RELATIONSHIP BETWEEN CARBOHYDRATE-METABOLISM AND SERUM INSULIN-LIKE GROWTH-FACTOR SYSTEM IN POSTMENOPAUSAL WOMEN - COMPARISON OF ENDOMETRIAL CANCER-PATIENTS WITH HEALTHY CONTROLS

Insulin is a major regulator of circulating insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1), suppressing the hepatic production of IGFBP-1. Postmenopausal age, obesity, hypertension, and impaired g lucose tolerance, which are known risk factors for endometrial cancer, are all associated with hyperinsulinemia and insulin resistance. In t his study, we investigated the relationship among serum insulin, gluco se, insulin-like growth factors (IGF-I and IGF-II), and IGFBP-1, -2, a nd -3 in 32 nondiabetic postmenopausal women with endometrial cancer a nd in 18 healthy controls. The mean fasting levels of glucose and insu lin were higher, whereas the mean basal IGF-I, IGF-II, and IGFBP-3 lev els were lower in the endometrial cancer patients than in the healthy control subjects. The mean fasting IGFBP-1 and IGFBP-2 levels did not differ between the groups, and no correlation was found between fastin g insulin and IGFBP-1 concentrations or between insulin and IGFBP-2 co ncentrations in either of the study groups. During an oral glucose tol erance test, the mean glucose levels at 1 and 3 h as well as the mean insulin level at 3 h were significantly higher in the endometrial canc er patients than in the controls, and the area under the glucose curve was larger in the first group. An oral glucose load resulted in a sim ilar fall in serum IGFBP-1 levels in endometrial cancer patients and c ontrols (51% and 55% at 3 h). When the cancer patients were divided in to two subgroups according to the body mass index (kilograms per m2), the obese group had higher glucose and insulin indices than the nonobe se group. No difference was found by the same measures in healthy cont rols. The fasting serum IGFBP-1 levels tended to be lower in the obese than in the normal weight subjects, but the difference did not reach statistical significance. In summary, these results provide preliminar y evidence that the inverse relation between fasting insulin and IGFBP -1, well established in children and young adults, disappears in elder ly women, although short term suppression by insulin still occurs. Fur ther, our data indicate that in addition to carbohydrate metabolism, p ostmenopausal women with endometrial cancer have alterations in their circulating IGF system compared to controls.