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Effect of long-term exogenous hyperinsulinemia and fructose or glucose supplementation on triglyceride turnover in rats.

We examined the effect of long-term (6 months) hyperinsulinemia on VLDL-triglyceride turnover in male Wistar rats. Hyperinsulinemia was induced in rats by daily s.c. injection of Ultralente insulin (6 U/day at 19:00). Fructose (F) or glucose (G) was supplied in the drinking water (10%) in order to prevent hypoglycemia. The rats were divided into 5 groups: (1) hyperinsulinemia with F water: group F + I; (2) hyperinsulinemia with G water: group G + I; (3) F water alone: group F; (4) G water alone: group G; and (5) control rats without sugar water group C. After 6 months of daily insulin injection triglyceride secretion rate (TGSR) was estimated using Triton WR1339 in all the rats. Groups F + I and G + I were obese and hypoglycemic compared to the other groups. Fasting plasma glucose level of group F was higher than any other group value. TGSR of group F + I was significantly higher than that of the control group, while that of group G + I was not, indicating that long-term hyperinsulinemia can stimulate hepatic triglyceride production when the rats were supplemented only with fructose. On the other hand, the rats in group G + I showed the lowest plasma free fatty acid level of all and their postheparin lipolytic activity was significantly elevated compared to that of the control rats. Moreover, they had suppressed plasma triglyceride levels and its fractional catabolic rate was significantly increased, suggesting that hyperinsulinemia can still stimulate triglyceride removal from the circulation of glucose supplemented rats even at month 6. In conclusion, exogenous hyperinsulinemia can stimulate hepatic triglyceride secretion even after 6 months duration when supplemented with fructose, while its stimulating effect on triglyceride removal from the circulation can be seen only with glucose supplementation. Thus, the effect of long-term hyperinsulinemia on plasma triglyceride turnover differs depending on the supplemented monosaccharides.

Animals↗

Influence of apo E phenotype on postprandial triglyceride and glucose responses in subjects with and without coronary heart disease.

Apolipoprotein E phenotypes and fasting lipid and other biochemical parameters were determined in 51 patients with recently diagnosed coronary heart disease (CHD) and 164 control subjects. The age of the participants was 62.5 +/- 6.6 (S.D.) and 63% were male. Forty-eight CHD cases and 51 control subjects were also studied for 8 h after a fat-rich meal. Apo E phenotypes did not differ significantly between CHD cases and control subjects although there was a tendency for under-representation of E2/E3 in the cases (6% versus 16%). Fifteen CHD cases and 37 (of 164) control subjects had at least one epsilon 4 allele. Fasting plasma triglyceride concentrations were not different between CHD cases and controls but were significantly elevated in subjects with an epsilon 4 allele. CHD cases did, however, have a significantly elevated fasting insulin compared with controls. Postprandial triglyceride responses were not different between CHD cases and controls. However, postprandial triglyceride responses were elevated in subjects (CHD cases and controls) who had an epsilon 4 allele. In multivariate analysis, both epsilon 4 allele status and body mass index (BMI) were significant determinants of postprandial triglyceride responses. Postprandial glucose responses were also elevated in subjects with an epsilon 4 allele. When comparison of CHD cases and controls was restricted to those without an epsilon 4 allele, CHD cases showed a borderline significant (P = 0.05) difference in time course from controls, with a slower decline in plasma triglyceride from the peak response. Fasting and postprandial triglyceride and postprandial glucose responses are strongly dependent on the presence of an epsilon 4 allele. The elevation in postprandial triglyceride responses associated with an epsilon 4 allele can obscure differences associated with the presence of CHD and suggests that although elevated postprandial triglyceride response may be a risk factor for CHD, it is not the major reason for the association between the possession of an epsilon 4 allele and coronary disease.

Aged↗

Influence of serum triglyceride levels on the risk for myocardial infarction in 12,510 middle aged males: interaction with serum cholesterol.

