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N-Glycan Profile and Kidney Disease in Type 1 Diabetes.

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.

journal_name

Diabetes Care

journal_title

Diabetes care

authors

Bermingham ML,Colombo M,McGurnaghan SJ,Blackbourn LAK,Vučković F,Pučić Baković M,Trbojević-Akmačić I,Lauc G,Agakov F,Agakova AS,Hayward C,Klarić L,Palmer CNA,Petrie JR,Chalmers J,Collier A,Green F,Lindsay RS,Macrury S

doi

10.2337/dc17-1042

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

79-87

issue

eissn

0149-5992

issn

1935-5548

pii

dc17-1042

journal_volume

pub_type

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N-Glycan Profile and Kidney Disease in Type 1 Diabetes.