N-Glycan Profile and Kidney Disease in Type 1 Diabetes

Mairead L. Bermingham (Lead / Corresponding author), Marco Colombo, Stuart J. McGurnaghan, Luke A. K. Blackbourn, Frano Vučković, Maja Pučić Baković, Irena Trbojević-Akmačić, Gordan Lauc, Felix Agakov, Anna S. Agakova, Caroline Hayward, Lucija Klarić, Colin N. A. Palmer, John R. Petrie, John Chalmers, Andrew Collier, Fiona Green, Robert S. Lindsay, Sandra Macrury, John A. McKnightAlan W. Patrick, Sandeep Thekkepat, Olga Gornik, Paul M. McKeigue, Helen M. Colhoun, on behalf of the SDRN Type 1 Bioresource Investigators

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalDiabetes Care
Volume41
Issue number1
Early online date16 Nov 2017
DOIs
Publication statusPublished - Jan 2018

Keywords

  • Adult
  • Blood Glucose/metabolism
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1/blood
  • Diabetic Nephropathies/blood
  • Female
  • Glomerular Filtration Rate
  • Glycated Hemoglobin A/metabolism
  • Glycoproteins/blood
  • Glycosylation
  • Humans
  • Hyperglycemia/blood
  • Immunoglobulin G/blood
  • Male
  • Middle Aged
  • Polysaccharides/blood
  • Retrospective Studies
  • Sample Size
  • Scotland

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