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- Materials and Methods
This study analyzed quality of life in patients with type 1 diabetes that received islet transplantation. Twenty-three subjects were followed over 3 years. In addition to an interview, patients self-completed two standardized psychometric questionnaires, HSQ 2.0 and DQOL, before and after transplant, and scores were compared. Analysis was also adjusted for potential “confounders” such as graft dysfunction, insulin therapy and adverse events. DQOL: the Impact score significantly improved at all time points of the follow-up; satisfaction and worry scales also significantly improved at selected time points. Longitudinal analysis demonstrated that reintroduction of insulin had a negative effect on all three scales, but significant improvement in Impact scale persisted even after adjusting for this factor. HSQ 2.0: only the Health Perception scale preliminarily showed significant improvement at most time points. Longitudinal analysis showed loss of significance when insulin therapy was considered. Other scores were improved only at selected time points or not affected. Bodily pain scale showed deterioration at selected times. Interview: glucose control stability, not insulin independence, was reported as the main beneficial factor influencing QOL. In conclusion, islet transplantation has a positive influence on patients' QOL, despite chronic immunosuppression side effects. Re-introduction of insulin modifies QOL outcomes.
- Top of page
- Materials and Methods
In this study, we used psychometric instruments to evaluate QOL in a cohort of patients that underwent islet transplantation. Results of an initial analysis showed significant improvement in the Impact scale of DQOL at all time points in the 3 years of follow-up post-islet transplantation. The Worry scale was improved in the first 18 months, as was Satisfaction scale (with the exception of the 9 months time point). Also, the score that addresses the patient Health Perception in the HSQ 2.0 was significantly higher at most of the time points in the first 3 years. This means that when each patient was compared to himself, with time post-islet transplant as the only variable, islet transplantation showed an overall beneficial influence on the health-related quality of life in the first 3 years. Worry about illness was lower than before, the impact of islet transplant as a treatment was positive on the patient, and general perception of health was improved. Interestingly, the Impact scale was already marginally improved and the Satisfaction scale was significantly improved on the waiting list. These outcomes could be related to the high expectations and the psychological positive effect of waiting for a transplant. It is often difficult to reach statistical significance when performing comparisons with very small sample sizes, and statistical significance from analytical methods of comparison would likely require extremely large differences. This might be the explanation as to why, at selected time points, the initial comparisons made in our preliminary analysis of the data using paired t-test (illustrated in Table 1) were not able to reach statistical significance. However, these comparisons were only meant as preliminary analysis of the data, and a more appropriate repeated measures analysis of the longitudinal data was conducted as described in the statistical methods section.
When we analyzed in greater detail the scores of our patients' questionnaires, using a longitudinal statistical analysis of the first 2 years post-transplant, and additionally considering factors that could represent statistical ‘confounders’, we found that, albeit somehow reduced, the overall benefit persisted. Confounders significant for any of the outcomes considered included return, at any time point, to insulin therapy; and any important health problem likely related to immunosuppressive therapy (adverse events grade 3 and 4 NCI) in the 3 months before the test. Indeed, when considering the occurrence of an adverse event and, most importantly, reinstatement of insulin therapy, we found that these factors influenced the outcome, independently of the time, as most of the scores lost statistical significance; one of the scales (bodily pain in HSQ 2.0) showed significant deterioration in the first 2 years after islet infusion.
Impact was the only scale of the DQOL questionnaire that appeared not influenced by these factors, after 3 months post-completion and onwards. The positive influence (‘Impact’) of islet transplantation on the life of these patients remains, therefore, independent of the events that follow the transplant, such as restarting insulin therapy and experiencing adverse events.
Satisfaction scale and worry scale of DQOL and Health Perception scale of HSQ 2.0 lost their significance, when corrected for insulin therapy and presence of adverse events, showing that these very factors had a confounding role on the benefit observed in the initial analysis, where time post-transplantation was the only variable considered.
The day of the compilation of the questionnaires, patients met the psychologist for a verbal evaluation of the personal satisfaction about different aspects of life after islet transplantation. During these conversations, the most frequently reported beneficial effect of islet transplantation was stability of glucose control and absence of hypoglycemic episodes resulting in a feeling of independence and reliability, not experienced before the transplant. Also, transplanted patients reported that being part of and helping research for future generations, was worthy the adverse events that they tolerated. In this colloquial analysis, being able to remain insulin-free was not, in general, indicated as a fundamental element in the patients' well-being, even if this was mentioned as desirable.
