Increased Gluconeogenesis is One Cause of Cystic Fibrosis Related Diabetes (CFRD)
Information source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cystic Fibrosis; Diabetes Mellitus
Intervention: Ibuprofen (Drug)
Phase: N/A
Status: Completed
Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Summary
People with CF have a high incidence of diabetes, called CFRD. CFRD is an important cause of
worsened morbidity and mortality, thus understanding the pathophysiology underlying its
development is imperative. Insulin deficiency has been well recognized as one cause of CFRD;
however the clinical presentation and studies of pathogenesis indicate that the etiology is
more complex. There is strong evidence that normal metabolism of carbohydrate, protein and
fat is altered in CF. We believe that the inflammatory response to chronic underlying lung
disease is responsible for insulin resistance and alters substrate metabolism, and that
these changes, in addition to insulin deficiency cause CFRD. Our global hypothesis is
that hyperglycemia is caused, in part, by high rates of gluconeogenesis resulting from
excessive amino acid substrate availability caused by cytokine-mediated protein catabolism.
We further hypothesize that inflammation alters normal fatty acid metabolism leading to
lipogenesis, an energy wasteful pathway. We will recruit 24 adult CF subjects and 10
controls (similar in distribution in lean tissue mass, age and gender) and will categorize
them according to glucose tolerance (OGTT), as well as insulin secretion and insulin
sensitivity using the Tolbutamide-stimulated IVGTT and the Minimal Model. Clinical status
will be characterized by measuring pulmonary function and modified NIH scores, in addition
to measuring levels of circulating cytokines. Gluconeogenesis (GNG) will be quantified by
measuring the incorporation 2H into the 2nd, 5th and 6th carbons of glucose. Amino acid
turnover rates will be measured using stable isotopes of lactate and alanine and whole body
protein turnover (WBPT) will be measured using [1-13C]leucine and [15N2]urea. Fat
metabolism will be evaluated by measuring ketone body turnover using stable isotopes, and by
quantifying lipogenesis using the isotopomer equilibration method. Key enzymes of fatty
acid metabolism will also be measured. We will utilize indirect calorimetry to measure
resting energy expenditure. Subjects will be recruited from the CF centers at the University
of Texas- Southwestern and the South Central CF Consortium.
Our proposal is intended to better describe the unique metabolism of people with CF, and to
provide a comprehensive evaluation of pathophysiologic changes which contribute to the
development of CFRD and to wasting; and are part of the applicant's long-range goal which is
to identify the underlying causes of CF related diabetes and catabolism so that
disease-specific therapies can be developed. We fully expect that the proposed studies will
provide new and important information.
Clinical Details
Official title: Increased Gluconeogenesis is One Cause of CFRD
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Primary Purpose: Diagnostic
Eligibility
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Both.
Criteria:
cystic fibrosis with any type of glucose tolerance
Locations and Contacts
University of Texas Southwestern, Dallas, Texas 75390-9063, United States
Additional Information
Starting date: March 2003
Last updated: March 1, 2010
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