Journal
DIABETES CARE
Volume 41, Issue 1, Pages 79-87Publisher
AMER DIABETES ASSOC
DOI: 10.2337/dc17-1042
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Funding
- JDRF [1-SRA-2016-334-Q-R]
- Croatian National Science Foundation [UIP-2014-09-7769]
- EU FP7 Methods for Integrated Analysis of Multiple Omics Datasets (MIMOmics)
- University of Edinburgh
- Diabetes UK
- Chief Scientist Office, Scotland
- JDRF
- endowed chair from the AXA Research Fund
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OBJECTIVEPoorer 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 METHODSUsing 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 HbA(1c), albumin-to-creatinine ratio (ACR), and eGFR slope. Models were adjusted for age, sex, duration of type 1 diabetes, and total serum IgG.RESULTSHigher HbA(1c) 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 x 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 x 10(-4)).CONCLUSIONSHigher HbA(1c) 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- 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.
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