c-peptide and Hyperparathyroidism--Secondary

We have examined the effect of a four-week intravenous treatment with 1 alpha-hydroxyvitamin D3 on insulin sensitivity in 14 patients on chronic hemodialysis compared with 10 healthy control subjects by the insulin tolerance test. Compared to controls, the uremic patients have featured increased levels of parathyroid hormone (1085.0 +/- 822.1 vs 74.2 +/- 8.7 pg/ml, p < 0.001), insulin resistance (the rate constant for plasma glucose disappearance, K(in): 3.1 +/- 0.5 vs 4.5 +/- 0.4%/dk, p < 0.002), increased levels of insulin (30.5 +/- 7.3 vs 20.4 +/- 2.8 microIU/ml, p < 0.04) and increased levels of C-peptide (6.0 +/- 2.1 vs 3.9 +/- 12, ng/ml, p < 0.001). Following treatment with 1 alpha-hydroxyvitamin D3, levels of parathyroid hormone decreased from 1085.0 +/- 822.1 to 772.1 +/- 620.1 pg/ml (p < 0.004), the K(in) values increased significantly (from 3.1 +/- 0.5 to 4.1 +/- 0.4%/dk, p < 0.004) and reached the level near to that of controls, the insulin concentrations decreased from 30.5 +/- 7.3 to 28.7 +/- 9.2 microIU/ml (p > 0.05) and C-peptide concentrations increased from 6.0 +/- 2.1 to 7.5 +/- 2.5 ng/ml (p < 0.02). In summary, uremic patients with secondary hyperparathyroidism developed insulin resistance and hyperinsulinemia. Intravenous 1 alpha-hydroxyvitamin D3 treatment has improved insulin sensitivity directly or by reducing secondary hyperparathyroidism in uremic patients on chronic hemodialysis.

Topics: Adult; Blood Glucose; C-Peptide; Calcium; Female; Glucose Tolerance Test; Humans; Hydroxycholecalciferols; Hyperparathyroidism, Secondary; Infusions, Intravenous; Insulin Resistance; Kidney Failure, Chronic; Male; Parathyroid Hormone; Radioimmunoassay; Renal Dialysis; Treatment Outcome

To evaluate the role of calcitriol on insulin secretion in uraemia, nine patients on maintenance haemodialysis, never treated with vitamin D nor with calcium-channel blockers, were studied. Baseline glucose, insulin, C peptide, calcium, intact PTH, and calcitriol serum values were measured, and after an oral load of 75 g glucose, insulin and C peptide were also determined at 15, 30, 45, 60, and 120 min. Following 14 days of treatment with oral calcitriol (0.5 microgram/day), the same study protocol was applied. Serum calcitriol values, which were low as expected, increased after therapy, but did not reach the values observed in healthy controls. Despite no change in total serum calcium, intact PTH values decreased significantly (182 vs 88.3 ng/ml, P less than 0.003). Baseline serum insulin was significantly increased after calcitriol (7.5 vs 35 microU/ml, P less than 0.001). Similarly, an enhancement in insulin secretion following calcitriol was observed at 15 min (34 vs 70, P less than 0.01) and 30 min (57 vs 96 microU/ml, P less than 0.01). Computation of the total area under the curve confirmed these results. Changes in C peptide profile paralleled those described for insulin. These data confirm that vitamin D modulates pancreatic beta-cell secretion and suggest that calcitriol may regulate insulin release in uraemic patients.

Topics: Adult; Blood Glucose; C-Peptide; Calcitriol; Calcium; Female; Humans; Hyperparathyroidism, Secondary; Insulin; Insulin Secretion; Male; Middle Aged; Parathyroid Hormone; Uremia