Fall In Triglycerides Research Articles

Short-term effect of laparoscopic sleeve gastrectomy on hyperlipidemic obese patients

Introduction Obesity has become a global epidemic and a major health problem in the twenty-first century. Studies have demonstrated that weight loss lowers increased serum total cholesterol and low-density lipoprotein (LDL) cholesterol and raises high-density lipoprotein (HDL) cholesterol. One of the most recent procedures for managing weight loss in obese people with other options is laparoscopic sleeve gastrectomy (LSG). Objectives The aim of this study was to evaluate the short-term effect of laparoscopic sleeve gastrectomy on lipid profile in hyperlipidemic obese patients during the nine months of postoperative care. Methods From July 2020 to October 2021, 50 hyperlipidemic obese patients who were eligible for bariatric surgery underwent this prospective study at Main University Hospital in Alexandria, Egypt. Before and one, three, six, and nine months after the surgical intervention, measurements of body weight, body mass index (BMI), waist circumference, fasting and postprandial blood sugar, serum cholesterol, triglyceride, HDL, and LDL levels were taken. Results The patients’ average age was 33.72±7.95 years. BMI, weight, blood sugar, and other measurements all significantly decreased. The mean body mass index (BMI) of the patients was 48.59±5.78 kg/m2 before surgery, however, it was reduced to 32.58±3.91 kg/m2 nine months afterwards. Studies revealed a statistically significant rise in HDL levels in the serum and a statistically significant fall in triglycerides, total cholesterol, and LDL levels. Results also revealed a favorable association between preoperative differences in age, BMI, and diabetes state and postoperative lipid profile alterations. Conclusion Laparoscopic sleeve gastrectomy (LSG) decreases body mass index, improves glucose and lipid metabolism, and alters the lipid profile by significantly lowering total cholesterol, triglycerides, and LDL cholesterol while significantly raising HDL cholesterol.

Intravenous Insulin Versus Conservative Management in Hypertriglyceridemia-Associated Acute Pancreatitis.

Context and ObjectiveHypertriglyceridemia is implicated in ~5% of cases of acute pancreatitis. It is assumed that intravenous insulin is effective in lowering triglyceride (TG) concentrations in hypertriglyceridemia-associated acute pancreatitis (HAAP). However, the efficacy of intravenous insulin versus conservative management alone is not known.Design and SettingCharts of 106 patients who were admitted with HAAP and had TG concentrations >1000 mg/dL at admission were reviewed. Patients who received intravenous insulin for at least 8 hours were included in the intravenous insulin group, while the rest were considered to have received conservative management. We compared the change in TG concentrations from baseline in the 2 groups.ResultsFifty-one patients received intravenous insulin while 55 patients were managed conservatively. Baseline TG concentrations were higher in the intravenous insulin group (median [25th, 75th percentile] 3307 [2106, 4425] mg/dL vs 2304 [1416, 2720] mg/dL; P < 0.001). The TG concentrations declined rapidly in both groups, reaching below 1000 mg/dL by day 3 and < 500 mg/dL by day 4. TG concentrations in the intravenous insulin group had decreased by 69% and 85% on days 2 and 4, respectively. The fall in the conservative management group was 63% and 79%, which was not statistically different than the change in the intravenous insulin group.ConclusionOur results show that intravenous insulin did not result in a more rapid fall in TG compared with conservative treatment in patients with HAAP. Fasting and intravenous fluids were effective in lowering TG concentrations rapidly, with no further contribution from insulin.

Skeletal muscle expression of p43, a truncated thyroid hormone receptor α, affects lipid composition and metabolism.

