Vanadium Salts in the Treatment of Human Diabetes Mellitus

Oral insulinmimetic properties and safety of sodium metavanadate (NaVO₃) in human IDDM and NIDDM, and vanadyl sulfate (VOSO₄) in NIDDM are reviewed and new studies are presented. In a single blind placebo lead in trial with VOSO₄, glucose metabolism in a two-step euglycemic insulin clamp did not increase in any of three subjects (age 57.7±0.9 yrs; M/F 1/2; BMI 39±10 kg/m²; HbA1 10.7±1.3%) after 6 weeks vanadyl therapy dosed at 25 mg V daily. However, insulin sensitivity improved in 3 of 5 subjects (age 56.2±6.0 yrs; M/F 5/0; BMI 31.9±5.4 kg/m²; HbA1 10.7±2.1%) when dosed at 50 mg V daily, from 30-83% and 9-230% at 0.5 and 1.0 mU/kg insulin, respectively; and insulin sensitivity improved in 3 of 5 subjects (age 52.0±8.6 yrs; M/F 3/2; BMI 39.0±7.8 kg/m²; HbA1 6.9±1.0%) when dosed at 100 mg V daily, from 47-775% and 16-75% at 0.5 and 1.0 mU/kg insulin, respectively. Basal hepatic glucose production (HGP) and suppression of HGP by insulin were unchanged at both doses. There was no change in fasting blood glucose, glycohemoglobin, or mean systolic, diastolic, mean arterial blood pressures or in mean heart rates on 24 hr ambulatory monitors. Peak serum V levels for the 25 and 50 mg V dose were 15.7±3.7 and 79.1±24.0 ng/ml, respectively. 50 and 100 mg V doses caused some gastrointestinal intolerance, without biochemical evidence of toxicity. V is well tolerated for six weeks, but at these doses do not dramatically improve insulin sensitivity or glycemic control in all individuals.