N-Glycan Profile and Kidney Disease in Type 1 Diabetes

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 - https://www.scopus.com/pages/publications/85038936211

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 -