Abstract
Aims/hypothesisHigh 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.MethodsWe 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.ResultsWe 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/interpretationTaken together, circulating MBL levels are associated with diabetic nephropathy and are dependent on glycaemic control, possibly in an MBL2-genotype-dependent manner.
Highlights
High levels of circulating mannan-binding lectin (MBL) have been demonstrated to be associated with the clinicalDiabetologia (2016) 59:853–858 manifestation of type 1 diabetes [1] and the development of diabetic nephropathy [2]
Diabetic-nephropathy-associated circulating MBL levels normalise after simultaneous pancreas–kidney (SPK), but not after kidney transplantation alone Given that SPK makes the patients normoglycaemic and restores kidney function, we sought to determine whether
MBL levels associate with vascular endothelial growth factor (VEGF) levels in a polymorphismdependent manner When patients were divided into wildtype MBL and MBL polymorphism groups, it was clear that VEGF levels increased after SPK in patients with an MBL polymorphism (Fig. 1e)
Summary
High levels of circulating mannan-binding lectin (MBL) have been demonstrated to be associated with the clinicalDiabetologia (2016) 59:853–858 manifestation of type 1 diabetes [1] and the development of diabetic nephropathy [2]. High levels of circulating mannan-binding lectin (MBL) have been demonstrated to be associated with the clinical. Enhanced glycation results in increased MBL activity and the subsequent activation of the complement system [4] and high levels of cytokines specific to type 1 diabetes [5]. Specific single nucleotide polymorphisms (SNPs) in the MBL2 gene and promoter region result in inter-individual variations in circulating levels of functional MBL (0–4,000 μg/l). Diabetes mellitus is strongly associated with microvascular complications (including retinopathy, neuropathy and nephropathy), and vasculopathy resulting from hyperglycaemia has been shown to be dependent on MBL and lectin complement pathway activation [9]
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