title: Intravenous calcitriol normalizes insulin sensitivity in uremic patients.
abstract: Recent studies suggest that secondary hyperparathyroidism and/or vitamin D deficiency are responsible for the insulin resistance in chronic renal failure. We investigated the effect of a 12-week intravenous treatment 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 vs. 41 +/- 4 ng/liter, P < 0.001), insulin resistance (insulin sensitivity index, SI: 4.9 +/- 0.8 vs. 9.5 +/- 0.9 min-1/(microU/ml), P < 0.002), 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 fractional clearance (0.033 +/- 0.004 vs. 0.085 +/- 0.009 min-1, P < 0.0002). Following treatment with 1,25 dihydroxycholecalciferol, the parathyroid hormone levels decreased significantly to 237 +/- 30 ng/liter (P < 0.05), the insulin sensitivity index (SI: 9.6 +/- 2.2, P < 0.05) reached a value similar to that of control subjects, and posthepatic insulin 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 treatment led to a significant reduction of parathyroid hormone levels and to a complete normalization of insulin sensitivity in the hemodialysis patients. Thus, intravenous 1,25 dihydroxycholecalciferol improves insulin resistance in uremic patients, acting per se or by reducing secondary hyperparathyroidism.
authors.affiliation: Department of Medicine III, University of Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Kautzky-Willer
authors.forename: G
authors.initials: G
authors.lastname: Pacini
authors.forename: U
authors.initials: U
authors.lastname: Barnas
authors.forename: B
authors.initials: B
authors.lastname: Ludvik
authors.forename: C
authors.initials: C
authors.lastname: Streli
authors.forename: H
authors.initials: H
authors.lastname: Graf
authors.forename: R
authors.initials: R
authors.lastname: Prager
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002117:Calcitriol / Q000008:administration & dosage*; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000378:metabolism; D007275:Injections, Intravenous; D007333:Insulin Resistance; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D006435:Renal Dialysis; D014511:Uremia / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D010281:Parathyroid Hormone; D002117:Calcitriol; D005947:Glucose