title: IGF-Binding Proteins in Type-1 Diabetes Are More Severely Altered in the Presence of Complications.
abstract: OBJECTIVE
  Reduced levels of free and total insulin-like growth factor 1 (IGF-I) have been observed in type-1 diabetes (T1D) patients. The bioavailability of IGF-I from the circulation to the target cells is controlled by multifunctional IGF-binding proteins (IGFBPs). The aim of this study was to profile serum IGFBPs in T1D and its complications.
  
  
  METHODS
  We measured the IGFBP levels in 3662 patient serum samples from our ongoing Phenome and Genome of Diabetes Autoimmunity (PAGODA) study. IGFBP levels of four different groups of T1D patients (with 0, 1, 2, and ≥3 complications) were compared with healthy controls.
  
  
  RESULTS
  Three serum IGFBPs (IGFBP-1, -2, and -6) are significantly higher in T1D patients, and these alterations are greater in the presence of diabetic complications. IGFBP-3 is lower in patients with diabetic complications. Analyses using quintiles revealed that risk of T1D complications increases with increasing concentrations of IGFBP-2 (fifth quintile ORs: 18-60, p < 10(-26)), IGFBP-1 (fifth quintile ORs: 8-20, p < 10(-15)), and IGFBP-6 (fifth quintile ORs: 3-148, p < 10(-3)). IGFBP-3 has a negative association with T1D complications (fifth quintile ORs: 0.12-0.25, p < 10(-5)).
  
  
  CONCLUSIONS
  We found that elevated serum levels of IGFBP-1, -2, and -6 were associated with T1D, and its complications and IGFBP-3 level was found to be decreased in T1D with complications. Given the known role of these IGFBPs, the overall impact of these alterations suggests a negative effect on IGF signaling.
authors: Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, USA; Department of Biostatistics and Epidemiology, Augusta University, Augusta, GA, USA.
authors: Ashok
authors: A
authors: Sharma
authors: Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, USA; Department of Pathology, Augusta University, Augusta, GA, USA.
authors: Sharad
authors: S
authors: Purohit
authors: Center for Biotechnology and Genomic Medicine, Augusta University , Augusta, GA , USA.
authors: Shruti
authors: S
authors: Sharma
authors: Center for Biotechnology and Genomic Medicine, Augusta University , Augusta, GA , USA.
authors: Shan
authors: S
authors: Bai
authors: Center for Biotechnology and Genomic Medicine, Augusta University , Augusta, GA , USA.
authors: Wenbo
authors: W
authors: Zhi
authors: Center for Biotechnology and Genomic Medicine, Augusta University , Augusta, GA , USA.
authors: Sithara Raju
authors: SR
authors: Ponny
authors: Center for Biotechnology and Genomic Medicine, Augusta University , Augusta, GA , USA.
authors: Diane
authors: D
authors: Hopkins
authors: Center for Biotechnology and Genomic Medicine, Augusta University , Augusta, GA , USA.
authors: Leigh
authors: L
authors: Steed
authors: Pediatric Endocrine Associates , Atlanta, GA , USA.
authors: Bruce
authors: B
authors: Bode
authors: Pediatric Endocrine Associates , Atlanta, GA , USA.
authors: Stephen W
authors: SW
authors: Anderson
authors: Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, USA; Department of Pathology, Augusta University, Augusta, GA, USA.
authors: Jin-Xiong
authors: JX
authors: She
keywords: IGF-1; IGF-binding proteins; IGFBP; diabetes mellitus; diabetic complications; insulin-like growth factor 1; type 1