Yoshino G, Kazumi T, Iwai M, Matsushita M, Matsuba K, Uenoyama R, Iwatani I, Baba S
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Atherosclerosis. 1989 Jan;75(1):67-72. doi: 10.1016/0021-9150(89)90208-6.
We examined the long-term effect of pravastatin, a new potent inhibitor of endogenous cholesterol biosynthesis, on glucose and lipid metabolism in hyperlipidemic NIDDM. Ten patients (5 on sulfonylurea, 5 on diet) were studied over 12 months. Five were WHO type IIa and 5 were type IIb. Blood was taken before and then 1, 6 and 12 months after initiating 10 or 20 mg daily of pravastatin. The cholesterol concentration in whole plasma and very low density lipoprotein (VLDL), plasma triglyceride and apolipoprotein (apo) B were all significantly decreased within the first month. These changes lasted for 1 year. High density lipoprotein (HDL)-cholesterol increased in the first month but returned to base line thereafter. Low density lipoprotein (LDL)-cholesterol tended to decrease in the first month, and was suppressed significantly from the 6th month (11%) to the 12th month (16%). The effect of pravastatin on LDL-cholesterol in NIDDM was slower and weaker than that published for non-diabetic hypercholesterolemia. Therefore, the mechanism by which pravastatin suppresses plasma cholesterol levels in these two conditions may differ. After 1 year, no adverse effects were noted on hematopoietic, hepatic or renal function. Blood glucose level, hemoglobin A1c and the insulin response to oral glucose were unchanged. In addition, serum creatine phosphokinase showed no abnormal increase. Careful ophthalmological examinations before and after pravastatin treatment revealed no development of new lenticular opacities. Thus, pravastatin appears to be a safe and effective drug for the long-term treatment of NIDDM with hypercholesterolemia.
我们研究了新型强效内源性胆固醇生物合成抑制剂普伐他汀对非胰岛素依赖型糖尿病（NIDDM）高脂血症患者糖代谢和脂代谢的长期影响。对10例患者（5例服用磺脲类药物，5例采用饮食控制）进行了为期12个月的研究。其中5例为世界卫生组织（WHO）IIa型，5例为IIb型。在开始每日服用10或20毫克普伐他汀之前以及之后1个月、6个月和12个月采集血样。全血浆和极低密度脂蛋白（VLDL）中的胆固醇浓度、血浆甘油三酯和载脂蛋白（apo）B在第一个月内均显著下降。这些变化持续了1年。高密度脂蛋白（HDL）胆固醇在第一个月升高，但此后恢复到基线水平。低密度脂蛋白（LDL）胆固醇在第一个月有下降趋势，从第6个月（下降11%）到第12个月（下降16%）受到显著抑制。普伐他汀对NIDDM患者LDL胆固醇的作用比对非糖尿病高胆固醇血症患者报道的作用起效更慢、效果更弱。因此，普伐他汀在这两种情况下抑制血浆胆固醇水平的机制可能不同。1年后，未观察到对造血、肝脏或肾脏功能有不良影响。血糖水平、糖化血红蛋白A1c以及口服葡萄糖后的胰岛素反应均未改变。此外，血清肌酸磷酸激酶未出现异常升高。普伐他汀治疗前后仔细的眼科检查未发现新的晶状体混浊形成。因此，普伐他汀似乎是长期治疗伴有高胆固醇血症的NIDDM的一种安全有效的药物。