OBJECTIVE: To study the influence of different levels of serum (s)-triglycerides in relation to s-cholesterol on the risk of myocardial infarction. DESIGN AND SUBJECTS: A 6-13 (mean 10) year follow-up of 12,510 middle-aged men. Fasting s-triglycerides and s-cholesterol were measured at the screening examination. SETTING: Section of Preventive Medicine at the Department of Internal Medicine, Malmö General Hospital, an urban hospital for 240,000 inhabitants in southern Sweden. INTERVENTION: In minor groups of patients there were interventions addressing high lipid levels, high alcohol consumption, hypertension and glucose intolerance. MAIN OUTCOME MEASURE: Myocardial infarction was used as an end-point. RESULTS: 446 myocardial infarctions occurred. The cumulative incidence rates were for the lowest triglyceride quartile 1.2%, for the second 3.2%, for the third 4.1% and for the highest 5.6%. After adjustment for age, year of screening, body mass index, diabetes, smoking, hypertension and s-cholesterol there was a significant relationship between triglycerides and the relative risk for myocardial infarction (P for trend=0.0087). For increasing levels of triglycerides, adjusted for the above factors except cholesterol, the impact of a certain cholesterol value for the occurrence of myocardial infarction was increased (P for trend=0.0092). CONCLUSIONS: The present study emphasizes the interaction between cholesterol and triglyceride values for the risk of myocardial infarction. It is concluded that at triglyceride values above 1.0 mmol/l and cholesterol above 6.8 mmol/l there is an increasing interaction between cholesterol and triglyceride levels that might be of importance when evaluating the cardiovascular risk of middle aged men.

Age Distribution↗

Apolipoprotein E4 phenotype increases non-fasting serum triglyceride concentration in infants - the STRIP study.

As genetically determined apolipoprotein E (apo E) phenotypes influence serum cholesterol concentration, we analysed whether serum triglyceride values are also affected by the apo E phenotypes in infants. Non-fasting serum triglyceride values were measured in 7- and 13-month-old participants in the STRIP project, a randomised, prospective trial aimed at reducing children's exposure to known atherosclerosis risk factors (n=1062). The mean+/-S.D. non-fasting serum triglyceride concentrations in 7-month-old infants with apo E4/4 (n=36), E3/4 (n=209), E3/3 (n=412), and E2/3 (n=66) were 2. 05+/-1.24, 1.81+/-0.90, 1.63+/-0.90, and 1.71+/-0.83 mmol/l, respectively. Triglyceride concentrations were higher in infants with apo E4/4 or 3/4 than in those with apo E3/3 (P-value for difference 0.01 and 0.009, respectively). The apo E phenotype similarly influenced non-fasting serum triglyceride concentrations at the age of 13 months. The differences in serum triglyceride values in apo E4(+) infants (apo E3/4 and 4/4 infants combined) and apo E4(-) infants (apo E2/3 and 3/3 infants combined) occurred independently of the relative weight of the infant, milk type used at 7 months of age (breast milk or formula), and time elapsed from the previous meal. To conclude, apo E phenotypes regulate non-fasting serum triglyceride values in healthy infants. Apo E3/4 and apo E4/4 predispose infants to higher values than apo E3/3 phenotype, suggesting that the varepsilon4 allele may increase atherosclerosis risk also via it's effect on postprandial triglyceride metabolism.

Apolipoprotein E4↗

Chronic changes in plasma triglyceride levels do modify platelet membrane microviscosity in rats.

Lipid metabolism disorders were proposed to mediate numerous cell membrane alterations in various forms of hypertension. Elevated plasma triglycerides were found to be associated with changes in membrane structure and function related to altered microviscosity in particular domains of the cell membrane. The aim of our study was to determine if an abnormal triglyceride metabolism might play a causal role in these alterations of membrane dynamics. Using genetically hypertensive rats of the Prague hereditary hypertriglyceridemic (HTG) strain we investigated whether the elevation of circulating triglycerides induced by high fructose intake and/or their lowering by chronic gemfibrozil treatment (for 10 weeks starting at the age of 6 weeks) are followed by reciprocal changes in membrane microviscosity. Two different fluorescent probes exploring either the outer membrane leaflet (TMA-DPH anisotropy) or the membrane lipid core (DPH anisotropy) were used in platelets of HTG rats. DPH (diphenylhexatriene) fluorescence anisotropy was decreased in platelets of fructose-treated HTG animals with highly elevated plasma triglyceride levels, whereas it was increased in gemfibrozil-treated HTG rats in which triglyceride levels were almost normalized. On the contrary, TMA-DPH (trimethylamino-diphenylhexatriene) anisotropy was not substantially altered in platelets from HTG rats by the above modifications of circulating triglycerides. No changes of plasma cholesterol or blood pressure were associated with the triglyceride-dependent modifications of membrane core microviscosity. Our interventional study demonstrates a major causal role of circulating triglycerides in the control of the microviscosity of membrane lipid core.

