- 學位論文
血糖控制對statins在第二型糖尿病人之療效影響評估
Evaluation about the Impact of Glycemic Control on the Efficacy of Statins in Patients with Type 2 Diabetes
摘要
胰島素阻抗為type 2糖尿病發生的主要原因，肇因於臟器脂肪組織釋放過多的游離脂肪酸進入肝門脈循環，導致胰島素阻抗及高胰島素血症(hyperinsulinemia)；胰島素阻抗不僅降低糖尿病人對胰島素的敏感度(insulin sensitivity)、增加肝醣釋出，同時產生血糖耐受性(glucose tolerance)異常及高胰島素血症，造成病人的高血糖濃度，形成葡萄糖毒性作用(glucotoxicity)；高胰島素血症會增加糖尿病人游離脂肪酸濃度(non-esterified fatty acid, NEFA)，形成脂質毒性作用(lipotoxicity)等胰島素阻抗現象(syndrome of insulin resistance)。 高血脂症(hyperlipidemia)尤其是低密度脂蛋白膽固醇過高，為動脈粥樣硬化(atherosclerosis)的主要危險因子，而動脈粥樣硬化在冠心症(coronary heart disease, CHD)及其他心血管疾病扮演極重要的角色。研究顯示，降低血漿總膽固醇1%，冠心症的發生率減少2%；LDL-C降低1%，冠心症的發生率減少1~2%；HDL-C每增加1mg/dl，可減少冠心症的死亡率約3.5%。HMG-CoA還原酶抑制劑(3-hydroxy- 3-methyl- glutaryl- coenzyme A reductase inhibitors, statins)，可藉由抑制肝臟的膽固醇合成及增加肝臟細胞LDL-受體數量與活性，有效的降低血漿總膽固醇及LDL-C濃度，對降低冠心症發生率及死亡率有正面的評價。 研究目的- 本次研究在於評估，第二型糖尿病人，良好的血糖控制對statin藥品的降膽固醇療效之影響。 研究設計、方法- 自2002年1月1日起至2002年10月31日止，隨機抽樣台南市新樓醫院心臟內科、神經內科、新陳代謝科與家庭醫學科門診病人共計1,325人進行研究，受試者須符合下列條件方予收案，1.服用statin類藥品之病人，符合全民健保降血脂藥物給付規定；2.排除罹患甲狀腺功能偏低、嚴重肝腎病變(血清creatinine＞3mg/dl；肝硬化、急性阻塞性肝病)患者3.病人併服下列藥品：賀爾蒙替代療法(HRT)、類固醇、利尿劑或酗酒者也予排除。納入之受試者首先由藥師給予疾病、藥物、飲食與生活習性改善等的相關衛教，之後並持續定期追蹤(HbA1c每1- 2個月檢測一次；cholesterol每3- 4個月檢測一次)，記錄每個病人之HbA1c值及cholesterol值，且每3- 4個月主動與病人電話聯絡一次，至2003年12月31日設定為本次實驗觀察截止日期。且本次實驗受試者必需連續服用statin類藥品6個月以上；所服用的statins為目前上市且普遍使用的劑量，共有五種，分別為lovastatin 20mg、pravastatin 10mg、simvastatin 20mg、fluvastatin 40mg及atorvastatin 10mg。統計方法使用SPSS 10軟體程式作統計分析及比較。 研究結果- 總計有1,003人完成評估研究，其中非糖尿病者有524人(52%)，糖尿病人有479人(48%)；完成評估的受試者中，男性382人(38%)，女性621人(62%)；我們將1,003名病人分成3組，分別為A.非糖尿病者，524人;B.糖尿病人血糖控制良好者(HbA1c≦7)，176人；與C.糖尿病人血糖控制不良者(HbA1c>7)，303人。我們發現，在降血清膽固醇療效與服藥前後膽固醇差異的交叉比較，糖尿病人血糖控制不良者(HbA1c>7)服用fluvastatin (-25.8mg/dl, P=0.014)、simva- statin (-33.7mg/dl, P=0.021)與atorvastatin (-26.2mg/dl, P=0.024)的療效，皆遠低於糖尿病人血糖控制良好者(HbA1c≦7)，且P<0.05在水準上的平均差異很顯著。 結論- 這次評估實驗我們發現，整體而言，這次評估實驗發現，血糖控制良好患者(HbA1c≦7)服用statins後，總膽固醇降低約24%；與血糖控制不良者(HbA1c>7)服藥後，總膽固醇值僅降低約15%，兩者比較，前者(HbA1c≦7)明顯優於後者(HbA1c>7)，呈顯著意義(P< 0.05)。因此，對於併發高血脂的第二型糖尿病人，良好的血糖控制有益statin藥品的降膽固醇療效。
並列摘要
The population of Diabetes Mellitus in most countries, especially type 2 diabetes, is increasing. It has been estimated that diabetes will affect 220 million people by 2010. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) demonstrated that (Diabetic Control and Complications Trial, DCCT, in patients with type 1 diabetes, 1983~1993), the value of tight glycemic control, plasma sugar and glycosylated hemoglobin (HbA1c), in significance delaying the onset and slowing the progression of serious long-term diabetic complications, including retinopathy, nephropathy, neuropathy and cardiovascular disease. The late findings this true from the United Kingdom Prospective Diabetes Study (UKPDS) in patients with type 2 diabetes. Hypercholesterolemia, especially the low-density lipoprotein cholesterol (LDL-C), plays a major role in the etiology of atherosclerosis, and in the development of coronary heart disease (CHD) and other vascular diseases. The 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG- CoA) reductase inhibitors, categorized as statins, are the most efficient drugs for the treatment of hypercholesterolemia. Statins inhibit endogenous cholesterol synthesis in the liver and increase the expression of LDL–receptors, resulting in an increase in up-regulated catabolism of plasma LDL-C. It has been shown that lowing of LDL-C reduces the incidence of CHD. Objective- To assess the efficacy of statins in patients with good glycemic controlled type 2 diabetes. Research design and methods- Total 1,325 patients were enrolled in this randomized study from January 1, 2002 to December 31, 2003. Participants in this study were excluded as following: 1.Hypothyroidism, 2.Obstructive liver disease, 3.Chronic renal disease (creatinine＞3mg/dl), 4.Alcoholism, 5.Drugs with pregestins, anabolic steroids, and cortico- steroids), and 6.Statins treatment less than 6 months, or discontinue off and on. Lipid-lowering drugs were treated as following: lovastatin 20mg, pravastatin 10mg, simvastatin 20mg, fluvastatin 40mg, and atorvastatin 10mg. Laboratory profiles, including serum cholesterol and HbA1c, were collected every 3- 4 month as a routine from the beginning to the ending of this progress. Data was analysis statistical with SPSS 10. Results- Total 1,003 patients were collected, and divided 3 separate classes. 1.Patients with no diabetes, 524 participants. 2.Diabetes with good controlled (HbA1c≦7), 176 participants. And 3. Diabetes below controlled (HbA1c>7), 303 participants. From data, fluvastatin (-25.8 mg/dl, P=0.014), simvastatin (-33.7mg/dl, P=0.021), and atorvastatin (-26.2mg/dl, P=0.024), we found that, the lipid- lowing efficacy in diabetes patients with good control is more effective than those of diabetes below controlled, are statistical significantly. Conclusions- Most patients, improved glycemic control can be very effective for reducing total cholesterol levels by 24%, benefit from statins. The goal of this study suggests that good glycemic controlled benefits the efficacy of statins in type 2 diabetes.
參考文獻
延伸閱讀
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