N A L A R T I C L E The Effect of Acarbose on Insulin Sensitivity in Subjects With Impaired Glucose Tolerance JEAN-LOUIS CHIASSON, MD ROBERT G. JOSSE, FRCP LAWRENCE A. LEITER, MD MARKO MIHIC, MD DAVID M. NATHAN, MD CAROL PALMASON, ART ROBERT M. COHEN, MD THOMAS M.S. WOLEVER, DM, PHD OBJECTIVE — To study the effect of acarbose, an a-glucosidase inhibitor, on postpran- dial plasma glucose and insulin and insulin sensitivity in subjects with impaired glucose tol- erance (1GT). RESEARCH DESIGN AND METHODS— Subjects with IGT were randomly treated in a double-blind fashion with placebo (n = 10) or acarbose (n = 8) at 100 mg t.i.d. for 4 months. All subjects were submitted before randomization and at the end of the study to a standardized breakfast and a 12-h daytime plasma glucose and plasma insulin profile, and insulin sensitivity was measured as steady-state plasma glucose (SSPG) using the insulin suppression test. RESULTS— While placebo had no effect on postprandial plasma glucose and plasma insulin incremental area under the curve (AUC) (3.03 ± 0.5 vs. 3.76 ± 0.6 mmol • h" 1 • I" 1 , P = NS; 1,488 ± 229 vs. 1,609 ± 253 pmol • tr 1 • I" 1 , P = NS), acarbose resulted in a significant reduction for both glucose (1.44 ± 0.3 vs. 4.45 ± 0.9 mmol • lr 1 • H, P = 0.002) and insulin (626.7 ± 104.3 vs. 1,338.3 ± 220.5 pmol • tr 1 • I" 1 , P = 0.003). The reduction in 12-h plasma glucose and insulin AUC on acarbose (11.2 ±2.1 mmol • h" 1 • I" 1 and 7.5 ± 0.7 nmol • h" 1 • I" 1 ) was significantly greater than that on placebo (4.0 ±1.6 mmol • tr 1 • I" 1 and 0.8 ± 0.4 nmol • lr 1 • I- 1 ) (P = 0.014 and 0.041). While SSPG was not affected by placebo (13.9 ± 0.4 vs. 13.8 ± 0.3 mmol/l; P = NS), it was significantly improved by acarbose (10.9 ± 1.4 vs. 13.1 ± 1.5 mmol/l, P < 0.004) and was also significantly different from placebo at 4 months (P < 0.02). CONCLUSIONS — It is concluded that in subjects with IGT, acarbose treatment decreases postprandial plasma glucose and insulin and improves insulin sensitivity. Acarbose may therefore be potentially useful to prevent the progression of IGT to N1DDM. I n the U.S. population 40-74 years of age, the prevalence of impaired glucose tolerance (IGT) is 16% (1). IGT is known to be a major risk factor for the development of NIDDM. All patients who develop NIDDM are thought to pass through a phase of IGT. This is supported by the high incidence of 1-5% per year of NIDDM developing in an IGT population with a cumulative prevalence as high as 40% (2-4). Insulin resistance, with sec- ondary hyperinsulinemia, is thought to be a major underlying abnormality leading to the development of NIDDM. But it is only when the (3-cells fail to compensate for the insulin resistance that glucose intolerance will develop initially as IGT and, with fur- ther deterioration, as NIDDM (5). These observations have stimulated interest in the treatment of subjects with From the Research Center Q.-L.C), Hotel-Dieu de Montreal, and the Department of Medicine, University of Montreal, Montreal; St. Michael's Hospital and Department of Nutritional Sciences (R.G.J., L.A.L., T.M.S.W), University of Toronto; St. Joseph's Health Center (M.M.), Toronto, Canada; the Massachusetts General Hospital and Harvard University (D.M.N.), Boston, Massachusetts; Bayer, Inc. (C.P), Toronto; and the University of Cincinnati Medical Center (R.M.C.), Cincinnati, Ohio. Address correspondence and reprint requests to Jean-Louis Chiasson, MD, Research Center, Hotel-Dieu de Montreal, 3850 St. Urbain Street, Montreal (Quebec) H2W 1T8, Canada. E-mail: chiassoj@ere.mon- treal.ca. Received for publication 21 December 1995 and accepted in revised form 30 May 1996. AUC, area under the curve; IGT, impaired glucose tolerance; SSPG, steady-state plasma glucose. IGT with the hope of preventing its pro- gression to NIDDM. Theoretically, a drug of choice for such an intervention study should be one that decreases hyperinsu- linemia and improves insulin sensitivity Acarbose, an a-glucosidase inhibitor that delays the absorption of carbohydrates from the small intestine, decreases the post- prandial rise in plasma glucose and plasma insulin in both diabetic and nondiabetic subjects (6,7). The present study was designed to evaluate the effect of acarbose on insulin sensitivity in subjects with IGT. RESEARCH DESIGN AND METHODS — Eighteen obese subjects (seven women and eleven men) with IGT participated in this study (Table 1). At baseline, all subjects underwent the fol- lowing: 1) a standardized breakfast test; 2) a 12-h daytime plasma glucose and plasma insulin profile; and 3) an insulin suppression test to measure insulin sensi- tivity. They were then randomized in a double-blind fashion to placebo (n = 10) or acarbose (n = 8) for 4 months. Acarbose was started at 50 mg t.i.d. taken with the first bite of each meal for 2 weeks and then increased to 100 mg t.i.d. for the rest of the study They were all advised on a weight-maintaining diet based on dietary history and a 24-h dietary recall. After 4 months of treatment, all of the baseline tests were repeated. The 12-h profile, including the breakfast test, was done under placebo or acarbose. Ten matched obese control subjects with normal glu- cose tolerance were also submitted to an insulin sensitivity test. The standard breakfast test (Enrich 450 kcal; 55% carbohydrate, 30% fat, and 15% protein) was given at 7:00 A.M. and ingested over 15 min. Blood samples were drawn at time 0, 60, 90, and 120 min for measurement of plasma glucose and plasma insulin. This was followed by lunch and dinner at 12:00 noon and 5:00 P.M. These meals were individualized based on dietary history and were similar for the first and second profile. Plasma samples were drawn at 12:00 noon, 1:00, 2:00, 4:00, 5:00, 6:00, and 7:00 P.M. On 1190 DIABETES CARE, VOLUME 19, NUMBER 11, NOVEMBER 1996 Downloaded from http://diabetesjournals.org/care/article-pdf/19/11/1190/444499/19-11-1190.pdf by guest on 27 November 2022