title: Acute and chronic effects of glyceryl trinitrate therapy on insulin and glucose regulation in humans.
abstract: This study examined the effect of acute and sustained transdermal glyceryl trinitrate (GTN) therapy on insulin and glucose regulation. Totally, 12 males (18-30 years) underwent a glucose tolerance test at baseline (visit 1), 90 minutes after acute transdermal GTN 0.6 mg/h (visit 2), following 7 days of continuous GTN (visit 3), and 2 to 3 days after stopping GTN (visit 4). At each visit, plasma glucose and insulin concentrations were measured before and 30, 60, 90, and 120 minutes after a 75-g oral glucose load. Indices of glucose metabolism that were examined included the insulin sensitivity index, the homeostasis model assessment of insulin resistance (HOMA-IR), and the insulinogenic index. The acute administration of GTN had no effect on glucose and insulin responses (visit 2). However, after 7 days of GTN exposure (visit 3) there was an increase in the mean glucose concentration measured after the oral glucose load. On visit 1, the mean glucose concentration (± standard deviation) following the 75 g oral glucose challenge was 5.7 ± 0.5 µmol/L. On visit 3, after 7 days of transdermal GTN therapy, the mean glucose concentration after the oral glucose was significantly higher; 6.2 ± 0.5 µmol/L (P < .015; 95% confidence intervals 0.25-0.77). There was also an increase in the HOMA-IR index; on visit 1, the median HOMA-IR (interquartile range) was 5.2 (3.9) versus 6.9 (6.8) on visit 3 (P < .015). Other indices of glucose metabolism did not change. These observations document that GTN therapy modifies glucose metabolism causing evidence of increased insulin resistance during sustained therapy in normal humans.
authors.affiliation: Department of Medicine, Division of Cardiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sean
authors.initials: S
authors.lastname: Jedrzkiewicz
authors.forename: John D
authors.initials: JD
authors.lastname: Parker
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000009:adverse effects*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000009:adverse effects*; D012720:Severity of Illness Index; D013997:Time Factors; D057968:Transdermal Patch; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D005996:Nitroglycerin