Animals↗

Effects of chronic di(2-ethylhexyl) phthalate intake on the secretion and removal rate of triglyceride-rich lipoproteins in rats.

This work intends to characterize the nature of the plasma triglyceride level decrease in male Wistar rats fed with diets supplemented with 2% (w/w) di(2-ethylhexyl) phthalate (DEHP), a packaged-food chemical contaminant. After being fed for 21 days, the animals were assessed to determine plasma and liver lipids or to quantify the in vivo hepatic secretion and in vitro plasma removal of triglyceride-rich lipoproteins. The liver cholesterol and triglyceride contents in DEHP-fed rats were closely similar to those found in controls, co-existing with a decrease in plasma cholesterol (19%), phospholipid (14%) and triglyceride (36%) levels. The decrease of the plasma triglyceride pool size was not associated with a reduction in hepatic secretion of triglyceride. The total triglyceride lipase activity rose (32%) due to a remarkable increase (100%) of the extrahepatic lipoprotein lipase activity. We can conclude that extrahepatic lipoprotein lipase activity accounts for the hypotriglyceridaemic effect of DEHP through an increase of triglyceride removal rate.

Administration, Oral↗

Response of plasma triglycerides to dietary change in patients on hemodialysis.

The effect of reduction in dietary carbohydrate content of meal formula diets on plasma triglyceride concentrations was studied in 12 patients receiving chronic hemodialysis. Fasting plasma triglycerides decreased over a 10-day period in 11 of 12 patients in response to a decreased proportion of carbohydrate (from 50 to 35% of total daily calories) regardless of the type of fat used. Postprandial insulin responses were also significantly lower in the patients on the diets lower in carbohydrate. In addition, triglyceride kinetics were studied in three groups of patients. Patients with renal failure (dialyzed and undialyzed) had lower triglyceride production rates than those of control subjects, despite higher plasma triglyceride concentrations. Elevated (greater than 150 mg/100 ml) fasting plasma triglycerides are associated with lower triglyceride production rates in patients with chronic renal failure and may not be improved by conventional hemodialysis. A long-term study of the efficacy of reduction in dietary carbohydrate on plasma triglycerides is needed since routine hemodialysis does not appear to correct the lipid abnormality in patients with chronic renal failure.

Adult↗

Effects of KRN4884, a novel pyridinecarboxamidine type KATP channel opener, on serum triglyceride levels in rats.

1. The effects of KRN4884, a novel pyridinecarboxamidine type KATP channel opener, on serum triglyceride levels were investigated in Sprague-Dawley rats. 2. Oral administration of KRN4884 (3 mg kg-1) for 10 days caused a significant reduction in serum triglyceride levels, which was comparable to that of clofibrate (160 mg kg-1). Reduction in serum triglyceride levels by KRN4884 and clofibrate were accompanied by a reduction in triglyceride levels both in chylomicron and in very low density lipoprotein. KRN4884 treatment did not affect serum concentrations of total cholesterol and phospholipid, but did increase free fatty acid levels. Clofibrate reduced total cholesterol, phospholipid and free fatty acid levels. 3. Administration of clofibrate significantly decreased triglyceride secretion rate as measured by the Triton WR-1339 injection procedure, while KRN4884 did not. 4. Rats receiving KRN4884 exhibited an increase in lipoprotein lipase (LPL) activity both in adipose tissue and in skeletal muscle. There was an inverse correlation between serum triglyceride levels and tissue LPL activities. KRN4884 did not change hepatic triglyceride lipase (HTGL) activity. Clofibrate affected neither LPL nor HTGL activities. 5. It is concluded that administration of KRN4884 results in reduced serum triglyceride levels which may be due to the enhancement of LPL activity in peripheral tissues.

ATP-Binding Cassette Transporters↗

Plasma lipoproteins and the synthesis and turnover of plasma triglyceride in normal and genetically obese mice.

