24-25-dihydroxyvitamin-d-3 and Diabetes-Mellitus

Topics: 24,25-Dihydroxyvitamin D 3; Diabetes Mellitus; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Observational Studies as Topic; Randomized Controlled Trials as Topic

Decreased glomerular filtration rate (GFR) leads to reduced production of 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 (25[OH]D3). Effects of low GFR on vitamin D catabolism are less well understood. We tested associations of estimated GFR (eGFR) with the circulating concentration of 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), the most abundant product of 25(OH)D3 catabolism, across populations with a wide range of GFRs.. Cross-sectional study.. 9,596 participants in 5 cohort studies and clinical trials: the Diabetes Control and Complications Trial (N=1,193), Multi-Ethnic Study of Atherosclerosis (N=6,470), Cardiovascular Health Study (N=932), Seattle Kidney Study (N=289), and Hemodialysis Study (N=712).. eGFR.. Circulating 24,25(OH)2D3 concentration.. GFR was estimated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration equation. Vitamin D metabolites were measured by mass spectrometry.. Circulating 24,25(OH)2D3 concentration was correlated with circulating 25(OH)D3 concentration (Pearson r range, 0.64-0.88). This correlation was weaker with lower eGFRs. Moreover, the increment in 24,25(OH)2D3 concentration associated with higher 25(OH)D3 concentration (slope) was lower with lower eGFRs: 2.06 (95% CI, 2.01-2.10), 1.77 (95% CI, 1.74-1.81), 1.55 (95% CI, 1.48-1.62), 1.17 (95% CI, 1.05-1.29), 0.92 (95% CI, 0.74-1.10), 0.61 (95% CI, 0.22-1.00), and 0.37 (95% CI, 0.35-0.39) ng/mL of 24,25(OH)2D3 per 10 ng/mL of 25(OH)D3 for eGFRs≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m2 and end-stage renal disease treated with hemodialysis, respectively. As a result, at a 25(OH)D3 concentration of 20 ng/mL, mean 24,25(OH)2D3 concentrations were 2.92 (95% CI, 2.87-2.96), 2.68 (95% CI, 2.64-2.72), 2.35 (95% CI, 2.26-2.45), 1.92 (95% CI, 1.74-2.10), 1.69 (95% CI, 1.43-1.95), 1.14 (95% CI, 0.62-1.66), and 1.04 (95% CI,1.02-1.07) ng/mL for each category, respectively. This interaction was independent of other relevant clinical characteristics. Race, diabetes, urine albumin excretion, and circulating parathyroid hormone and fibroblast growth factor 23 concentrations more modestly modified the association of 24,25(OH)2D3 with 25(OH)D3.. Lack of direct pharmacokinetic measurements of vitamin D catabolism.. Lower eGFR is associated strongly with reduced vitamin D catabolism, as measured by circulating 24,25(OH)2D3 concentration.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Observational Studies as Topic; Randomized Controlled Trials as Topic; Young Adult

Topics: 24,25-Dihydroxyvitamin D 3; Diabetes Mellitus; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Observational Studies as Topic; Randomized Controlled Trials as Topic

In order to elucidate if changes in vitamin D metabolism play a role for diabetic bone loss, the serum concentrations of the major vitamin D metabolites were studied in 26 adult male ambulatory insulin-treated diabetics, selected to have normal renal function and a duration of diabetes below 11 years. The patients were studied during usual metabolic control and exhibited wide ranges of hyperglycaemia and glycosuria. The serum concentrations of the major metabolites of vitamin D, 25-hydroxyvitamin D(2 + 3) (25OHD), 24,25-dihydroxyvitamin D(2 + 3) (24,25(OH)2D), and 1,25-dihydroxyvitamin D(2 + 3) (1,25(OH)2D), were measured in diabetics, and in age and sex matched controls. The diabetics had slightly decreased serum levels of 25OHD (42.0 nmol/l versus 55.5 nmol/l in normals, P less than 0.05), markedly decreased serum levels of 24,25(OH)2D (2.98 nmol/l versus 5.91 nmol/l, P less than 0.01), but serum levels of 1,25(OH)2D were virtually normal (64.2 pmol/l versus 68.3 pmol/l, ns). The close correlation between serum concentrations of 25OHD and 24,25(OH)2D observed in the normal subjects, was absent in the diabetics. There were no correlations between the serum levels of any of the vitamin D metabolites and the measured indices of glucose and calcium metabolism. It is concluded that insulin-dependent diabetic patients demonstrate definite alterations in serum levels of vitamin D metabolites, the significance of which remains unknown at present.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Adult; Calcifediol; Calcitriol; Diabetes Mellitus; Dihydroxycholecalciferols; Ergocalciferols; Humans; Insulin; Male; Middle Aged; Vitamin D