Intravenous Fat Tolerance Test Research Articles

Effects of bezafibrate on the serum lipoprotein lipid and apolipoprotein composition, lipoprotein triglyceride removal capacity and the fatty acid composition of the plasma lipid esters

Bezafibrate has been shown to effectively reduce elevated levels of very low density lipoprotein (VLDL) in hypertriglyceridaemia. It has also been claimed to be particularly effective in increasing high density lipoprotein (HDL) concentrations. In the present study 15 hypertriglyceridaemic patients (9 type IIB, 1 type III and 5 type IV) were investigated before and after 2 months' treatment with bezafibrate (600 mg daily) in an effort to clarify further the effects of the drug on lipoprotein metabolism. The serum triglycerides decreased by 46% ( P < 0.001) corresponding to a significant reduction of both the VLDL (−43%, P < 0.001) and the low density lipoprotein (LDL) (−27%, P < 0.05) triglycerides. The serum cholesterol decreased by 13% ( P < 0.001), mainly due to reduction of the VLDL cholesterol (−51%, P < 0.001). There was no significant reduction of the LDL cholesterol in the whole group (−10%, n.s.). However, if only the patients with hypercholesterolaemia were considered, there was a significant reduction of LDL cholesterol by 19% ( P < 0.01). HDL triglycerides and HDL cholesterol increased by 20% ( P < 0.05) and 22% ( P < 0.001) respectively. While the concentration of apolipoprotein (apo) B decreased by 15% ( P < 0.01) there were significant increases of apo A-I (+14%, P < 0.001) and apo A-II (+30%, P < 0.001) analogous to the increase of HDL lipid concentration. However, the ratio between apo A-I and apo A-II decreased significantly during therapy (−12%, P < 0.001) indicating that the increase of HDL may have preferentially affected the HDL-3 fraction. There were highly significant reductions of both the ratio between LDL and HDL cholesterol (−24%, P < 0.001) and the ratio between apo B and apo A-I (−25%, P < 0.001), changes which should be favourable with regard to atherogenicity. Significant increases of both the plasma post-heparin lipoprotein lipase activity (+20%, P < 0.001) and the fractional removal rate (K 2) at the intravenous fat tolerance test (+30%, P < 0.001) indicate that one of the mechanisms behind the effects of the drug on lipoprotein metabolism may be an increased removal of circulating triglyceride-rich lipoproteins. Bezafibrate treatment caused significant changes in the plasma lipid fatty acid composition, mainly by increasing the mono-unsaturated fatty acids (palmitoleate and oleate) concomitant with a significant decrease in the content of linoleate. Very similar changes have been recorded during clofibrate treatment. The mechanisms behind these changes as well as their significance are at present obscure.

Determination of the K 2 lipid clearance coefficient by centrifugation. A comparison with the gordis test and spectrophotometric measurement

The K 2 lipid clearance coefficient was calculated for the intravenous fat tolerance test (iv FTT), after estimating triglycerides by spectrophotometry, the Gordis technique or by preparative ultracentrifugation. The best correlation between the K 2 values ( r = 0.95, p < 0.001) is for the results of the Gordis test and ultracentrifugation. Spectrophotometry shows poorer correlations: r = 0.66 and p < 0.05 with the Gordis test, and r = 0.78 and p < 0.01 with ultracentrifugation. Spectrophotometry is only suitable for detection but the two other techniques can be applied to more detailed studies. Ultracentrifugation is faster, less laborious and less liable to error.

The effect of cyproterone acetate on serum lipids in normal men.

In a male anti-fertility study 7 volunteers received the anti-androgen cyproterone acetate (5 or 10 mg daily) orally in a paired study. A significant reduction in serum-cholesterol and LDL-cholesterol, and a significant increase in the intravenous-fat-tolerance-test (IVFTT) was observed. Thus low doses of cyproterone acetate reduced the serum testosterone concentration and some of the atherosclerotic risk factors.

Hyperlipidemia and pancreatitis.

AbstractA total of 117 patients with pancreatitis were studied during the acute attack and after remission, and 32.5% were found to have hyperlipidemia, nearly all of type IV. There did not seem to be a relationship between hyperlipidemia and alcohol intake, although nearly 80% of the patients were alcoholics. No defect in triglyceride turnover could be demonstrated by intravenous fat tolerance tests or postheparin lipolytic activity measurements. No correlation was found between hyperlipidemia and steatosis of the liver or diabetes.It is suggested that the increase in serum triglyceride levels might be due to an increased synthesis or mobilization. It is also suggested that the hypertriglyceridemia does not directly induce an attack of pancreatitis, but might predispose a patient to develop pancreatitis when other provoking factors are also present.

