Musholt Petra B, Schöndorf Thomas, Pfützner Andreas, Hohberg Cloth, Kleine Iris, Fuchs Winfried, Hehenwarter Silvia, Dikta Gerhard, Kerschgens Benedikt, Forst Thomas
Institute for Clinical Research and Development, Mainz, Germany.
J Diabetes Sci Technol. 2009 Nov 1;3(6):1442-50. doi: 10.1177/193229680900300626.
The aim of our study was to examine the efficacy of short-term intravenous insulin intervention followed by oral pioglitazone/metformin therapy to prevent patients from continuous insulin application.
This prospective, open-label, 4-month pilot study comprised of 14 diabetes patients (5 female, 9 male; age 60 +/- 2 years; body mass index 29 +/- 3.2 kg/m(2); hemoglobin A1c [HbA1c] 7.6 +/- 1.1%) with (1) insufficient glycemic control under a dose of metformin >or=1700 mg/day and/or metformin plus additional oral antidiabetes drugs (OADs) and (2) appropriate residual beta-cell function. Initially, an inpatient 34 h continuous intravenous insulin infusion was performed, and metformin was given (2x 850 mg/day). Insulin was stopped, and pioglitazone 30 mg/day was added at the second inpatient day. Patients were followed for four months. Efficacy parameters [change of HbA1c, fasting blood glucose [FBG], intact proinsulin, adiponectin, and high-sensitivity C-reactive protein (hsCRP)] were assessed after initial normalization of blood glucose values by intravenous insulin and at the study end point.
During the acute insulin intervention, FBG levels were stabilized in all study subjects. In the following OAD treatment period, five patients showed an improvement of HbA1c > 0.5% [35.7%; seven patients remained stable (50.0%), two patients were nonresponders (14.3%)]. Fasting glucose values dropped after insulin infusion (-17.7%; p < .001). This effect was maintained during the consecutive OAD treatment period (glucose +0.3%, not significant (NS); HbA1c -6.0%; p < .05). The initial decrease in fasting intact proinsulin levels was also maintained during the study (end value -41%, p < .05). Improvements in hsCRP values (postinsulin value, -15%, NS; end value -37%; p < .05) and adiponectin values (postinsulin value +15%, NS; end value +128%; p < .001) were demonstrated at end point only after continued glitazone intake.
Our pilot study demonstrated that a beneficial effect of a short-term intravenous insulin application on glycemic control was effectively maintained by pioglitazone/metformin treatment for at least 4 months. In addition, the oral therapy significantly improved cardiovascular risk parameters.
我们研究的目的是检验短期静脉注射胰岛素干预，随后口服吡格列酮/二甲双胍治疗，以防止患者持续应用胰岛素的疗效。
这项前瞻性、开放标签、为期4个月的试验性研究纳入了14例糖尿病患者（5例女性，9例男性；年龄60±2岁；体重指数29±3.2kg/m²；糖化血红蛋白[HbA1c]7.6±1.1%），这些患者（1）在二甲双胍剂量≥1700mg/天和/或二甲双胍加用其他口服抗糖尿病药物（OADs）治疗下血糖控制不佳，且（2）具有适当的残余β细胞功能。最初，进行了34小时的住院持续静脉胰岛素输注，并给予二甲双胍（2×850mg/天）。在住院第二天停用胰岛素，并加用30mg/天的吡格列酮。对患者进行了4个月的随访。在静脉胰岛素使血糖值初步正常化后以及研究终点时，评估疗效参数[HbA1c、空腹血糖[FBG]、完整胰岛素原、脂联素和高敏C反应蛋白（hsCRP）的变化]。
在急性胰岛素干预期间，所有研究对象的FBG水平均稳定。在随后的OAD治疗期间，5例患者的HbA1c改善>0.5%[35.7%]；7例患者保持稳定（50.0%），2例患者无反应（14.3%）。胰岛素输注后空腹血糖值下降（-17.7%；p<0.001）。在连续的OAD治疗期间，这种效果得以维持（血糖+0.3%，无统计学意义（NS）；HbA1c-6.0%；p<0.05）。空腹完整胰岛素原水平的初始下降在研究期间也得以维持（终值-41%，p<0.05）。仅在持续服用格列酮后，终点时hsCRP值（胰岛素后值，-15%，NS；终值-37%；p<0.05）和脂联素值（胰岛素后值+15%，NS；终值+128%；p<0.001）有所改善。
我们的试验性研究表明，吡格列酮/二甲双胍治疗可有效维持短期静脉注射胰岛素应用对血糖控制的有益作用至少4个月。此外，口服治疗显著改善了心血管风险参数。
