METABOLIC EFFECTS OF SODIUM METAVANADATE IN HUMANS WITH INSULIN-DEPENDENT AND NONINSULIN-DEPENDENT - DIABETES-MELLITUS IN-VIVO AND IN-VITROSTUDIES

To investigate the efficacy and mechanism of action of sodium metavana date as an oral hypoglycemic agent, five insulin-dependent diabetes me llitus (IDDM) and five noninsulin-dependent diabetes mellitus (NIDDM) patients mere studied before and after 2 weeks of oral sodium metavana date (NaVO3; 125 mg/day). Glucose metabolism measured during a two-ste p euglycemic insulin clamp was not significantly increased by vanadate therapy in patients with IDDM, but was improved by 29% during the low dose (0.5 mU/kg . min) insulin infusion and 39% during the high dose (1.0 mU/kg . min) in patients with NIDDM. The changes in glucose metab olism were largely accounted for by an increase in nonoxidative glucos e disposal, as measured by indirect calorimetry. Basal hepatic glucose production and suppression of hepatic glucose production by insulin w ere unchanged by vanadate therapy. There was a significant decrease in insulin requirements in the patients with IDDM (39.1 +/- 6.6 to 33.8 +/- 4.7 U/day; P < 0.05). Cholesterol levels significantly decreased i n both IDDM (4.53 +/- 0.16 vs. 4.27 +/- 0.22 mmol/L; P = 0.06) and NID DM (6.92 +/- 0.75 vs. 5.28 +/- 0.46 mmol/L; P < 0.05). After NaVO3 the rapy, there was a 1.7- to 3.9-fold increase in basal mitogen-activated protein and S6 kinase activities in mononuclear cells from patients w ith IDDM and NIDDM that mimicked the effect of insulin stimulation in controls. The most common adverse effect of oral NaVO3 was mild gastro intestinal intolerance. These data suggest that vanadate or related ag ents may have a potential role as adjunctive therapy in patients with diabetes mellitus.