The behavior of blood glucose, plasma free fatty acids and cortisol has been studied after insulin administration in subjects with diabetes mellitus without known complications and with normal plasma cortisol circadian rhythm. The mean plasma cortisol response to hypoglycemia in the diabetic subjects was below that of the normal controls, but not statistically significant. The slower rise to normal in the diabetic group was probably due to the lesser degree of hypoglycemia. DIABETES 77:124-26, March, 1968.Intravenous administration of insulin in the normal subject is followed by rapid decrease in the blood levels of glucose and plasma free fatty acids (FFA). 1>2 Hypoglycemia stimulates the hypothalamic-pituitary axis with a consequent increase in plasma levels of cortisol, 3 growth hormone, 4 -5 epinephrine 6 and norepinephrine. 7 Increased secretion of these hormones serves to restore blood sugar toward normal levels 8 and to elevate plasma FFA, 9 " 11 The increase in plasma cortisol resulting from the intravenous insulin injection is dependent on the integrity of the hypothalamic-pituitary-adrenal structures. 3 -12 Therefore an increase of this hormone after induced hypoglycemia has been used as a test of the function of the hypofhalamic-pituitary-adrenal axis. 3 ' 13 There have been many studies of adrenal function in diabetes mellitus, 14 " 20 but we are not aware of investigations of the above regulatory pathways. Accordingly, we have examined the levels of blood sugar and plasma FFA and cortisol after intravenous injection of insulin in diabetic patients. In the same persons the circadian rhythm of plasma cortisol has been observed also because its variations may influence the response to hypoglycemic stress, 21 and because alterations in diabetes with vascular complication have been described. 22 METHODSCrystalline insulin (o.i I.U. per kg. body weight) was given intravenously at 9:00 a.m. to twelve diabetic patients aged twenty-three to seventy years. Ten apparently normal subjects, aged eighteen to fifty-six years, served as controls. The diabetic patients were judged to be under control from treatment with a standard diet (25 calories per kg. of body weight per day) composed of 45 per cent protein, 40 per cent carbohydrate and 15 per cent fat. None had been treated with insulin, and only a few had received tolbutamide. None had detectable vascular complications. After receiving the intravenous insulin, eight of the patients had tachycardia, tremor, perspiration and a decrease in blood sugar of more than 50 mg. per 100 ml. The patients were fasting for over twelve hours prior to testing.Venous blood samples were obtained before and 15, 30, 45, 60, 90, 120 min. after insulin. Prior to testing, the behavior of plasma cortisol was examined during the day by collecting specimens at 8, 12, 16, and 24 hrs. from diabetic subjects, and subsequently compared with those of fifteen normal subjects.Plasma cortisol was measured by a fluorimetric method (Tarquini and Toccafondi 23 ) in the control sample prior to insu...
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