Hypoglycemia.

Except in diabetic patients receiving insulin or sulfonylureas, hypoglycemia is a rare disorder. It is identified by modified Whipple's criteria consisting of neuroglycopenic symptoms, a blood glucose level equal to or less than 40 mg/dL, and relief of symptoms by glucose use. The sources of the body glucose are dietary intake, glycogenolysis, and [figure: see text] gluconeogenesis. The metabolism of glucose involves oxidation and storage as glycogen or fat. Causes of hypoglycemia include medications or toxins capable of decreasing blood glucose, disorders associated with fasting hypoglycemia, and postprandial hypoglycemic disorders. The most common type of hypoglycemia is insulin-induced hypoglycemia in diabetics. Insulinoma is rare; however, it is the most common hormone-secreting islet cell tumor. The diagnosis is made by the occurrence of hypoglycemia in the presence of symptoms of neuroglycopenia and inappropriately high levels of insulin and C-peptide. In hospitalized patients, the diagnosis is best made by prolonged fast. Most insulinomas are small and require invasive methods for precise localization. In surreptitious insulin use, hypoglycemia is associated with low plasma C-peptide. Postprandial hypoglycemia occurs in response to feeding and is generally caused by excessive insulin effect. It is seen in patients with postgastric surgery and rarely in early diabetes mellitus. Idiopathic postprandial hypoglycemia is rare and seems to be caused by subtle abnormalities of insulin response to food. Treatment of postprandial hypoglycemia consists of frequent small meals, with deletion of refined carbohydrate and increased protein intake. Primary treatment of insulinoma is surgical resection of the tumor.

Racial differences in the correlation between gonadal androgens and serum insulin levels.

OBJECTIVE: We previously demonstrated a direct correlation between serum insulin levels and gonadal androgens (testosterone and androstenedione) in a group of obese hyperandrogenic predominantly black women. Subsequent work by others in predominantly white women showed conflicting results. To examine these potentially important racial differences further, 14 premenopausal females from each ethnic group, of similar age, BMI, and waist-to-hip ratio, were studied. RESEARCH DESIGN AND METHODS: We measured baseline gonadal androgens, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and leutinizing hormone (LH)/follicle-stimulating hormone ratio. Serum glucose, insulin, and C-peptide were measured at baseline and during a 2-h oral glucose tolerance test (area under the curve [AUC]). Insulin sensitivity was measured by glucose decrement during the first 15 min of an intravenous insulin tolerance test. RESULTS: Simple correlation analysis revealed a significant direct correlation in blacks (but not whites) between gonadal androgens and AUC for glucose, insulin, and C-peptide. Race-by-covariate interaction models reinforced the simple correlation finding. Cholesterol level was also correlated to all androgens in blacks, but not in whites. We also found that whites had higher serum triglycerides and greater AUC glucose than blacks. CONCLUSIONS: We conclude that there is a significant direct correlation between gonadal androgens and stimulated glucose, insulin, and C-peptide in blacks but not in whites. Thus, the previously reported direct correlation between gonadal hyperandrogenism and hyperinsulinemia may be a race-dependent phenomenon, hitherto an unreported observation. The implications of these findings are discussed.

Case report: amelioration of insulin resistance in diabetes with dehydroepiandrosterone.

In hyperandrogenic females, the ratio of dehydroepiandrosterone (DHEA) to testosterone may be an important determinant of insulin sensitivity. This study involved changes in insulin sensitivity and glucose metabolism with therapeutic manipulation of DHEA (S)/testosterone in a female patient with non-insulin-dependent diabetes and hyperandrogenism. Therapeutic intervention included 1-month treatment with 0.25 mg dexamethasone at bedtime and 1-month dexamethasone + DHEA. Insulin sensitivity and glucose tolerance were assessed before and after each treatment regimen by examining: 1) fasting and oral glucose tolerance test glucose and insulin levels, 2) hypoglycemic response to intravenous insulin, and 3) erythrocyte insulin receptor binding. With dexamethasone alone, DHEAS, testosterone, and their ratio were reduced with a concomitant increase (30%) in oral glucose tolerance test insulin levels and a decrease (33%) in erythrocyte insulin binding. With DHEA + dexamethasone, the ratio of DHEAS/testosterone increased 16-fold along with a marked improvement in insulin sensitivity, as determined by a more than 30% reduction in fasting and oral glucose tolerance test insulin levels, a threefold stimulation of the rate of glucose disappearance with intravenous insulin, and a 30% increase in insulin binding. DHEA improved insulin sensitivity and reduced fasting and oral glucose tolerance test glucose levels and ameliorated the diabetic state. The ratio of DHEAS/testosterone is an important regulator of insulin sensitivity and glucose tolerance and that DHEA therapy may be beneficial in the treatment of certain forms of insulin resistance.

