Validation of the BETA-2 Score: An Improved Tool to Estimate Beta Cell Function After Clinical Islet Transplantation Using a Single Fasting Blood Sample

Abstract

The beta score, a composite measure of beta cell function after islet transplantation, has limited sensitivity because of its categorical nature and requires a mixed‐meal tolerance test (MMTT). We developed a novel score based on a single fasting blood sample. The BETA‐2 score used stepwise forward linear regression incorporating glucose (in millimoles per liter), C‐peptide (in nanomoles per liter), hemoglobin A1c (as a percentage) and insulin dose (U/kg per day) as continuous variables from the original beta score data set (n = 183 MMTTs). Primary and secondary analyses assessed the score's ability to detect glucose intolerance (90‐min MMTT glucose ≥8 mmol/L) and insulin independence, respectively. A validation cohort of islet transplant recipients (n = 114 MMTTs) examined 12 mo after transplantation was used to compare the score's ability to detect these outcomes. The BETA‐2 score was expressed as follows (range 0–42): normalBETA−20.166667emnormalscore=)(normalfasting0.166667emnormalC−normalpeptide0.166667emfalse(normalnmolfalse/normalLfalse)×(1−normalinsulin0.166667emnormaldose0.166667emfalse[normalunitsfalse/normalkgfalse])normalFasting0.166667emnormalplasma0.166667emnormalglucose0.166667emfalse(normalmmolfalse/normalLfalse)×normalHbA1normalc(%)×1000 A score <20 and ≥15 detected glucose intolerance and insulin independence, respectively, with >82% sensitivity and specificity. The BETA‐2 score demonstrated greater discrimination than the beta score for these outcomes (p < 0.05). Using a fasting blood sample, the BETA‐2 score estimates graft function as a continuous variable and shows greater discrimination of glucose intolerance and insulin independence after transplantation versus the beta score, allowing frequent assessments of graft function. Studies examining its utility to track long‐term graft function are required.

BETA-2 score is an early predictor of graft decline and loss of insulin independence after pancreatic islet allotransplantation

“…The original validation of the BETA‐2 score by Forbes et al presented the ability of BETA‐2 to detect insulin independence and glucose intolerance at the time of measurement. BETA‐2 showed >88% specificity and sensitivity in detecting insulin independence with a cut‐off of 15, whereas a BETA‐2 cut‐off of 20 had >82% sensitivity and specificity in detecting glucose intolerance . Our subsequent external BETA‐2 validation presented very similar results .…”

“…BETA‐2 score was calculated from the fasting blood glucose (mmol/L), C‐peptide (nmol/L), HbA1c (%), and insulin dose (U/kg per day) as described by Forbes et al…”

“…Initial islet graft decline is only evident in subtle subclinical changes in blood glucose control that could previously only be detected using metabolic stimulation tests, which carry substantial logistical burdens . The recently developed BETA‐2 score can measure islet function with the precision of stimulation tests but is logistically more convenient and based on information from a single blood sample (fasting blood glucose, C‐peptide, and hemoglobin A1c [HbA1c]) …”

Bioengineering of an Intraabdominal Endocrine Pancreas

“…The capillary blood glucose level, data from continuous glucose monitoring, results of a mixed-meal tolerance test, homeostasis model assessment (HOMA2) indexes, and Beta and BETA-2 scores (composite scores of beta-cell function after islet transplantation) 5 are shown in Figure 1, and details of the monitoring of the patient are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.…”

Assessment of simple indices based on a single fasting blood sample as a tool to estimate beta-cell function after total pancreatectomy with islet autotransplantation - a prospective study

“…BETA‐2 score was calculated from the fasting blood glucose (mg/dl), C‐peptide (ng/ml), HbA1c (%), and insulin dose (U/kg/day) as described by Forbes et al . …”