Thyroid hormone is a major regulator of metabolism and mitochondrial function. Thyroid hormone also affects reactions in almost all pathways of lipids metabolism and as such is considered as the main hormonal regulator of lipid biogenesis. The aim of this study was to explore the possible involvement of p43, a 43 Kda truncated form of the nuclear thyroid hormone receptor TRα1 which stimulates mitochondrial activity. Therefore, using mouse models overexpressing p43 in skeletal muscle (p43-Tg) or lacking p43 (p43-/-), we have investigated the lipid composition in quadriceps muscle and in mitochondria. Here, we reported in the quadriceps muscle of p43-/- mice, a fall in triglycerides, an inhibition of monounsaturated fatty acids (MUFA) synthesis, an increase in elongase index and an decrease in desaturase index. However, in mitochondria from p43-/- mice, fatty acid profile was barely modified. In the quadriceps muscle of p43-Tg mice, MUFA content was decreased whereas the unsaturation index was increased. In addition, in quadriceps mitochondria of p43-Tg mice, we found an increase of linoleic acid level and unsaturation index. Last, we showed that cardiolipin content, a key phospholipid for mitochondrial function, remained unchanged both in quadriceps muscle and in its mitochondria whatever the mice genotype. In conclusion, this study shows that muscle lipid content and fatty acid profile are strongly affected in skeletal muscle by p43 levels. We also demonstrate that regulation of cardiolipin biosynthesis by the thyroid hormone does not imply p43.

The effect of defatted cocoa powder on cholesterol-induced changes of serum lipids in rats

Cocoa has been known for many health benefits, but its lipid-lowering activity still remains unresolved. To investigate effects of varying amounts of defatted cocoa on serum lipids in cholesterol-fed rats. Forty-eight male Sprague-Dawley rats were randomly assigned into four cholesterol-free (control) and four cholesterol-supplemented (experimental) diets containing 0, 1, 2 or 3% defatted cocoa (DC) and given ad libitumto the rats for ten weeks. Serum total cholesterol (TC), low- and very low-density lipoprotein cholesterol (LDL-C and VLDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were quantified, atherogenic index (AI) was calculated, and other biological parameters were assessed. Food intake and body weight did not respond to DC. Compared to 0% DC, 3% DC had the most prominent effect on serum lipids inducing significant fall in LDL-C and TG, and rise in TC/TG in cholesterol-deprived rats, and increase in VLDL-C and AI, and decrease in HDL-C in cholesterol-fed rats. Compared to cholesterol-deprived rats, 3% DC caused significant rise in VLDL-C, AI and TC/TG, and fall in TG in cholesterol-fed rats. This lipid-modifying effect was markedly substantiated by corresponding linear trend responses to DC. Differences in lipid variables of rats fed on DC diets were less evident. Results suggest that, in contrast to cholesterol-free situations, defatted cocoa is seemingly incapable of counteracting the atherogenic effect of cholesterol in rats, perhaps in an interaction that is likely to have clinical implications in cardiometabolic conditions.

Changes in blood pressure and lipids associated with rural to urban migration in Tanzania

High levels of rural to urban migration are a feature of most developing countries, and are thought to be associated with an increase in non-communicable disease risk factors. We studied rural to urban migrants in Tanzania and found a mixed pattern of change over 6 months, with an increase in low-density lipoprotein cholesterol and weight, a fall in triglycerides and an apparent fall in blood pressure.

Effect of n‐3 fatty acids on carotid atherosclerosis and haemostasis in patients with combined hyperlipoproteinemia: A double‐blind pilot study in primary prevention

Background. Intake of n‐3 polyunsaturated fatty acids (n‐3 PUFA) either from natural sources or dietary supplementation is inversely associated with atherothrombosis.Aim. A double‐blind pilot study was designed to address the impact of n‐3 PUFA on atherosclerosis, haemostasis and vascular status in patients with combined hyperlipoproteinemia.Methods. Carotid intima‐media thickness (C‐IMT), texture of intima‐media complex (T‐IMC), lipids and platelet function were evaluated in 64 patients with combined hyperlipoproteinemia who received placebo or n‐3 PUFA (6 g/day) for 2 years. C‐IMT and T‐IMC were assessed by B‐mode ultrasound. Lipids and platelet function were determined by validated methods.Results. C‐IMT increased in placebo, but not in n‐3 PUFA group with respect to baseline. In contrast T‐IMC decreased in n‐3 PUFA, but not in placebo; in both cases, however, treatment effect did not reach statistical significance. A fall of triglycerides, concomitant to a rise of high‐ and low‐density lipoprotein cholesterol (HDL and LDL), was observed in the active treated group. Platelet function was significantly reduced by n‐3 PUFA.Conclusions. Results show a favourable effectiveness of n‐3 PUFA on IMT progression and T‐IMC that deserves to be confirmed in larger studies. Despite the small sample size, the beneficial effect of n‐3 PUFA on platelet function, triglycerides and HDL‐C is clearly highlighted.