Immunohistochemical localization of renin and angiotensin in the ovary: comparison between normal women and patients with histologically proven polycystic ovarian disease.

OBJECTIVE: This study was designed to test the hypothesis that the ovarian renin-angiotensin system may play a role in polycystic ovarian disease (PCOD). DESIGN: The immunohistochemical distribution of renin and angiotensin in ovaries from seven women with histologic diagnosis of PCOD was compared with that of normal ovaries. RESULTS: The large cystic follicles of polycystic ovaries (PCO) presented intense immunostaining for renin and angiotensin in both theca and granulosa cells (GCs). In developing follicles of normal ovaries, the immunostaining was restricted to the theca cell layer, with the exception of the immediately preovulatory follicles which displayed intense positivity of granulosa as well as theca cells. Atretic follicles of normal ovaries showed staining of both theca and GCs. In both normal and PCO, patches of hilus cells were intensely stained. Luteal cells also consistently stained both in normal ovaries and in the occasional corpus luteum present in polycystic ovaries. CONCLUSIONS: This study highlights the link between the ovarian renin-angiotensin system and those ovarian compartments known to be actively engaged in androgen secretion and/or luteinization and suggests that there may be an association between the ovarian renin-angiotensin system and PCOD.

Pepstatin inhibition of proteinase-free human renin.

The kinetics of inhibition of proteinase-free human renin and of pepsin by the carboxyl proteinase inhibitor pepstatin have been examined. Inhibition was of the tight-binding type with both enzymes. Inhibition of crude human renin was of the classical, freely reversible type, but most of the renin-like activity of the preparation was due to contaminating proteinases which could be separated chromatographically from the renin. These results clarify previous kinetic studies of pepstatin inhibition of human renin.

Proteinase activity of human renin preparations: the International Reference Preparation (Renin Standard 68/356).

1. Several commonly used preparations of human renin, including the International Reference Preparation (Renin Standard 68/356), were examined for the presence of contaminating proteinase activity by using a 14C-glycinated bovine haemoglobin substrate assay. 2. All of the human renin preparations tested cleaved haemoglobin even in the presence o di-isopropylfluorophosphate and ethylenediaminetetra-acetate (EDTA). For a given amount of renin activity, varying amounts of proteinase activity were seen. The pH optimum also varied between preparations. 3. Small peptide inhibitors of human renin were not able to inhibit the proteinase activity. Furthermore a diazoacyl reagent and pepstatin, both potent inhibitors of aspartic acid-active site proteinases, were only partially inhibitory. 4. These and other observations suggest that the proteinase activity of the human renin preparations is not due to renin itself, but to contaminating proteinases of different types. Since these enzymes may produce angiotensin I or peptides which may interfere in renin assays, crude preparations of renin which contain proteinase activity, including the International Reference Preparation, should be used with caution or replaced by proteinase-free human renin which can be easily prepared by use of suitable affinity chromatography.

Depressed plasma testosterone and fractional binding of testosterone in obese males.

Plasma testosterone (T), fractional binding of T to T-binding globulin (TeBG), LH, and FSH were evaluated in 22 obese men. Only 1 of 12 men weighing from 176-200% of ideal body weight (group I) had a low T concentration, while 9 of 10 men greater than 200% of ideal weight (group II) had plasma T concentrations 2 SD below the normal mean. The fractional binding of T to TeBG was equally and significantly decreased in both groups. As a result, the mean and individually calculated free T concentrations (free T index) were normal in group I. In contrast, the mean free T index in group II was significantly less than normal males and group I. Individually, 1 of 7 group II men had a free T index 2 SD below the normal mean. LH and FSH were normal in both groups. These studies indicate that in most obese males a low or low normal T is offset by decreased binding to TeBG, resulting in a normal free T index. However, some morbidly obese males are unable to alter their hypothalamic-hypophyseal-gonadal axis to maintain a normal free T index.