N-glycan profile and kidney disease in type 1 diabetes

Bermingham, M. L. et al. (2018) N-glycan profile and kidney disease in type 1 diabetes. Diabetes Care, 41(1), pp. 79-87. (doi: 10.2337/dc17-1042) (PMID:29146600)

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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.

Item Type:Articles
Additional Information: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 FP7 Methods for Integrated Analysis of Multiple Omics Datasets (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 Research Fund. H.M.C. is funded by an endowed chair from the AXA Research Fund.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lindsay, Dr Robert and Petrie, Professor John
Authors: Bermingham, M. L., Colombo, M., McGurnaghan, S. J., Blackbourn, L. A.K., Vučković, F., Pučić Baković, M., Trbojević-Akmačić, I., Lauc, G., Agakov, F., Agakova, A. S., Hayward, C., Klarić, L., Palmer, C., Petrie, J. R., Chalmers, J., Collier, A., Green, F., Lindsay, R. S., Macrury, S., McKnight, J. A., Patrick, A. W., Thekkepat, S., Gornik, O., McKeigue, P. M., and Colhoun, H. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Diabetes Care
Publisher:American Diabetes Association
ISSN:0149-5992
ISSN (Online):1935-5548
Published Online:16 November 2017

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