Hypolipidemic drugs in North India and their effect on lipid profile

A study of prescribing patterns was carried out by conducting a medical audit of 112 prescriptions of outpatients on lipid-lowering therapy at a tertiary care teaching hospital in North India. Over the IP-week study, fenofibrate resulted in a 48.68% fall in triglyceride, 32.67% rise in HDL-c and 27.13% fall in Lp(a) levels. Bezafibrate resulted in a 45.30% fall in triglyceride and 14.95% rise in HDL-c levels. Atorvastatin resulted in a 26.98% fall in total cholesterol, 26.59% fall in triglyceride, 41.23% fall in LDL-c and 27.38% fall in Lp(a) levels. Simvastatin resulted in a 29.44% fall in total cholesterol, 23.62% fall in triglyceride and 38.01% fall in LDL-c levels. 80.00% of patients reported adverse effects within 6 weeks of use of hypolipidemic drugs. The overall incidence of adverse effects varied from 60% with atorvastatin to 88.89% with bezafibrate. 43.33% of patients had serum Lp(a) levels higher than normal at the beginning of the study. No significant correlation of Lp(a) levels was obtained with other lipoproteins though patients with higher triglyceride levels were more often found to have associated higher serum Lp(a) levels. It is concluded that the use of drugs which selectively lower lipoprotein(a) levels should be emphasized.

Should surgeons treat diabetes in severely obese people?

Many people enjoy the opportunity of eating more than they need with little requirement for physical exertion. In the USA the proportion of adults aged 20–74 years with a body mass index greater than 30 kg/m 2 Prescott-Clark P Primatesta P Health survey for England 1996. Stationery Office, London1996 Google Scholar has increased from 12-3% in 1976–80 to 22-5% in 1988–94. 1 Flegal KM Carroll MD Kuczmarski RJ Johnson CL Overweight and obesity in the United States: prevalence and trends, 1960–1994. Int J Obes Relat Metab Disord. 2000; 22: 39-47 Crossref Scopus (2537) Google Scholar In the UK this proportion rose from 6% to 16% in men and from 8% to 17-3% in women between 1980 and 1996. 2 Prescott-Clark P Primatesta P Health survey for England 1996. Stationery Office, London1996 Google Scholar Obesity predisposes to type 2 diabetes via insulin resistance, impaired glucose tolerance, and pancreatic [3-cell failure, 3 DeFronzo RA The Triumvirate: b-cell, muscle, liver, a collusion responsible for NIDDM. Diabetes. 1987; 37: 667-687 Crossref Google Scholar and largely explains the worldwide increase in this disease. 4 Hodge AM Zimmet P The epidemiology of obesity. Bailliere's Clin Endocrinol Metab. 1994; 8: 577-599 Summary Full Text PDF PubMed Scopus (88) Google Scholar As might be expected, if maintained, the potential benefits of weight loss are remarkable (panel). 5 Jung RT Obesity as a disease. Br Med Bull. 1997; 53: 307-321 Crossref PubMed Scopus (280) Google Scholar Weight loss of 10 kg can achieve greater reductions in HbA1c and fasting plasma glucose than treatment with Metformin, with similar reductions in diabetes-related deaths, and improved control of lipid and blood pressure without the need for additional drug treatment. 6 UK Prospective Diabetes Study (UKPDS) GroupEffect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998; 352: 854-865 Summary Full Text Full Text PDF PubMed Scopus (7402) Google Scholar Weight loss should therefore be the main aim of treatment in overweight individuals with type 2 diabetes, but is rarely achieved. Indeed, weight gain is a major complication of treatment whether with sulphonylureas, insulin, or the thiazolidinediones. In the quest for normoglycaemia, drugs are used as surrogates for weight loss, which alone acts at the cause of the disease. Further weight gain is the price paid for short-term improvement in glucose concentrations. Tabled 1 Based on figure from reference 5 Mortality 20–25% fall in total mortality 30–40% fall in diabetes-related deaths 40–50% fall in obesity-related cancer deaths Blood pressure Fall of 10 mm Hg systolic Fall of 20 mm Hg diastolic Angina 91% reduction in symptoms 33% increase in exercise tolerance Lipids 10% fall in total cholesterol 15% fall in LDL cholesterol 30% fall in triglycerides 8% increase in HDL cholesterol Diabetes >50% reduction in risk of developing diabetes 30–50% fall in fasting blood glucose 15% fall in HbA1c Open table in a new tab

Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes.

Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high-density lipoproteins (HDLs) towards apolipoprotein (apo) B-containing lipoproteins are key steps in HDL metabolism. The effects of exogenous hyperinsulinaemia on plasma CET and EST, measured with isotope methods, were evaluated in 10 male normotriglyceridaemic (plasma triglycerides <2.0 mmol L-1) patients with type 2 diabetes and 10 individually matched healthy subjects during a two-step hyperinsulinaemic euglycaemic clamp over 6-7 h. No between-group differences in baseline plasma lipid parameters were observed, but the HDL cholesteryl ester content was lower (P < 0.02) and the HDL triglyceride content was higher (P < 0.05) in diabetic patients. Baseline CET and EST were similar in the groups. In both groups, hyperinsulinaemia decreased plasma triglycerides (P < 0.01) and the HDL triglyceride content (P < 0.01) compared with saline infusion in healthy subjects, whereas the HDL cholesteryl ester content increased (P < 0.05 vs. saline infusion) in diabetic patients. CET was similarly decreased by hyperinsulinaemia in both groups (P < 0.01 vs. saline infusion). In contrast, the change in EST in either group was not different from that during saline administration. In the combined group, baseline CET was positively correlated with plasma triglycerides (Rs = 0.68, P < 0.01). The HDL cholesteryl ester content was negatively (Rs = -0.48, P < 0.05) and the HDL triglyceride content was positively (Rs = 0.64, P < 0.01) correlated with CET. Insulin infusion decreases plasma CET in conjunction with a fall in triglycerides but does not decrease cholesterol esterification in healthy and type 2 diabetic subjects, indicating that acute hyperinsulinaemia has a different effect on these processes involved in HDL metabolism. Despite unaltered fasting plasma CET, HDL core lipid composition was abnormal in diabetic patients, suggesting that additional mechanisms may contribute to changes in HDL metabolism in diabetes mellitus.

DIET AND SHORT TERM PLASMA LIPOPROTEIN-LIPID CHANGES AFTER EXERCISE IN TRAINED MEN

1887 To test the effect of diet on the short-term lipid response to exercise, fourteen moderately trained (V̇O2max: 50.2 ± 6.7 ml·kg−1·min−1), healthy men (mean age: 27.8 ± 4.3 yr) were alternately fed a high fat (60 ± 6.7 % fat) and a high carbohydrate (63 ± 3.2% carbohydrate) isoenergetic diet for two weeks in a randomized crossover design. During the last four days of the treatments, fasting total cholesterol, triglyceride, HDL-cholesterol, and HDL3-cholesterol were measured the day before, and again immediately, 24 h, and 48 h after exercise (4190 kJ, 70% V̇O2max). LDL-cholesterol and HDL2-cholesterol were calculated. Lipid concentrations were adjusted for plasma volume changes after exercise. A 2 (diet) × 4 (time) ANOVA with repeated measures revealed no significant interaction between the diet and exercise treatments. Furthermore, diet alone did not influence lipid concentrations in these trained men. Exercise resulted in an increase in HDL-C (10.7%) and HDL3-C (8.5%) concentrations and a concomitant fall in triglyceride (−25%) and total cholesterol (−3.5%). Thus, we conclude that diet composition does not affect the short-term changes in blood lipids and lipoproteins that accompany a single session of aerobic exercise in moderately trained men.

