動機:
糖尿病是一種高盛行率疾病，造成許多大血管與小血管病變的慢性併發症，並與心臟血管疾病死亡關係密切，糖尿病及其併發症嚴重危害國人健康，同時也造成醫療費用的沉重負擔，因此本研究目的為利用雷射杜卜勒血流訊號分析 (時域、複雜度及頻域分析) 之各項參數，探討因糖尿病或糖尿病前期造成生理及調控活動改變現象，希望研究結果有助於發展糖尿病早期偵測及臨床療效評估指標。
方法:
本研究由新陳代謝科門診疑似糖尿病病人中招募受試者，配合「口服葡萄糖水耐受試驗(OGTT)」的流程，進行雷射杜卜勒微流儀非侵入式量測，依據OGTT結果，將受試者分為糖尿病 (Group A)、糖尿病前期 (Group B)及正常(Group C) 三組，分別將雷射杜卜勒血流訊號進行時域、複雜度(ApEn)及頻域分析，計算出各式參數以探討因糖尿病或糖尿病前期造成生理及調控活動改變現象。
結果與討論:
本研究發現如下:
(1).時域分析: 發現時域參數 FDT(Foot Delay Time)、FRT(Foot Raising Time)，在糖尿病或糖尿病前期組較正常人組顯著下降，而FDT_CV、FRT_CV顯著上升，此參數可幫助瞭解因糖尿病造成微循環血流及血管特性改變。
(2).複雜度分析: 發現時域參數AD (pulse-to-mean ratio)和PW (Pulse Width)之ApEn (approximate entropy) 值在糖尿病顯著或接近顯著上升，而AD和PW值在三組間無顯著差異，此參數可反應體內為維持生理恆定而活化生理調控機制的現象，因此ApEn值可以比時域參數更早被偵測，幫助建立糖尿病早期偵測指標。
(3).頻域分析: 發現第一至第三頻帶 (FR1~FR3)的相對能量比例值 (REC)在糖尿病或糖尿病前期皆較正常人顯著下降且呈逐漸遞減趨勢，此參數有助於進一步探討調控機制發生的可能機轉，並幫助發展糖尿病早期偵測及及療效評估指標。
結論:
本研究利用雷射杜卜勒血流訊號分析等非侵入式量測評估方式，應用於糖尿病或糖尿病前期產生結構性、功能性及調控活動改變的現象，有助於發展糖尿病早期偵測及臨床療效評估指標，達成「早期偵測、早期治療」目標，不僅可提升國人健康狀況，減少醫療支出，更可以有效避免或延緩併發症發生，提升國人生活品質，進一步做為未來發展居家照護及遠距醫療基礎。

Motivations:
Diabetes mellitus is a high prevalence disease and can increase cardiovascular mortality . It is well established that diabetes can lead to both micro- and macrovascular complications, and it seriously endangers people's health. The aim of this study was using signal analysis of skin-surface laser doppler signals to investigate pathological changes and microcirculatory regulatory mechanisms caused by diabetic or prediabetic state. The findings might aid in the development of new noninvasive methods for the early detection of diabetes and for monitoring disease progression.

Methods:
The experimental design of the present study employed the oral glucose tolerance test (OGTT) to assign the subjects into three groups (diabetic, prediabetic, and normal groups) for investigating pathological changes and the regulatory mechanisms underlying these different states. Laser Doppler flowmetry(LDF) signals were analyzed by time-domain, frequency-domain and complexity analysis methods.
Results and Discussion:
Findings from our study are summarized below:
(1).Time-domain analysis: Relative to the normal group, FDT(Foot Delay Time) and FRT(Foot Raising Time) were significantly shorter in prediabetic group, FDT was significantly shorter in diabetic group, and FRTCV and FDTCV were significantly larger in prediabetic and diabetic groups. The present results may help to discriminate differences in the elastic properties of local vascular beds during diabetes or even during prediabetic stages.
(2).Complexity analysis: AD(pulse-to-mean ratio) and PW(Pulse Width) did not differ significant among diabetic, prediabetic, and normoglycemic groups. ApEn(approximate entropy) values of AD and PW were significantly larger and marginally larger in the diabetic group than in the prediabetic and normoglycemic groups. The presence of increased complexity in the LDF index sequence may be partly attributed to the adaptability of the microcirculatory regulatory activities or the impairment of the homeostasis mechanism of microcirculatory-blood-flow perfusion. The present findings may aid in the development of an index for early detection of prediabetes.
(3).Frequency-domain analysis: The relative energy contribution (REC) of 1st frequency band (FR1) was significantly smaller in diabetic subjects than in normal subjects. The REC of 2nd to 3rd frequency bands (FR2–FR3) were significantly smaller in diabetic and prediabetic groups than in normal group. The REC of FR1–FR3 from normal to prediabetic and diabetic groups showed a progressive decrease. The present findings may help to identify the microcirculatory regulatory mechanisms and aid in the development of a noninvasive method for the early detection of prediabetes and the monitoring of disease progression.
Conclusion:
The present findings can help to identify structural, functional changes and the different microcirculatory regulatory mechanisms in diabetes and prediabetes by applying signal analysis to the LDF signals. 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 could be clinically useful in preventing disease progression and reducing the risk of concomitant end-organ damage. In the future, it is hoped that the present technique can reduce medical costs and be used in the development of home-care and telemedicine applications.

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