DPP-IV Inhibition Prior to Development of Diabetes in Patients With Cystic Fibrosis
Status:
Unknown status
Trial end date:
2016-06-01
Target enrollment:
Participant gender:
Summary
Cystic fibrosis related diabetes (CFRD) is a common co-morbidity in patients with CF. The
underlying pathophysiology of cystic fibrosis related diabetes (CFRD) is still a matter of
investigation. In addition to localized tissue damage developing similar to that of the
exocrine pancreas, other mechanisms may be involved. We have shown that a potential
contributing factor to the patho-physiology of CFRD may be an abnormal gut derived hormonal
profile, specifically of lower incretin hormone responses, prior to development of CFRD.
We propose that an altered incretin response, probably due to impaired interaction of
nutrients with the gut mucosa due to thickened secretions, may play a role in the development
of the disease. Specifically, low GIP and GLP-1, may explain the poor β-cell function
observed in these patients prior to CFRD appearance. These incretins have known trophic
effects on β-cells, and thus their lower levels may contribute to the development of
quantitative as well as qualitative defects in β-cell function and thus may lead to the
development of CFRD. Thus, increasing levels of these incretins using a DPP-IV inhibitor may
improve glucose metabolism and delay/prevent the development of CFRD.
We hypothesize that Saxagliptin will increase the oDI compared to placebo and will thus
provide relative protection from diabetes development and in addition we expect that
Saxagliptin will lead to overall increased insulin concentrations and thus shift the
metabolic milieu to a more anabolic state. This will manifest as weight gain and reduction in
inflammation.