N-Glycan Profile and Kidney Disease in Type 1 Diabetes

Mairead L. Bermingham; Marco Colombo; Stuart J. McGurnaghan; Luke A.K. Blackbourn; Frano Vučković; Maja Pučić Baković; Irena Trbojević-Akmačić; Gordon Lauc; Felix Agakov; Anna S. Agakova; Caroline Hayward; Lucija Klarić; Colin N.A. Palmer; John R. Petrie; John Chalmers; Andrew Collier; Fiona Green; Robert S. Lindsay; Sandra Macrury; John A. McKnight; Alan W. Patrick; Sandeep Thekkepat; Olga Gornik; Paul M. McKeigue; Helen M. Colhoun; Scottish Diabetes Research Network (SDRN) Type 1 Bioresource Investigators

doi:10.2337/dc17-1042

N-Glycan Profile and Kidney Disease in Type 1 Diabetes

Mairead L. Bermingham
, Marco Colombo
, Stuart J. McGurnaghan
, Luke A.K. Blackbourn
, Frano Vučković
, Maja Pučić Baković
, Irena Trbojević-Akmačić
, Gordon Lauc
, Felix Agakov
, Anna S. Agakova
, Caroline Hayward
, Lucija Klarić
, Colin N.A. Palmer
, John R. Petrie
, John Chalmers
, Andrew Collier
, Fiona Green
, Robert S. Lindsay
, Sandra Macrury
, John A. McKnight

Alan W. Patrick, Sandeep Thekkepat, Olga Gornik, Paul M. McKeigue, Helen M. Colhoun, Scottish Diabetes Research Network (SDRN) Type 1 Bioresource Investigators

Research output: Contribution to journal › Article › peer-review

97 Citations (Scopus)

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 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 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.

RESULTS Higher 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 < 3.79×10^-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 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-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.

Original language	English
Pages (from-to)	79-87
Number of pages	9
Journal	Diabetes care
Volume	41
Issue number	1
Early online date	6 Nov 2017
DOIs	https://doi.org/10.2337/dc17-1042
Publication status	Published - Jan 2018
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

type 1 diabetes
N-glycosylation patterns
Kidney disease

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10.2337/dc17-1042Licence: In Copyright

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Bermingham, M. L., Colombo, M., McGurnaghan, S. J., Blackbourn, L. A. K., Vučković, F., Baković, M. P., Trbojević-Akmačić, I., Lauc, G., Agakov, F., Agakova, A. S., Hayward, C., Klarić, L., Palmer, C. N. A., Petrie, J. R., Chalmers, J., Collier, A., Green, F., Lindsay, R. S., Macrury, S., ... Scottish Diabetes Research Network (SDRN) Type 1 Bioresource Investigators (2018). N-Glycan Profile and Kidney Disease in Type 1 Diabetes. Diabetes care, 41(1), 79-87. https://doi.org/10.2337/dc17-1042

@article{668d88ea7ab24650a304fccb0973e337,

title = "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 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.",

keywords = "type 1 diabetes, N-glycosylation patterns, Kidney disease",

author = "Bermingham, \{Mairead L.\} and Marco Colombo and McGurnaghan, \{Stuart J.\} and Blackbourn, \{Luke A.K.\} and Frano Vu{\v c}kovi{\'c} and Bakovi{\'c}, \{Maja Pu{\v c}i{\'c}\} and Irena Trbojevi{\'c}-Akma{\v c}i{\'c} and Gordon Lauc and Felix Agakov and Agakova, \{Anna S.\} and Caroline Hayward and Lucija Klari{\'c} and Palmer, \{Colin N.A.\} and Petrie, \{John R.\} and John Chalmers and Andrew Collier and Fiona Green and Lindsay, \{Robert S.\} and Sandra Macrury and McKnight, \{John A.\} and Patrick, \{Alan W.\} and Sandeep Thekkepat and Olga Gornik and McKeigue, \{Paul M.\} and Colhoun, \{Helen M.\} and \{Scottish Diabetes Research Network (SDRN) Type 1 Bioresource Investigators\}",

year = "2018",

month = jan,

doi = "10.2337/dc17-1042",

language = "English",

volume = "41",

pages = "79--87",

journal = "Diabetes care",

issn = "0149-5992",

publisher = "American Diabetes Association Inc.",

number = "1",

}

Bermingham, ML, Colombo, M, McGurnaghan, SJ, Blackbourn, LAK, Vučković, F, Baković, MP, 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, McKnight, JA, Patrick, AW, Thekkepat, S, Gornik, O, McKeigue, PM, Colhoun, HM & Scottish Diabetes Research Network (SDRN) Type 1 Bioresource Investigators 2018, 'N-Glycan Profile and Kidney Disease in Type 1 Diabetes', Diabetes care, vol. 41, no. 1, pp. 79-87. https://doi.org/10.2337/dc17-1042

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 - https://www.scopus.com/pages/publications/85038936211

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 -

N-Glycan Profile and Kidney Disease in Type 1 Diabetes

Abstract

UN SDGs

Keywords

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