使用曲格列酮治疗的肥胖受试者的糖耐量和胰岛素抵抗得到改善。

Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone.

作者信息

Nolan J J, Ludvik B, Beerdsen P, Joyce M, Olefsky J

机构信息

Department of Medicine, University of California, San Diego 92093.

出版信息

N Engl J Med. 1994 Nov 3;331(18):1188-93. doi: 10.1056/NEJM199411033311803.

DOI:10.1056/NEJM199411033311803

PMID:7935656

Abstract

BACKGROUND

Troglitazone decreases insulin resistance and hyperglycemia in patients with non-insulin-dependent diabetes mellitus (NIDDM), but its effects on subjects without diabetes are not known.

METHODS

We performed oral and intravenous glucose-tolerance tests, studies with the euglycemic-hyperinsulinemic clamp, meal-tolerance tests, and 24-hour blood-pressure measurements at base line and after the administration of troglitazone, 200 mg orally twice daily, or placebo for 12 weeks in 18 nondiabetic obese subjects, 9 of whom had impaired glucose tolerance.

RESULTS

The mean (+/- SD) rates of glucose disposal increased from 4.7 +/- 1.7 to 6.0 +/- 1.7 mg per kilogram of body weight per minute (P = 0.004) and from 9.0 +/- 1.8 to 9.9 +/- 1.3 mg per kilogram per minute (P = 0.02) during insulin infusions of 40 and 300 mU per square meter of body-surface area per minute, respectively, in the troglitazone group. The insulin-sensitivity index, calculated from the results of intravenous glucose-tolerance tests, increased from 0.7 +/- 0.6 x 10(-4) to 1.6 +/- 0.9 x 10(-4) in subjects given troglitazone, and their glycemic response to oral glucose and to mixed meals decreased. The mean fasting plasma insulin concentration decreased by 48 percent (P = 0.002), and the plasma insulin response to oral glucose and mixed meals decreased by 40 and 41 percent, respectively. The changes were similar in the subjects with normal glucose tolerance and those with impaired glucose tolerance. Systolic and diastolic blood pressure decreased by 5 +/- 2 mm Hg (P = 0.05) and 4 +/- 2 mm Hg (P = 0.04), respectively, after treatment with troglitazone. There were virtually no changes in the placebo group.

CONCLUSIONS

Troglitazone decreases insulin resistance and improves glucose tolerance in obese subjects with either impaired or normal glucose tolerance. The ability of troglitazone to reduce insulin resistance could be useful in preventing NIDDM:

摘要

背景

曲格列酮可降低非胰岛素依赖型糖尿病（NIDDM）患者的胰岛素抵抗和高血糖，但对非糖尿病患者的影响尚不清楚。

方法

我们对18名非糖尿病肥胖受试者进行了口服和静脉葡萄糖耐量试验、正常血糖-高胰岛素钳夹试验、进餐耐量试验以及24小时血压测量，这些受试者中9人糖耐量受损。在基线时以及给予曲格列酮（每日口服200mg，分两次服用）或安慰剂12周后进行上述试验。

结果

在曲格列酮组中，当胰岛素输注速率分别为每分钟每平方米体表面积40mU和300mU时，葡萄糖处置的平均（±标准差）速率分别从每分钟每千克体重4.7±1.7mg增加至6.0±1.7mg（P = 0.004）以及从每分钟每千克体重9.0±1.8mg增加至9.9±1.3mg（P = 0.02）。根据静脉葡萄糖耐量试验结果计算的胰岛素敏感性指数，在服用曲格列酮的受试者中从0.7±0.6×10⁻⁴增加至1.6±0.9×10⁻⁴，并且他们对口服葡萄糖和混合餐的血糖反应降低。空腹血浆胰岛素平均浓度降低了48%（P = 0.002），对口服葡萄糖和混合餐的血浆胰岛素反应分别降低了40%和41%。葡萄糖耐量正常的受试者和糖耐量受损的受试者的变化相似。曲格列酮治疗后，收缩压和舒张压分别降低了5±2mmHg（P = 0.05）和4±2mmHg（P = 0.04）。安慰剂组几乎没有变化。