TY - JOUR
T1 - IGF-binding proteins in type-1 diabetes are more severely altered in the presence of complications
AU - Sharma, Ashok Kumar
AU - Purohit, Sharad B
AU - Sharma, Shruti
AU - Bai, Shan
AU - Zhi, Wenbo
AU - Ponny, Sithara Raju
AU - Hopkins, Diane
AU - Steed, Leigh
AU - Bode, Bruce
AU - Anderson, Stephen W.
AU - She, Jin-Xiong
N1 - Publisher Copyright:
© 2016 Sharma, Purohit, Sharma, Bai, Zhi, Ponny, Hopkins, Steed, Bode, Anderson and She.
PY - 2016
Y1 - 2016
N2 - Aims: 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. Design: 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). Conclusion: 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.
AB - Aims: 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. Design: 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). Conclusion: 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.
KW - Diabetes mellitus
KW - Diabetic complications
KW - IGF-1
KW - IGF-binding proteins
KW - IGFBP
KW - Insulin-like growth factor 1
KW - Type 1
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U2 - 10.3389/fendo.2016.00002
DO - 10.3389/fendo.2016.00002
M3 - Article
AN - SCOPUS:84962514834
SN - 1664-2392
VL - 7
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
IS - JAN
M1 - 2
ER -