin regimen were obtained from medical records. After adjusting for neuropathic symptoms, sleep apnoea risk and poor self‐reported sleep quality, higher sleep variability was significantly associated with poorer glycaemic control (standard deviation of sleep duration, B = 0.100, P = 0.004; and standard deviation of mid‐sleep time, B = 0.068, P = 0.04). In addition, standard deviations of sleep duration and mid‐sleep time were highly correlated, suggesting that participants changed their sleep duration along with sleep timing. After adjusting for covariates, the standard deviation of sleep duration (P = 0.009) and standard deviation of mid‐sleep time (P = 0.012) were associated with higher insulin requirement. In summary, higher sleep variability, which likely reflects sleep deprivation alternating with sleep compensation along with shifts in their circadian timing, was associated with poorer glycaemic control and higher insulin requirement in patients with type 1 diabetes. Increased sleep regularity may improve metabolic control in type 1 diabetes.