本研究目的藉由在已使用胰島素並加入thiazolidinedione (TZD)治療第2型糖尿病的收案病人探討其臨床表現Glycated hemoglobin (HbA1c)和胰島素減少的劑量及副作用(體重增加和增加水腫發生)。因TZD會增加胰島素的敏感性，降低胰島素阻抗，所以TZD加胰島素可以降低胰島素劑量、降低HbA1c和增加體重、水腫的發生。研究中根據世界衛生組織的標準，收案病人均已被診斷為第2型糖尿病，且使用胰島素治療至少三個月(有或沒有合併使用口服降血糖藥物)，雖然持續使用同類胰島素但血糖並未獲得良好的控制。根據收案標準和排除條件，篩選至最後有38人符合進入本研究分析，這38人確定使用TZD之前有使用胰島素至少三個月和使用TZD之後一直持續使用胰島素。最主要影響效力的變項(primary efficacy)是HbA1c和胰島素劑量，其次影響效力的第二變項(secondary efficacy)包括體重變化和水腫情形。38位收案病人的分析探討，依四項評估指標進行分析：(1) HbA1c改變；(2)胰島素劑量減少；(3)病人體重變化；(4)病人水腫變化。研究結果顯示HbA1c的改變、病人的體重及水腫變化均有統計上的意義。病人在收案前使用SG/Glinides、metformin、AGI口服降血糖藥物和胰島素治療或單獨胰島素治療，血糖沒有得到適當的控制，收案後把TZD加入在已使用胰島素治療第2型糖尿病的病人，病人血糖有獲得較好控制和有減低胰島素劑量的趨勢，顯示TZD加胰島素比單獨使用胰島素可將血糖控制在較好的情況，也可以使已經在使用胰島素的病人減低胰島素劑量。當發生水腫時，通常可藉由減少TZD劑量和或加利尿劑來控制。總之，雖然要注意TZD加胰島素可能產生的副作用(水腫和體重增加)，但是當病人有血糖控制不好時，TZD合併胰島素應該是可以被考慮使用的。
關鍵字: 胰島素、thiazolidinedione、第2型糖尿病、糖化血色素

The aim of this study is conferring the clinical manifestations and side effects in type 2 diabetics who treated by insulin with thiazolidinedione (TZD). TZD would raise the insulin sensitivity and reduce the insulin impedance, so TZD with insulin could decrease the insulin dosage, HbAlc and the morbidity of weight and dropsy gain. The patients who included this study according to the standard of WHO were type 2 diabetics treated with insulin for 3 months at least. The same kind of insulin was used in this period and the blood sugar couldn’t get control well. According to the included and excluded criteria, there were 38 patients fitted this analysis. They used insulin for 3 month at least before treating TZD, and kept taking insulin after treating TZD. In this study, the primary efficacy was to estimate HbAlc and record insulin dosage, the secondary efficacy included the change of weight and the situation of dropsy. The evaluation of this study showed that the mean value on 38 patients according to 4 appraisal targets: (1) the change of HbAlc; (2) decreasing the insulin dosage; (3) the weight change of the patients; (4) the dropsy change of the patients. After included this case, the patients were combined with TZD in type 2 diabetics who treated insulin. We found that the patients’ blood sugar were controlled well and seem decreased insulin dosage. It was shown that TZD with insulin could control blood sugar better than treating insulin only, and also could decrease insulin dosage in the patients who were using insulin. When dropsy occurred, we could suggest decreasing TZD dosage or adding the diuretic. Briefly, we might have to pay attention the side effect such as dropsy or weight gain occurred when we use TZD with insulin. And then the patient’s blood sugar out of control, it could be considered to treat by TZD with insulin.

Key words: insulin, thiazolidinedione, type 2 diabetics, Glycated hemoglobin (HbA1c)

目錄
中文摘要………………………………………………………………... II
Abstract………………………………………………………………….. III
致謝……………………………………………………………………… IV
表目錄…………………………………………………………………...VII
圖目錄…………………………………………………………………...VIII
一、前言
1. 糖尿病的流行病學……………………………………………… 1
2. 糖尿病的診斷 …………………………………………………. 2
3. 糖尿病的定義…………………………………………………… 3
4. 糖尿病的分類…………………………………………………… 4
5. 第2型糖尿病之藥物治療……………………………………… 6
6. 第2型糖尿病合併藥物治療………………………………........ 18
7. 胰島素的治療………………………………………………........ 21
8. Thiazolidinediones(TZD)加胰島素的治療……………………… 24
二、研究目的…………………………………………………………… 25
三、研究方法
1.收案病人………………………………………………………….. 25
2.資料來源………………………………………………………….. 26
3.評估方法………………………………………………………….. 26
4.收案流程………………………………………………………….. 27
5.臨床評估………………………………………………………….. 28
6.安全評估………………………………………………………….. 28
7.統計分析………………………………………………………….. 28
四、結果
1. 收案病人基本特性和臨床特性………………………………… 29
2. TZD和胰島素合併治療的效力…………………………………. 30
五、討論
1.收案38位病人的分析探討……………………………………….. 42
2. 收案38位病人使用其它降血糖藥物是否影響本研究TZD加入已
使用胰島素治療的第2型糖尿病人治療效果分析…………. 51
3.收案38位病人以HbA1c(9%)、使用胰島素種類(Levemir或Novom
為factor的分組分析……………………..…………………… 51
4. 收案38位病人以HbA1c(9%)、使用胰島素種類(Levemir或Novomix)為factor其伴隨使用其它降血糖藥物是否影響本研究TZD加入已使用胰島素治療的第2型糖尿病人的治療效果分組分析………………54
六、研究的限制(Limitations of the Study) ……………………………. 57
七、結論………………………………………………………………… 57
八、參考文獻…………………………………………………………… 58



表目錄
表 1. Baseline demographic and clinical characteristics…………………30
表 2. Biochemistry and characteristic before and after treatment
with thiazolidinedione and insulin(N=38) ………………………. 32
表3. Biochemistry and characteristic before and after treatment with
thiazolidinedione and insulin(HbA1c小於等於9% N= 15) ………. 38
表4. Biochemistry and characteristic before and after treatment with
thiazolidinedione and insulin (HbA1c大於9% N=23) ……………. 39
表5. Biochemistry and characteristic before and after treatment with
thiazolidinedione and insulin (Levemir N=33) ……………………..40
表6. Biochemistry and characteristic before and after treatment with
thiazolidinedione and insulin (Novomix N=5) …………………….. 41
表7. HbA1c改變……………………………………………………….. 44
表8. 胰島素劑量減少…………………………………………………. 47
表9. 體重變化………………………………………………………….. 49
表10. 水腫變化………………………………………………………… 50


圖目錄
圖1. 研究參與者的登入和追蹤…………………………………………27
圖2. 已使用胰島素的第2型糖尿病病人合併TZD治療平均308天後HbA1c從基礎值的變化………………………………………………………… 33
圖3. 已使用胰島素的第2型糖尿病病人合併TZD治療平均308天後胰島素劑量從基礎值的變化…………………………………………............ 33
圖4. 已使用胰島素的第2型糖尿病病人合併TZD治療平均308天後體重從基礎值的變化………………………………………………………… 34
圖5. 已使用胰島素的第2型糖尿病病人合併TZD治療平均308天後水腫發生率從基礎值的變化………………………………………………… 34

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