Exenatide yields beta cell improvement and weight loss in individuals with diabetes but has not been well-studied in individuals with prediabetes….
We recruited healthy volunteers with BMI 25-37 kg/m2 with prediabetes as defined by FBG 100-125 mg/dl or 2hr glucose 141-199 mg/dL on screening OGTT. Insulin-mediated glucose uptake was quantified with the modified insulin suppression test with steady-state plasma glucose concentrations (SSPG). Beta cell function was calculated using the insulinogenic index (ΔI/ΔG).
Subjects were randomized, double-blind, to exenatide (EX), 10 mcg BID, or placebo (P) for 30wks. All subjects took a hypocaloric diet with biweekly oversight by study dietitians for 18wk. During the last 12wks, no dietary counseling was provided.
We hypothesized that individuals assigned to EX would experience greater increase in insulin secretion, weight loss, and improved insulin sensitivity than the P group. 68 subjects were randomized and 10 dropped out. At baseline, subjects were NS different with regard to mean age, BMI(33 kg/m2), sex, SSPG, or insulinogenic index. EX and P subjects had lost 8.8 and 7.8% of initial body weight at 18wks and 8.9 and 8.1%,at 30wks respectively (NS between groups).
Despite reduction in insulin resistance, beta cell function increased in the EX group (ΔI/ΔG 1.4 to 1.6). In the P group, beta cell function decreased (2.3 to 2.0) (p=0.13). Insulin resistance decreased significantly in both groups, and was correlated with weight loss (r=0.46, p<0.01). FBG decreased but was NS in both groups. 2hr glucose decreased significantly in both groups, reverting from IGT to NGT on average (NS between groups). Change in FBG was predicted by % weight loss, whereas change in 2hr glucose was predicted by change in insulinogenic index.
In conclusion, obese prediabetic subjects assigned to EX plus hypocaloric diet lose weight, improve insulin sensitivity, and revert from IGT to NGT. Insulin resistance and FBG decrease in proportion to weight loss, whereas 2 hr glucose decreases in proportion to insulinogenic index. Despite reduction in insulin resistance, beta cell function increased with EX, but not P. Otherwise, intensive dietary management alone appears to yield comparable results to EX plus diet.
Author(s): TRACEY MCLAUGHLIN, MARCIA PECK, NICOLE COGHLAN, CINDY LAMENDOLA, DANIELLE WEISS: ADA Scientific Sessions Late Breaking Abstract Sunday, June 26, 2011 Abstract -34LB