Diet,pregnancy, and lactation: Effects on adipose tissue,lipoprotein lipase,and fat cell size

Adipose tissue fat cell size and lipoprotein lipase (LPL) activity were determined in the retroperitoneal and subscapular depots of nonpregnant, pregnant, and postpartum rats fed either a standard laboratory diet or a high-fat diet containing 55% fat by wieght. High-fat feeding for 20 days increased, in nonpregnant rats, fat cell size and LPL activity two-to threefold in both depots. In pregnant rats at term, fat cell size was increased and LPL activity was depressed in both dietary groups. Twenty days postpartum, both retroperitoneal fat cell size and LPL activity were decreased in proportion to the size of the litter. Rats not allowed to lactate had fat cell sizes and LPL activity that were not significantly different than in nonpregnant controls. Fat cell size and LPL activity in rats nursing four pups were reduced to 77% and 36% of control, respectively. Those nursing a normal-sized litter of eight pups demonstrated a further reduction of fat cell size to 38% and of LPL activity to 2% of nonpregnant control values. High-fat feeding and obesity did not prevent the fat loss and decreased LPL activity associated with lactation; fat cell size was decreased to 61% and LPL activity to 3% of control values. Values for the subscapular depot followed essentially the same pattern as that observed for the retroperitoneal depot. Mammary LPL activity was increased more than tenfold in animals nursing four or eight pups compared with values at term, whereas no activity was detected in rats not allowed to lactate.     

A developmental study of progesterone, corticosterone, cortisol, and cortisone in the adrenal glands of the embryonic chick.

Pairs of adrenal glands were removed from embryonic chicks at 2-day intervals between 9 and 21 days of incubation. Four corticosteroids (progesterone, corticosterone, cortisol, and cortisone) were separated by column chromatography and their concentrations were determined using the competitive protein-binding assay of Murphy [(1967) J. Clin. Endocrinol. Metab.27, 973–990]. Further identification of cortisol in embryonic chicks was carried out using thin layer and paper chromatography followed by the double isotope assay. Total corticosteroid/pair adrenal glands rose from 9 ng at 9 days to a peak of 38 ng at 15 days. The concentration declined to 21 ng at 19 days and then rose again at hatching.Over the 12-day period studied corticosterone accounted for one third of the total adrenal corticosteroids measured. At hatching corticosterone and its precursor, progesterone accounted for 71% of the total, indicating establishment of the adult pattern of predominance of corticosterone.This report, along with our previous paper [(1974) Gen. Comp. Endocrinol.24, 364–372], provides base line normal gland and circulating steroid levels. It emphasizes that several corticosteroids are being synthesized and secreted during embryonic development.     

Comparison of glucose,fructose, sorbitol,and xylitol utilization in humans during insulin suppression

During fructose, sorbitol, and xylitol perfusions, carbohydrate utilization was studied by continuous indirect calorimetry and compared with glucose utilization during pharmacologic inhibition of endogenous insulin secretion. The experiment was performed in 28 normal volunteers divided into 5 groups (glucose, fructose, sorbitol, xylitol, and saline), each subject being its own control. Insulin suppression was obtained by means of a constant infusion of epinephrine (6 μg/min) and propranolol (0.08 mg/min). After 90 min, during plasma insulin steady state, each sugar or polyol was infused at a rate of 6 mg/kg/min for 120 min. In contrast with a rise in plasma glucose from 161 ± 6 mg/dl to 291 ± 14 mg/dl during glucose infusion, glucose levels remained unchanged during infusion of the glucose substitutes. Carbohydrate oxidation showed a rise of 24, 65, 76, and 44 mg/min during infusions of glucose, fructose, sorbitol, and xylitol, respectively. Lipid oxidation rates decreased by 7, 20, 33, and 23 mg/min during the same infusions. These results indicate that fructose, sorbitol, and xylitol are oxidized at a higher rate than glucose during suppression of endogenous insulin secretion, without any significant rise in glycemia.     

