We aimed to identify the microcirculatory regulatory mechanisms in diabetic and prediabetic humans using a noninvasive method combining spectral analysis with laser-Doppler flowmetry (LDF) measurements on the skin surface. LDF signals were measured by a moorVMS-LDF device to measure the microcirculatory blood flow flux with a time constant of 0.001 s, a cutoff frequency of 14.9 kHz, and a sampling frequency of 40 Hz. The laser operating wavelength and output power were 400-700 nm and 6 mW, respectively. LDF signals were obtained noninvasively in 115 subjects, who were assigned to three groups (diabetic, prediabetic, and normal) according to the results of the oral glucose tolerance tests. A Morlet mother wavelet transform was applied to the measured 20-min LDF signals, and periodic oscillations with five characteristic frequency peaks were obtained within the following frequency bands: 0.0095-0.02, 0.02-0.06, 0.06-0.15, 0.15-0.4, and 0.4-1.6 Hz (defined as FR1-FR5), respectively. The relative energy contribution (REC) of FR1 was significantly smaller (by using the Kruskal-Wallis test followed by Dunn's multiple-comparison tests) in diabetic subjects than in normal subjects. The REC of FR2-FR3 was significantly smaller in diabetic and prediabetic subjects than in normal subjects. The REC of FR1-FR3 from normal to prediabetic and diabetic subjects showed a progressive decrease. The present findings may aid in the development of a noninvasive method for the early detection of prediabetes and the monitoring of disease progression. This may be useful in preventing disease progression and reducing the risk of concomitant end-organ damage.

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MOTIVATIONS:The present study performed laser-Doppler flowmetry (LDF) measurements on the skin surface around the ankle with the aim of verifying if beat-to-beat analysis of the LDF waveform can help to discriminate the microcirculatoryblood-flow (MBF) characteristics between diabetic, prediabetic, and healthy subjects. METHODS: 84 subjects were assigned to three groups (diabetic, prediabetic, and normal) according to the results of oral glucose tolerance tests. Beat-to-beat analysis was performed on the pulsatile LDF waveform to obtain foot delay time (FDT), flow rise time (FRT), and the corresponding MBF-variability parameters (FDTCV and FRTCV). RESULTS: Relative to the control group, FDT and FRT were significantly shorter in prediabetic subjects, FDT was significantly shorter in diabetic subjects, and FRTCV and FDTCV were significantly larger in prediabetic and diabetic subjects. There were no significant associations for FRT after adjustment for age and gender. CONCLUSION: The present results indicate that FRT may help to discriminate differences in the elastic properties of local vascular beds during diabetes or even during prediabetic stages. The proposed blood-filling-volume model can help to explain the underlying mechanism. The present findings may aid the noninvasive early detection of diabetes-associated vascular damage, and could be used in the development of home-care and telemedicine applications.