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Hypoglycemia or low blood glucose is dangerous and can result in unconsciousness, seizures, and even death. It is a common and serious side effect of insulin therapy in patients with diabetes. Hypoglycemic monitor is a noninvasive monitor that measures some physiological parameters continuously to provide detection of hypoglycemic episodes in type 1 diabetes mellitus patients (T1DM). Based on heart rate (HR), corrected QT interval of the ECG signal, change of HR, and the change of corrected QT interval, we develop a genetic algorithm (GA)-based multiple regression with fuzzy inference system (FIS) to classify the presence of hypoglycemic episodes. GA is used to find the optimal fuzzy rules and membership functions of FIS and the model parameters of regression method. From a clinical study of 16 children with T1DM, natural occurrence of nocturnal hypoglycemic episodes is associated with HRs and corrected QT intervals. The overall data were organized into a training set (eight patients) and a testing set (another eight patients) randomly selected. The results show that the proposed algorithm performs a good sensitivity with an acceptable specificity.