Fig. 4

Appearance of UG + and BG + in Part II survey with refined protocol. Each line represents an individual diabetic mouse in Part II. The period surveyed by the UG testing is illustrated by open bars, concluding at the age of each 1st UG + moment represented as open circles. This contrasts with the gray bars of BG testing in Fig. 2, as these have been replaced with the non-invasive UG testing in Part II. BG testing were then immediately performed starting from the day of the 1st UG+, with corresponding ages for the 1st and 2nd BG + marked with gray circles and black circles, respectively. The 2nd UG + is indicated with open triangles, and the duration between 1st and 2nd BG + is represented by black lines. Mice are categorized based on two types of diabetes onset: the acute type (31/37, 83.8%), where 1st and 2nd BG + occur consecutively with very short black lines, and the insidious type (6/37, 16.2%), where the 2nd BG + is observed a week after the 1st BG+, resulting in extended black lines in the upper part of the figure. The majority of mice, 30 out of 37 (81.1%), exhibit their 1st UG + and 1st BG + simultaneously in the same day, indicated by vertically overlapping open and gray circles in the middle part. Using this refined protocol, it takes less than 50 bleedings to identify the 1st BG + moment in these 37 diabetic mice. Additionally, hundreds of negative BG results are saved among the 23 non-diabetic mice. Interestingly, during the twice-weekly UG survey, 7 mice are found to have UG + first (while BG remains normal), followed by their own 1st BG + results in subsequent tests. These findings strongly suggest that during the progression of spontaneous diabetes, the appearance of a small amount of glucose in the urine primarily coincides, and sometimes even precedes, the 1st BG + moment, making the ultrasensitive UG testing an excellent tool to assist in diabetes diagnosis