P1152 APPLICATION OF AN ALPHA-GLUCOSIDASE INHIBITOR IN THE TREATMENT OF GLYCOGEN STORAGE DISEASE TYPE 1. A FEASIBILITY STUDY IN HEALTHY SUBJECTS.

Abstract

Introduction: Uncooked cornstarch (UCCS) is widely used to maintain normoglycemia in patients with glycogen storage disease type 1 (GSD1). However, compliance of the UCCS treatment is suboptimal because of the unpleasant taste of the UCCS. Acarbose, an alpha-glucosidase inhibitor supposed to delay carbohydrate digestion, added to a carbohydrate rich meal, might be an alternative approach in the treatment of GSD1. A cross-over study in healthy subjects was conducted to investigate the feasibility to apply an alpha-glucosidase inhibitor in the treatment of GSD1. This study compared the absorption profile after ingestion of UCCS with that after ingestion of corn pasta with acarbose. Methods: Seven healthy male volunteers (age: 23 ± 1 (mean ± SE) years, BMI 22 ± 1.1 kg/m2) ingested at least one week apart UCCS in 250 ml water or corn pasta with 12.5 mg of acarbose (CPac). Both test meals contained an equivalent of 50 g of glucose and were naturally enriched with 13C. During the 6 hours following consumption of the test meals plasma glucose and insulin were monitored. Using a primed continuous infusion of D-[6,6-2H2]glucose, the systemic appearance of exogenous glucose (RaE) was estimated, which reflects the intestinal carbohydrate absorption. Results: Significant higher total glucose responses were observed between 60 and 150 min after consumption of UCCS compared to CPac (p<0.04). Insulin responses between 60 and 240 min were significantly higher after ingestion of UCCS than those after ingestion of CPac (p<0.03). In the fasting state, before ingestion of the test meals, the endogenous glucose production was 2.24 ± 0.09 mg/kg/min. Between 30–180 min the mean RaE after consumption of UCCS (2.27 ± 0.24 mg/kg/min) was significantly higher than the mean RaE of CPac (1.16 ± 0.14 mg/kg/min)(p<0.02). Six hours after ingestion of UCCS the recovery of glucose was significantly higher than after ingestion of CPac (88 ± 6% and 45 ± 4% of the administered dose respectively, p<0.02). Conclusion: After ingestion of UCCS the mean RaE between 30 and 180 min equals the rate of endogenous glucose production. Addition of 12.5 mg of acarbose to corn pasta does not result in an absorption profile able to provide for the glucose requirements. The low 6 hours recovery of glucose after ingestion of CPac (45%) indicates that the digestion of corn pasta is inhibited to some extent. Acarbose applied in combination with the amount and type of carbohydrate used in this study is not a suitable alternative in the treatment of GSD1.