EFFECT OF DEXAMETHASONE ON ORAL GLUCOSE TOLERANCE IN HEALTHY ADULTS

Objective: To determine the dose-response and time course of action of a single dose of dexamethasone on plasma glucose and insulin dynamics in healthy adults. Methods: Participants included healthy adults who met the following inclusion criteria: 18 to 65 years of age, body mass index of 18 to 25 kg/m(2), no family history of diabetes mellitus, not taking any medication known to affect glucose tolerance, and nonpregnant state for female participants. Each participant underwent 3 sequential blocks of 75-g oral glucose tolerance tests (OGTTs) on days 1, 2, and 3; this sequence was repeated on 3 different occasions separated by more than 2 weeks. On the first day of each block, participants reported to the research center after a 10- to 12-hour overnight fast, and fasting baseline blood samples for glucose, insulin, and C-peptide were obtained. Baseline (0 mg) OGTT was then performed with a 75-g glucose load, and blood samples were collected at 30, 60, 90, and 120 minutes for measurements of glucose, insulin, and C-peptide. After the baseline OGTT on day 1, a single dose of either 2-, 4- or 8-mg of dexamethasone was administered orally. Twenty-four and 48 hours later, participants returned for additional OGTTs. Results: Ten healthy volunteers (4 male and 6 female) were enrolled. The effect of dexamethasone was maximal 24 hours after 8-mg dexamethasone compared with the effect observed after no dexamethasone administration. At 60 minutes during the OGTT (following 8-mg dexamethasone), blood glucose increased from 127 +/- 7.1 mg/dL (6.35 +/- 0.36 mmol/L) to 176 +/- 19 mg/dL (8.8 +/- 0.95 mmol/L), insulin increased from 49.3 +/- 3.2 mu IU/mL (342 +/- 22 pmol/L) to 119.7 +/- 10.1 mu IU/mL (831 +/- 70 pmol/L), and C-peptide increased from 6376 +/- 510 pg/L (1913 +/- 153 pmol/L) to 10143 +/- 1016 pg/L (3043 305 pmol/L); the 60-minute levels returned towards baseline at 48 hours. Smaller changes were observed with 2- and 4-mg dexamethasone. Twenty-four hours after 8-mg dexamethasone, there was a 2.2- and 1.5-fold increase in homeostasis model assessment of insulin resistance and homeostasis model assessment of beta cells, respectively, and a 2.5-fold decrease in the Matsuda sensitivity index. Conclusions: A single oral dose of 8-mg dexamethasone increases blood glucose, insulin, and C-peptide levels maximally at 24 hours, 1 hour following 75-g OGTT. A dexamethasone stress test might identify persons at increased risk for type 2 diabetes. (Endocr Pract. 2010:16:770-777)