Consensus Report Defines Treatment Success in β-Cell Replacement Therapy
A failed β-cell graft is defined by the absence of any evidence for clinically significant C-peptide production. Photo Credit: Carol Werner.
β-cell replacement therapy could be considered as a treatment for β-cell failure, regardless of the etiology, without requiring undetectable C-peptide levels, and accompanied by either problematic hypoglycemia or hyperglycemia, according to a new consensus report published in Transplantation.
Although pancreas and islet cell transplantation have become established approaches for β-cell replacement therapy, a clear definition of graft functional and clinical outcomes has not been established.
To develop a joint consensus statement, the International Pancreas & Islet Transplant Association (IPITA) and European Pancreas & Islet Transplantation Association (EPITA) held a workshop with the goal of defining function and failure of current and future forms of β-cell replacement therapy.
An outcome of the workshop was the proposal that treatment success can be assessed by using a 4-tiered system that evaluated functional and clinical outcomes. For treatment to be considered a success, the following is needed:
- Optimal β-cell graft function can be defined by near-normal glycemic control (HbA1c ≤6.5% [48 mmol/mol]) without severe hypoglycemia or requirement for insulin, and C-peptide measurement above pretransplant baseline.
- Good β-cell graft function is defined as HbA1c <7.0% (53 mmol/mol) without severe hypoglycemia, a 50% or greater reduction in the need for insulin requirements, and C-peptide measurement above pretransplant baseline.
Treatment is considered unsuccessful with the following functional/clinical outcomes:
- Marginal β-cell graft function is defined by failure to achieve HbA1c <7.0% (53 mmol/mol), severe hypoglycemia that is higher than baseline, less than 50% reduction in insulin requirements, and C-peptide measurement above pretransplant baseline.
- A failed β-cell graft is defined by all measurements remaining at baseline, with no improvement.
"Baseline assessment of hypoglycemia awareness, hypoglycemia severity, and glycemic variability/lability is helpful for monitoring whether a marginally functioning graft is continuing to provide any clinical impact," write the authors, although they caution that the proposed classification of function and clinical outcomes "is a work in progress and should be validated and further refined based on results from implementation in future prospective investigation."
Rickels MR, Stock PG, de Koning EJP, et al. Defining outcomes for β-cell replacement therapy in the treatment of diabetes: a consensus report on the Igls criteria from the IPITA/EPITA opinion leaders workshop [published online March 9, 2018]. Transplantation. doi: 10.1097/TP.0000000000002158