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Low Insulin-like Growth Factor-1 Influences Fatigue and Quality of Life in Children With Inflammatory Bowel Disease

Lucia Casadonte, Chantal J.*; Brown, Jeffrey*; Strople, Jennifer*; Neighbors, Katie*; Fei, Lin; Alonso, Estella M.*

Journal of Pediatric Gastroenterology and Nutrition: November 2018 - Volume 67 - Issue 5 - p 616–621
doi: 10.1097/MPG.0000000000002057
Original Article: Gastroenterology: Inflammatory Bowel Disease

Objective: Fatigue is common among patients with inflammatory bowel disease (IBD). Proinflammatory cytokines are elevated in chronic inflammation and can induce “sickness behaviors,” such as fatigue. Chronic inflammatory states also lead to growth hormone resistance, demonstrated by low levels of insulin-like growth factor (IGF-1) and elevated growth hormone. This study evaluated the relationship between IGF-1, proinflammatory cytokine levels, and fatigue in patients with IBD.

Methods: In this prospective study children with IBD, ages 10 to 16 years, were recruited from a subspecialty ambulatory clinic. Participants and their parents completed age-appropriate generic and disease-specific health-related quality of life (HRQOL) instruments. Serum samples obtained at the same encounter were analyzed for Th17 cytokine and IGF-1 levels. HRQOL scores were compared to a healthy sample and HRQOL scores and cytokine levels were compared by IGF-1 z score quartiles.

Results: A total of 67 patients with IBD were recruited, median age of 13.7 years (interquartile range, 11.7–15.3). Forty-eight (72%) had inactive disease based on Physician Global Assessment. Patients with IBD reported lower generic HRQOL (P = 0.0006) and more fatigue (P = 0.0004) than a healthy sample. Patients with IGF-1 z scores in the lowest quartile had significantly lower disease-specific HRQOL (P = 0.01) and more fatigue (P = 0.02) than the remainder of the cohort. Serum interleukin (IL)-10, IL-17A, IL-6, and interferon-γ were significantly higher in patients with IBD with IGF-1 z scores in the lowest quartile (P < 0.05).

Conclusions: Children with subclinical IBD experience more fatigue and lower generic HRQOL than healthy children. Lower IGF-1 z scores are associated with more fatigue, and this relationship may be mediated through proinflammatory cytokines.

*Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Northwestern Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL

Department of Pediatrics, Division of Biostatistics and Epidemiology, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Address correspondence and reprint requests to Chantal J. Lucia Casadonte, MD, Pediatric Gastroenterology, The University of Kansas, 3901 Rainbow Blvd, Mail Stop 4004 Kansas City, KS 66160 (e-mail:

Received 20 December, 2017

Accepted 11 May, 2018

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (

This work was made possible by a grant from the Scoby Family.

The authors report no conflicts of interest.

© 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,