A comparative study of the efficacy of simvastatin and gemfibrozil in combined hyperlipoproteinemia: prediction of response by baseline lipids, apo E genotype, lipoprotein(a) and insulin

Combined hyperlipoproteinemia (CHL) can be difficult to treat because of the heterogeneous nature of the lipoprotein abnormalities. We compared the relative efficacies of simvastatin and gemfibrozil and sought predictors of responsiveness in terms of the baseline lipids and other potential metabolic determinants (plasma insulin, Lp(a) and apo E genotype). Sixty-six subjects entered a cross-over, randomized trial involving 12 weeks on each drug. Efficacy was assessed after 6 and 12 weeks on each treatment. Simvastatin lowered total cholesterol 24%, triglycerides 12%, LDL cholesterol 33%, raised HDL cholesterol 13% and substantially reduced the cholesterol:triglyceride ratio in VLDL and IDL. Gemfibrozil lowered total cholesterol 5%, triglycerides 44%, raised HDL 26% and reduced VLDL and IDL lipids more than simvastatin did. LDL size increased with both treatments and HDL size increased with simvastatin. Responsiveness (25% fall in cholesterol or 40% fall in triglycerides) was shown by 31/61 subjects when taking simvastatin (cholesterol-lowering) and by 44/60 taking gemfibrozil (triglyceride-lowering). Responsiveness was greatest in those with apo E 2 genotype with both drugs ( P<0.05). Unexpectedly, responders to simvastatin tended to have lower baseline total cholesterol but higher triglyceride levels than those whose cholesterol or triglyceride was lowered by gemfibrozil. Nevertheless, more hypercholesterolemic subjects responded to simvastatin and more hypertriglyceridemic subjects to gemfibrozil. Lp(a) ( P=0.04) and plasma insulin concentrations ( P=0.03) were negative predictors of percentage triglyceride-lowering with gemfibrozil. The difference between the two drugs in triglyceride-lowering lessened with rising insulin and falling HDL cholesterol. Thus, the responsiveness to the two major classes of lipid lowering drugs can be partly predicted from baseline lipids and related metabolic parameters.

The Effects of High- and Medium-Dose Metformin Therapy on Cardiovascular Risk Factors in Patients With Type II Diabetes

To study the dose response to metformin in type II diabetic patients. Type II diabetic patients with a BMI > 25 were treated with 3,000 mg/day (n = 27), 1,500 mg/day (n = 25), or placebo (n = 23) for 6 months. Venous blood samples were taken at each visit for plasma glucose and insulin, HbA1c, triglyceride and cholesterol, plasminogen activator inhibitor-1 (PAI-1) antigen and activity, tissue plasminogen activator (tPA), and euglobulin clot lysis time (ECLT). Blood pressure was recorded at each visit. There were no changes in BMI or blood pressure. Blood glucose fell (mean) by 3.6 mmol/l in the high-dose and 0.5 mmol/l in the low-dose group over the 6-month study (P < 0.001 and NS compared with placebo). HbA1c and plasma insulin fell in both treatment groups (HbA1c, P < 0.001; insulin, P < 0.003 and 0.03). There was a fall in triglyceride (P < 0.05) and cholesterol (P < 0.008) with high-dose metformin. PAI-1 antigen and activity fell by approximately 20% of baseline in both treatment groups (PAI-1 antigen high dose, P < 0.01; PAI-1 antigen low dose, P < 0.002: PAI-1 activity high and low dose, P < 0.003). There were significant falls in total tPA in both groups (P < 0.004), but the overall effect was a fall in ECLT (P < 0.03). The results indicate that metformin has favorable effects on cardiovascular risk factors associated with type II diabetes. The effects on glycemic control and lipids are dose-dependent, while the enhanced fibrinolytic response is independent of the doses used.

