N-Glycan Profile and Kidney Disease in Type 1 Diabetes

Mairead L. Bermingham (Lead / Corresponding author), Marco Colombo, Stuart J. McGurnaghan, Luke A. K. Blackbourn, Frano Vučković, Maja Pučić Baković, Irena Trbojević-Akmačić, Gordan 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. McKnightAlan W. Patrick, Sandeep Thekkepat, Olga Gornik, Paul M. McKeigue, Helen M. Colhoun, on behalf of the SDRN Type 1 Bioresource Investigators

Research output: Contribution to journalArticle

10 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 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.

Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalDiabetes Care
Volume41
Issue number1
Early online date16 Nov 2017
DOIs
Publication statusPublished - Jan 2018

Fingerprint

Kidney Diseases
Type 1 Diabetes Mellitus
Polysaccharides
Diabetic Nephropathies
Albumins
Creatinine
Immunoglobulin G
Linear Models
Serum
Transforming Growth Factors
Glomerular Filtration Rate
Glycosylation
Epidermal Growth Factor Receptor
Glycoproteins
Research Design
Kidney
Research

Keywords

  • Adult
  • Blood Glucose/metabolism
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1/blood
  • Diabetic Nephropathies/blood
  • Female
  • Glomerular Filtration Rate
  • Glycated Hemoglobin A/metabolism
  • Glycoproteins/blood
  • Glycosylation
  • Humans
  • Hyperglycemia/blood
  • Immunoglobulin G/blood
  • Male
  • Middle Aged
  • Polysaccharides/blood
  • Retrospective Studies
  • Sample Size
  • Scotland

Cite this

Bermingham, M. L., Colombo, M., McGurnaghan, S. J., Blackbourn, L. A. K., Vučković, F., Pučić Baković, M., ... on behalf of the 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
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. ; on behalf of the SDRN Type 1 Bioresource Investigators. / N-Glycan Profile and Kidney Disease in Type 1 Diabetes. In: Diabetes Care. 2018 ; Vol. 41, No. 1. pp. 79-87.
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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 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.",
keywords = "Adult, Blood Glucose/metabolism, Cross-Sectional Studies, Diabetes Mellitus, Type 1/blood, Diabetic Nephropathies/blood, Female, Glomerular Filtration Rate, Glycated Hemoglobin A/metabolism, Glycoproteins/blood, Glycosylation, Humans, Hyperglycemia/blood, Immunoglobulin G/blood, Male, Middle Aged, Polysaccharides/blood, Retrospective Studies, Sample Size, Scotland",
author = "Bermingham, {Mairead L.} and Marco Colombo and McGurnaghan, {Stuart J.} and Blackbourn, {Luke A. K.} and Frano Vučković and {Pučić Baković}, Maja and Irena Trbojević-Akmačić and Gordan Lauc and Felix Agakov and Agakova, {Anna S.} and Caroline Hayward and Lucija Klarić 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 {on behalf of the SDRN Type 1 Bioresource Investigators}",
note = "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 FP7Methods for Integrated Analysis of MultipleOmicsDatasets (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 care.diabetesjournals.org Bermingham and Associates 7 Research Fund. H.M.C. is funded by an endowed chair from the AXA Research Fund.",
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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, McKnight, JA, Patrick, AW, Thekkepat, S, Gornik, O, McKeigue, PM, Colhoun, HM & on behalf of the 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

N-Glycan Profile and Kidney Disease in Type 1 Diabetes. / Bermingham, Mairead L. (Lead / Corresponding author); 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.; on behalf of the SDRN Type 1 Bioresource Investigators.

In: Diabetes Care, Vol. 41, No. 1, 01.2018, p. 79-87.

Research output: Contribution to journalArticle

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 - Pučić Baković, Maja

AU - Trbojević-Akmačić, Irena

AU - Lauc, Gordan

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 - on behalf of the SDRN Type 1 Bioresource Investigators

N1 - 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 FP7Methods for Integrated Analysis of MultipleOmicsDatasets (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 care.diabetesjournals.org Bermingham and Associates 7 Research Fund. H.M.C. is funded by an endowed chair from the AXA Research Fund.

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 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.

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 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.

KW - Adult

KW - Blood Glucose/metabolism

KW - Cross-Sectional Studies

KW - Diabetes Mellitus, Type 1/blood

KW - Diabetic Nephropathies/blood

KW - Female

KW - Glomerular Filtration Rate

KW - Glycated Hemoglobin A/metabolism

KW - Glycoproteins/blood

KW - Glycosylation

KW - Humans

KW - Hyperglycemia/blood

KW - Immunoglobulin G/blood

KW - Male

KW - Middle Aged

KW - Polysaccharides/blood

KW - Retrospective Studies

KW - Sample Size

KW - Scotland

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U2 - 10.2337/dc17-1042

DO - 10.2337/dc17-1042

M3 - Article

C2 - 29146600

VL - 41

SP - 79

EP - 87

JO - Diabetes Care

JF - Diabetes Care

SN - 0149-5992

IS - 1

ER -

Bermingham ML, Colombo M, McGurnaghan SJ, Blackbourn LAK, Vučković F, Pučić Baković M et al. N-Glycan Profile and Kidney Disease in Type 1 Diabetes. Diabetes Care. 2018 Jan;41(1):79-87. https://doi.org/10.2337/dc17-1042