Nakamura T, Ushiyama C, Suzuki S, Shimada N, Sekizuka K, Ebihara L, Koide H
Department of Medicine, Misato Junshin Hospital, Saitama, Japan.
Diabet Med. 2001 Apr;18(4):308-13. doi: 10.1046/j.1464-5491.2001.00463.x.
Troglitazone, a newly developed thiazolidinedione derivative, has been shown to ameliorate microalbuminuria in diabetic animal model and in human diabetic nephropathy in short-term studies. The aim of the present study was to determine whether troglitazone or sulphonylurea affect micro- albuminuria, macroalbuminuria, or serum type IV collagen concentrations in patients with diabetic nephropathy.
We studied 32 normotensive patients with type 2 diabetes mellitus associated with microalbuminuria (n = 16) or macroalbuminuria (n = 16) and 20 healthy controls. The patients were randomly assigned to one of two groups: those treated with glibenclamide (5.0 mg/day) (n = 8) and those treated with troglitazone (400 mg/day) (n = 8). They received the drug regimen for 12 months. Serum type IV collagen was measured with sandwich enzyme immunoassay.
Type IV collagen concentrations in macroalbuminuric patients were higher than those in microalbuminuric patients (P < 0.05) and healthy controls (P < 0.01). Troglitazone reduced urinary albumin excretion (UAE) in micro-albuminuric patients from 126 microg/min (range 58--180 microg/min) to 42 microg/min (range 14--80 microg/min) (P < 0.01) and also reduced serum type IV collagen levels gradually at 3, 6 and 12 months after treatment (P < 0.05). However, glibenclamide did not affect UAE and type IV collagen levels in micro- albuminuric diabetes patients. In addition, neither troglitazone nor gliben- clamide changed UAE and type IV collagen levels in macroalbuminuric patients.
These data suggest that troglitazone is an effective treatment for renal injury in patients with early diabetic nephropathy.
曲格列酮是一种新开发的噻唑烷二酮衍生物,短期研究表明它可改善糖尿病动物模型和人类糖尿病肾病中的微量白蛋白尿。本研究的目的是确定曲格列酮或磺脲类药物是否会影响糖尿病肾病患者的微量白蛋白尿、大量白蛋白尿或血清IV型胶原浓度。
我们研究了32例血压正常的2型糖尿病患者,其中16例伴有微量白蛋白尿,16例伴有大量白蛋白尿,以及20名健康对照者。患者被随机分为两组:一组接受格列本脲治疗(5.0毫克/天)(n = 8),另一组接受曲格列酮治疗(400毫克/天)(n = 8)。他们接受该药物治疗方案12个月。采用夹心酶免疫测定法测定血清IV型胶原。
大量白蛋白尿患者的IV型胶原浓度高于微量白蛋白尿患者(P < 0.05)和健康对照者(P < 0.01)。曲格列酮可使微量白蛋白尿患者的尿白蛋白排泄量(UAE)从126微克/分钟(范围58 - 180微克/分钟)降至42微克/分钟(范围14 - 80微克/分钟)(P < 0.01),并且在治疗后3、6和12个月时血清IV型胶原水平也逐渐降低(P < 0.05)。然而,格列本脲对微量白蛋白尿糖尿病患者的UAE和IV型胶原水平无影响。此外,曲格列酮和格列本脲均未改变大量白蛋白尿患者的UAE和IV型胶原水平。
这些数据表明曲格列酮是早期糖尿病肾病患者肾脏损伤的有效治疗药物。