Idiopathic edema: pathogenesis, clinical features, and treatment

Previously published findings are reviewed and new data are presented relating to the clinical features, pathophysiology, and treatment of the idiopathic edemas, a group of disorders diagnosed by exclusion of the known causes of edema. The disorders occur almost exclusively in women, show diurnal (postural), not “cyclic” fluctuations in severity, often cause discomfort and occasionally pain, and may be aggravated by prolonged orthostasis, hot environments, menses, and some drugs. Among the pathophysiologic factors known to be important in edema formation, in general: (1) Hypoproteinemia is more commonly the result than the cause of idiopathic edema; (2) elevated capillary hydrostatic pressure is seldom the primary cause, except perhaps in rare cases of occult congestive heart failure; (3) changes in tissue pressure may limit the progression of, but do not initiate, the edema; (4) changes in capillary wall permeability and (5) changes in capillary diffusion area, perhaps because of excessive dilatation of precapillary sphincters appear to be of importance; (6) abnormalities of lymphatic flow are not demonstrable; and (7) the upright posture is an important contributor to the excessive transudation in over 80% of the patients studied (“orthostatic edema”) but not in the remaining minority of patients (“nonorthostatic edema”). By balance studies with constant diets and by an abbreviated “posture test”, it has been shown that (A) the majority of patients with “orthostatic edema” have excessive orthostatic sodium (Na) retention that results from an excessive orthostatic fall in glomerular filtration rate, frequently associated with excessive renal tubular reabsorption of the subnormal filtered Na load because of orthostatic hyperaldosteronism, and (B) about 30%–40% of patients with orthostatic edema have “orthostatic water retention”, demonstrable by an inability to excrete more than 55% of a 20 ml/kg water load during 4 hr in the upright posture. In most of these patients but not in most other types of edema, orthostatic excretion of the water load is restored to normal by ethanol (a known inhibitor of vasopressin release). Improvement in orthostatic renal excretion by external compression of the legs and persistence of excessive orthostatic changes in leg volume despite restricted Na intake support microscopic evidence that a capillary “leak” may be the primary cause of most orthostatic edemas. Reduced dopamine excretion has been reported and linked to the causation of some types of idiopathic edema. Obesity is often associated with edema that differs from other idiopathic edemas in that it usually disappears with caloric restriction and weight loss. In occasional patients, undue sensitivity to heat may play a role as important as that of posture. Treatment of idiopathic edema includes avoidance of excessive salt intake, reduction of the duration of standing and sitting, and administration of conventional diuretics, preferably at 7 or 8 p.m., followed by recumbency for several hours before sleep. Hyperaldosteronism has responded to subtotal adrenalectomy (which is not recommended) and constitutes a strong indication for the use of spironolactone, which facilitates recumbent excretion of Na retained in the upright posture. Sympathomimetic amines (ephedrine, phenylephrine, and preferably dextroamphetamine) are the only agents that will usually significantly reduce the excessive weight gain from morning to evening (the hallmark of orthostatic edema), perhaps by preventing excessive capillary pooling and transudation. They have been used safely, effectively, and without loss of their efficacy, for up to 20 yr in several patients. Elastic stockings and garments are occasionally useful and regular exercise, especially swimming, may be beneficial.     

Serum thyroxine, free T4, triiodothyronine, and reverse-T3 in diphenylhydantoin-treated patients.

In order to determine the effects of the administration of diphenylhydantoin (DPH) on various parameters of thyroid function, serum samples from 47 male adults receiving therapeutic doses of DPH and 45 euthyroid control subjects were analyzed for total thyroxine (T₄) and an index of free T₄ concentration, using both a competitive protein-binding assay (CPBA) and a solid-phase radioimmunoassay (RIA), total 3,5,3′-triiodothyronine (T₃), 3,3′,5′-triiodothyronine (reverse-T₃, rT₃), and TSH, each measured by specific RIA. Mean total T₄ by both methods was depressed in the DPH group to 0.78 of the control level. Free T₄ Index by RIA was decreased on the average in DPH-patients exactly in proportion to the depression in total T₄. By the CPBA, the difference between two groups in Free T₄ Index was less marked but still significant (DPH/controls = 0.86, p < 0.01). The concentrations of total T₃ were virtually identical in the DPH and the control groups. The average $\text{T}{}_3\text{T}{}_4$ ratio was significantly higher in the DPH patients than in the controls (0.0178 versus 0.0132, p < 0.001). Serum rT₃ was depressed by DPH-treatment in approximately the same proportion to the decrease in total T₄. None of the DPH-patients had an elevated serum TSH. The above findings are interpreted as indirect evidence in support of the view that DPH stimulates T₄ metabolism, particularly the conversion of T₄ to T₃. The normal level of free T₃ may help to maintain a euthyroid state in spite of the decrease in free T₄. The data also define the “euthyroid” ranges for total and free T₄ levels by these methods in patients receiving DPH.     

