No effect of calcitriol on insulin-mediated glucose uptake in healthy subjects

Administration of active vitamin D (calcitriol) improves insulin sensitivity in uraemic patients. These patients have subnormal plasma calcitriol concentrations in parallel with increased intact parathyroid hormone (PTH) concentrations. It is therefore unclear whether the improvement in insulin sensitivity results from a direct effect of calcitriol or from amelioration of secondary hyperparathyroidism. So far, no evidence has been presented that insulin sensitivity is specifically affected by calcitriol in healthy subjects. We investigated the effect of (supra)therapeutic doses of calcitriol on insulin sensitivity in healthy volunteers. In a double-blind parallel group design, 18 healthy male subjects received in random order either placebo or 1.5 micrograms of calcitriol per day by mouth for 7 days. Insulin-mediated glucose uptake, i.e. insulin sensitivity, was assessed using the euglycaemic clamp technique. Mean glucose disposal rate, i.e. M-value, was not significantly affected by placebo or calcitriol treatment (placebo: 7.1 +/- 1.3 mg kg-1 min-1 before and 7.2 +/- 1.5 mg kg-1 min-1 after treatment; calcitriol 7.0 +/- 1.4 mg kg-1 min-1 and 7.2 +/- 1.4 mg kg-1 min-1). There were no significant changes in mean plasma glucose, insulin, phosphate, bicarbonate and ionized calcium concentrations after administration of placebo or calcitriol. Furthermore, platelet intracellular calcium concentration (assessed by fluorescence spectroscopy) and mean arterial blood pressure (24 h ambulatory measurement) did not change with placebo and calcitriol treatment. On the other hand, mean intact PTH concentration decreased significantly (P < 0.01) with calcitriol treatment, but not with placebo. In addition, mean 24 h urinary calcium excretion increased significantly (P < 0.05) with calcitriol administration but was unchanged with placebo. Administration of (supra)physiological doses of calcitriol has no effect on insulin sensitivity in healthy subjects, despite a significant decrease in PTH concentrations. These observations are compatible with the notion that the effect of calcitriol on insulin sensitivity is present only in uraemic calcitriol-depleted patients.