Background Troglitazone decreases insulin resistance and hyperglycemiain 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-tolerancetests, studies with the euglycemic-hyperinsulinemic clamp, meal-tolerancetests, and 24-hour blood-pressure measurements at base lineand after the administration of troglitazone, 200 mg orallytwice daily, or placebo for 12 weeks in 18 nondiabetic obesesubjects, 9 of whom had impaired glucose tolerance.
Results The mean (±SD) rates of glucose disposal increasedfrom 4.7 ±1.7 to 6.0 ±1.7 mg per kilogram of bodyweight 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 insulininfusions of 40 and 300 mU per square meter of body-surfacearea per minute, respectively, in the troglitazone group. Theinsulin-sensitivity index, calculated from the results of intravenousglucose-tolerance tests, increased from 0.7 ±0.6 x 10-4to 1.6 ±0.9 x 10-4 in subjects given troglitazone, andtheir glycemic response to oral glucose and to mixed meals decreased.The mean fasting plasma insulin concentration decreased by 48percent (P = 0.002), and the plasma insulin response to oralglucose and mixed meals decreased by 40 and 41 percent, respectively.The changes were similar in the subjects with normal glucosetolerance and those with impaired glucose tolerance. Systolicand diastolic blood pressure decreased by 5 ±2 mm Hg(P = 0.05) and 4 ±2 mm Hg (P = 0.04), respectively, aftertreatment with troglitazone. There were virtually no changesin the placebo group.
Conclusions Troglitazone decreases insulin resistance and improvesglucose tolerance in obese subjects with either impaired ornormal glucose tolerance. The ability of troglitazone to reduceinsulin resistance could be useful in preventing NIDDM.
Source Information
From the Department of Medicine, University of California, San Diego, Division of Endocrinology and Metabolism, La Jolla (J.J.N., B.L., P.B., J.O.), and the Veterans Affairs Medical Center, San Diego, Calif. (M.J.).
Address reprint requests to Dr. Olefsky at the Division of Endocrinology and Metabolism, 9111-G, University of California, San Diego, La Jolla, CA 92093.
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