1. Lipoproteins in the plasma of mice were characterized by agarose-gel chromatography and polyacrylamide-gel electrophoresis: genetically obese (ob/ob) mice exhibited hyperlipoproteinaemia (compared with lean mice), largely owing to an increase in the concentration of cholesterol in high-density lipoprotein. Plasma concentrations of triglyceride and phospholipid were not markedly increased in genetically obese mice. 2. The formation of glycerolipids in liver and plasma was investigated with (14)C-labelled precursors. The synthesis of hepatic triglyceride and phospholipid from glucose or palmitate was enhanced in ob/ob mice, compared with lean mice. The rate of entry of triglyceride into plasma, calculated from the time-course of incorporation of (14)C from [(14)C]palmitate into plasma triglyceride, was increased in ob/ob mice (0.5mumol of fatty acid/min, compared with 0.2 in lean mice). 3. The removal from plasma of murine lipoprotein triglyceride-[(14)C]fatty acid was increased in ob/ob mice (half-time 2.2min, compared with 7.2min in lean mice). Similar results were obtained with an injected lipid emulsion (Intralipid). 4. From these measurements, estimates of the rates of turnover of plasma triglyceride in mice (fed on a mixed diet, female, 3 months old) are about 1.0mumol of fatty acid/min in ob/ob mice, and 0.25 in lean mice. 5. The major precursor of hepatic and plasma triglyceride in lean and ob/ob mice was calculated to be plasma free fatty acid. 6. These results are discussed, in connexion with the role of the liver in triglyceride metabolism in mice, especially in relation to genetic obesity.

Animals↗

Nitrogen sparing effect of structured triglycerides containing both medium-and long-chain fatty acids in critically ill patients; a double blind randomized controlled trial.

BACKGROUND AND AIMS: Patients with sepsis and trauma are characterised by hypermetabolism, insulin resistance and protein catabolism. Fat emulsions containing medium chain triglycerides have been suggested to be beneficial for these patients since medium chain fatty acids are a more readily available source of energy when compared to long chain fatty acids. The aim of this study was to compare a medium and long chain triglyceride emulsion consisting of structured triglycerides (ST) with a long chain triglyceride (LCT) emulsion in terms of effects on nitrogen balance, energy metabolism and safety. METHODS: 30 ICU patients with sepsis or multiple injury received a fat emulsion with ST or 20% LCT (1.5 g triglycerides/kg body weight/day) as a component of total parenteral nutrition (TPN), for 5 days in a double blind randomised parallel group design. The main analysis was made on the 3 day per protocol population due to lack of patients at day 5. RESULTS: There were no differences in baseline characteristics of the two groups receiving either the LCT or the ST emulsion. The efficacy analysis was performed on the per protocol population (n=9 ST, n=11 LCT). There was a significant difference between the two treatments regarding daily nitrogen balances when the first 3 days were analysed P=0.0038). This resulted in an amelioration of the nitrogen balance on day 3 in the group on ST as compared to those on LCT (0.1+/-2.4 g vs -9.9+/-2.1 g P=0.01). The 3 day cumulative nitrogen balance was significantly better in the group receiving ST compared to those on LCT (-0.7+/-6.0 vs -16.7+/-3.9 P=0.03). This better cumulative nitrogen balance on day 3 was also preserved as a tendency (P=0.061) in the analysis of the intention to treat population, but on day 5 there was no significant difference (P=0.08). The ST emulsion was well tolerated and no difference was found compared to the LCT emulsion regarding respiratory quotient, energy expenditure, glucose or triglyceride levels during infusion. CONCLUSION: Administration of a structured triglyceride emulsion resulted in an amelioration of nitrogen balance despite no effect on energy expenditure in short term administration over 3 days to ICU patients when compared to a long chain triglyceride emulsion. No side effects linked to medium chain triglycerides were noted.

Adult↗

Effect of exogenous or endogenous gastric inhibitory polypeptide (GIP) on plasma triglyceride responses in rats.

We examined the effects of exogenous and endogenous GIP on plasma triglyceride levels in rats, pretreated with a fat-enriched diet, during intraduodenal infusion of a lipid test meal (Lipomul, 8 ml/h). Following the fat load the plasma triglyceride levels increased nearly linearly from a fasting value of 0.621 +/- 0.031 mmol/l to 3.32 +/- 0.403 mmol/l at 150 min. Simultaneously, the plasma GIP levels rose from 47.1 +/- 5.1 at fasting to a peak value of 268.4 +/- 32.2 pmol/l at 120 min. When porcine GIP was infused intravenously during the fat load, the plasma triglyceride increments were significantly smaller (control 1.64 +/- 0.264 mmol/l versus 0.949 +/- 0.114 mmol/l during GIP infusion at 60 min; p less than 0.002). GIP infusion in the absence of the fat load did not change fasting triglyceride levels. The effect of endogenous GIP was investigated by neutralization of GIP by injection of GIP antiserum (0.3 ml). Rats pretreated with the antiserum exhibited a significantly greater triglyceride increment late in the time course of the fat load. These data demonstrate that exogenous and endogenous GIP are able to lower the plasma triglyceride response to a fat load. Both, inhibition of fat absorption or stimulation of triglyceride uptake by peripheral tissues may be responsible for the GIP effects. The gut peptide GIP seems to represent an important hormonal regulator of postprandial triglyceride response.

