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Wathik Alsalim

Physician

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Glucose-lowering effect of the DPP-4 inhibitor sitagliptin after glucose and non-glucose macronutrient ingestion in non-diabetic subjects.

Author

  • Lena Ohlsson
  • Wathik Alsalim
  • Richard D Carr
  • Andrea Tura
  • Giovanni Pacini
  • Andrea Mari
  • Bo Ahrén

Summary, in English

AIM: Recent studies suggest that the incretin concept is not restricted to glucose ingestion but relevant also after non-glucose macronutrient administration. We therefore hypothesized that raising incretin hormones reduces circulating glucose after both glucose and non-glucose macronutrient ingestion in healthy subjects. MATERIAL AND METHODS: Twelve healthy subjects received the dipeptidyl peptidase-4 inhibitor sitagliptin (100mg) or placebo before ingestion of glucose, fat (olive oil) or protein mix in equicaloric amounts (8 kcal/kg) plus paracetamol (1g). The 120-min AUC of intact GLP-1, glucose, insulin, C-peptide, glucagon and paracetamol, and model-derived insulin secretion (ISR), insulin sensitivity, insulin clearance and glucose absorption were measured. RESULTS: The increased plasma intact GLP-1 levels after each macronutrient was augmented by sitagliptin. This was associated with a robust lowering of glucose: glucose excursion after oral glucose was diminished, and glucose fell below baseline after oral fat and protein. In spite of lower glucose, AUC(C) (-peptide) and ISR did not differ significantly between sitagliptin and placebo after any macronutrient. AUC(glucagon) , insulin sensitivity and insulin clearance were also not different between sitagliptin and placebo. Glucose absorption after oral glucose was reduced by sitagliptin, whereas AUC(paracetamol) was not statistically different between sitagliptin and placebo. CONCLUSIONS: Physiological elevation of intact GLP-1 levels after ingestion of glucose and non-glucose macronutrients is robustly glucose-lowering in healthy subjects. Hence, the incretin concept is not restricted to glucose ingestion in normal physiology. The glucose-lowering action of sitagliptin at these low glucose levels in healthy subjects may have complex mechanisms, involving both islet-dependent and islet-independent mechanisms.

Department/s

  • Medicine, Lund
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2013

Language

English

Pages

531-537

Publication/Series

Diabetes, Obesity and Metabolism

Volume

15

Issue

6

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Endocrinology and Diabetes

Status

Published

ISBN/ISSN/Other

  • ISSN: 1462-8902