Prediction of nocturnal hypoglycemia by an aggregation of previously known prediction approaches: proof of concept for clinical application.

BACKGROUND AND OBJECTIVE: Nocturnal hypoglycemia (NH) is common in patients with insulin-treated diabetes. Despite the risk associated with NH, there are only a few methods aiming at the prediction of such events based on intermittent blood glucose monitoring data and none has been validated for clinical use. Here we propose a method of combining several predictors into a new one that will perform at the level of the best involved one, or even outperform all individual candidates. METHODS: The idea of the method is to use a recently developed strategy for aggregating ranking algorithms. The method has been calibrated and tested on data extracted from clinical trials, performed in the European FP7-funded project DIAdvisor. Then we have tested the proposed approach on other datasets to show the portability of the method. This feature of the method allows its simple implementation in the form of a diabetic smartphone app. RESULTS: On the considered datasets the proposed approach exhibits good performance in terms of sensitivity, specificity and predictive values. Moreover, the resulting predictor automatically performs at the level of the best involved method or even outperforms it. CONCLUSION: We propose a strategy for a combination of NH predictors that leads to a method exhibiting a reliable performance and the potential for everyday use by any patient who performs self-monitoring of blood glucose.

A linear functional strategy for regularized ranking.

Regularization schemes are frequently used for performing ranking tasks. This topic has been intensively studied in recent years. However, to be effective a regularization scheme should be equipped with a suitable strategy for choosing a regularization parameter. In the present study we discuss an approach, which is based on the idea of a linear combination of regularized rankers corresponding to different values of the regularization parameter. The coefficients of the linear combination are estimated by means of the so-called linear functional strategy. We provide a theoretical justification of the proposed approach and illustrate them by numerical experiments. Some of them are related with ranking the risk of nocturnal hypoglycemia of diabetes patients.

Assessment of blood glucose predictors: the prediction-error grid analysis.

BACKGROUND: Prediction of the future blood glucose (BG) evolution from continuous glucose monitoring (CGM) data is a promising direction in diabetes therapy management, and several glucose predictors have recently been proposed. This raises the problem of their assessment. There were attempts to use for such assessment the continuous glucose-error grid analysis (CG-EGA), originally developed for CGM devices. However, in the CG-EGA the BG rate of change is estimated from past BG readings, whereas predictors provide BG estimation ahead of time. Therefore, the original CG-EGA should be modified to assess predictors. Here we propose a new version of the CG-EGA, the Prediction-Error Grid Analysis (PRED-EGA). METHODS: The analysis is based both on simulated data and on data from clinical trials, performed in the European FP7-project "DIAdvisor." Simulated data are used to test the ability of the analyzed CG-EGA modifications to capture erroneous predictions in controlled situation. Real data are used to show the impact of the different CG-EGA versions in the evaluation of a predictor. RESULTS: Using the data of 10 virtual and 10 real subjects and analyzing two different predictors, we demonstrate that the straightforward application of the CG-EGA does not adequately classify the prediction performance. For example, we observed that up to 70% of 20 min ahead predictions in the hyperglycemia region that are classified by this application as erroneous are, in fact, accurate. Moreover, for predictions during hypoglycemia the assessments produced by the straightforward application of the CG-EGA are not only too pessimistic (in up to 60% of cases), but this version is not able to detect real erroneous predictions. In contrast, the proposed modification of the CG-EGA, where the rate of change is estimated on the predicted BG profile, is an adequate metric for the assessment of predictions. CONCLUSIONS: We propose a new CG-EGA, the PRED-EGA, for the assessment of glucose predictors. The presented analysis shows that, compared with the straightforward application of the CG-EGA, the PRED-EGA gives a significant reduction of the misclassification cases. A reduction by a factor of at least 4 was observed in the study. Moreover, the PRED-EGA is much more robust against uncertainty in the input and references.