Research Design and Methods
Study was performed with Baylor College of Medicine Institutional Review Board approval, and informed consent was obtained in accordance with federal/institutional guidelines.
Subjects with type 1 diabetes using multiple daily injections or insulin pump, aged 13–22 years, with diabetes for ≥1 year, BMI <90th percentile for age, hemoglobin >12 g/dl, and hemoglobin A1C <8.5% were recruited. One subject had treated hypothyroidism with no other chronic conditions. Subjects were not on any concomitant medications, which affected blood glucose concentrations. Pregnant/lactating females were excluded. Two subjects failed screening. One subject had hypoglycemia needing rescue glucose boluses with insulin alone and did not participate in further studies.
Eight subjects completed the three-part study. Followed by a baseline study with insulin alone, subjects were randomized to two different doses of exenatide (1.25 and 2.5 μg), administered in a double-blinded randomized controlled manner. Studies were at least 3 weeks apart. All subjects had type 1 diabetes (antibody positive), with minimal or no endogenous C-peptide response to meals. (A pilot study done previously suggested that higher doses [7–10 μg] of exenatide used in normal BMI subjects with type 1 diabetes resulted in hypoglycemia, and hence the lowered doses were examined.)
At 0800 h, the prebreakfast insulin bolus was administered based on patient's usual insulin-to-carbohydrate ratio. Postbolus, subjects drank 12 ounces of a standard liquid meal (Boost High Protein Drink, 360 calories, 50 g carbohydrates, and 12 g fat), enriched with 1 g of [13C]glucose within 10 min. Breath samples for 13CO2 analysis were collected in duplicates at 17 time points until 1300 h. Usual insulin basal rates or glargine were maintained during study.
On the days subjects received the study drug of 1.25 μg (~0.02 μg/kg) or 2.5 μg (~0.04 μg/kg) exenatide along with insulin, the prandial insulin was reduced by 20%.
Plasma glucose was measured using a bedside YSI glucose analyzer (2300 Stat Plus; Yellow Springs Instruments, Yellow Springs, OH) throughout the study at regularly timed intervals. Blood samples were collected pre- and postprandially for exenatide, insulin, C-peptide, GLP-1, and glucagon. Blood was processed as previously described elsewhere.
The DCA 2000 Hemoglobin A1C System (Bayer, Elkhart, IN) was used for measuring the percentage concentration of hemoglobin A1C.
Hormonal analysis and 13CO2 was measured as previously described elsewhere.
Repeated-measures ANOVA models were applied for each variable. If treatment effect was significant, then pairwise comparisons in treatment means were made among three groups with Tukey's multiple comparison procedure adjustment. The analyses were performed using SAS version 9.2.
Graphs were generated using Graph Pad Prism version 5 (Graph Pad Software, San Diego, CA). Area under the curve was calculated using the trapezoidal rule. Data were considered significant at P < 0.05.
Diabetes Care. 2010;33(6):1294-1296. © 2010 American Diabetes Association, Inc.
Cite this: The Role of Adjunctive Exenatide Therapy in Pediatric Type 1 Diabetes - Medscape - Jun 01, 2010.