Effect of Gemfibrozil Treatment in Sulfonylurea-Treated Patients with Noninsulin-Dependent Diabetes Mellitus*

This study was initiated to 1) assess gemfibrozil's ability to lower plasma triglyceride (TG) concentration in patients with NIDDM, and 2) determine whether this effect was associated with any changes in glycemic control. Measurements were made of mean hourly plasma glucose, insulin, TG, and FFA concentrations from 1200-1600 h in response to a test meal; hepatic glucose production (HGP); insulin-stimulated glucose uptake during a hyperinsulinemic glucose clamp study (MCR); and fasting plasma lipoprotein TG and cholesterol concentrations in 12 patients with NIDDM before and 3 months after gemfibrozil treatment. Although ambient plasma TG and FFA concentrations fell significantly, plasma glucose, insulin, HGP, concentrations fell significantly, plasma glucose, insulin, HGP, and glucose MCR did not change. However, when patients were divided into two groups, those with fasting plasma glucose levels above 9 mmol/L (fair control) and those with levels below 9 mmol/L (good control), a different phenomenon was observed. Patients in fair control had significant decreases in mean hourly plasma concentrations of glucose (15.1 +/- 1.7 to 12.6 +/- 0.9 mmol/L; P less than 0.001), insulin (523 +/- 59 to 471 +/- 75 pmol/L; P less than 0.001), FFA (652 +/- 150 to 504 +/- 76 mumol/L), and HGP (9.5 0.4 to 8.1 +/- 0.4 mumol/kg.min; P less than 0.005), and an increase in glucose MCR (2.63 +/- 0.49 to 3.72 +/- 0.54 mL/kg.min; P less than 0.07) in association with a fall in TG from 6.9 +/- 1.3 to 3.5 +/- 0.9 mmol/L (P less than 0.001). Although fasting low density lipoprotein cholesterol increased (1.8 +/- 0.2 to 2.7 +/- 0.2 mmol/L; P less than 0.05), the ratio of total to high density lipoprotein cholesterol decreased (6.84 +/- 0.88 to 5.80 +/- 1.05; P less than 0.02). Despite a significant fall in mean hourly TG concentration (4.6 +/- 0.7 to 3.8 +/- 0.7 mmol/L; P less than 0.001), neither insulin, FFA, HGP, nor glucose MCR changed in patients in good control. Furthermore, the mean hourly plasma glucose concentration increased from 9.2 +/- 0.7 to 11.7 +/- 1.4 mmol/L (P less than 0.001). Low density lipoprotein cholesterol also increased in this group (1.9 +/- 0.2 to 2.7 +/- 0.2 mmol/L; P less than 0.02), but, as before, the ratio of total to high density lipoprotein cholesterol decreased (8.15 +/- 1.93 to 6.36 +/- 1.03; P less than 0.02).

Evaluation of the efficacy and safety of Diamicron ® in non-insulin-dependent diabetic patients

The efficacy and safety of gliclazide (Diamicron ®) were studied in 29 NIDDM patients (19 men and 10 women aged 25–68 years) who failed to improve with diet or with diet plus a sulfonylurea. All patients were overweight and had fasting blood glucose levels consistently above 150 mg/dl (8.24 mmol/l). After withdrawal of oral hypoglycemics where applicable, they received 40 mg Diamicron ® three times daily with meals. The dose was increased by 40–80 mg/day until optimum control was obtained or up to a maximum of 320 mg/day. Treatment lasted for 12 months. At the end of this period the mean fasting blood glucose level had fallen by 35% from 238 to 154 mg/dl and the mean 2-h postprandial blood glucose level had fallen by 28% from 237.7 to 195 mg/dl. The mean glycosylated hemoglobin level also fell by 30% from 10.10 to 7.02%, i.e. within the normal range. In addition, there was a 19% fall in triglyceride and a 10% fall in cholesterol levels, with no change in body weight. No changes were observed for serum insulin, C-peptide and glucagon levels, thyroid function tests, blood counts, liver and kidney function tests, uric acid, electrolytes, blood pressure or heart rate. No clinical or ECG abnormalities were observed in patients with or without cardiovascular disease. There were two presumptive hypoglycemic reactions, but these did not require treatment. Adverse effects were reported by 22 patients, including dizziness and light-headedness, diarrhea, nausea, palpitations and pruritus, but none required modification of Diamicron ® therapy. The results therefore show that Diamicron ® is safe, effective and well tolerated in suitably selected NIDDM patients.

