Ignite Creation Date:
2024-05-05 @ 11:34 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00082238
Status:
COMPLETED
Last Update Posted:
2018-03-14
First Post:
2004-05-03
Brief Title:
Increased Gluconeogenesis is One Cause of Cystic Fibrosis Related Diabetes CFRD
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Study Overview
Official Title:
Increased Gluconeogenesis is One Cause of CFRD
Status:
COMPLETED
Status Verified Date:
2018-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 1-13Cleucine and 15N2urea 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
Detailed Description:
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 1-13Cleucine and 15N2urea 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 applicants 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
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 applicants 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01DK058603 | NIH | None | httpsreporternihgovquickSearchR01DK058603 |