INCREASED INSULIN RESPONSIVENESS AFTER CS-045 TREATMENT IN DIABETES-ASSOCIATED WITH WERNERS-SYNDROME

Werner's syndrome is a rare inheritated disorder characterized by acce lerated aging and is often accompanied by diabetes mellitus or impaire d glucose tolerance. Previous reports suggest that insulin resistance is involved in the development of diabetes associated with Werner's sy ndrome. In the present study, chroman-2-ylmethoxy)benzyl]-2,4-thiazoli dinedione, a new oral hypoglycemic agent which reportedly reduces insu lin resistance, was administered to 2 Werner's syndrome patients. The patients were hospitalized for the duration of the study. During a pre treatment period lasting 8 weeks the patients received a controlled di et, however, their previous treatment was unchanged. Throughout the 4- week treatment period, each subject's blood glucose level was measured 7 times each day (07:30, 10:00, 11:30, 14:00, 17:30, 20:00, 22:00) fo r 1 week at 8, 4, and 1 week before treatment and at 2 and 4 weeks aft er treatment. To assess insulin action, the euglycemic glucose clamp t echnique was performed in these subjects at insulin infusion rates of 20, 120 and 400 mU/kg/min before and after 4 weeks of treatment. After 4 weeks of treatment with CS-045, the mean blood glucose level at eac h time point measured in this study was markedly lower compared to the corresponding pretreatment level. The mean glucose disposal rate, as estimated using the euglycemic glucose clamp technique, was increased from 0.01 +/- 0.00, 2.58 +/- 0.11 and 5.61 +/- 0.37 mg/kg/min to 2.53 +/- 0.12, 4.20 +/- 0.13 and 9.20 +/- 0.13 mg/kg/min in case 1 and from 0.01 +/- 0.00, 2.83 +/- 0.63, 5.42 +/- 0.68 mg/kg/min to 1.59 +/- 0.3 2, 5.70 +/- 0.66, and 11.84 +/- 0.82 mg/kg/min in case 2 at insulin in fusion rates of 20, 120 and 400 mU/kg/min, respectively. The dose-resp onse curves obtained after the treatment were shifted to the left. The present study is the first to report the administration of CS-045 in Werner's syndrome and the results suggest that CS-045 improves glucose tolerance in Werner's syndrome by increasing insulin responsiveness.