Examination of the Igls Criteria for Defining Functional Outcomes of β-cell Replacement Therapy: IPITA Symposium Report

Abstract

Context The Igls criteria were developed to provide a consensus definition for outcomes of β-cell replacement therapy in the treatment of diabetes during a January 2017 workshop sponsored by the International Pancreas & Islet Transplant Association (IPITA) and the European Pancreas & Islet Transplant Association (EPITA). In July 2019, a symposium at the 17 th IPITA World Congress was held to examine the Igls criteria after two years in clinical practice, including validation against continuous glucose monitoring (CGM)-derived glucose targets, and to propose future refinements that would allow for comparison of outcomes with artificial pancreas system approaches. Evidence acquisition Utilization of the criteria in various clinical and research settings were illustrated by population as well as individual outcome data of four islet and/or pancreas transplant centers. Validation against CGM metrics was conducted in 55 islet transplant recipients followed-up to 10 years from a fifth center. Evidence synthesis The Igls criteria provided meaningful clinical assessment on an individual patient and treatment group level, allowing for comparison both within and between different β-cell replacement modalities. Important limitations include the need to account for changes in insulin requirements and C-peptide levels relative to baseline. In islet transplant recipients, CGM glucose time-in-range improved with each category of increasing β-cell graft function. Conclusions Future Igls 2.0 criteria should consider absolute rather than relative levels of insulin use and C-peptide as qualifiers with treatment success based on glucose assessment using CGM-metrics on par with assessment of HbA1c and severe hypoglycemia events.

Feasibility and efficacy of combined pancreatic islet-lung transplantation in cystic fibrosis-related diabetes–PIM study: A multicenter phase 1–2 trial

“…At 1-year follow-up, SF-36 questionnaire analysis showed improvements in the parameters of physical functioning, role limitationsphysical, bodily pain, general perceptions of health, vitality, and emotional role limitations (Table S6). No variation was observed regarding social functioning, while the mental health score increased slightly from 44 [40][41][42][43][44][45][46][47][48][49][50][51] to 47 [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57]. The Physical Component Score increased from 28 to 54 [46-56], while the Mental Component Score remained stable at 51 [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] versus 53 [40][41][42][43]…”

“…No variation was observed regarding social functioning, while the mental health score increased slightly from 44 [40][41][42][43][44][45][46][47][48][49][50][51] to 47 [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57]. The Physical Component Score increased from 28 to 54 [46-56], while the Mental Component Score remained stable at 51 [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] versus 53 [40][41][42][43][44][45][46][47]…”

“…Given that insulin independence or C-peptide levels alone are not good markers for metabolic efficacy, the use of composite markers, such as the Beta, Beta 2, Igls scores, which take into account Cpeptide, HbA1c, fasting glycemia, insulin needs, and hypoglycemia parameters, have been proposed as better alternatives. 40 However,…”

“…For type 1 diabetes patients, islet transplantation has been developed without a clear definition of the functional and clinical outcomes which define graft success. Given that insulin independence or C‐peptide levels alone are not good markers for metabolic efficacy, the use of composite markers, such as the Beta, Beta 2, Igls scores, which take into account C‐peptide, HbA1c, fasting glycemia, insulin needs, and hypoglycemia parameters, have been proposed as better alternatives 40 . However, these scores cannot be applied to CFRD patients, due to the presence of persistent endogenous insulin secretion with detectable C‐peptide, the low reliability of HbA1c in CF patients, and the low number of hypoglycemic events linked to residual insulin secretion.…”

“…these scores cannot be applied to CFRD patients, due to the presence of persistent endogenous insulin secretion with detectable C-peptide, the low reliability of HbA1c in CF patients, and the low number of hypoglycemic events linked to residual insulin secretion.As no definitive score of metabolic control has been validated for CFRD, we applied a modified version of the existing beta score, tailored to CFRD by removing the C-peptide component and replacing this with weight, an important metabolic marker for CF patients.Further work on the validation of such scores is merited and would be of use in future clinical studies. Recently, the Igls 2.0 score, based on HbA1c values and CGM data, has been proposed 40. Applied to our six patients with CGM data, combined islet-lung transplantation was a success in five out of six patients versus four out of six with our composite score.…”