Naslov
N-Glycan profile and kidney disease in type 1 diabetes

Autori
Bermingham, Mairead L. ; Colombo, Marco ; McGurnaghan, Stuart J. ; Blackbourn, Luke A.K. ; Vučković, Frano ; Pučić Baković, Maja ; Trbojević- Akmačić, Irena ; Lauc, Gordan ; Agakov, Felix ; Agakova, Anna S. ; Hayward, Caroline ; Klarić, Lucija ; Palmer, Colin N.A. ; Petrie, John R. ; Chalmers, John ; Collier, Andrew ; Green, Fiona ; Lindsay, Robert S. ; Macrury, Sandra ; McKnight, John A. ; Patrick, Alan W. ; Thekkepat, Sandeep ; Gornik, Olga ; McKeigue, Paul M. ; Colhoun, Helen M.

Izvornik
Diabetes care (0149-5992) 41 (2017), 1; 79-87

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
type 1 diabetes

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Interdisciplinarne prirodne znanosti

POVEZANOST RADA