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Clinical results of islet transplantation
No full textIslet transplantation is considered an advanced therapy in the treatment of type-1 diabetes, with a progressive improvement of clinical results as seen in the Collaborative Islet Transplant Registry (CITR) report. It is an accepted method for the stabilization of frequent hypoglycemia, or severe glycemic lability, in patients with hypoglycemic unawareness, poor diabetic control, or a resistance to intensive insulin-based therapies. Worldwide data confirm a positive trend in this field, with the integrated management of pivotal factors: adequate islet mass, immunosuppressive protocols, additional anti-inflammatory therapy, and pre-transplant allo-immunity assessment. Insulin independence has been observed in several clinical trials with different rate, ranging 100-65% of patients; the maintenance of this condition during the follow-up progressively decreased, actually arranged on 44% 3 years after the last infusion, according to data reported from the CITR. Successful duration is progressively increasing, with ≥13 years being the longest reported insulin-free condition on record. The immediate results of functioning islet transplantation are an improvement in hypoglycemic awareness and a reduction in the glycated hemoglobin level. Furthermore, many studies have shown its influence on the chronic complications of diabetes, such as peripheral neuropathy, retinopathy, and macroangiopathy. Pre-transplant nephropathy remains an exclusion criterion as immunosuppressive therapy can exacerbate kidney-function deterioration. The problems linked to immunosuppression following islet transplantation for the treatment of type-1 diabetes need to be considered in order to achieve the correct risk/benefit ratio for each patient
Islet cell transplantation
No full textIslet cell transplantation is an attractive alternative therapy to conventional insulin treatment or vascularized whole pancreas transplantation for type 1 diabetic patients. It represents a successful example of somatic cell therapy in humans based on complex procedures for islet isolation from whole pancreas. The islets, that are only 1% of the total pancreas tissue, are isolated by two steps method starting with collagenase digestion that operates a rapid dissociation of the stromal component of the gland, while preserving islet anatomical integrity. After digestion, islets are then separated from exocrine tissue by centrifugation in density gradients. Transplantation consists of a simple injection of few milliliter-purified tissue in the portal vein through a percutaneous trans- hepatic approach performed in local anesthesia. Several studies have now demonstrated that islet transplant can replace pancreatic endocrine function without major side effects and with liver viability preservation in selected patients affected by longterm type 1 diabetes. It can restore endogenous insulin secretion, achieve insulin independence in more than 80% of patients, and recover the metabolism of glucose, protein and lipids. Improved control of glycated HbAlc, reduced risk of recurrent hypoglycemia and of diabetic complications are also seen as important benefits of islet cell transplantation, irrespective of the status of insulin independence. Many protocols are now on going for reduction of immunosuppression therapy in recipients, induction of tolerance, and prolongation of graft function
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The clinical impact of islet transplantation
No full textIslet cell transplantation has recently emerged as one
of the most promising therapeutic approaches to improving
glycometabolic control in diabetic patients
and, in many cases, achieving insulin independence.
Unfortunately, many persistent flaws still prevent islet
transplantation from becoming the gold standard
treatment for type 1 diabetic patients. We review the
state of the art of islet transplantation, outcomes, immunosuppression
and—most important—the impact
on patients’ survival and long-term diabetic complications
and eventual alternative options. Finally, we
review the many problems in the field and the challenges
to islet survival after transplantation. The rate
of insulin independence 1 year after islet cell transplantation
has significantly improved in recent years
(60% at 1 year posttransplantation compared with 15%
previously). Recent data indicate that restoration of
insulin secretion after islet cell transplantation is associated
with an improvement in quality of life, with
a reduction in hypoglycemic episodes and potentially
with a reduction in long-term diabetic complications.
Once clinical islet transplantation has been successfully
established, this treatment could even be offered
to diabetic patients long before the onset of diabetic
complications
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