Animals↗

Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan-bound lipoprotein lipase.

Apolipoprotein A5 (APOA5) is associated with differences in triglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasma triglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In human APOA5 transgenic mice (hAPOA5tr), catabolism of chylomicrons and very low density lipoprotein (VLDL) was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL). Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by cross-breeding a human LPL transgene with the apoa5 knock-out and the hAPOA5tr to an lpl-deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5-deficient mice; however, overexpression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr high density lipoprotein, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL-mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line. A direct interaction between LPL and apoAV was found by ligand blotting. It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycan-bound LPL for lipolysis.

Allosteric Site↗

Fasting triglycerides as a predictor of long-term mortality in middle-aged men with combined hyperlipidaemia.

OBJECTIVE: To study cholesterol, triglycerides, smoking and blood pressure as potential predictors of long-term mortality in middle-aged males with combined hyperlipidaemia. METHODS: The study included 104 healthy men aged 40-49 years with total serum cholesterol >6.45 mmol/L and fasting triglycerides >2.55 mmol/L within the randomized diet and smoking cessation trial of the Oslo study (n=1232). RESULTS: Thirty-three subjects died during the 24-year observation period. Univariate analysis showed that only age, fasting triglycerides and smoking were significantly related to mortality. An analysis for trend through quartiles of triglycerides showed a statistically significant association with mortality (p=0.049). Subjects in the lowest triglyceride quartile (2.55-2.75 mmol/L) had a 70%, reduction in mortality compared with the remaining subjects (>2.75 mmol/L) (RR=0.30, 95% CI 0.10-0.90, p=0.014). Non-smokers had a 60% reduced mortality compared with smokers (RR=0.40, 95% CI 0.17-0.94, p=0.019). When studied in a Cox regression analysis, with age, triglycerides and smoking as independent variables, triglycerides were significantly related to mortality, 1st quartile vs. 2nd, 3rd and 4th quartiles: risk rate=0.24, (95% CI 0.07-0.77, p=0.02). For non-smokers vs. smokers, the Cox analysis showed a risk rate=0.39, (95% CI 0.15-1.02, p=0.054). CONCLUSION: This study indicates that high levels of fasting triglycerides (>2.75 mmol) are independently associated with increased late mortality in healthy middle-aged men with combined hyperlipidaemia.

Adult↗

Medium-chain fatty acids: evidence for incorporation into chylomicron triglycerides in humans.

The purpose of this study was to evaluate the fatty acid composition of chylomicron triglycerides isolated from subjects fed liquid-formula diets containing 40% of total energy as medium- (C8:0 and C10:0) or long-chain (C16-C18) triglycerides (MCT, LCT) for 6 d. Medium-chain fatty acids (MCFA) comprised 8% of total chylomicron triglyceride fatty acids after the first MCT meal. After 6 d of continued MCT feeding, chylomicron triglyceride MCFA content increased to 13%. When subjects were fed the LCT (soybean oil) diet, C16:0, C18:1, and C18:2 comprised nearly 90% of the chylomicron triglyceride fatty acids. The mass of triglyceride transported in chylomicrons isolated from subjects fed the MCT diet was approximately 20% of that found when subjects consumed the LCT diet. We conclude that although total triglyceride production during MCT ingestion is low, the chylomicron triglycerides that are synthesized contain significant amounts of MCFA.

Chylomicrons↗

Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.

The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in approximately 16% of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n=419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12% of Caucasians, 14% of African-Americans and 28% of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25-50% of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

Apolipoprotein A-V↗

Individual serum triglyceride responses to high-fat and low-fat diets differ in men with modest and severe hypertriglyceridemia.

