Predictors of Circulating Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-Binding Protein-3 in Critical Illness

Details

• Personal Author:
  Ahasic AM ; Bajwa EK ; Christiani, David C. ; Mantzoros CS ; Su L ; Tejera P ; Thompson BT ; Wei Y
• Description:
  Objective: To characterize predictors of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in acute critical illness with the hypothesis that acute factors associated with critical illness will more strongly predict circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 than chronic clinical or genetic factors. Design: Observational study nested within a large prospective study using multivariable linear regression to model circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 with acute and chronic clinical variables, and genotype from five polymorphisms in insulin-like growth factor pathway genes. Setting: ICUs from two large academic medical centers. Patients: Five hundred forty-three Caucasian patients with risk factors for acute respiratory distress syndrome and available plasma from early in critical illness. Interventions: None. Measurements and Main Results: Total insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 were measured in plasma using IMMULITE assays (Siemens, Malvern, PA). We examined age, gender, body mass index, cirrhosis, and diabetes, as well as Acute Physiology, Age, and Chronic Health Evaluation III score, acute hepatic dysfunction, pneumonia and aspiration, sepsis/septic shock, acute respiratory distress syndrome, and receipt of corticosteroids. Body mass index, cirrhosis, and acute respiratory distress syndrome were strongly associated with insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels; Acute Physiology, Age, and Chronic Health Evaluation III was strongly associated with insulin-like growth factor-1 levels; and age was strongly associated with insulin-like growth factor-binding protein-3. Five polymorphisms (IGF1: rs1520220, rs35767, rs2946834; IGFBP1: rs4619; IGFBP3: rs2854746) were analyzed for associations with plasma levels. When genotypes were added to models, rs2854746 was significantly associated with plasma insulin-like growth factor-binding protein-3. Genotype explained an additional 2% of variability with an overall adjusted R-square of 0.18. Conclusions: Despite the acute derangements of critical illness, both acute and chronic health factors significantly influence circulating levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 early in critical illness. rs2854746 is also significantly associated with insulin-like growth factor-binding protein-3 levels in this ICU cohort. Overall, phenotypic and genotypic factors explained only a modest amount of variability in insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. Further research is needed to understand how to apply these findings to patient care. [Description provided by NIOSH]
• Subjects:
  Blood Cohort Studies Genetics Growth Hematologic Diseases Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Acute Respiratory Distress Syndrome Blood Sugar Disorders Cohort Studies Critical Care Genes Genotype Growth Factors Insulin-like Growth Factor-1 Insulin-like Growth Factor-binding Protein-3 Molecular Epidemiology Morphology Polymorphisms Proteins Respiratory System Disorders Single-nucleotide

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• ISSN:
  0090-3493
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Connecticut ; Massachusetts ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  43
• Issue:
  12
• NIOSHTIC Number:
  nn:20052821
• Citation:
  Crit Care Med 2015 Dec; 43(12):2651-2659
• Contact Point Address:
  Amy M. Ahasic, MD, MPH, FCCP, Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
• Email:
  amy.ahasic@yale.edu
• Federal Fiscal Year:
  2016
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Critical Care Medicine
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:02697c850ad7421e333c40f85b9cd98b77d61ec77ab1ef3be0c6b7355f89fe85341899addd8dba7ef66825a24699c4f97d0d5a13a5e7912f6ee947fd98b25e78
• Download URL:
  https://stacks.cdc.gov/view/cdc/212289/cdc_212289_DS1.pdf
• File Type:
  [PDF - 202.96 KB ]