The apparent discordance between the results of the two standardized instruments (DQOL and HSQ 2.0) and the verbal communication with a professional in the evaluation of QOL, when insulin therapy was specifically examined, may be explained as follows: the interview looks for the patient global (general) QOL, while questionnaires force the patients to dissect QOL in different aspects, explore different areas and analyze the specific components of QOL; this is probably why the importance of insulin was revealed more by these tests than by the interview.
Notwithstanding that the positive influence (as the Impact scale showed) of islet transplantation on the life of the patients was confirmed by our study, we expected a better outcome, with significant improvement of other scales of the questionnaires. One possible explanation could be related to the high educational and socioeconomic status of this selected cohort of patients and the consequent general better health status than the average population with type 1 diabetes mellitus. The high baseline QOL of this particular group of subjects can, possibly, reduce the magnitude of the improvement after islet transplantation.
Another important factor is that insulin independence, after the completion of an islet transplant protocol, probably leads patients to consider themselves cured, and consequently to compare themselves and their QOL to a nondiabetic population. Even if this can be understood from a psychological perspective, it is not correct from a clinical standpoint, since type 1 diabetes is a complex chronic disease, with metabolic alterations and complications, and islet transplantation has resulted in adequate but transient glycemic control without insulin administration, while several features of type 1 diabetes persist.
The longitudinal regression analysis employed in this study allowed us to simultaneously assess changes from baseline at multiple time points. Additionally, using these regression-modeling methods allowed us to assess ‘a confounding effect’, i.e. whether inclusion of another variable (the potential confounder) in the model resulted in a different interpretation of the relationship of interest. Thus, adjusting for insulin therapy, graft dysfunction and adverse events may affect (‘confound’) the estimate of the relationship between time and the outcome of interest (e.g. Satisfaction).
Analysis of the scores adjusted for confounders revealed changes in the significance of the results, different from our initial unadjusted analysis and from our expectations. Still, we feel that the discrepancy between the scores obtained with questionnaires and the outcome of the interviews might indicate that the former is not enough to get a complete picture of the patients' QOL. And this suggests that additional objective psychometric instruments might be needed and that the verbal consultation with a professional must be integrated in the overall QOL evaluation. At the visit, during follow-up with the psychologist, even if the reason for satisfaction is very subjective and the expectations of most patients change with time, the most frequent factor for the recipient's well-being was good glycemic control and disappearance of brittle diabetes, because metabolic stability and absence of hypoglycemia led the patients to independency from other people and the ability to conduct normal life and take responsibilities. These factors persist even if insulin therapy is restarted, and none of the patients ever regretted his/her islet transplant, since overall QOL improved, even if he/she was back on insulin.
The enhanced daily functioning, as a function of independency, is usually best described by the scale Role Limitation-Physical Health of the HSQ 2.0 questionnaire. No significant improvement was observed on this scale at any of the time points studied. In a previous study (10) this very scale demonstrated a good correlation with the Impact scale of the DQOL, which instead is significantly improved in our study. We believe that a further analysis by more deeply investigating some aspects of this scale and by increasing the number of patients will result in improved outcome.
The lack of better QOL scores could also be explained by the analysis of two heterogeneous populations, islet after kidney and islet alone recipients. As soon as the number of patients in each population is larger, we will analyze them independently in order to test this hypothesis.
Also we believe that, in addition to the psychometric instruments utilized for this study, the use of a hypoglycemia-fear specific questionnaire would be very useful to capture the fundamental benefit for a patient with type 1 diabetes that receives an islet transplant (20).
We also want to analyze in detail the deterioration of the bodily pain scale score, trying to correlate it with the presence of other adverse events, even at lower grade of severity according to NCI. These can be very discomforting for the patient under immunosuppression (e.g. mouth ulcers, a common side effect of rapamycin) and can possibly explain the lower scores of this specific scale after transplantation.
A recent report on QOL in a small group of patients that were followed up for 12 months suggested that while hypoglycemia fear improved significantly after transplant, all scores of the SF 36 questionnaire did not (20). This is quite consistent with our observations obtained in a larger group of patients and with a longer follow-up; it is therefore conceivable that rather than an improvement in general health related QOL, diabetes-specific aspects of QOL are more likely to show benefit from an islet transplant.
In summary, our data showed that islet transplantation results in improvement of selected aspects of QOL, and that there is little, if any, negative impact of the procedure, an important observation in view of the question as to whether chronic immunosuppression side effects might outweigh the benefits of improved metabolic control (21). We also show that re-introduction of insulin therapy is a fundamental independent variable that affects QOL outcomes, and we suggest that larger patient samples and longer follow-ups will strengthen our conclusions. We also suggest that the definition of more specific psychometric instruments should be considered.