Insulin resistance in
Werner's syndrome (WS) is probably due to defective signaling distal to the
insulin receptor. To analyze the metabolic effects of
troglitazone (TRO) in these patients, we performed frequently sampled iv
glucose tolerance tests.
Glucose kinetics were analyzed by the minimal model. Five patients with WS (mean age, 41.2 yr; body mass index, 17.0 kg/m2) were treated with TRO (400 mg/day) for 4 weeks. Each subject underwent a 75-g OGTT and frequently sampled iv
glucose tolerance tests. Treatment reduced the area under the curve of
glucose and
insulin in the OGTT by 26% and 43%, respectively.
Glucose tolerance, as manifested by the
glucose disappearance rate improved significantly (1.36 +/- 0.16 to 1.94 +/- 0.30%/min; P < 0.05). Although the first phase insulin secretion was unchanged,
insulin sensitivity and
glucose effectiveness increased significantly [0.47 +/- 0.11 to 1.38 +/- 0.37 x 10(-4) min/pmol.L (P < 0.05) and 1.72 +/- 0.17 to 2.52 +/- 0.24 x 10(-2) min-1 (P < 0.05), respectively]. However, treatment did not change
glucose effectiveness at zero
insulin. In patients with WS, TRO ameliorates
glucose intolerance mediated by increased
insulin sensitivity as well as
glucose effectiveness, as assessed by minimal model analysis. TRO may modulate the postreceptor signaling component and be a clinically useful regimen for the treatment of patients with the intracellular
insulin signaling defect.