過氧化物增殖劑活化受體-γ基因多型性對於第二型糖尿病服用Pioglitazone治療的反應

研究背景：Thiazolidinediones(TZDs)為過氧化物增殖劑活化受體-γ (peroxisome proliferator–activated receptor-γ (PPAR-γ)的增敏劑，TZD目前被廣泛用於治療第二型糖尿病，主要可以抑制胰島素抗組性，仍有25%的第二型糖尿病病患使用TZD治療之後，不能有效降低空腹血糖，在體外實驗研究指出PPAR-γ基因變異會影響TZD治療的效果。因此，我們的研究目的在觀察PPAR-γ rs880663基因多型性是否會影響台灣第二型糖尿病病患使用pioglitazone治療的反應。研究方法；本次研究收集了274位第二型糖尿病病患，依據2006年美國糖尿病學會和歐洲糖尿病研究學會準則給予口服降血糖藥物，穩定藥物治療四個月，其中177位服用pioglitazone (30 mg/day)治療，97位沒有服用pioglitazone治療當作控制組。篩選的條件為年齡30-80歲，糖化血色素控制在7-11.5%，身體質量指數大於18.5 kg/m2；排除第一型糖尿病病患、有使用胰島素治療、有全身性疾病、急性併發症及癌症。PPAR-γ rs880663基因分型使用TaqMan即時定量聚合酶連鎖反應方法完成。研究結果：第二型糖尿病人使用pioglitazone治療四個月之後，糖化血色素、空腹血糖、空腹胰島素、胰島素抗阻性指數、三酸甘油酯、GPT及高敏感度C反應蛋白有顯著性的下降；體重、身體質量指數、高密度脂蛋白膽固醇及肌酸酐有顯著性的增加；此外，我們也發現PPAR-γ rs880663 CC 群病人在服用pioglitazone治療四個月後，空腹胰島素及胰島素抗阻性指數改變值下降最多，與CT及TT 群有顯著性的差異，相對的，高密度脂蛋白膽固醇改變值在CC群病人增加最多，與CT及TT 群有顯著性的差異。結論：本研究結果指出PPAR-γ rs880663基因多型性可能為影響台灣人第二型糖尿病病患服用pioglitazone治療的反應。當病人帶有PPAR-γ rs880663 CC基因型對於pioglitazone治療反應較好，比帶有CT或TT基因型的好。

關鍵字

第二型糖尿病；胰島素增敏劑；胰島素抗阻性；基因多型性；過氧化物增殖劑活化受體-γ

並列摘要

Background：Thiazolidinediones(TZDs) are agonists of peroxisome proliferator–activated receptor-γ (PPAR-γ). TZD has widely been used in type 2 diabetic patients mainly by inhibition of insulin resistance. However, 25% of type 2 diabetic patients treated with TZD didn’t reduction in fasting plasma glucose. In vitro study has suggested that PPAR-γ gene variants may influence efficacy of TZD. Our aim is to investigate the effect of PPAR-γ rs880663 gene polymorphism on the response to pioglitazone in type 2 diabetic patients in Taiwan. subjects and Methods: This study included 274 diabetic patients, 177 treated with pioglitazone (30 mg/day) and 97 didn’t be treated with pioglitazone during a course of 4 months. Included criteria: patients with type 2 diabetes aged 30-80 years, HbA1c 7-11.5% and BMI > 18.5 kg/m2. Patients with type 1 diabetes, insulin therapy, systemic illness, acute diseases and malignancy were excluded. Genotyping of the PPAR-γ rs880663 SNP were performed with real-time TaqMan PCR method. Results: After 4 month-treatment of pioglitazone in type 2 diabetic patients, fasting glucose, HbA1c, fasting insulin, HOMA-IR, triglyceride, GPT and hs-CRP were significantly decreased. BMI, body weight, HDL-C and creatinine were significantly increased. However, we found that the change of the fasting insulin and HOMA-IR after 4 months of pioglitazone treatment in CC group significantly decreased as compared to CT and TT groups of PPAR-γ rs880663(P=0.016 and 0.004 ). In contrast, the change of HDL-C in CC group were significantly increased than in CT and TT groups (P = 0.025). Conclusion: Our results implicate that PPAR-γ rs880663 gene polymorphism might affect the response to pioglitazone treatment in type 2 diabetic patients. Patients with CC genotype in PPAR-γ rs880663 had a better therapeutic response to pioglitazone than patients with the CT and TT genotype.

並列關鍵字

Type 2 diabetes ； thiazolidinedione ； insulin resistance ； gene polymorphism ； PPAR-γ

參考文獻

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過氧化物增殖劑活化受體-γ基因多型性對於第二型糖尿病服用Pioglitazone治療的反應

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