Normalization of Multiple Hemostatic Abnormalities in Uremic Type 1 Diabetic Patients After Kidney-Pancreas Transplantation

Abstract

To evaluate the effects of kidney-pancreas transplantation on hemostatic abnormalities in uremic type 1 diabetic patients, we conducted a cross-sectional study involving 12 type 1 diabetic patients, 30 uremic type 1 diabetic patients, 27 uremic type 1 diabetic patients who had a kidney-pancreas transplant, 12 uremic type 1 diabetic patients who had a kidney-alone transplant, and 13 healthy control subjects. We evaluated platelet and clotting system. Platelets in the group of uremic type 1 diabetic patients were significantly larger than platelets in the other groups. Resting calcium levels were significantly higher in the uremic type 1 diabetic patients and uremic type 1 diabetic patients who had a kidney-alone transplant than in the type 1 diabetic patients who had a kidney-pancreas transplant and control subjects. CD41 expression was significantly reduced in platelets from the uremic type 1 diabetic patients compared with the other groups. Levels of hypercoagulability markers in the type 1 diabetic patients who had a kidney-pancreas transplant and, to a lesser extent, the uremic type 1 diabetic patients who had a kidney-alone transplant but not the uremic type 1 diabetic patients were similar to those of the control subjects. A reduction in natural anticoagulants was evident in the uremic type 1 diabetic patients, whereas near-normal values were observed in the type 1 diabetic patients who had a kidney-pancreas transplant and uremic type 1 diabetic patients who had a kidney-alone transplant. Hemostatic abnormalities were not observed in type 1 diabetic patients who had a kidneypancreas transplant. This finding might explain the lower cardiovascular death rate observed in type 1 diabetic patients who had a kidney-pancreas transplant compared with uremic type 1 diabetic patients who had a kidney-alone transplant or uremic type 1 diabetic patients.

Impact of Islet Transplantation on Diabetes Complications and Quality of Life

“…Our group demonstrated that restoration of normoglycemia with kidney-pancreas transplantation has a large effect on hemostasis; therefore, some effect in islet-transplanted patients was expected as well (Table 1) [68]. Preliminary and unpublished data from our group confirmed that ITA patients, bearing a functioning graft, showed a better morphology of platelets, lower resting platelet calcium and CD41 expression (meaning less activated platelets), and reduced levels of prothrombotic factors compared with T1D patients on the waiting list (Table 1) …”

Circulating IGF-I and IGFBP3 Levels Control Human Colonic Stem Cell Function and Are Disrupted in Diabetic Enteropathy

“…The gold standard treatment for long-standing T1D is SPK, which affords stable glycometabolic control, near-normalize risk factors and prolonged survival (Table S4)(Fiorina et al, 2004; Fiorina et al, 2005; Folli et al, 2010; Secchi et al, 1998; Smets et al, 1999). However, individuals with T1D+ESRD are also treated with kidney transplantation alone but remain diabetic (K+T1D)(Fiorina et al, 2001).…”

Twelve-Month Pancreas Graft Function Significantly Influences Survival Following Simultaneous Pancreas-Kidney Transplantation

“…While it is clear that intensive glucose control results in reduction in both microvascular and macrovascular complications in T1DM, (19,20), the impact of pancreas transplantation on complications of diabetes, including nephropathy, retinopathy, and neuropathy, is more subtle (1,7,8). One potential explanation is that stabilization of diabetes control may lead to a reduction in cardiac events, a hypothesis supported by others (21)(22)(23)(24)(25). However, since 5-yr pancreas graft survival following SPK is only 71% (12), explanations other than euglycemia must be considered to account for the improved outcomes.…”