Richard E. Bailey

Plasma Insulin and Glucose Responses of Healthy Subjects to Varying Glucose Loads During Three-hour Oral Glucose Tolerance Tests

The plasma glucose and plasma immunoreactive insulin concentrations of twelve healthy, nonobese, adult subjects were compared following administration of oral glucose loads of 50, 75 and 100 gm., and 1.75 gm./kg. body weight. The time of occurrence and the magnitude of maximal plasma glucose and insulin concentrations were unaffected by the 25 gm. increases in glucose load. The 50 gm. glucose load gave the smallest plasma glucose response during the three-hour tests and this response was statistically distinguishable from the plasma glucose responses due to the 100 gm. and 1.75 gm./kg. loads (p < 0.05). The plasma glucose responses due to the other loads did not differ from each other. Insulin responses, estimated by either summing allthe plasma insulin values or by measuring the areas under the curves, increased approximately 35 per cent with the first 25 gm. glucose load increment (50 to 75 gm.) and 27 per cent with the second 25 gm. load increment (75 to 100 gm.) during the three-hour study. The differences in insulinresponses between the 50 gm. load and the 100 gm. or 1.75 gm./kg. loads were highly significant (p < 0.01) while the difference between the insulin responses following the 75 gm. and 1.75 gm./kg. loads had lower significance (p < 0.05). Differences in insulin responses of the other loads were not significant. Increases in glucose loads above 120 gm. did not further increase the insulin response. This provides evidence that maximal insulin responses provoked by an oral glycemic stimulus alone in subjects are achieved with 100 gm. A wide range was observed in the plasma insulin concentrations among these healthy individuals for any given load, at any one time, and was probably due to biological variation. The fact that incremental changes in glucose load particularly influenced plasma glucose and insulin concentrations relatively late in the glucose tolerance tests, and that mean insulin peakconcentrations did not differ, indicates that increasing glucose load results in a more prolongedinsulinogenic stimulus rather than the acute release of greater quantities of insulin relatively abruptly. These studies provide evidence that the response associated with increasing glucose load is to some extent a function of the quantity of glucose ingested, and that the significant increases in insulin response commonly occur in association with concurrent alterations in plasma glucose concentrations. The results also indicate that the 50 gm. glucose load results in a different plasma glucose response than does the 100 gm. and 1.75 gm./kg. loads and consequently requires different criteria for interpretation of glucose tolerance testing.

Fluorometric determination of the oral hypoglycemic agent β-phenethylbiguanide using alkaline ninhydrin

Summary A fluorometric method for determining β-phenethylbiguanide (PEBG) in microgram and submicrogram quantities is described. This method is based upon a reaction with alkaline ninhydrin. The lower practical limit of PEBG which can be detected by this method is 0.025 μg/ml. The method is not specific for PEBG and applicability for measurements in biological media will require separation of PEBG from other guanidinium compounds.

The effect of heparin on aldosterone secretion and metabolism in primary aldosteronism (1)

Abstract In 1957 it was reported that administration of heparin to patients with and without edema caused natriuresis and in some cases slight potassium retention (2). Subsequent work using heparin as well as certain heparinoids indicated that a concomitant decline in aldosterone excretion rates occurred when these agents were administered (3, 4, 5) and Veyrat and coworkers (6) have provided evidence that the heparinoid Ro I-8307 reduced aldosterone secretion in sodium depleted normal subjects. In order to investigate further the means by which heparin alters aldosterone production, two patients with primary aldosteronism were given heparin and aldosterone secretion rates and the excretion of metabolites of aldosterone were studied under metabolic balance conditions.

TOLBUTAMIDE TEST: A MISLEADING RESPONSE.

carcinoma of the cervix, the amount of radiation delivered to the gonads makes preservation of ovarian function a near impossibility. The older literature affirms that even after radium therapy alone for cervical cancer continued ovarian activity as evidenced by regular menstruation was infrequent. Successful pregnancy after radium treatment for a malignant growth on the cervix is an extremely rare occurrence. In the majority of cases reported before 1942 it was the omission of external radiation which permitted maintenance of genital function in these patients. In the case presented here, and also in the cases recently reported by Ivey (1963) and Whelton and McSweeney (1964), no external x-ray treatment was given. One of the most critical physical laws which govern the amount of radiation delivered to a given point from a radioactive source is the inverse square law. The intensity of radiation decreases by the square of the distance from the source to the selected point. In the cases reported in the literature the preservation of ovarian function can be attributed in great measure to the increased distance from the radium sources at which the gonads were located because of intrauterine gestation, recent parturition or abortion, or a large exophytic growth. In the case reported by Whelton and McSweeney the radium application was made about eight weeks post-partum, and in Iveys case there was a large exophytic growth. However, in the case presented here the growth was of an ulcerative type, and the radium application was made 18 months after the birth of the last child. The existence of amenorrhoea-for nine months in Iveys case, 12 months in Whelton and McSweeneys case, and only two episodes of bleeding in about four years in our case-indicates the action of radiation on the gonads. In Iveys and Whelton and McSweeneys cases the patients were young, being aged 21 and 26 years respectively, while our patient was about 31 years old when the radium was applied. For patients over 40, 1,000 r delivered at the ovaries is sufficient to induce the menopause. This dose is quite inadequate for a young woman, and 2,000 r delivered at the ovaries may well permit future ovulation. The inverse square law also explains the presence of a functioning endometrium in these cases. The doses at the fundus may drop to 10% of that delivered at the cervix. Patency of the cervix is rare, though obviously patency should have been there for the sperm to ascend in those cases where pregnancy has occurred. In Iveys cases and the case reported by Whelton and McSweeney dilatation of the cervix had been carried out before the pregnancy. In the case reported here it was not possible to pass a uterine sound at any stage. Intense irradiation of the cervix destroys its inherent ability to dilate during parturition, but moderate radiation can be tolerated without apparent loss of this function. Stricture of the endocervical canal and possible scarring in the adjacent paracervical tissues would almost certainly result in deep tears in most of the cases if spontaneous delivery were attenmpted. Hence caesarean section is the treatment of choice. Of the two cases referred to from the literature one has had since two more children born by caesarean section, and both the mothers have re-established regular periods. The case reported here has to be further followed up. Among children born to mothers whose ovaries had received a subliminal castration dose of radiation no gross congenital defect, abnormal development, or behaviour problem has been observed. However, the follow-up on all of the children is not complete, and the possibility of a genetic defect in a future generation cannot be ruled out if children should be born to any of these individuals.

Practical considerations in angiotensin II antibody production

Abstract When cost considerations are paramount, one immunization with angiotensin II-rabbit serum albumin immunogen into multiple sites in rabbits suffices to produce high-titer antisera which are clinically useful for radioimmunoassays. Although sustained antibody responses may occur after one or two immunizations with an angiotensin II-poly- l -lysine immunogen, titers are impractically low for clinical work.