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標題: | 隨機分派研究探討pioglitazone相較於linagliptin對於腎臟排除尿鈣的影響 A randomized controlled trial evaluating the impact of pioglitazone versus linagliptin on renal calcium excretion |
作者: | Feng-Jung Nien 粘峯榕 |
指導教授: | 曾慶孝 |
關鍵字: | 糖尿病,愛妥糖,糖漸平,骨質疏鬆,鈣,多中心前瞻性研究, thiazolidinedione,diabetes,osteoporosis,calcium,randomized control trial,multicenter,pioglitazone,linagliptin, |
出版年 : | 2017 |
學位: | 碩士 |
摘要: | 糖尿病是一種全球普遍卻又對人體健康有著重大影響的疾病,與骨質疏鬆也有著密切的關係。但是其中機轉目前仍未完全清楚。Thiazolidinedione(TZD)據國外研究顯示可能會造成老年女性骨鬆與骨折機率增加;但對青壯年或男性的影響目前仍無結論。而我國針對thiazolidinedione影響骨代謝的相關研究更是缺乏。高尿鈣被認為是一種骨質疏鬆的危險因子。有一項研究顯示使用愛妥糖(一種在臨床上廣為使用的TZD)可能會直接抑制副甲狀腺素分泌而導致尿鈣增加,繼而造成骨質流失。而近年來處方率越來越高的Dipeptidyl peptidase-4 (DPP4)抑制劑則被認為不會影響骨質與鈣質平衡。本研究將探討愛妥糖相較糖漸平(一種DPP4抑制劑)是否會影響腎臟對於鈣質的排出,期能藉此研究進一步了解TZD對於骨骼系統所造成之影響及可能的病生理機轉。
本計劃為多中心前瞻性研究(台大總院、雲林分院),並將以隨機分配對照實驗的方式來進行。研究對象為年滿40歲以上男性或停經後女性目前使用口服降血糖藥(不包括TZD或DPP4i) 控制已超過3個月,且最近三個月糖化血色素為7.0~8.5%未達標之第二型糖尿病病人。並排除黃斑部水腫、中重度視網膜病變、心衰竭(NYHA class III~IV)、慢性腎病變(stage4~5)病人、活動性肝病者(AST 或ALT大於正常上限之2.5倍)、其他內分泌腺功能異常、血中維生素D低下、骨質疏鬆併骨折病史或目前骨折正接受治療或癌症患者。 符合條件之志願者隨機分為A、B組。二組分別加上愛妥糖或糖漸平治療連續48週。期間每12週檢測一次血糖及肝、腎功能。且試驗前以及第48週檢測血中鈣、鎂、磷離子、肌酸酐、副甲狀腺素、維生素D及尿液鈣、肌酸酐濃。尿鈣排出多寡以Spot urine calcium creatinine ratio(SUCCR)、Fractional excretion of calcium (FECa)、estimated daily calcium(mg/day)估算。並比較組內前後以及組間差異。 本研究共收案18人(pioglitazone 9人、linagliptin 9人),結果發現各組在使用藥物前後或是兩組相比較的SUCCR(p=1.00)、FECa(p=0.78)、estimated daily calcium amount (p=0.94),皆無統計學上差異。 總結,使用愛妥糖相較於糖漸平對於第二型糖尿病患者尿鈣的排出並無差異。 Context: Diabetes mellitus is a common disease with much impact on human’s health and is related to osteoporosis. But the mechanism remains unclear. The foreign researches revealed thiazolidinedione (TZD) would increase the risk of osteoporosis and bone fracture, especially elderly women. However, it is still controversial in terms of the youth and men. Hypercalciuria has been reported to be a risk of osteoporosis, and one study also found pioglitazone might suppress parathyroid hormone secretion and cause increased calciuria. In Taiwan, the prescription of dipeptidyl peptidase 4(DPP4) inhibitors is increasing in the past few years. DPP4-inhibitors have been found to have neutral effect on bone and calcium homeostasis. However, there is few related study to analyze the relationship between TZD, DPP4 inhibitor, especially the effect on urine calcium excretion. Therefore, we designed a randomized controlled trial to evaluate the effect of pioglitazone versus linagliptin on urine calcium excretion. Design: This is a 48-week multicenter (National Taiwan university hospital and National Taiwan university hospital, Yun-Lin branch) randomized controlled study. We examined the effects of pioglitazone (30mg/day) or linagliptin (5mg/day) on bone metabolism, aiming at urine calcium excretion. This study recruited adult (age more than 40 years) type 2 diabetes patients who were on oral antidiabetic drugs (excluding TZD and DPP4 inhibitor) prior to this study with a recent HbA1c between 7.0~8.5%. Eligible volunteers were randomized (1:1) into group A and B. During the following 48 weeks, group A and B received OAD(s)+ pioglitazone and OAD(s)+ linagliptin respectively. Serum calcium, phosphorus, magnesium, creatinine, intact parathyroid hormone, 25(OH)D, urine calcium, creatinine level were checked prior and after 48 weeks’ treatment. The primary objective is to assess the effect of pioglitazone versus linagliptin on kidney by measurement of fractional excretion of calcium (FECa), Spot Urine Calcium Creatinine ratio (SUCCR), and estimated daily calcium amount over the 48 weeks treatment period. The within-group and between-group differences were examined. Result: Total 18 (pioglitazone 9, linagliptin 9) subjects were randomized into 2 group evenly and completed 48-week study. Linaglitin has neutral effect on urine calcium excretion and PTH level as expected. Compared with linagliptin, pioglitazone also demonstrated neutral effect on SUCCR (p=1.00), FECa (p=0.78), and estimated daily calcium amount (p=0.94). Conclusion: Urine calcium excretion fraction, daily urine calcium amount and serum iPTH level remained unchanged after a 48-week treatment in both groups, which suggests that pioglitazone has similar neutral effect as linagliptin on urine calcium excretion. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69044 |
DOI: | 10.6342/NTU201703355 |
全文授權: | 有償授權 |
顯示於系所單位: | 臨床醫學研究所 |
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