Treatment of hypercholesterolemia with the HMG CoA reductase inhibitor, simvastatin

We report the results of a two center study on the use of the HMG Co A reductase inhibitor, simvastatin, in 44 patients suffering from familial hypercholesterolemia or from primary hypercholesterolemia of unknown etiology. The study included two separate phases: Phase I was part of a multicenter, 4-week, placebo-controlled trial; phase II was a 6-month, open extension trial, the object of which was to reduce low density lipoprotein (LDL) cholesterol levels to below the 50th percentile by increasing the dose of simvastatin, by the use of additional lipid-lowering medication, or both. Our phase I results were commensurate with those reported for the entire international cohort of 272 patients, indicating a clear dose-response relationship, with approximately 75% of the maximum reduction in LDL-C levels being achieved with 20 mg/day and over 90% of the maximum being achieved with 40 mg of simvastatin per day. In the open extension trial, the results from the 2 centers were essentially similar. Total cholesterol fell by 29% on the 20 mg/day dose and by 34% on the full dose of 40 mg/day. LDL-C levels were reduced by 40% on the 40 mg/day schedule, and triglycerides also fell to between 20% and 40% below baseline values. HDL-C concentration rose by 14% and 17.6%. The effects of simvastatin were uniform, both within and between the two cohorts. The addition of cholestyramine caused a further substantial reduction in LDL-cholesterol to below 55% of the initial value in four patients, whereas bezafibrate further enhanced the fall in triglycerides and the increase in high-density lipoprotein cholesterol, but had only a slight effect on LDL-C levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Dietary Fish Oil on Lipid Abnormalities in Patients on Continuous Ambulatory Peritoneal Dialysis

Fifteen patients receiving continuous ambulatory peritoneal dialysis (CAPD) were given 10 mL of a dietary fish oil rich in omega-3 fatty acids (MaxEPA) b.i.d. for eight weeks without other dietary manipulation. Fasting lipids, vitamins A and E, and glucose were measured at 0, 4, and 8 weeks, and again at 4 and 8 weeks after the cessation of treatment. Basal serum triglyceride concentrations were raised, and fell by 29% (p &lt; 0.005) with treatment, returning to baseline values over the washout period. The fall in triglyceride during treatment correlated with the initial value (As = 0.57; p &lt; 0.05). Total, HDL and LDL cholesterol, apolipoprotein A, vitamin A, glucose, lean body mass, and dietary fat/CHO intake were unchanged throughout. Apolipoprotein B concentrations tended to rise during the first half of treatment but fell thereafter. Vitamin E concentrations rose significantly during supplementation and fell after withdrawal (p &lt; 0.001 for both). Supplementation with dietary fish oil significantly reduced hypertriglyceridemia. Its long-term use might be accompanied by beneficial effects on the excess cardiovascular morbidity seen in patients on CAPD.

Fish oil modifies lipids and reduces platelet aggregability in haemodialysis patients.

