TY - JOUR
T1 - Simultaneous pancreas–kidney transplantation in patients with type 1 diabetes reverses elevated MBL levels in association with MBL2 genotype and VEGF expression
AU - Bijkerk, Roel
AU - van der Pol, Pieter
AU - Khairoun, Meriem
AU - van Gijlswijk-Jansen, Danielle J.
AU - Lievers, Ellen
AU - de Vries, Aiko P.J.
AU - de Koning, Eelco J.
AU - de Fijter, Hans W.
AU - Roelen, Dave L.
AU - Vossen, Rolf H.A.M.
AU - van Zonneveld, Anton Jan
AU - van Kooten, Cees
AU - Reinders, Marlies E.J.
N1 - Funding Information:
This work was supported by the Dutch Kidney Foundation (grant KSTP 11.005).
Publisher Copyright:
© 2016, The Author(s).
PY - 2016/4
Y1 - 2016/4
N2 - Aims/hypothesis: High levels of circulating mannan-binding lectin (MBL) are associated with the development of diabetic nephropathy and hyperglycaemia-induced vasculopathy. Here, we aimed to assess the effect of glycaemic control on circulating levels of MBL and the relationship of these levels with vascular damage. Methods: We assessed MBL levels and corresponding MBL2 genotype, together with vascular endothelial growth factor (VEGF) levels as a marker of vascular damage, in type 1 diabetes patients with diabetic nephropathy before and after simultaneous pancreas–kidney (SPK) transplantation. We included diabetic nephropathy patients (n = 21), SPK patients (n = 37), healthy controls (n = 19), type 1 diabetes patients (n = 15) and diabetic nephropathy patients receiving only a kidney transplant (n = 15). Fourteen diabetic nephropathy patients were followed up for 12 months after SPK. Results: We found elevated circulating MBL levels in diabetic nephropathy patients, and a trend towards elevated circulating MBL levels in type 1 diabetes patients, compared with healthy control individuals. MBL levels in SPK patients completely normalised and our data indicate that this predominantly occurs in patients with a polymorphism in the MBL2 gene. By contrast, MBL levels in kidney transplant only patients remained elevated, suggesting that glycaemic control but not reversal of renal failure is associated with decreased MBL levels. In line, levels of glucose and HbA1c, but not creatinine levels and estimated GFR, were correlated with MBL levels. VEGF levels were associated with levels of MBL and HbA1c in an MBL-polymorphism-dependent manner. Conclusions/interpretation: Taken together, circulating MBL levels are associated with diabetic nephropathy and are dependent on glycaemic control, possibly in an MBL2-genotype-dependent manner.
AB - Aims/hypothesis: High levels of circulating mannan-binding lectin (MBL) are associated with the development of diabetic nephropathy and hyperglycaemia-induced vasculopathy. Here, we aimed to assess the effect of glycaemic control on circulating levels of MBL and the relationship of these levels with vascular damage. Methods: We assessed MBL levels and corresponding MBL2 genotype, together with vascular endothelial growth factor (VEGF) levels as a marker of vascular damage, in type 1 diabetes patients with diabetic nephropathy before and after simultaneous pancreas–kidney (SPK) transplantation. We included diabetic nephropathy patients (n = 21), SPK patients (n = 37), healthy controls (n = 19), type 1 diabetes patients (n = 15) and diabetic nephropathy patients receiving only a kidney transplant (n = 15). Fourteen diabetic nephropathy patients were followed up for 12 months after SPK. Results: We found elevated circulating MBL levels in diabetic nephropathy patients, and a trend towards elevated circulating MBL levels in type 1 diabetes patients, compared with healthy control individuals. MBL levels in SPK patients completely normalised and our data indicate that this predominantly occurs in patients with a polymorphism in the MBL2 gene. By contrast, MBL levels in kidney transplant only patients remained elevated, suggesting that glycaemic control but not reversal of renal failure is associated with decreased MBL levels. In line, levels of glucose and HbA1c, but not creatinine levels and estimated GFR, were correlated with MBL levels. VEGF levels were associated with levels of MBL and HbA1c in an MBL-polymorphism-dependent manner. Conclusions/interpretation: Taken together, circulating MBL levels are associated with diabetic nephropathy and are dependent on glycaemic control, possibly in an MBL2-genotype-dependent manner.
UR - https://www.scopus.com/pages/publications/84959497569
U2 - 10.1007/s00125-015-3858-3
DO - 10.1007/s00125-015-3858-3
M3 - Article
C2 - 26768002
AN - SCOPUS:84959497569
SN - 0012-186X
VL - 59
SP - 853
EP - 858
JO - Diabetologia
JF - Diabetologia
IS - 4
ER -
