TY - JOUR
T1 - N-Glycan Profile and Kidney Disease in Type 1 Diabetes
AU - Bermingham, Mairead L.
AU - Colombo, Marco
AU - McGurnaghan, Stuart J.
AU - Blackbourn, Luke A.K.
AU - Vučković, Frano
AU - Baković, Maja Pučić
AU - Trbojević-Akmačić, Irena
AU - Lauc, Gordon
AU - Agakov, Felix
AU - Agakova, Anna S.
AU - Hayward, Caroline
AU - Klarić, Lucija
AU - Palmer, Colin N.A.
AU - Petrie, John R.
AU - Chalmers, John
AU - Collier, Andrew
AU - Green, Fiona
AU - Lindsay, Robert S.
AU - Macrury, Sandra
AU - McKnight, John A.
AU - Patrick, Alan W.
AU - Thekkepat, Sandeep
AU - Gornik, Olga
AU - McKeigue, Paul M.
AU - Colhoun, Helen M.
AU - Scottish Diabetes Research Network (SDRN) Type 1 Bioresource Investigators
PY - 2018/1
Y1 - 2018/1
N2 - 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 from818 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 regressionmodelswere used to investigate associations betweenN-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 patternswere seen for ACR and greatermean 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-b pathways that are implicated in DKD. Furthermore, N-glycans are associatedwithACR and eGFR slope. These data suggest that the role of altered N-glycans in DKD warrants further investigation.
AB - 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 from818 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 regressionmodelswere used to investigate associations betweenN-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 patternswere seen for ACR and greatermean 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-b pathways that are implicated in DKD. Furthermore, N-glycans are associatedwithACR and eGFR slope. These data suggest that the role of altered N-glycans in DKD warrants further investigation.
KW - type 1 diabetes
KW - N-glycosylation patterns
KW - Kidney disease
UR - http://www.scopus.com/inward/record.url?scp=85038936211&partnerID=8YFLogxK
U2 - 10.2337/dc17-1042
DO - 10.2337/dc17-1042
M3 - Article
SN - 0149-5992
VL - 41
SP - 79
EP - 87
JO - Diabetes care
JF - Diabetes care
IS - 1
ER -
