Circulating very-low-density lipoprotein characteristics resulting from fatty liver in an insulin resistance rat model.

The close association between nonalcoholic fatty liver and insulin resistance is now widely recognized. While the former is characterized by excessive intrahepatic triglyceride accumulation, the latter induces overproduction of very-low-density lipoprotein (VLDL) particles. It has not been well elucidated whether these apparently opposite mechanisms impact on VLDL characteristics or not. The aim of the present study was to evaluate the VLDL secretion and features resulting from insulin resistance and fatty liver in rats fed a sucrose-rich diet (SRD, i.e. addition of sucrose to drinking water during 12 weeks). No differences in calorie intake were observed in comparison to controls. Both groups showed similar weight gains throughout the treatment period. However, SRD rats showed an increased proportion of body fat as assessed by X-ray absorptiometry, increased visceral obesity, liver weight and fat accumulation in the liver (p < 0.04). Histological study revealed moderate micro- and macrovesicular steatosis. Fasting insulin, triglyceride and free fatty acid (FFA) levels increased while VLDLs decreased in SRD rats (p < 0.05). The chemical composition of VLDLs of SRD rats showed a higher percentage of triglycerides, and the VLDL triglyceride/protein ratio, an estimator of lipoprotein size, suggests that VLDL particles of SRD rats are larger than those of controls (p < 0.0005). FFA levels correlated with VLDL triglycerides (r = 0.49, p = 0.03) and liver fat content correlated with plasma triglycerides (r = 0.65), VLDL triglycerides (r = 0.55) and triglyceride/protein ratio (r = 0.52, p < 0.02). The VLDL secretion rate assay showed an increase in SRD rats (p < 0.02), confirming an overproduction despite liver fat accumulation. Our findings are consistent with an insulin resistance development model in which hepatic lipid content would constitute an important determinant of a triglyceride-rich, large-particle VLDL secretion; both features would increase its atherogenic potential.

Low adiponectin levels in primary hypertriglyceridemic male patients.

BACKGROUND AND AIMS: Adiponectin is an adipokine highly and specifically expressed by adipose cells with antiatherogenic and antiinflammatory activities. The aim of the present study was to evaluate plasma adiponectin concentration in patients with primary hypertriglyceridemia and its relationship with metabolic parameters. METHODS AND RESULTS: Male patients with primary hypertriglyceridemia and without the metabolic syndrome (n=22) were compared with normotriglyceridemic individuals (n=25). Plasma adiponectin concentration was measured by standardised enzyme-linked immunosorbent assay. Body mass index, waist circumference, glucose, insulin and non-esterified fatty acid levels, lipoprotein profile, and CETP activity were evaluated. Adiponectin levels were significantly decreased in hypertriglyceridemic patients in comparison with normotriglyceridemic subjects (4292+/-1717 vs. 6939+/-3249 ng/ml, p<0.005, respectively). Adiponectin was negatively associated with glucose (r=-0.44, p<0.01), insulin (r=-0.37, p<0.01), HOMA (r=-0.40, p<0.01), triglycerides (r=-0.36, p<0.01), VLDL-C (r=-0.34, p<0.05), and CETP (r=-0.47, p<0.001). Positive and significant correlations were observed with QUICKI (r=0.49, p<0.001) and HDL-C (r=0.33, p<0.05). In the multiple linear regression analysis, considering waist circumference, QUICKI, Log-triglycerides, HDL-C, and CETP as independent variables, Log-adiponectin showed a positive correlation with QUICKI, with an r(2)=0.229 and p<0.001. Therefore, the independent variable QUICKI explained the 23% of the variance in Log-adiponectin concentration. CONCLUSIONS: We found low adiponectin levels in a population of primary hypertriglyceridemic men without the metabolic syndrome and an independent relationship between adiponectin concentration and insulin resistance. A reduction in insulin sensitivity and its impact on adiponectin concentration could be linked to high non-esterified fatty acid levels, increased triglyceride synthesis in the liver and impaired catabolism of triglyceride-rich lipoproteins.

Circulating small dense LDL, endothelial injuring factors and fibronectin in healthy postmenopausal women.

BACKGROUND: In postmenopausal women (PMW), an adverse lipoprotein pattern and high risk of coronary artery disease has been described. Studies of the mechanisms promoting the higher atherogenic risk observed in healthy PMW are relevant. We evaluated the interactions among several circulating factors involved in the endothelial injury and inflammation in relation to LDL characteristics, beyond LDL cholesterol. METHODS: Lipoprotein profile, including apolipoproteins A-I and B, small dense LDL, hepatic lipase, cholesterol transfer protein (CETP), LDL composition and oxidability were assessed in PMW (n=30) in comparison to premenopausal (PreMW, n=28). The following emerging factors were measured: homocysteine, phospholipase A2, ferritin, hs-CRP and fibronectin from extracellular vascular matrix. Insulin-resistance was evaluated by waist circumference, HOMA and TG/HDL cholesterol ratios. RESULTS: The risk index apo B/apo A-I was significantly increased in PMW (p<0.0001), PMW showed higher proportion of small dense LDL which correlated with the increase in hepatic lipase activity (p<0.005) and with insulin-resistance markers (p<0.05), but not with CETP. Phospholipase A2 (p<0.05), homocysteine (p<0.005), hs-CRP (p<0.005), fibronectin (p<0.05) and ferritin (p<0.0001) were increased in PMW. LDL oxidability positively correlated with waist (p<0.02), homocysteine (p<0.05), fibronectin (p<0.05), hs-CRP (p<0.04), phospholipase A2 (p<0.05), and small dense LDL (p<0.01). After adjusting by menopausal condition, age and waist, LDL oxidability remained associated with waist (beta: 0.35, p=0.047), homocysteine (beta: 0,36 p<0,038), fibronectin (beta: 0,41 p=0.05), and small dense LDL (beta: 0.36, p=0.027). CONCLUSIONS: Evaluation of classic and non-traditional circulating risk factors in hypoestrogenism reflected endothelial and subendothelial inflammation and subclinical atherogenic processes.

