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/m2, 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 μIU/mL (342 ± 22 pmol/L) to 119.7 ± 10.1 μIU/mL (831 ± 70 pmol/L), and C-peptide increased from 6376 ± 510 pg/L (1913 ± 153 pmol/L) to 10 143 ± 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 β 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.
Abdelmannan
Dima
D
Department of Clinical and Molecular Endocrinology, Case Western Reserve University, Cleveland VA Medical Center , Cleveland, Ohio 44106-4951 , USA. dima.abdelmannan@gmail.com
Tahboub
Rundsara
R
Genuth
Saul
S
Ismail-Beigi
Faramarz
F
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000008:administration & dosage* / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006262:Health; D006801:Humans; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D055815:Young Adult
D001786:Blood Glucose; D003907:Dexamethasone; D005947:Glucose