Acute and Chronic Effects of Glyceryl Trinitrate Therapy on Insulin and Glucose Regulation in Humans

作者：Jedrzkiewicz Sean; Parker John D^*

来源：Journal of Cardiovascular Pharmacology and Therapeutics, 2013, 18(3): 211-216.

DOI：10.1177/1074248412467693

• glyceryl trinitrate
• glucose
• insulin
• insulin resistance
• human

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 mu mol/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 mu mol/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.

• 出版日期2013-5