Changes in insulin metabolism during treatment with valproate (VPA) were investigated in a study of 51 patients receiving monotherapy (31 male and 20 female) and 45 healthy controls at University of Oulu, and Hospital of Children and Adolescents, University of Helsinki, Finland. VPA-treated patients had fasting hyperinsulinemia, while the fasting serum proinsulin and C-peptide levels did not differ from controls. Proinsulin/insulin and C-peptide/insulin ratios were reduced in VPA-treated patients, and fasting plasma glucose levels were lower compared to controls. These changes were independent of the sex, seizure type, weight gain, and pretreatment weight, and were not due to weight gain or obesity. VPA does not induce insulin secretion but interferes with insulin metabolism in the liver, resulting in hyperinsulinemia and reduced plasma glucose. The obesity induced by VPA is secondary to the increase in circulating insulin. 
COMMENT. VPA causes hyperinsulinemia and consequent fall in plasma glucose by interference with insulin metabolism in the liver. The hyperinsulinemia may then induce increased weight gain.
Serum total amylase, pancreatic amylase and lipase in VPA-treated epilepsy children. In a study of 23 patients, serum pancreatic amylase was decreased at 6 and 12 months treatment with VPA, whereas serum total amylase and lipase were unchanged. Non-pancreatic isoenzyme activities of amylase were higher at 6 or 12 months. Nonpancreatic amylase, probably derived from salivary glands, may be increased in children treated with VPA, and is not a reason to interrupt therapy. Measurement of serum pancreatic amylase and/or lipase is indicated when total amylase is increased without clinical symptoms of pancreatitis.