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Effect of Lipase Inhibition on Gastric Emptying of, and the Glycemic and Incretin Responses to, an Oil/Aqueous Drink in Type 2 Diabetes Mellitus

University of Adelaide, Department of Medicine, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia

Address all correspondence and requests for reprints to: Dr. Karen L. Jones, National Health and Medical Research Council/Diabetes Australia Senior Research Fellow, Department of Medicine, University of Adelaide, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. E-mail: karen.jones{at}adelaide.edu.au.

This study examined the effects of the lipase inhibitor, orlistat, on gastric emptying of, and the glycemic and incretin hormone responses to, a drink containing oil and glucose components in patients with type 2 diabetes. Seven patients (aged 58 ± 5 yr), managed by diet alone, consumed 60 ml olive oil (labeled with 20 MBq ^99mTc-V-thiocyanate) and 300 ml water containing 75 g glucose (labeled with 6 MBq ⁶⁷Ga-EDTA), on two occasions, with and without 120 mg orlistat, positioned in the left lateral decubitus position with their back against a camera. Venous blood samples, for measurement of blood glucose and plasma insulin, glucagon-like peptide-1 and glucose-dependent insulintropic polypeptide were obtained immediately before, and after, the drink. Gastric emptying of both oil (P < 0.001) and glucose (P < 0.0005) was faster after orlistat compared with control. Postprandial blood glucose (P < 0.001) and plasma insulin (P < 0.05) were substantially greater after orlistat compared with control. In contrast, plasma glucagon-like peptide-1 (P < 0.005) and glucose-dependent insulintropic polypeptide (P < 0.05) were less after orlistat. In conclusion, inhibition of fat digestion, by orlistat, may exacerbate postprandial glycemia, as a result of more rapid gastric emptying and a diminished incretin response.

This study was supported by project grants from the Royal Adelaide Hospital and the National Health and Medical Research Council (NH&MRC) of Australia. Salary of K.L.J. is derived from a Fellowship jointly awarded by the NH&MRC and Diabetes Australia. Salary of C.F. is provided by the Florey Research Fellowship of the Royal Adelaide Hospital.

Abbreviations: GIP, Glucose-dependent insulintropic polypeptide; GLP-1, glucagon-like peptide-1.

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