Oral levo-norgestrel — Testosterone effects on spermatogenesis, hormone levels, coagulation factors and lipoproteins in normal men

Four healthy men volunteered to be treated for eight to nine months with daily oral levo-norgestrel (250 <g) and oral testosterone (200–600 mg) as a possible contraceptive. This was followed by a recovery phase of 5–10 months. The oral steroid combination significantly decreased sperm count in 3 of 4 subjects, and significantly increased abnormal spermatozoa, serum LH was decreased during treatment but serum FSH remained constant, except for one volunteer. Serum testosterone was decreased except for 2 daily peaks associated with the oral testosterone. During the recovery period, sperm counts and morphology, serum testosterone and serum LH returned to normal, whereas serum FSH levels were increased. Platelet aggregability induced by ADP, increased in 3 volunteers during treatment as did fibrinolytic activity and fibrinolytic capacity (2 of 3 subjects). There was a reduction in the hepatic triglyceride lipase activity but no change was seen in serum triglycerides, serum cholesterol, serum LDL, serum HDL, peripheral lipoprotein lipase activity and the intravenous fat tolerance test. No other toxicological side effects were seen.

Intralipid clearance and lipoprotein pattern in men with advanced alcoholic liver cirrhosis

Twelve male patients with advanced alcoholic cirrhosis of the liver were found to have markedly low serum lipid and lipoprotein concentrations. Serum triglyceride and cholesterol concentrations were about 50% of matched control values. The very low density lipoproteintriglyceride concentration was only one-third of control values and the cholesterol concentrations in very low density and low density lipoproteins were far below control values. The mean high density lipoprotein cholesterol concentration was not significantly decreased, but in three of 12 patients extremely low values were found. These findings may reflect a failure of lipoprotein synthesis secondary to a bad nutritional state and metabolic disturbances in this advanced stage of liver cirrhosis. By means of the intravenous fat tolerance test with Intralipid it could be shown that substantial amounts of triglycerides could be cleared from the plasma in these patients. However, studies on the long-term Intralipid clearance capacity have to be performed before any general recommendations about the inclusion of fat emulsions in parenteral nutrition of these patients can be made.

Pronounced lipoprotein lipid reduction obtained by combined lipid-lowering treatment in patients with atherosclerotic disease

The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50–60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30–40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K 2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K 2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated.

The influence of starvation on the removal mechanisms of plasma triglycerides in man

In 14 obese male subjects (whose plasma triglyceride (TG) levels lay between 72 and 491 mg/dl), total plasma cholesterol, plasma TG, “hepatic” TG lipase (HTGL) and (“extrahepatic”) lipoprotein lipase (LPL) activity in post-heparin plasma, and the k 2 of the intravenous fat tolerance test (IVFTT) were measured when on a normal isocaloric diet and after one and two weeks of total starvation. A pronounced and significant decrease of plasma TG and a less pronounced but (after two weeks) also significant decrease of plasma cholesterol concentration during starvation were found. LPL activity was not significantly influenced by starvation for two weeks. There was a significant decrease of HTGL activity after one and two weeks of starvation. On a normal diet, a negative correlation existed between TG and k 2, but no relationship could be demonstrated between the lipase activities and k 2 or between the lipase activities and plasma TG. After one week and after two weeks of starvation, inverse correlations between k2 and TG, as well as between LPL activity and plasma TG, and positive correlations between LPL activity and k 2 were found. The results of this study are compatible with the following hypothesis concerning the regulation of plasma TG concentration. Both on a normal diet and during prolonged starvation, a reduced fractional removal rate of plasma TG is responsible for an increase in plasma TG concentration. Independent of the nutritional state, k2 seems to be a reliable estimate for the fractional removal rate of endogenous plasma TG. In the fed state, the extent of hypertriglyceridaemia is also influenced by the influx rate of plasma TG.

