Free, bioavailable 25-hydroxyvitamin D levels and their association with diabetic ketoacidosis in children with type 1 diabetes at diagnosis

Abstract

BackgroundConsidering the roles of 25-hydroxyvitamin D (25OHD) in glucose homeostasis and immune modulation, vitamin D deficiency may be related to the development of type 1 diabetes (T1DM) and diabetic ketoacidosis (DKA). We evaluated the total, free, bioavailable 25OHD levels and vitamin D binding protein (VDBP) levels and genotypes between T1DM patients and controls.MethodsThis retrospective, cross-sectional study included 84 children with T1DM (38 boys and 46 girls, 8.0 ± 3.6 years) and 1:1 age- and sex-matched healthy controls. A multiplex liquid chromatography-tandem mass spectrometry-based assay was used to simultaneously measure vitamin D metabolites.ResultsPatients with T1DM had lower levels of total 25OHD (16.3 ± 5.1 vs. 19.9 ± 6.5 ng/mL, P< 0.001) and VDBP (146.0 ± 27.8 vs. 224.9 ± 36.1 µg/mL, P = 0.001), but higher free 25OHD (8.0 ± 2.5 vs. 6.5 ± 2.3 pg/mL, P< 0.001) than controls. Patients who presented with DKA had lower levels of 25OHD in the total (15.0 ± 4.6 vs. 17.6 ± 5.2 ng/mL, P = 0.020), free (7.5 ± 2.6 vs. 8.4 ± 2.4 pg/mL, P = 0.059), and bioavailable (2.3 ± 0.9 vs. 2.8 ± 0.8 ng/mL, P = 0.014) forms than those without DKA at the T1DM diagnosis. The lower the total, free, and bioavailable 25OHD levels at diagnosis, the lower the pH and HCO3-. The proportions of the VDBP genotypes did not differ between the patients and controls.ConclusionPatients with T1DM had higher levels of free 25OHD than healthy children, despite lower levels of total 25OHD. However, patients with DKA exhibited lower levels of bioavailable 25OHD than those without DKA at the T1DM diagnosis. The lower the concentrations of free and bioavailable 25OHD, the more severe the acidosis at the initial T1DM presentation.

The role of free vitamin D and vitamin D binding protein in SARS‐Cov‐2 infection in children

“…Similar to our findings, in a study of children with type 1 diabetes mellitus, the mean BAVD levels in the control group were found to be between the two study groups (DM with or without ketoacidosis). Although there was no significant difference between the study and control groups, BAVD levels were significantly reduced in type 1 diabetes mellitus with ketoacidosis 27 …”

“…Although there was no significant difference between the study and control groups, BAVD levels were significantly reduced in type 1 diabetes mellitus with ketoacidosis. 27 Previous studies have reported that the positive effects of vitamin D on the innate and adaptive immune system and immune response modulation may prevent lung and cardiovascular system damage and decrease thrombotic events. 28 Furthermore, vitamin D may prevent virus entry and replication by protecting the integrity of physical barriers and may reduce organ damage and thrombotic events by increasing levels of angiotensin-converting enzyme 2, nitric oxide, and antioxidants or by reducing inflammatory cytokine and free radical levels.…”

25OHVitamin D Levels in a Canarian Pediatric Population with and without Type 1 Diabetes: The Role of Acidosis

“…Those studies that evaluate the effect of acidosis on 25OHVitamin D levels, in general, report lower levels in patients presenting with acidosis. Choe et al recently reported lower levels of 25OHVitamin D in children with T1D compared to controls (16 vs. 19.9 ng/mL; p < 0.001) [11]. In agreement with our results, they did not find any differences between the T1D group presenting without acidosis and the control group (17.6 vs. 19.9 ng/mL), whereas the difference remained in the T1D group with acidosis compared with controls (15 vs. 19.9 ng/mL; p < 0.001).…”

“…A clear explanation of the pathophysiological pathways leading to the reported difference in 25OHVitamin D levels in patients with DKA at the moment of T1D onset is still lacking. Choe et al explored in some depth the levels of total, free, and bioavailable 25OHVitamin D, as well as vitamin D binding protein (VDBP) [11]. They concluded that T1D patients presented significantly lower total but higher free 25OHVitamin D levels than healthy children.…”

“…It has been described that acidosis (or low levels of bicarbonate) influences the levels of 25OHVitamin D, resulting in lower levels compared to patients with normal pH and bicarbonate levels. The exact mechanisms responsible for this phenomenon have not yet been fully explained [11].…”