IMPROVEMENT IN GLUCOSE-TOLERANCE AND INSULIN-RESISTANCE IN OBESE SUBJECTS TREATED WITH TROGLITAZONE
IMPROVEMENT IN GLUCOSE-TOLERANCE AND INSULIN-RESISTANCE IN OBESE SUBJECTS TREATED WITH TROGLITAZONE
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DOI：
10.1056/nejm199411033311803
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发表时间：
1994-11-03
影响因子：
158.5
通讯作者：
OLEFSKY, J
中科院分区：
文献类型：
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作者：
NOLAN, JJ;LUDVIK, B;OLEFSKY, J
背景资料。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疗效尚不清楚。我们对18名非糖尿病肥胖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，膳食耐量试验，24小时酸血压测量，并在服用曲格列酮后，每天两次口服200 mg，或服用安慰剂12周，其中9人糖耐量受损。曲格列酮组平均葡萄糖处置速率(+/-SD)分别从4.7±-1.7 mg/kg体重每分钟增加到6.0±-1.7 mg/分钟体重(P=0.004.0 5)，从9.0+/-1.8 mg/kg每分钟增加到9.9+/-1.3 mg/分钟(P=0.0 2)。根据静脉葡萄糖耐量试验的结果计算，服用曲格列酮的受试者的胰岛素敏感性指数从0.7+/-0.6×10(-4)增加到1.6+/-0.9×10(-4)，他们对口服葡萄糖和混合膳食的血糖反应降低。空腹血浆胰岛素平均浓度降低48%(P=0.002)，口服葡萄糖和混合餐的胰岛素反应分别降低40%和41%。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下降5+/-2 mm Hg(P=0.05)和4+/-2 mm Hg(P=0.04)。安慰剂组几乎没有变化。曲格列酮降低胰岛素抵抗，改善糖耐量受损或正常的肥胖受试者的葡萄糖耐量。曲格列酮降低胰岛素抵抗的能力可能有助于预防NIDDM。
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, acid 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.