In a study of nonsurgical therapy of Cushing's disease, 62 patients received O,p'-dichlorodiphenyldichloroethane (O,p'DDD), 16 of whom also received cobalt irradiation of the pituitary. After an initial treatment period averaging eight months, a remission of the disease was obtained in 38 of the 46 patients given O,p'DDD alone and in all patients who received drug combined with radiation. Although 60 per cent of these patients subsequently relapsed, additional courses of drug or radiation therapy were usually effective, and 63 per cent of the entire group of patients have so far been kept under control without adrenalectomy. (Forty patients have been followed for at least two years after the initial course of treatment.). O,p'DDD produced little gastrointestinal discomfort; an increased serum cholesterol was the main side effect. This drug allows long-term medical management of Cushings disease in most cases. Whether the combination of O'p'DDD with pituitary radiation is the best therapy has not been established.

Regular insulin was infused from one to five days in seven adult diabetic volunteers previously treated with subcutaneous insulin three times a day. Through a catheter inserted in a peripheral vein, a small pump delivered 66 ± 10 units of insulin per day in a 131.0 ± 4.0 ml. solution at mean rates of 26 ± 4 mU./min. between meals and 373 ± 58 mU/min. during meals; 40 per cent of the total daily dose was given during the three meal periods. These rates were precalculated. Patients were ambulatory. Blood glucose was assayed every fifteen minutes for eight hours during the postprandial periods and hourly otherwise. The over-all highest mean values were observed ninety minutes after breakfast (138 ± 17 mg./100 ml.) and four hours after dinner (121 ± 18); the lowest were 73 ± 7, 64 ± 7, 72 ± 15 at the end of the three high concentration insulin infusion periods and 56 ± 7 at 6 a.m. During insulin infusions the mean values of blood glucose parameters were as follows: 89 ± 7 mg./100 ml. for the mean blood glucose level; 66 ± 9 for the mean amplitude of glycemic excursion; and 17 ± 5 for the modified Schlichtkrull's M coefficient. Insulin infusions gave significantly lower blood glucose levels during the night and at breakfast than insulin three times a day, and higher blood glucose values before lunch. Both technics gave very good control of diabetes. Insulin infusions without blood glucose monitoring are feasible for several days in ambulatory patients.

Summary. Significant sex differences were observed in 24 young lean men and women submitted to two mixed isocMorie meals (880 KcM; protein 40 g; carbohydrate 90 g; fat 40 g;) at 8.15 AM and 12.45 PM. After an overnight fast venous blood glucose levels were lower in women than in men. Plasma insulin responses were lower after the afternoon meal than after the morning one in men bu~ not in women. Thus women did not present the well known cycle of insulin secretion described in men. Estradiol benzoate, 10 mg per day given intra-muscularly for eight days in six men who served as their own control, lowered fasting venous blood glucose levels and enhanced post prandial plasma insulin levels after the morning and the afternoon meal as well. It is suggested that the sex related differences in venous blood glucose and plasma insulin patterns may be due in part to estrogens.Key words: Blood glucose, plasma insulin, meals, diurnal patterns, estrogens.Diurnal and circadian changes in blood glucose and plasma insulin levels have been described in man by several authors [1--13]. The insulin secretion induced by oral glucose [1,6,7, 11,13], tolbutamide [2,13] or isoealorie meals [3,5] was more pronounced in the morning than in the afternoon. Blood glucose levels were lower in the morning than in the afternoon in response to various stimuli [1, 2, 6, 7, 9--13], but not after meals [3].After 3 and 4 days of total fast, plasma insulin levels were higher in the morning than in the afternoon in normal young men [1r These studies were done mainly or only in men.In male rats a daily rhythm of plasma glucose and insulin levels [15] and a diurnal cycle in the pancreatic beta and alpha 2 cells nuclear size [16] were described.The possibility that the circadian variations observed in blood glucose and plasma insulin levels might be sex-related has not been studied until now. However sex-related differences have been observed in substrate and hormone studies. Women responded more than men to several stimuli of Growth Hormone (GH) secretion [17]. Merimee and Fineberg have recently shown [18] that in fasting women venous blood glucose levels decrease more than in fasting men, without significant differences in plasma insulin levels. In rats blood glucose levels were higher fasting in females than in males [19]. Estrogen administration enhanced GI-I secretion in men [17,20], insulin secretion in the rat [21--23] and lowered the post absorptive blood glucose levels in men [17].The aim of this study was to compare the diurnal changes of venous glucose and plasma insulin values in men and women submitted, after an overnight fast, to two identical meals at 8.15 A?r and 12.45 PM. Some men were reinvestigated after parenterM estradiol benzoate administration.