It is not yet clear whether a low-fat or a high-fat diet is more suitable for the treatment of hypertriglyceridemia. Therefore, we conducted a dietary study with nonobese hypertriglyceridemic men using a randomized crossover design. After a 2-wk acclimation period, the subjects were randomly assigned to 2 groups. One group consumed a low-fat (29% of energy) diet for 3 wk, followed first by a 2-wk washout period, then a 3-wk high-fat (40% of energy) diet period. The second group consumed the low- and high-fat diets in reverse order. Both diets were isocaloric, rich in monounsaturated fatty acids (MUFAs) and long-chain (n-3)-PUFAs, and contained no alcohol. Absolute amounts of long-chain (n-3)-PUFAs and fiber were similar, as were the fatty acid and carbohydrate compositions. Serum triglyceride concentrations in fasting subjects decreased during the high-fat diet period by 34% (95% CI = -19 to -46%, P = 0.001), and during the low-fat diet period by 31% (95% CI = -0.5 to -51.8%, P = 0.048). Triglyceride concentrations did not differ between the low- and high-fat diet periods. However, the high-fat diet lowered triglyceride concentrations more effectively in all subjects with a baseline triglyceride concentration < 4.5 mmol/L, whereas the low-fat diet lowered triglyceride levels more effectively in half of the subjects with a baseline value > 4.5 mmol/L. Based on these findings, we recommend a high-fat triglyceride-lowering diet for patients with only slightly elevated serum triglyceride concentrations (<4.5 mmol/L). However, a lower-fat diet is more suitable for some subjects with more distinctly elevated triglyceride concentrations.

Adult↗

Serum triglycerides as an independent risk factor for death from coronary heart disease in middle-aged Norwegian men.

The relation between nonfasting serum triglycerides and death from coronary heart disease was studied in 37,546 men aged 35-49 years who were examined during 1972-1977 in four counties in Norway. During an average follow-up period of nine years, 369 deaths from coronary heart disease occurred. In univariate analysis, log(triglycerides) were a weak, but statistically significant predictor of coronary death in the age groups 40-44 and 45-49 years. Within-area analysis showed that a high triglyceride area represented no extreme. When other coronary risk factors were adjusted for, log(triglycerides) remained a significant independent predictor at ages 45-49 years and at higher levels of serum cholesterol. The predictive strength of serum cholesterol was largely the same whether log(triglycerides) were taken into account or not, whereas the predictive strength of log(triglycerides) depended on whether serum cholesterol was accounted for. The strength of coronary death prediction of the logarithm of serum triglycerides was hardly greater than might be explained by the fact that triglycerides are an indicator of the usual cholesterol level of the subject.

Adult↗

Propofol in a medium- and long-chain triglyceride emulsion: pharmacological characteristics and potential beneficial effects.

UNLABELLED: Hypertriglyceridemia is a possible unwanted effect during long-term propofol sedation while using a formulation containing long-chain triglycerides (LCT) from soybean oil. The use of propofol formulated in a solvent consisting of medium-chain triglycerides (MCT) and LCT might reduce the risk. Because a new solvent may affect the pharmacological profile of propofol, in this prospective, randomized, controlled, and double-blinded study we compared the pharmacodynamic and kinetic characteristics of propofol diluted in MCT/LCT fat solution with those of propofol formulated in LCT fat emulsion. In addition, serum triglyceride levels were measured during and after the administration of both drugs. Thirty patients likely to require mechanical ventilation over at least 48 h were randomized to receive either propofol 2% MCT/LCT (Group 1) or propofol 2% LCT (Group 2). Infusion rates of propofol (2.34 +/- 0.83 mg. kg(-1). h(-1) in Group 1 versus 2.31 +/- 0.6 mg. kg(-1). h(-1) in Group 2), the plasma propofol concentrations during infusion (0.95 +/- 0.53 versus 0.98 +/- 0.32 micro g/mL), and the concentrations and arousal behavior after discontinuation of the drug did not show significant differences. Plasma triglyceride concentrations during sedation did not differ between the groups, whereas there was a tendency toward a more rapid triglyceride elimination in Group 1 after termination of the propofol administration. IMPLICATIONS: Propofol diluted in an emulsion of medium- and long chain-triglycerides shows equivalent pharmacological properties during long-term sedation compared with its hitherto well known formulation containing long-chain triglycerides only. In addition, potential favorable effects on the plasma triglyceride profile could be found.

Adult↗