Introduction: BETA-2 was developed to more conveniently and precisely assess islet graft function than commonly used beta-score, which requires a stimulation test. After validation of BETA-2 in our cohort of patients in relation to 90-min glucose in a mixed meal tolerance test and beta-score, we decided to assess the practical utility of BETA-2 in monitoring islet allograft function in individual patients.

Methods: We retrospectively analyzed BETA-2 calculations during clinical evaluations in islet allotransplantation (ITx) recipients with up to 3 islet infusions. We specifically looked in reference to previously established BETA-2 cut-offs for the detection of glucose intolerance <18 and insulin independence >13.

Results: We analyzed 298 BETA-2 scores calculated in 14 patients (7 women and 7 men) with an average age of 42.9 ± 9.5 years. In these patients, BETA-2 correlated well with islets function. Four patients, who experienced stable, long-term insulin independence after only one transplant, had a BETA-2 continuously over 18 (Fig 1).

Another 3 patients required a second transplant to reach the same outcome with the same BETA-2 characteristic (Fig 2).

In those patients, despite only discrete changes in fasting glucose level, the BETA-2 decreased to below 18 and continued gradually declining. This drop in BETA-2 always predicted islet dysfunction, the need for insulin support and subsequent transplant, which became clinically obvious as BETA-2 dropped below 13 (Fig 3 and 4).

In the remaining patients, even when BETA-2 eventually reached peak above 18 after subsequent transplant, islet function gradually declined without obvious reason within a year or 2 with BETA-2 below 13 requiring re-introduction of insulin support. (Fig 4).

One of these patients has not been able to stop insulin completely despite 3 subsequent transplants but BETA-2 has never increased above 18, which confirms utility of BETA-2. 12% (14/121) of BETA-2 measurements above 18 were made during the early period after iTx, when insulin was administered irrespectively of beta-cell function, in order to facilitate islet engraftment. In 80.2% of cases (142/177) where BETA-2 value was above the cut-off of 13, patients were off-insulin. The remaining 19.8% were on insulin due to failing islet function with dropping BETA-2 or supporting post infusion islet engraftment as described above. BETA-2 calculations below 13 were in 94.4% (113/121) in patients receiving insulin. Remaining 6.6% of BETA-2 calculations (8/121) were below the cut-off of 13, yet patients were still off insulin due to their non-compliance to the recommendation to resume insulin therapy based on clinically evident suboptimal glucose control.

Conclusion: BETA-2 score, based on only a single fasting blood sample is a very reliable tool for islet function assessment and allows early detection of islet graft decline before obvious clinical symptoms.