Effect of Lipase Inhibition on Gastric Emptying of, and the Glycemic and Incretin Responses to, an Oil/Aqueous Drink in Type 2 Diabetes Mellitus
A. Pilichiewicz,
D. O’Donovan,
C. Feinle,
Y. Lei,
J. M. Wishart,
L. Bryant,
J. H. Meyer,
M. Horowitz and
K. L. Jones
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 hormoneresponses to, a drink containing oil and glucose componentsin patients with type 2 diabetes. Seven patients (aged 58 ±5 yr), managed by diet alone, consumed 60 ml olive oil (labeledwith 20 MBq 99mTc-V-thiocyanate) and 300 ml water containing75 g glucose (labeled with 6 MBq 67Ga-EDTA), on two occasions,with and without 120 mg orlistat, positioned in the left lateraldecubitus position with their back against a camera. Venousblood samples, for measurement of blood glucose and plasma insulin,glucagon-like peptide-1 and glucose-dependent insulintropicpolypeptide were obtained immediately before, and after, thedrink. 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 comparedwith 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, inhibitionof fat digestion, by orlistat, may exacerbate postprandial glycemia,as a result of more rapid gastric emptying and a diminishedincretin response.
This study was supported by project grants from the Royal AdelaideHospital and the National Health and Medical Research Council(NH&MRC) of Australia. Salary of K.L.J. is derived froma Fellowship jointly awarded by the NH&MRC and DiabetesAustralia. Salary of C.F. is provided by the Florey ResearchFellowship of the Royal Adelaide Hospital.
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K. L. Feltrin, T. J. Little, J. H. Meyer, M. Horowitz, A. J. P. M. Smout, J. Wishart, A. N. Pilichiewicz, T. Rades, I. M. Chapman, and C. Feinle-Bisset Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length
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September 1, 2004;
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[Abstract][Full Text][PDF]
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. 