Homocysteinemia,ischemic heart disease,and the carrier state for homocystinuria

Precocious atherosclerosis occurs in homocystinuria due to cystathionine β-synthase deficiency and there is evidence that homocysteine may produce endothelial damage. Mild homocysteinemia has been reported in heterozygotes after methionine loads and it has been suggested that they could have an increased risk of atherogenesis. We measured plasma amino acids before and after a methionine load (100 mg per kg) in 17 obligatory heterozygotes, in 20 men under 50 yr with established ischemic heart disease, and in matched controls, to determine whether methionine loading allows identification of heterozygotes, and whether there is an altered rate of methionine metabolism in patients with premature coronary artery disease. The obligate heterozygotes had higher mean plasma concentrations of methionine and total homocysteine at 4, 8 and 12 hours after the load than their controls, and lower concentrations of total cysteine and taurine in fasting and all post load samples; however, there was considerable overlap of measurements in heterozygotes and their controls even when differential weightings were applied. There were no differences in mean plasma concentrations of methionine, total homocysteine or total cysteine between the patients with ischemic heart disease and their controls at any measurement point. However, two patients with premature coronary artery disease, identical twins, had persistent elevation of total plasma homocysteine and an exaggerated homocysteine response to methionine. Oral folate restored homocysteine concentrations before and after methionine to normal. We conclude that heterozygotes for cystathionine β-synthase deficiency have a reduced ability to metabolise methionine but that under normal western dietary conditions they are unlikely to have elevated plasma homocysteine concentrations, presumably because of enhanced homocysteine remethylation; because of this they are unlikely to have an increased risk of atherogenesis. With these small numbers we could show no evidence for a predominance of heterozygotes among patients with established premature coronary vascular disease, but two patients, identical twins, had persistent mild homocysteinemia responsive to folic acid which could have constituted an additional risk factor for atherogenesis.     

Glucagon,insulin, and glucose responses to physiologic testing in normal and massively obese adults

Ten normal adults and ten nondiabetic massively obese subjects were studied following 4–7 days on identical diets. Intravenous arginine challenge resulted in similar glucose and glucagon responses and threefold greater integrated insulin responses in the obese when compared to the normal subjects. Following oral glucose, glucagon responses were similar, whereas both basal and integrated insulin values were higher in the obese subjects. Basal and integrated insulin concentrations were greater during intravenous glucose testing in the obese subjects, whereas similar glucagon suppression was observed in both groups. Hourly blood samples obtained during a 24-hr period revealed that the obese glucose profile differed significantly from the normals. Insulin values were two- to four-fold higher in the obese subjects, whereas no significant difference was observed in the glucagon concentrations. The nadir and peak glucagon concentrations for both groups occurred at 8:00 a.m. and 8:00 p.m., respectively, and were positively correlated with plasma amino acid values, and were similar in both groups.     

Age,race, sex and other indices of risk in hypertension

Among the various criteria used in evaluating the prognosis of hypertensive patients the level of the diastolic blood pressure averaged over three or more visits is the most important index. Other indices also are useful and are essential in deciding on treating patients with average diastolic blood pressures below 105 mm Hg. Included among these are sex, age and race. Male sex, young age and black race are all associated with increased risk of morbidity and mortality.The lability of the hypertension is another indicator of risk. Patients with labile hypertension—high casual in relation to basal blood pressure—have a better prognosis than those who do not. Family history also should be considered. A history of premature death from hypertensive complications in a parent or sibling suggests that the patient may be at increased risk. Finally, the presence and extent of detectable target organ damage provides a major criterion of prognosis and indication for treatment.     

Comparative measurements of glucose, beta-hydroxybutyrate, acetoacetate, and insulin in blood and cerebrospinal fluid during starvation

The possibility that altered central nervous system (CNS) metabolism is reflected by changes in the constituents of the cerebrospinal fluid (CSF) was investigated. From eight obese subjects undergoing total starvation for weight reduction, overnight and 21-day fasting specimens of venous blood and lumbar CSF were obtained nearly simultaneously to determine the concentrations of glucose, beta-hydroxybutyrate (β-OHB), acetoacetate (AcAc), and immunoreactive insulin (IRI). After 21 days of starvation, the glucose concentration fell in both blood and CSF. The decrease in blood glucose was greater than the decline in CSF glucose, resulting in a diminished blood-CSF difference. Concentrations of β-OHB and AcAc in blood and CSF were elevated after prolonged fasting, but blood levels exceeded those in CSF, producing an increased blood-CSF ketone body difference. After an overnight and 21-day fast, the IRI levels in CSF were about one-half of the serum levels. These data suggest that metabolic alterations in CNS metabolism during prolonged starvation are reflected in substrate concentrations observed in CSF, and demonstrate that insulin is presented in the CSF of man.