TY - JOUR
T1 - N-Glycan Profile and Kidney Disease in Type 1 Diabetes
AU - Bermingham, Mairead L.
AU - Colombo, Marco
AU - McGurnaghan, Stuart J.
AU - Blackbourn, Luke A. K.
AU - Vučković, Frano
AU - Pučić Baković, Maja
AU - Trbojević-Akmačić, Irena
AU - Lauc, Gordan
AU - Agakov, Felix
AU - Agakova, Anna S.
AU - Hayward, Caroline
AU - Klarić, Lucija
AU - Palmer, Colin N. A.
AU - Petrie, John R.
AU - Chalmers, John
AU - Collier, Andrew
AU - Green, Fiona
AU - Lindsay, Robert S.
AU - Macrury, Sandra
AU - McKnight, John A.
AU - Patrick, Alan W.
AU - Thekkepat, Sandeep
AU - Gornik, Olga
AU - McKeigue, Paul M.
AU - Colhoun, Helen M.
AU - on behalf of the SDRN Type 1 Bioresource Investigators
N1 - This study was supported by funding from the Juvenile Diabetes Research Foundation (grant 1-SRA-2016-334-Q-R) and the Croatian National Science Foundation (grant UIP-2014-09-7769). F.A. and A.S.A. report grants from EU FP7Methods for Integrated Analysis of MultipleOmicsDatasets (MIMOmics). L.K. reports grants from University of Edinburgh. C.N.A.P. reports grants from Diabetes UK and Chief Scientist Office, Scotland, during the conduct of the study. J.R.P. reports grants from the Juvenile Diabetes care.diabetesjournals.org Bermingham and Associates 7 Research Fund. H.M.C. is funded by an endowed chair from the AXA Research Fund.
PY - 2018/1
Y1 - 2018/1
N2 - Objective: Poorer glycemic control in type 1 diabetes may alter N-glycosylation patterns on circulating glycoproteins, and these alterations may be linked with diabetic kidney disease (DKD). We investigated associations between N-glycans and glycemic control and renal function in type 1 diabetes.Research Design and Methods: Using serum samples from 818 adults who were considered to have extreme annual loss in estimated glomerular filtration rate (eGFR; i.e., slope) based on retrospective clinical records, from among 6,127 adults in the Scottish Diabetes Research Network Type 1 Bioresource Study, we measured total and IgG-specific N-glycan profiles. This yielded a relative abundance of 39 total (GP) and 24 IgG (IGP) N-glycans. Linear regression models were used to investigate associations between N-glycan structures and HbA1c, albumin-to-creatinine ratio (ACR), and eGFR slope. Models were adjusted for age, sex, duration of type 1 diabetes, and total serum IgG.Results: Higher HbA1c was associated with a lower relative abundance of simple biantennary N-glycans and a higher relative abundance of more complex structures with more branching, galactosylation, and sialylation (GP12, 26, 31, 32, and 34, and IGP19 and 23; all P < 3.79 × 10(-4)). Similar patterns were seen for ACR and greater mean annual loss of eGFR, which were also associated with fewer of the simpler N-glycans (all P < 3.79 × 10(-4)).Conclusions: Higher HbA1c in type 1 diabetes is associated with changes in the serum N-glycome that have elsewhere been shown to regulate the epidermal growth factor receptor and transforming growth factor-β pathways that are implicated in DKD. Furthermore, N-glycans are associated with ACR and eGFR slope. These data suggest that the role of altered N-glycans in DKD warrants further investigation.
AB - Objective: Poorer glycemic control in type 1 diabetes may alter N-glycosylation patterns on circulating glycoproteins, and these alterations may be linked with diabetic kidney disease (DKD). We investigated associations between N-glycans and glycemic control and renal function in type 1 diabetes.Research Design and Methods: Using serum samples from 818 adults who were considered to have extreme annual loss in estimated glomerular filtration rate (eGFR; i.e., slope) based on retrospective clinical records, from among 6,127 adults in the Scottish Diabetes Research Network Type 1 Bioresource Study, we measured total and IgG-specific N-glycan profiles. This yielded a relative abundance of 39 total (GP) and 24 IgG (IGP) N-glycans. Linear regression models were used to investigate associations between N-glycan structures and HbA1c, albumin-to-creatinine ratio (ACR), and eGFR slope. Models were adjusted for age, sex, duration of type 1 diabetes, and total serum IgG.Results: Higher HbA1c was associated with a lower relative abundance of simple biantennary N-glycans and a higher relative abundance of more complex structures with more branching, galactosylation, and sialylation (GP12, 26, 31, 32, and 34, and IGP19 and 23; all P < 3.79 × 10(-4)). Similar patterns were seen for ACR and greater mean annual loss of eGFR, which were also associated with fewer of the simpler N-glycans (all P < 3.79 × 10(-4)).Conclusions: Higher HbA1c in type 1 diabetes is associated with changes in the serum N-glycome that have elsewhere been shown to regulate the epidermal growth factor receptor and transforming growth factor-β pathways that are implicated in DKD. Furthermore, N-glycans are associated with ACR and eGFR slope. These data suggest that the role of altered N-glycans in DKD warrants further investigation.
KW - Adult
KW - Blood Glucose/metabolism
KW - Cross-Sectional Studies
KW - Diabetes Mellitus, Type 1/blood
KW - Diabetic Nephropathies/blood
KW - Female
KW - Glomerular Filtration Rate
KW - Glycated Hemoglobin A/metabolism
KW - Glycoproteins/blood
KW - Glycosylation
KW - Humans
KW - Hyperglycemia/blood
KW - Immunoglobulin G/blood
KW - Male
KW - Middle Aged
KW - Polysaccharides/blood
KW - Retrospective Studies
KW - Sample Size
KW - Scotland
UR - http://www.scopus.com/inward/record.url?scp=85038936211&partnerID=8YFLogxK
U2 - 10.2337/dc17-1042
DO - 10.2337/dc17-1042
M3 - Article
C2 - 29146600
SN - 0149-5992
VL - 41
SP - 79
EP - 87
JO - Diabetes Care
JF - Diabetes Care
IS - 1
ER -
