第二型糖尿病肌肉肌腱微循環定量分析：與臨床血液檢查和峰值攝氧量之相關性

Quantitative analyses of myotendinous microcirculation: association with clinical blood tests and VO2 peak in subjects with type 2 diabetes mellitus

盧彥禎(Yan-Jhen Lu)

指導教授 ： 王興國

國立臺灣大學/醫學院/物理治療學研究所/碩士(2020年)

https://doi.org/10.6342/NTU202002897

摘要

研究背景：糖尿病為高盛行率之慢性代謝性疾病，其高血糖與胰島素阻抗的情形易造成許多併發症，而糖尿病併發症也出現於骨骼肌肉系統，影響肌肉、肌腱表現，降低糖尿病患者身體活動功能，增加肌肉、肌腱病變發生率。於糖尿病肌肉肌腱中，潛在影響肌力之因素，包括微循環與組織組成等特徵。然而，糖尿病高血糖血脂是否影響這些潛在因素量化後特徵？並進而影響肌肉之功能表現？以及糖尿病肌肉內微循環與心肺適能下降是否具有相關性？等問題皆未在文獻中獲得回答或探討。
研究目的：本研究分為兩部分。第一部份：以醫學影像定量分析，探討糖尿病肌肉肌腱微循環特徵和血液生化檢測之相關性，比較糖尿病和非糖尿病組下肢肌肉肌腱定量分析結果之差異，以及探討這些特徵和肌肉力量之相關性。第二部份：比較糖尿病者和非糖尿病對照組在最大運動測試中，肌肉微循環內血液動力學表現差異，以及探討於糖尿病患者此表現與心肺適能之相關性。
研究設計：本研究為橫斷式研究。
研究對象：徵招第二型糖尿病患者，以及與糖尿病組年齡相仿之非糖尿病受試者，兩組皆排除會影響肌肉肌腱特徵與微循環的疾病。
研究方法：第一部份：使用磁振造影和超音波定量分析下肢肌肉肌腱微循環與組織組成特徵，包括灌注、血管滲透性與超音波組織特徵等，並收集糖尿病患者血液檢驗數值。第二部份：以紅外線光譜分析儀-腳踏車最大運動測試，分析股外側肌之微循環內血液動力學表現以及心肺適能指標(如：峰值攝氧量)。
統計分析：使用曼-惠特尼U檢定分析糖尿病與非糖尿病組，肌肉肌腱微循環與組織組成之差異；以及使用斯皮爾曼等級相關係數分析糖尿病肌肉或肌腱以上特徵與血液生化檢測、肌力表現和心肺適能之相關性。
結果：第一部份：本研究於磁振造影特徵分析，徵招糖尿病組28位；於超音波影像定量分析的部份，糖尿病組23位、控制組17位。經年齡、性別、糖尿病病史和身體質量指數調整後，糖化血色素與股四頭肌腱和髕骨肌腱之血管外細胞外容積呈現顯著正相關(r=0.840, r=0.929)，高密度脂蛋白膽固醇與股直肌之組織轉換參數呈現顯著正相關(r=0.914)。糖尿病組之內側腓腸肌肌肉厚度、肌肉走向紋路角度，以及單腳抬腳跟高度皆低於控制組(p=0.026, 0.024, 0.016)，而糖尿病組之內側腓腸肌與股直肌超音波回聲強度高於控制組(p=0.008, 0.044)。肌力與肌肉微循環和組成之間無統計上顯著相關性。第二部份：本研究徵招22位為糖尿病組，22位為非糖尿病控制組。糖尿病組股外側肌於休息、暖身和緩和時之氧飽和度均低於控制組(p=0.045, 0.047, 0.004)，峰值攝氧量、最大心率、峰值每分鐘通氣量和峰值氧脈之預估值百分比皆低於控制組(p=0.000, 0.002, 0.014, 0.009)，而總血紅素則於各階段皆無顯著差異。兩組之肌肉氧飽和度差值與峰值攝氧量和峰值氧脈呈現顯著正相關(r=0.608, 0.536)。
結論：第一部份：糖尿病糖化血色素會增加肌腱發炎反應，將促使肌腱病變發生；高密度脂蛋白膽固醇能增加糖尿病肌肉微循環，避免肌肉產生缺血問題。糖尿病會造成肌肉萎縮，以及肌肉組成的改變，使肌肉品質下降，進一步影響肌力與功能表現，因此需要未來研究探討運動介入對於改善糖尿病肌肉品質之效果。第二部份：糖尿病高血糖影響肌肉於休息與運動過程中之氧氣供應，使肌肉缺氧。運動中肌肉氧飽和度差值能反應肌肉利用氧氣之效率，以及峰值攝氧量中肌肉骨骼系統之限制，因此可推測糖尿病高血糖會減少肌肉氧氣供應，進而使運動能力下降，限制心肺適能。休息時肌肉氧飽和度能作為糖尿病肌肉品質之指標，建議未來研究建立休息時肌肉氧飽和度之常模，作為臨床糖尿病肌肉缺氧之篩檢依據。

