Type I diabetes may be an autoimmune disorder, although the evidence is largely circumstantial. The natural history of the disease after diagnosis includes partial remission in most patients, but only about 3 percent achieve transient insulin independence. beta Cell function, as indicated by the plasma concentration of C-peptide, is lost over 6 to 30 months and islet cell antibodies disappeared over 1 to 2 years. This article describes a pilot study in which 41 patients were treated with the immunosuppressive agent cyclosporine for 2 to 12 months. Of 30 patients treated within 6 weeks of diagnosis, 16 became insulin independent with concentrations of plasma C-peptide in the normal range and decreasing titers of islet cell antibodies. Of 11 patients who entered the study 8 to 44 weeks after diagnosis, two achieved this state. These results indicate that a controlled trial of the effects of cyclosporine in type I diabetes should be conducted.
In prepubertal children, insulin lispro given before meals is safe and significantly lowers postprandial glucose levels after breakfast and dinner compared with regular human insulin, and insulin lispro given after the meal provides similar benefits as regular human insulin before the meal.
A B S T R A C T The role of the human testis in the production of 17fi-estradiol (E2) was investigated by determining the concentration of E2 and testosterone in peripheral and spermatic vein plasma samples. Specimens were obtained from eight normal men, three men with hypogonadism, and two patients with the incomplete form of the feminizing testes syndrome. For comparison, similar studies were performed in four monkeys, 10 mongrel dogs, and 4 additional dogs who were given 1000 IU of human chorionic gonadotropin/day for 5 days. Plasma E2 was measured by radioimmunoassay utilizing sheep anti-E2 serum preceded by ether extraction and thin layer chromatographic separation of plasma steroids. Procedural blanks, which were subtracted from all reported values were 14.1 +0.74 (SEM) pg for deionized water and 13.1 ±0.66 pg for charcoaladsorbed pooled male plasma. Pooled male and pooled female control plasmas averaged 17 ±0.71 pg/ml and 95 +6.9 pg/ml, respectively; individual adult male specimens ranged between 8 and 28 with a mean of 18 ±1.4 pg/ml. In the eight normal men, the mean peripheral vein E2 concentration was 20 ±1.6 pg/ml, while the spermatic vein concentration was 50 times as great, 1049 ±57 pg/ml. All three patients with testicular abnormalities had low spermatic vein E2 concentrations (160, 280, and 416 pg/ml). Lesser E2 gradients were found across the simian (3-fold) and canine (approximately 12-fold) testes. Testicular testosterone gradients (human 110-, simian 10-, and canine 77-fold) were greater than the E2 gradients in all three species. In four dogs, HCG treatment elicited a 6-fold increase in peripheral and a 9-fold increase in spermatic vein testosterone concentrations; however, peripheral and spermatic vein E2 concentrations did not differ from control values. Spermatic vein E2 concentrations were > 4600 and 2210 pg/ml (post-HCG) in two patients with the incomplete form of the feminizing testes syndrome. Postorchiectomy, peripheral E2 and testosterone concentrations fell precipitously in both patients, confirming the major contribution of the testes, in this syndrome, to circulating E2 and testosterone. These studies provide direct evidence that the human testis secretes estradiol.
A B S T R A C T The secretion of androgens and estrogens by normal and abnormal testes was compared by determining the concentrations of dehydroepiandrosterone (DHEA), androstenedione (A4A), testosterone (T), estrone (El), and 17f-estradiol (E2) in peripheral and spermatic venous plasma samples from 14 normal men and 5 men with unilateral testicular atrophy. Four normal men and one patient with unilateral atrophy of the testis were given human chorionic gonadotropin (HCG) before surgery. Plasma estrogens were determined by radioimmunoassay; plasma androgens were measured by the double-isotope dilution derivative technique. Peripheral concentrations of these steroids before and after HCG were similar in both the normal men and the patients with unilateral testicular atrophy. In normal men, the mean +SE spermatic venous concentrations were DHEA, 73.1±+11.7 ng/ml; A4A, 30.7±7.9 ng/ml; T, 751±114 ng/ml; Ei, 306±55 pg/ml; and Ea, 1298±216 pg/ml. Three of four subjects with unilateral testicular atrophy had greatly diminished spermatic venous levels of androgens and estrogens. HCG treatment increased In the single subject with an atrophic testis who received HCG, the spermatic venous concentrations of androgens and estrogens were much less than in normal men similarly treated. We conclude that: (a) El is secreted by the human testis, but testicular secretion of El accounts for less than 5% of El production in normal men; (b) HCG stimulation produces increases in spermatic venous estrogens equal to or greater than the changes in androgens, including testosterone; and (c) strikingly decreased secretion of androgen and estrogen by unilateral atrophic human testes cannot be appreciated by analyses of peripheral steroid concentrations.
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