Correlations between intravenous fat tolerance and serum lipoproteins in normal and atherosclerotic subjects

Triglyceride (TG) and cholesterol concentrations in the major lipoprotein fractions and the intravenous fat tolerance test (IVFTT) k 2 value were determined in healthy controls (n = 35), in survivors of myocardial infarction (MI, n = 43) and in patients with peripheral vascular disease (PVD, n = 33). MI patients had the highest lipid concentrations in the lipoproteins except for HDL-cholesterol which was 26% lower in both MI and PVD patients compared to controls. For the other lipid concentrations, PVD patients had values between MI patients and control values. The mean k 2 values were, for MI patients 2.8%/min, for PVD patients 3.3%/min, and for controls 4.4%/min. Data were pooled from all 111 individuals and correlations between lipids in the lipoprotein fractions and the k 2 value were calculated. The highest r value was found for log k 2 versus log VLDL-TG ( r = −0.65, P < 0.001), but significant negative correlations between k 2 and LDL- as well as HDL-TG were also demonstrated. A strong positive correlation was found between k 2 and HDL-cholesterol. When partial regression analysis was carried out, this relationship prevailed also when the effects of both VLDL-TG and total TG were eliminated ( r = 0.32, P < 0.001). These results support the concept that the IVFTT k 2 value independently gives an estimate of TG removal processes from plasma and reflects HDL activity on TG catabolism.

A simple method for the intravenous fat-tolerance test.

A simple method for measuring intravenous fat tolerance with an artificial fat emulsion (intralipid) was studied and compared with the currently used method of Carlson and Rossner [J. Lab. Invest. 29, 271-280 (1972)]. The proposed method uses as little as 3 mL of whole blood to follow, by nephelometry, the elimination of intravenously administered fat emulsions. There is a high correlation between the K2 values obtained by the current method for plasma and those obtained by the proposed method (r = 0.903). The latter is simpler, quicker, and more acceptable to patients.

Etude du coefficient d’épuration lipidique K&lt;sub&gt;2&lt;/sub&gt; chez les sujets atteints d’hyperlipoprotéinémie de type IV avant et après réduction de l’hypertriglycéridémie par un traitement diététique adapté

An intravenous fat tolerance test (IV FTT) was performed in a group of patients with type IV hyperlipoproteinemia before and after reduction of triglyceride level, the latter is obtained through a diet adapted to the nutritional sensitivity, body weight remaining constant. Before the diet the increase in cholesterol (CT) and triglycerides (TG) was related in both obese and non-obese patients to an increase in very-low-density lipoproteins (VLDL), while other lipoprotein fractions were not affected. In these patients, K&lt;sub&gt;2&lt;/sub&gt; is significantly lower than in controls whatever the nutritional sensitivity. However, K&lt;sub&gt;2&lt;/sub&gt; is lower in obese patients than in patients with normal weight, VLDL-CT and VLDL-TG are tremendously reduced by the relevant diet and K&lt;sub&gt;2&lt;/sub&gt; is constantly and significantly increased, although it does not reach a normal value in obese subjects. There is a highly significant correlation between VLDL-TG levels and K&lt;sub&gt;2&lt;/sub&gt; in obese and non-obese subjects. Several physiopathological explanations are discussed to account for the variation of K&lt;sub&gt;2&lt;/sub&gt; according to TG levels. The results obtained support the view that the K&lt;sub&gt;2&lt;/sub&gt; defect is secondary to the hyperlipoproteinemia.

Intravenous fat tolerance in obese Africans with varying grades of carbohydrate tolerance

An intravenous fat tolerance test (IVFTT) was performed and fasting plasma lipid values determined in 12 healthy normal weight, 18 obese non-diabetic, 9 obese chemical diabetic and 10 obese symptomatic diabetic African subjects. Their insulin responses to an oral glucose load were also determined. Mean plasma triglyceride levels were similar in the normal weight and obese non-diabetic groups but were significantly raised in the two diabetic groups, being highest in the symptomatic diabetics. The fractional removal-rate of an intravenous injection of the fat emulsion Intralipid ® was significantly less in each of the obese diabetic groups compared with the normal weight or obese non-diabetic group. There was a significant negative correlation in all but the symptomatic diabetic group between the fasting triglyceride level and the rate constants for the IVFTT. These results suggest that the rate of triglyceride clearance is an important determinant of the basal plasma triglyceride concentration in urban African subjects.

RISK FACTORS FOR ISCHÆMIC HEART-DISEASE IN NORMAL MEN AGED 40: Edinburgh—Stockholm Study