關鍵字

糖尿病 ； 肌肉骨骼系統併發症 ； 肌肉肌腱微循環 ； 肌肉脂肪浸潤 ； 肌力表現相關因素

並列摘要

Background: Diabetes mellitus (DM) is recognized as a global epidemic chronic metabolic disease, and its hyperglycemia and insulin resistance could cause numerous complications, some of which may affect the musculoskeletal system, and may have further impacts on muscles and tendons performances. Therefore, physical fitness levels may decrease, and the incidence of tendinopathy and myopathy may increase in patients with type 2 DM. In diabetic muscles and tendons, factors including microcirculatory characteristics and tissue compositions may affect muscles strength. However, the influence of hyperglycemia and dyslipidemia affecting the quantitative characteristics of muscles and tendons, and the results interpretation in muscle performances, and the correlation between muscle microcirculations and the lower cardiorespiratory fitness in patients with type 2 DM are still remained unclear.
Purpose: This study was divided into two parts. The first part of study: (1) To examine the correlation between microcirculatory properties in muscles and tendons and blood biochemical tests by using magnetic resonance imaging (MRI) in patients with type 2 DM. (2) To compare the results of quantitative analyses in muscles and tendons between the DM group and the control group. (3) To examine the correlation between these quantitative characteristics and muscles strength in patients with type 2 DM. The second part of study: (1) To compare the hemodynamic performances of muscle microcirculations during maximal exercise testing between the DM group and the control group. (2) To examine the correlation between these performances and cardiorespiratory fitness in patients with type 2 DM.
Design: This study was a cross-sectional study.
Participants: The patients with type 2 DM was recruited as the experimental group, and participants without DM and with age-match to DM group as the control group. The participants with conditions that might affect the characteristics and microcirculation status of muscles and tendons were excluded in both groups.
Methods: The first part of study: The participants were assessed for quantitative characteristics of microcirculations and tissue compositions in muscles and tendons, including perfusion, permeability, and ultrasound tissue characteristics, by using MRI and B-mode ultrasound. The blood biochemical test parameters were collected in the hospital. The second part of study: The participants were assessed for hemodynamic performances of microcirculations in vastus lateralis (VL) and cardiorespiratory fitness (i.e. V̇O2 peak) by near-infrared spectroscopy (NIRS)-maximal cycling test.
Statistical analysis: Mann-Whitney U test was used to compare the differences of muscles and tendons microcirculations and compositions between the DM group and the control group. Spearman's rank correlation coefficient was used to analyze the correlation between blood biochemical tests, muscle performances, and cardiorespiratory fitness and these muscles and tendons variables.
Results: The first part of study: In MRI analysis, the DM group was consisted of 28 participants. In the quantitative analysis of ultrasound images, 23 and 17 participants were recruited as the DM group and the control group respectively. After adjustment for age, gender, duration of DM, and BMI, there were significant correlations between hemoglobin A1c (HbA1c) and both the volume of extravascular extracellular space per unit volume of tissue (Ve) of the quadriceps tendon and the patellar tendon (r=0.840, r=0.929), and there was a significant correlation between high-density lipoprotein (HDL) and the volume transfer constant (Ktrans) of the rectus femoris (RF)(r=0.914). The muscle thickness and pennation angle of medial gastrocnemius (MG), and the height of one-leg heel raise were significantly lower in the DM group than the control group (p=0.026, 0.024, 0.016). The echo intensity of MG and RF were higher in the DM group (p=0.008, 0.044). There were no significant correlations between muscles strength and both muscles microcirculations and compositions. The second part of study: The DM group and the control group were both recruited 22 participants. The oxygen saturation (StO2) of VL during resting, warm-up, and cool-down were significantly lower in the DM group than the control group (p=0.045, 0.047, 0.004). The percent-predicted V̇O2 peak, percent-predicted HR max, percent-predicted peak minute ventilation (V̇E), and percent-predicted peak O2 pulse were significantly lower in the DM group (p=0.000, 0.002, 0.014, 0.009). No significant differences in total hemoglobin during all stages were found between groups. There were significant correlations between StO2 changes and both V̇O2 peak and peak O2 pulse (r=0.608, 0.536).
Conclusion: The first part of study: HbA1c can increase tendons inflammation reactions and promote the incidence of tendinopathy. HDL can increase muscles microcirculation and prevent the condition of muscle ischemia. Type 2 DM leads to muscles atrophy and changes in muscles composition, thus worsening muscles quality, which may have further impacts on muscles strength and performances. Therefore, further investigations of exercise intervention for improving muscles quality are needed. The second part of study: In type 2 DM, hyperglycemia affects the oxygen supply of muscles during resting and exercise, and lead to muscle hypoxic. The muscle StO2 changes during exercise can reflect the efficiency of oxygen utilization and the limitation of musculoskeletal system in V̇O2 peak. Therefore, it can be speculated that DM hyperglycemia reduces muscle oxygen supply, further reduces exercise capacity, and limits cardiorespiratory fitness. Resting muscle StO2 can be used as an indicator of diabetic muscle quality. We recommend future researches for establishing the norm of resting muscle StO2 as a basis for screening muscle hypoxia in patients with type 2 DM.

並列關鍵字

diabetes mellitus (DM) ； musculoskeletal complications ； microcirculation of muscles and tendons ； muscle fat infiltration ； factors of muscle performances

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