Increased Gluconeogenesis is One Cause of Cystic Fibrosis Related Diabetes (CFRD)

NCT00082238 | Completed

• 2 other identifiers: 58603DK (completed)R01DK058603
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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 \[1-13C\]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.

Conditions

Cystic Fibrosis; Diabetes Mellitus

Study Arms (2)

Cystic fibrosis (CF)

EXPERIMENTAL

Other: Stable isotopes

Healthy volunteers

ACTIVE COMPARATOR

Other: Stable isotopes

Interventions

Stable isotopes OTHER

Stable isotopes were used to quantify gluconeogenesis GNG, hepatic glucose production (HGP), and protein breakdown.

Cystic fibrosis (CF); Healthy volunteers

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

cystic fibrosis with any type of glucose tolerance

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

University of Texas Southwestern

Dallas, Texas, 75390-9063, United States

Location

Related Publications (1)

• Hardin DS, Ahn C, Rice J, Rice M, Rosenblatt R. Elevated gluconeogenesis and lack of suppression by insulin contribute to cystic fibrosis-related diabetes. J Investig Med. 2008 Mar;56(3):567-73. doi: 10.2310/JIM.0b013e3181671788.

  PMID: 18418124 RESULT

MeSH Terms

Conditions

Cystic Fibrosis; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Dana S Hardin, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2004
• First Posted: May 5, 2004
• Study Start: March 1, 2003
• Primary Completion: March 1, 2005
• Study Completion: March 1, 2005
• Last Updated: March 14, 2018

Record last verified: 2018-03

Locations

US (1)