Recent studies suggest that secondary hyperparathyroidism and/or vitam
in D deficiency are responsible for the insulin resistance in chronic
renal failure. We investigated the effect of a 12-week intravenous tre
atment with 1,25 dihydroxycholecalciferol on glucose metabolism in 10
hemodialysis patients compared with 10 healthy control subjects by the
frequently-sampled intravenous glucose tolerance test, analyzed with
the minimal model technique. Compared to control subjects, the uremic
patients featured elevated levels of parathyroid hormone (432 +/- 60 v
s. 41 +/- 4 ng/liter, P < 0.001), insulin resistance (insulin sensitiv
ity index, S-I: 4.9 +/- 0.8 vs. 9.5 +/- 0.9 min(-1)(mu U/ml), P < 0.00
2), increased posthepatic insulin delivery (6.48 +/- 2.48 vs. 2.73 +/-
3.14 nmol/liter in 4 hr, P < 0.001) and a reduced C-peptide fractiona
l clearance (0.033 +/- 0.004 vs. 0.085 +/- 0.009 min(-1), P < 0.0002).
Following treatment with 1,25 dihydroxycholecalciferol, the parathyro
id hormone levels decreased significantly to 237 +/- 30 ng/liter (P <
0.05), the insulin sensitivity index (S-I: 9.6 +/- 2.2, P < 0.05) reac
hed a value similar to that of control subjects, and posthepatic insul
in delivery decreased to 4.63 +/- 0.83 nmol/liter in 4 hr (P < 0.01),
while all the other parameters remained unchanged. In summary, uremic
patients with secondary hyperparathyroidism were found to be severely
insulin resistant and hyperinsulinemic. Intravenous vitamin D treatmen
t led to a significant reduction of parathyroid hormone levels and to
a complete normalization of insulin sensitivity in the hemodialysis pa
tients. Thus, intravenous 1,25 dihydroxycholecalciferol improves insul
in resistance in uremic patients, acting per se or by reducing seconda
ry hyperparathyroidism.