107 healthy men in Edinburgh and 82 in Stockholm, all aged 40 and selected at random, took part in a study aimed at identifying factors which might explain why, in men of this age, the mortality-rates from ischæmic heart disease are three times greater in Edinburgh men. Clinical measurements and electrocardiographic procedures were standardised, and steps taken to eliminate interlaboratory differences. Edinburgh men were shorter and fatter; had higher systolic and diastolic blood-pressures; smoked more cigarettes (but the number of cigarette smokers in the two groups was similar); drank more alcohol; had more E.C.G. abnormalities and lower exercise tolerance. They had higher levels of total serum-triglycerides and triglycerides in very low (V.L.D.L.), low (L.D.L.), and high (H.D.L.) density lipoproteins. Triglyceride clearance (assessed by an intravenous fat-tolerance test) was similar. Serum-cholesterol and L.D.L.-cholesterol concentrations were similar in both cities but cholesterol in V.L.D.L. was higher, and cholesterol in H.D.L. was lower, in Edinburgh men. The relative linoleic-acid content of plasma-triglycerides and of plasma-cholesterol esters were lower in Edinburgh men, and their subcutaneous adipose tissue glycerides had a lower polyunsaturated/ saturated fatty-acid ratio and a strikingly lower relative linoleic acid content. Edinburgh men had a greater total plasma-insulin response to a standardised glucose-tolerance test. The glucose response was the same in both cities. Plasma free fatty-acids and free glycerol were reduced by a lesser extent in Edinburgh men in response to a glucose load. Although the high incidence of ischæmic heart-disease in Scotland may be due to many factors, some of which are well established, this study points out metabolic factors which may provide new information on the pathogenesis of ischæmic heart-disease.

Increase of the lipoprotein‐lipase activity in human skeletal muscle during clof ibrate administration

Lipoprotein-lipase activity was determined in tissue from the skeletal muscle of the leg and the subcutaneous adipose tissue of the abdomen in fourteen patients before and after 1 month of clofibrate administration. The concentrations of serum triglycerides decreased by, on the average, 37% in a group of thirteen patients which mainly consisted of subjects with type-IV hyperlipoproteinaemia. Clofibrate administration was associated with an average increase of the skeletal muscle-tissue lipoprotein-lipase activity of 50% (P less than 0.005). There was a significant correlation between the percentage changes in skeletal muscle-tissue lipoprotein-lipase activity and those of the triglycerides concentrations and the K2-values in an intravenous fat tolerance test during clofibrate treatment. Adipose-tissue lipoprotein-lipase activity did not change significantly. One patient with type-I hyperlipoproteinaemia had very low values of skeletal muscle-tissue lipoprotein-lipase activity and moderately low adipose-tissue lipoprotein-lipase activity. In this patient, neither the tissue lipoprotein-lipase activity nor the triglycerides concentration changed during clofibrate therapy. Fasting serum insulin concentrations decreased significantly during clofibrate administration and the percentage decrease was significantly correlated to the percentage increase of skeletal-muscle lipoprotein-lipase activity. It is suggested that the lowering of insulin levels is a possible mechanism through which glucagon activity is enhanced and this may increase skeletal muscle-tissue lipoprotein-lipase activity.

Relation between triglycerides in human skeletal muscle and serum and the fractional elimination rate of exogenous plasma triglycerides

Muscle triglycerides, serum lipid and lipoprotein concentrations and an intravenous fat tolerance test were determined on thirteen survivors of myocardial infarction and on fourteen subjects referred to a Lipid Clinic but without myocardial infarction. The mean concentration of triglycerides in muscle and the fractional removal rate k2 of intravenous injected Intralipid were similar in patients with and without MI. In seventeen of these subjects type IV hyperlipoproteinaemia was found. In type IV patients the muscle triglyceride concentration was twice that found in patients without hypertriglyceridaemia. A negative correlation between muscle triglyceride concentration and the k2 value was found for all subjects with a correlation coefficient of -0.62 (P less than 0.001). No independent correlations were found between muscle triglyceride and serum triglyceride concentration or the triglyceride concentrations of the major lipoproteins.

Dyslipoproteinaemia in patients with active, chronic polyarthritis. a study on serum lipoproteins and triglyceride clearance (intravenous fat tolerance test)

<h2>Abstract</h2> Serum lipoproteins and the intravenous fat tolerance test were determined in 28 patients with active chronic polyarthritis, in most cases classical rheumatoid arthritis (RA). Two groups of RA patients were studied. One group was treated with only salicylates or other antiphlogistic drugs, the other also with steroids, cytostatics etc. The low concentration of total serum cholesterol, well known in RA, was found to result from low concentrations in all three lipoprotein fractions VLDL, LDL and HDL compared to randomly selected healthy male and female controls. A slight reduction of the total serum triglyceride (TG) concentration was observed, which corresponded to minor TG reductions in each lipoprotein class. As a consequence the LDL composition was altered containing more TG for each cholesterol value than controls. The cholesterol/TG ratio in VLDL in RA patients was higher than in controls. One possible explanation of these findings could be that in RA an accumulation of the intermediate density lipoprotein (IDL) occurred. The HDL cholesterol concentration in RA patients was very low compared to controls. When compared to the negative regression line which exists between VLDL-TG and HDL-cholesterol determined in controls, RA patients were found to have lower HDL-cholesterol than expected for any VLDL-TG concentration. The clinical implication of this finding may be of interest since it has been demonstrated that a low HDL-cholesterol concentration is associated with an increased risk for atherosclerotic manifestations. The lipoprotein data were similar in both RA groups independently of treatment. The fractional removal rate of intravenously injected exogenous TG (Intralipid) from the circulation was very high in RA patients compared to controls. This could be due to an increased flow past removal sites.

