The recent dramatic improvement in clinical outcomes in islet transplantation in type 1 diabetes with the Edmonton Protocol has led to considerable excitement in the field of diabetes (1,2). The unprecedented 1-year success rates provide considerable evidence of the clinical effectiveness of the procedure (2,3). However, the benefits of freeing or reducing insulin requirements for these patients must be weighed against the risks of the procedure itself, as well as the life-long immunosuppression. Before making this treatment available to a larger number of people with type 1 diabetes, measures of quality of care and of clinical effectiveness must be incorporated to fully evaluate the benefit of this treatment.

Episodes of severe hypoglycemia, a common occurrence in patients with labile type 1 diabetes and hypoglycemia unawareness, result in considerable fear and anxiety (4,5). When these concerns become an overwhelming burden for patients with type 1 diabetes, islet transplantation with the Edmonton Protocol is a potential solution (13). To determine the potential impact of islet transplantation on self-reported health-related quality of life (HRQL) outcomes, we compared islet-transplanted patients with pretransplant patients on measures of fear of hypoglycemia and anxiety.

Patients were asked to self-complete a battery of measures, including the Hypoglycemia Fear Survey (HFS) (4,5) and the Health Utilities Index Mark two (HUI2) (6). The HFS contains 23 questions that assess patients’ concerns and worries about hypoglycemia and the behaviors in which patients may engage to avoid low blood glucose. The emotion attribute of the HUI2 can be used as an index of anxiety (6). Our standard protocol for administration of HRQL questionnaires occurs at baseline (pretransplant); midtransplant (i.e., between the first and second); 1, 3, 6, and 12 months posttransplant; and annually thereafter. Because islet-transplanted patients may have completed multiple surveys during follow-up, we initially used only the last available HRQL assessment. Surveys were completed by 81 (46 pretransplant and 35 islet-transplanted) patients. Among the islet-transplanted patients, questionnaires were completed a median of 11.9 months (range 1–36) after transplant. Scores between the two groups of patients were compared using nonparametric statistical tests.

Fear of hypoglycemia was significantly lower in islet-transplanted (median 5.0) compared with pretransplant (median 47.0) patients for the HFS total score (P < 0.001). The magnitude of the difference in HUI2 emotion scores between pretransplant and islet-transplanted patients would be considered clinically important (6) (1.00 vs. 0.86, respectively), although the difference was not statically significant (P = 0.96). Among all islet-transplanted patients, the small number (n = 3) without C-peptide secretion and requiring exogenous insulin had substantially more fear about hypoglycemia (P = 0.041) and reported more anxiety on the HUI2 emotion attribute (P = 0.023) than islet-transplanted patients with successful transplants.

Because anxiety pre- and posttransplant could be related to the procedure itself, we also compared HFS and HUI2 emotion scores between pretransplant and islet-transplanted patients in the immediate posttransplant period; for these comparisons, we used all available HRQL assessments at 1 and 3 months posttransplant. We found that fear of hypoglycemia was lower, with a median HFS total of 30.0 for islet-transplanted patients (n = 20) at 1 month and 6.5 (n = 18) at 3 months, both of which were significantly lower (P < 0.01) than pretransplant. Conversely, the HUI2 emotion score was not significantly different from pretransplant at either 1 or 3 months posttransplant.

These initial evaluations of self-reported HRQL outcomes of in islet transplant recipients demonstrate that clinical success is associated with substantial reduction in emotional burden through reduced fear of hypoglycemia. General anxiety in islet-transplanted patients is reduced overall, which seems to be related to the freedom from requirement of exogenous insulin rather than to recovering from the transplant procedure itself. Although the interpretation of our initial data is interesting and informative, several limitations and questions remain. These initial data were collected cross-sectionally and on a relatively small but growing sample of islet-transplanted patients; even with the small sample sizes, the observed differences were statistically significant. Longitudinal assessments to measure within-person change over time are required to fully assess the impact on HRQL.

Shapiro AMJ, Lakey JRT, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen.
N Engl J Med
Ryan EA, Lakey JR, Rajotte RV, Korbutt GS, Kin T, Imes S, Rabinovitch A, Elliott JF, Bigam D, Kneteman NM, Warnock GL, Larsen I, Shapiro AM: Clinical outcomes and insulin secretion after islet transplantation with the Edmonton Protocol.
Ryan EA, Lakey JRT, Paty BW, Imes S, Korbutt GS, Kneteman NM, Bigam D, Rajotte EV, Shapiro AMJ: Successful islet transplantation: continued insulin reserve provides long-term glycemic control.
Cox D, Irvine A, Gonder-Frederick L, Nowacek G, Butterfield J: Fear of hypoglycemia: quantification, validation, and utilization.
Diabetes Care
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