Elevated MBL Levels in Type 1 Diabetic Patients Are Reversed After Simultaneous Pancreas-Kidney Transplantation.

Abstract

Aim: High levels of circulating Mannan-binding lectin (MBL) are associated with the development of diabetic nephropathy (DN). MBL is an essential component of the acute-phase immune response and initiates the lectin pathway of complement upon binding sugar moieties. In animals, an injurious effect of MBL on diabetic kidney changes has been observed and vasculopathy resulting from hyperglycemia has been shown to be dependent on MBL and lectin complement pathway activation. In humans, the effect of diabetic control on circulating levels of MBL has not been studied so far. Simultaneous pancreas-kidney transplantation (SPK) is an advanced treatment option for type I diabetes (T1D) patients with diabetic nephropathy. By assessing MBL in healthy control subjects and T1D patients before and following SPK, we studied the effect of T1D and SPK on the circulating levels of MBL. Methods: Circulating MBL levels were assessed using sandwich ELISA in plasma of DN (n=21) and SPK patients (n=37), healthy controls (n=19) and DM1 patients (n=15, DM ≥ 40 mL/min). To differentiate between diabetic control and renal failure as possible causes for change in the MBL levels, a subgroup of DN patients receiving a kidney but no pancreas transplant (n=15) were included. In addition, MBL levels were correlated with Hba1c and glucose levels. Results: We found significant elevated levels of MBL in plasma of DN patients compared to healthy controls. MBL levels in DN patients with a normal kidney function were also elevated, although not significant. MBL levels in patients receiving a SPK completely normalized compared to healthy controls. In contrast, MBL levels in DN patient receiving only a kidney transplant remained elevated, suggesting that diabetic control but not reversal of renal failure is associated with a decrease in circulating MBL. In line, glucose levels and Hba1C, but not creatinine levels in DN patients were significantly correlated with levels of MBL. Of interest, we also found a significant correlation between the plasma level of MBL and the duration of T1D before a SPK was needed, suggesting that elevated levels of MBL accelerate the disease progress. Conclusion: In short, we demonstrated that circulating levels of MBL are elevated in DN patients and normalized after SPK. The normalization of MBL levels was independent of renal function, but dependent on diabetic control.