Intravenous fat tolerance Correlation with very low density lipoprotein apoprotein b kinetics in man

The intravenous fat tolerance test (IVFTT) has been introduced as a measure of the fractional catabolic rate of the endogenous triglyceride of plasma. To assess the validity of this test we have compared this test in 21 normal and hyperlipidaemic subjects with direct measurement of the fractional catabolic rate of autologous radio-iodinated VLDL. There was a strong positive correlation between the rate constant K 2 of the IVFTT and the fractional catabolic rate of VLDL-apolipoprotein B ( r = +0.87). The two rates were considerably different in magnitude. The IVFTT appears to be a valid index of the fractional catabolic rate of VLDL. Its limitations and uses are discussed.

Intravenous Fat-Tolerance Test in Ischaemic Heart Disease and Peripheral Vascular Disease

1. The intravenous fat-tolerance test and serum lipid and lipoprotein measurements were carried out in ninety-three normal subjects, fifty-one patients with ischaemic heart disease and thirty patients with peripheral vascular disease. 2. The fractional turnover rate of exogenous triglyceride was significantly slower in patients with ischaemic heart disease and in patients with peripheral vascular disease than in normal men. The rate was also slower in normal men than normal women. 3. Serum triglyceride and cholesterol concentrations were higher in both vascular disease groups than in control subjects. 4. The proportion of both groups of patients who had a subnormal fractional turnover rate of exogenous triglyceride was 35%, and 32% of patients had hypertriglyceridaemia in the fasting state; 27% of patients were hypercholesterolaemic. 5. Although the intravenous fat-tolerance test did not provide significantly better discrimination between cardiovascular patients and control subjects than did measurement of serum triglyceride, the results suggest that hypertriglyceridaemia in such patients may be separable into a group in which impaired triglyceride clearance may be partly responsible, and a group in which overproduction of serum triglyceride may be the major mechanism of the hyperlipidaemia.

The influence of a proceeding intravenous glucose load on the intravenous fat tolerance test in man

In order to simplify the protocol of a population survey of lipid and carbohydrate metabolism a pilot study was carried out in order to investigate the feasibility of carrying out an intravenous fat tolerance test (IVFTT) immediately after an intravenous glucose tolerance test (IVGTT). No significant mean effect of the IVGTT on the IVFTT results was found, although in a few female subjects with extremely high fractional removal rates of exogenous fat there was a tendency for lower IVFTT values after the IVGTT.

Removal of exogenous plasma triglycerides in forearm muscle and subcutaneous tissue of hyper-and normotriglyceridaemic men.

Absolute arterio-venous removal and fractional removal of blood-borne exogenous triglyceride particles by skeletal and subcutaneous tissues were determined in eight normotriglyceridaemic and six hypertriglyceridaemic men. Estimations were made by simultaneously sampling blood from catheters inserted into a brachial artery, and in the distal direction, into a superficial and deep vein, draining subcutaneous tissue and skeletal muscle respectively. During the infusion of the fat emulsion IntralipidR for 3 hours steady arterial concentrations of exogenous TG particles were found, indicating first order kinetics. In all subjects absolute arterio-venous and fractional removal of triglycerides were about twice as high in skeletal muscle as in subcutaneous tissue. In skeletal muscle the fractional removal and absolute removal were significantly higher in normotriglyceridaemic than in hypertriglyceridaemic subjects (p less than 0.001). No decrease in removal with time was observed, which would have suggested saturation of removal sites. Mean fractional removal in skeletal muscle was significantly correlated with the k2 value determined by an intravenous fat tolerance test before the infusion study (r = 0.61, p less than 0.05). In subcutaneous tissue fractional removal was also significantly higher in normotriglyceridaemic subjects (p less than 0.05). The results suggest that in both skeletal muscle and subcutaneous tissue the removal system is impaired in hypertriglyceridaemic subjects. This finding supports the concept that a decreased elimination capacity in these tissues may partly account for triglyceride elevation in hypertriglyceridaemic subjects.