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A method is described for dispersing C14-labeled triglyceride in plasma to form low density fat particles which are similar in size, flotation and electrophoretic mobility to the particulate fat present in plasma during fat absorption. The removal rate in man of a trace dose (less than 1 mg) of this preparation of radioactive particulate fat is rapid. Small loads (2 g) of unlabeled lymph or emulsified fat given simultaneously significantly prolong the removal rate. This rate is comparable to that observed after administration of a similar load of labeled human chylomicrons.

Obesity and mild carbohydrate intolerance tend to coexist in man. Obesity per se increases basal insulin secretion and insulin responses to glucose, while mild carbohydrate intolerance is associated with impaired insulin responses. Adiposity may cause decreased tissue sensitivity to insulin and reduced glucose uptake, which in turn leads to hyperinsulinism. Prolonged obesity may unmask genetic diabetes at an earlier stage to account in part for their frequent association. Abnormal insulin secretion and reduced sensitivity to its action also may be responsible for alterations of fat mobilization observed only in the presence of both obesity and mild carbohydrate in tolerance.

When human subjects were given 1 gm. of d-glucuronolactone orally the ascorbic acid levels in plasma increased. There was an excess renal excretion of 8 mg. per hour of ascorbic acid accompanied by an excess excretion of 0.2 mg. per hour of xylulose.When the same subjects were given 1 gm. of d-glucuronic acid orally there was no increase in ascorbic acid levels in blood. Although no significant increase was noted in urinary ascorbic acid levels, the excess excretion of xylulose in the urine was 8.1 mg. per hour.The infusion of a dog with 1 gm. of d-glucuronolactone or d-glucuronic acid caused an increase in the ascorbic acid levels in blood. The renal excretion of ascorbic acid was 10.3 mg. per hour during the experiments with d-glucuronolactone and 11 mg. per hour during the experiments with d-glucuronic acid. The xylulose excretion was not significantly changed.

The unmasking of latent diabetes and aggravation of preexisting abnormalities in carbohydrate tolerance are well-known consequences of corticosteroid administration.1 The occasional occurrence of lipemia (milky plasma) in patients receiving high doses of glucocorticoids has suggested that administration of these drugs also may be associated with rather profound disturbances in lipid metabolism. Two patients were observed in whom marked lipemia and symptomatic diabetes developed while they were receiving high-dosage corticosteroid therapy for collagen disorders. One patient was studied in detail in order to explore the pathogenesis of this syndrome.Results of these investigations indicate that gross lipemia in such patients is a reversible form of exogenous lipemia which results from impaired metabolism of dietary fat. PATIENT SUMMARIES PATIENT 1. —A 16-year-old boy entered the Children's Orthopedic Hospital because of generalized weakness and diffuse muscle pain. He had been well until one month prior to admission when stomatitis, dysphagia, and generalized

A man with peripheral atherosclerosis manifested concurrent postsurgical hypothyroidism and braod-β disease (type 3 hyperlipoproteinemia). In the presence of both, low-density lipoprotein levels remained normal, but very low-density lipoprotein (VLDL) levels were markedly increased, β-migrating, and rich in cholesterol. During replacement therapy with levothyroxine, cholesterol and triglyceride levels were initially reduced to normal, and the diagnosis of broad-β disease became uncertain. Its persistence was suggested by the relative prominence of Sf12-100 lipoproteins, the cholesterol-rich composition of VLDL subfractions and of chylomicrons persisting late after an orally administered fat load, the preponderance of slower-migrating lipoproteins in the Sf20-60 subfraction. With time, moderate hyperlipoproteinemia returned, and broad-β disease was again clearly evident. Thus, secondary factors may interact with the primary metabolic defect to influence the chemical, and possibly clinical, expression of broad-β disease.

Plasma obtained after intravenous administration of heparin contains enzymatic activity catalyzing the hydrolysis of triglyceride (TG) in vitro.This activity is also apparent in vivoand results in a decrease in total plasma TG, an increase in products of TG hydrolysis, and a shift of the plasma lipoprotein spectrum from very low density to higher density fractions (1). From prior studies it appeared that no change occurred in total plasma cholesterol or phospholipid (1).Recent studies have shown that postheparin plasma also contains enzymatic activity catalyzing the hydrolysis of the phospholipids phosphatidyl ethanolamine or phosphatidyl choline (lecithin) in vitro(2,3). Hydrolysis occurs at the α’(C-1) fatty acid with the production of β (C-2) lyso derivatives. Results in the present study indicate that lipoprotein lecithin is hydrolyzed in parallel with TG in vivoafter intravenous heparin, and thus provide evidence for the in vivoaction of postheparin plasma phospholipase in man.Methods.Blood samples were obtained from 12 normal adult male subjects prior to and again after rapid intravenous administration of 5000 units of heparin.Plasma cholesterol and T G were analyzed after extraction in chloroform-methanol (2: 1, v: v) by standard AutoAnalyzer techniques(5).

