薬理と治療

Abstract

[Hypertriglyceridemia has been recognized as an independent risk factor for atherosclerosis. Increased plasma remnant lipoproteins underlie ypertriglyceridemia. Remnant lipoproteins are atherogenic since they are TG-rich and cholesterol-rich, and therefore cause cholesterol accumulation in the plaque of artery. Dyslipidemia in type 2 diabetic patients is characterized by increased plasma triglyceride(TG), remnant lipoprotein and LDL. The correction of increased plasma levels of both TG and LDL is very important to prevent atherosclerosis in type 2 diabetic patients. Fibrate decreases mainly plasma TG and renmnat lipoproteins, whereas statin decreases mainly plasma LDL. The combination therapy of fibrate and statin is therefore thought to be very effective for the correction, but little information is available in Japan. In this study we investigated the effect of the combination therapy on dyslipidemia, glycemic control and adverse reactions in diabetic patients with typeⅡb hyperlipidemia(hypertriglyceridemia plus hypercholesterolemia). Twenty two diabetic patients were studied. They were under 65 years old. They had type Ⅱb hyperlipidemia, i. e. increased plasma levels of TG(≧150 mg/dL)and LDL-cholesterol (≧120 mg/dL). They had normal renal function(plasma creatinine level<1.1 mg/dL)and normal liver function. Plasma lipid and remnant cholesterol were measured before and after the treatment. Plasma remnant cholesterol was determined as RLP-cholesterol(normal range <5.2 mg/dL)by the method of Nakajima et al. The combination therapy of fenofibrate and low dose statin over 10 months significantly reduced plasma TG by 62.3%(281→106 mg/dL), plasma LDL-cholesterol by 35.5%(166→107 mg/dL), and plasma remnant cholesterol by 60.1% (11.2→4.7 mg/dL), and raised plasma HDL-cholesterol by 15.0%(46→53 mg/dL). The combination therapy tended to reduce HbA1c(6.9→6.6%). Plasma CPK and creatinine levels were not changed before and after the treatment and no adverse reaction were observed over the study period. It is concluded that combination therapy of fenofibrate and low dose statin is very effective to reduce particularly plasma TG and remnant cholesterol as well as plasma LDL-cholesterol in diabetic patients. The combination therapy should be positively considered in diabetic patients with typeⅡb hyperlipidemia(hypertriglyceridemia plus hypercholesterolemia)if they have normal renal function., Hypertriglyceridemia has been recognized as an independent risk factor for atherosclerosis. Increased plasma remnant lipoproteins underlie ypertriglyceridemia. Remnant lipoproteins are atherogenic since they are TG-rich and cholesterol-rich, and therefore cause cholesterol accumulation in the plaque of artery. Dyslipidemia in type 2 diabetic patients is characterized by increased plasma triglyceride(TG), remnant lipoprotein and LDL. The correction of increased plasma levels of both TG and LDL is very important to prevent atherosclerosis in type 2 diabetic patients. Fibrate decreases mainly plasma TG and renmnat lipoproteins, whereas statin decreases mainly plasma LDL. The combination therapy of fibrate and statin is therefore thought to be very effective for the correction, but little information is available in Japan. In this study we investigated the effect of the combination therapy on dyslipidemia, glycemic control and adverse reactions in diabetic patients with typeⅡb hyperlipidemia(hypertriglyceridemia plus hypercholesterolemia). Twenty two diabetic patients were studied. They were under 65 years old. They had type Ⅱb hyperlipidemia, i. e. increased plasma levels of TG(≧150 mg/dL)and LDL-cholesterol (≧120 mg/dL). They had normal renal function(plasma creatinine level<1.1 mg/dL)and normal liver function. Plasma lipid and remnant cholesterol were measured before and after the treatment. Plasma remnant cholesterol was determined as RLP-cholesterol(normal range <5.2 mg/dL)by the method of Nakajima et al. The combination therapy of fenofibrate and low dose statin over 10 months significantly reduced plasma TG by 62.3%(281→106 mg/dL), plasma LDL-cholesterol by 35.5%(166→107 mg/dL), and plasma remnant cholesterol by 60.1% (11.2→4.7 mg/dL), and raised plasma HDL-cholesterol by 15.0%(46→53 mg/dL). The combination therapy tended to reduce HbA1c(6.9→6.6%). Plasma CPK and creatinine levels were not changed before and after the treatment and no adverse reaction were observed over the study period. It is concluded that combination therapy of fenofibrate and low dose statin is very effective to reduce particularly plasma TG and remnant cholesterol as well as plasma LDL-cholesterol in diabetic patients. The combination therapy should be positively considered in diabetic patients with typeⅡb hyperlipidemia(hypertriglyceridemia plus hypercholesterolemia)if they have normal renal function.]