Haemodialysis patients have an exceptionally high incidence of death from cardiovascular causes, related in part to abnormalities of lipids and platelets. Eskimos, however, have a low incidence of myocardial infarction and have a high dietary intake of fish, rich in omega-3 polyunsaturated fatty acids. We have, therefore, studied the effect of a fish oil MaxEPA, containing 3.6 g of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid on lipids and platelet function in haemodialysis patients. Following 8 weeks of therapy there was a 35% fall in triglycerides, a 10% rise of high-density lipoprotein (HDL) cholesterol, a 36% rise of HDL2 cholesterol fraction and a 54% rise of the HDL2:HDL3 cholesterol ratio. The platelet aggregation to adenosine diphosphate and collagen was significantly reduced. The activated whole-blood clotting time was prolonged from 141 to 153 s, and 69% of patients showed a reduction of factor VIII related antigen which is usually elevated in haemodialysis patients and is thought to be a marker of endothelial damage. The blood pressure fell from 147/82 to 124/74. We have thus shown that a dietary supplement of eicosapentaenoic acid produces potentially beneficial effects on lipids, platelets, and blood pressure and may help to protect against atheroma and thus cardiovascular mortality in high-risk haemodialysis patients.

Relationship between morphological changes and lipid-lowering action of p-chlorphenoxyisobutyric acid (CPIB) on hepatic mitochondria and peroxisomes in man

In order to elucidate the effect of long-term treatment with CPIB on the ultrastructure of the human liver, we measured the numerical and volume density of mitochondria and peroxisomes per cm 3 of liver tissue by morphometric procedures before and during prolonged intake of the drug in 16 patients with primary hypertriglyceridemia. We correlated the number and volume of mitochondria and peroxisomes to serum triglyceride and cholesterol concentrations and changes in order to obtain information on the interrelationship of organelle changes and lipid-lowering action. CPIB treatment resulted in significant increases in the numerical density of mitochondria and peroxisomes (38% and 50%, respectively, P < 0.01). The volume density for mitochondria and peroxisomes increased by 34% ( P < 0.01) and 23% (NS) respectively. After a marked proliferation of both organelles during the first months no further significant increase was observed. The fall in triglyceride and cholesterol levels during the initial period was followed by constant concentrations. A significant correlation between numerical and volume density of mitochondria and peroxisomes occurred during treatment indicating a well-balanced adapted process. There was a significant reverse correlation between the increase in volume density of mitochondria and the decrease in triglyceride levels, whereas no relation between the proliferation of peroxisomes and hypolipidemic action existed. In our study long-term treatment with CPIB had no toxic or carcinogenic effects on the human liver. Contrary to the fine structural changes in the rodents, the proliferation of peroxisomes is less pronounced and proportional to the increase in mitochondria. The correlation between mitochondrial proliferation and the triglyceride-lowering effect supports the hypothesis that CPIB reduces hepatic triglyceride synthesis by an increase in mitochondria associated with elevated activity of glycerol-3-phosphate dehydrogenase.

Biochemical disturbances associated with total hip replacement

A prospective study on 227 patients undergoing arthroplasty of the hip was carried out with reference to the effects on the cardiovascular and respiratory systems. Investigations revealed that the placing of acrylic bone cement and the prosthesis in the femoral shaft produced clinical and biochemical disturbances which were consistent with pulmonary microembolism. A fall in arterial oxygen tension during the procedure and hypoxaemia extending into the postoperative period with elevation of serum lipase and a fall in triglycerides supported the idea that embolisation with marrow fat occurred. The method of venting (by catheter or proximal hole) did not influence the biochemical disturbances. The implications of these findings are discussed.

Influence of carbon chain length of dietary fat on intestinal alkaline phosphatase in chylous ascites.

The long-term effects of chain length of dietary fat on intestinal lymphatic transport of alkaline phosphatase were investigated in two patients with chylous ascites due to leakage of intestinal lymph into the peritoneal cavity. Substitution of a medium-chain triglyceride diet for long-chain triglyceride resulted in a parallel fall in triglyceride and the intestinal isoenzyme of alkaline phosphatase in chylous ascites. The concentrations of lymph triglyceride were linearly related to lymph intestinal alkaline phosphatase levels, suggesting a positive relation between absorption of long-chain triglycerides and transport of mucosal alkaline phosphatase into lymph.