The behavior of a radioactive triglyceride-plasma complex prepared in vitro was compared to that of an “RE test emulsion” in normal and RE hyperfunctional rats. The removal rate and organ distribution of the particulate fat tracer was not influenced by RE hyperfunction. However, the corresponding dose of the “RE test emulsion” was removed more rapidly from plasma in RE hyperfunctional rats. Thus the particulate fat tracer does not appear to be removed by a phagocytic process and therefore behaves more like native lipid particles than foreign emulsified material.The capable technical assistance of Mrs. Betty Lyons and Miss Jackie Dempsey is gratefully acknowledged.

A young puppy with hyperlipemia presumably associated with lipoprotein lipase deficiency is reported. It appears that this rare abnormality of lipid metabolism may occur in mammals other than man.

A variety of abnormalities of glucose, insulin, and triglyceride transport have been observed in uremia. Most of these abnormalities appear to be interrelated and are reversible with amelioration of the uremic state.

Tolbutamide (Orinase), given intravenously to normal and diabetic patients caused a reduction of non-esterified fatty acid concentration only in those subjects who responded with hypoglycemia. Diabetics responding to tolbutamide with a prolonged depression of blood sugar showed a comparably sustained reduction of the fatty acid fraction.

The comparative effects of dietary starch and dextrose on plasma tri-glyceride levels were studied on a metabolic ward in 2 lipemic patients. Plasma triglyc-erides were elevated when these subjects ingested a virtually fat free diet. Substitution of starch for the high dextrose formula produced no further change in plasma triglyc-erides. Caloric restriction in one patient resulted in a marked decrease in triglyceride even though he continued to eat an 85% carbohydrate, 15% protein formula. Both patients complained of a feeling of fullness and had trouble finishing an isocaloric high starch diet. These observations show that isocaloric starch diets did not decrease plasma triglycerides but that caloric restriction while a high carbohydrate diet is fed, will result in lower plasma triglyceride levels. They suggest that, unless careful supervision of dietary intake is maintained, the effects of carbohydrate substitutions in diet may be related to changes in caloric balance rather than to the type of carbohydrate ingested.

There has been widespread coverage in the news media recently of the claim that the drinking of homogenized milk is a cause of excessive mortality from coronary artery disease in the United States. That this relationship might exist has been proposed by Oster,1 who postulates the existence of a group of diseases caused by the depletion of plasmalogen in cell membranes. He includes arteriosclerosis, myocardial infarction, and angina pectoris as representative disorders with this possible origin.Plasmalogens are a type of phospholipid usually found as a component of cell membranes of muscle and of the myelin sheath of nerve fibers. The major plasmalogen of myocardium is a choline phosphatide containing an unsaturated fatty acid in a typical ester linkage and a second fatty acid as a vinyl ether,2 thereby differing from the more usual phospholipid exemplified by lecithin. Fatty aldehydes or plasmals can be released from this second

Triglyceride metabolism was studied in a 14-month-old cretin boy. Prior to therapy, the child was found to have hypertriglyceridemia, hypercholesterolemia, and increased plasma pre-beta lipoproteins. An abnormality in lipoprotein lipase was suggested by low postheparin lipase activity (PHLA) in the child's plasma.With 13 weeks of therapy, the triglyceride level fell and the lipoprotein distribution and PHLA in fasting plasma became normal. By 20 weeks, all lipid measures were normal. After only five weeks of thyroid replacement and improved oral intake, a paradoxical increase in plasma triglyceride and appearance of chylomicrons occurred despite a marked increase in PHLA.

Blood amylase and plasma non-esterified fatty acid concentrations responded in a correlated way to glucagon, glucose, fructose, epinephrine and orinase. Apparently these two components are associated in some common metabolic process, extrapancreatic in location.