Alterations in the main steps of reverse cholesterol transport in male patients with primary hypertriglyceridemia and low HDL-cholesterol levels.

Hypertriglyceridemia is a complex pathological entity strongly connected to low HDL-C levels but controversially related to the risk of coronary artery disease. In this study, we evaluated the main steps of the antiatherogenic pathway called reverse cholesterol transport in a group of patients with primary hypertriglyceridemia and low HDL-C levels in comparison to normotriglyceridemic subjects with or without hypoalphalipoproteinemia. In patients with primary hypertriglyceridemia, low HDL-C levels were accompanied by decreased apo A-I and apo A-II concentrations. These reductions were manifested by a selective reduction in LpA-I:A-II particles. In addition, apo C-III Lp non B was found to be elevated and HDL lipid percentage composition showed a triglyceride enrichment and cholesterol depletion. The capacity of serum samples from hypertriglyceridemic patients to promote cellular cholesterol efflux was reduced, as evidenced by using two different cellular models, Fu5AH and J774 cells. This impaired cholesterol efflux promotion was also corroborated by incubations of isolated HDL fractions with Fu5AH cells. Lecithin:cholesterol acyltransferase (LCAT) activity, the driving force of reverse cholesterol transport, showed a tendency towards lower values in hypertriglyceridemic patients, but this difference was not statistically significant. Additionally, cholesteryl ester transfer protein (CETP) activity was increased in this group of patients. Therefore, hypertriglyceridemia was found to induce quantitative and qualitative alterations in HDL and its subclasses and, consequently, in some steps of reverse cholesterol transport. The abnormalities found in this antiatherogenic pathway and its promoters could constitute a possible connection between hypertriglyceridemia and atherosclerosis.

Higher values of hepatic lipase activity in postmenopause: relationship with atherogenic intermediate density and low density lipoproteins.

OBJECTIVE: To investigate the enzymatic activity of hepatic lipase (HL) in postmenopausal women (PMW) and reproductive age women (RAW); and to evaluate the relationship between this enzyme and the atherogenic intermediate density lipoproteins (IDL) and low density lipoproteins (LDL), and antiatherogenic high density lipoproteins (HDL) and its subfractions (HDL2 and HDL3). DESIGN: We studied 55 PMW receiving no hormonal treatment in a cross-sectional study in comparison with a control group of 55 RAW, matched by body mass index. Follicle-stimulating hormone was > 40 mUI/ml in PMW and 3-12 mUI/ml in RAW. PMW presented at least 1 year of natural menopause and no more than 10 years of amenorrhea with E2 serum concentration < 15 pg/ml. RESULTS: HL activity was significantly higher in PMW versus RAW (14.0 +/- 1.4 vs. 10.9 +/- 0.4 micromol of fatty acids/ml of postheparin plasma, respectively, mean +/- SEM, p < 0.001). In PMW, IDL cholesterol showed a positive correlation with LDL cholesterol (r = 0.28, p < 0.05), and HDL2 cholesterol was inversely correlated with HL activity (r = 0.31, p < 0.05). HL was positively correlated with plasma concentration of LDL cholesterol in both groups (r = 0.27, p < 0.05). The higher values of HL activity and IDL cholesterol were independent of age. CONCLUSIONS: Higher HL activity is associated with a more atherogenic profile in PMW.

Low-density lipoprotein composition and oxidability in atherosclerotic cardiovascular disease.

OBJECTIVES: To characterize low-density lipoprotein (LDL) chemical composition and oxidability in normolipidemic and dyslipidemic patients with atherosclerotic cardiovascular disease, as compared with matched control subjects. To evaluate LDL susceptibility to oxidation, we determined the cutoff points of thiobarbituric reactive substances (TBARS) in LDL after oxidative stress, as well as its resistance to oxidation. DESIGN AND METHODS: LDL (density 1.019-1.063 g/mL) of 24 men with atherosclerotic cardiovascular disease (12 normolipidemic and 12 dyslipidemic patients) and 18 age-matched healthy control men. LDL chemical composition was determined and apo B/cholesterol ratio was calculated. TBARS in native LDL and after 60 and 120 min of LDL oxidation with copper were measured. The conjugated diene production kinetics during LDL incubation with copper were also studied, lag time being an oxidation resistance marker. Cutoff points for the positivity criterion of apoB/cholesterol ratio in LDL and TBARS in native and oxidized LDL were evaluated using the receiver operator characteristic (ROC) graphic method. RESULTS: LDL were triglyceride-enriched, the apoB/cholesterol ratio being higher in patients than in controls, without differences between normolipidemic and dyslipidemic subgroups. We have established the following cutoff values to differentiate between patients and controls: 0.43 mg/mg for the apo B/cholesterol ratio in LDL; 3.0 nmol malondialdehyde/mg protein for TBARS in native LDL; 22 and 80 nmol malondialdehyde/mg protein after 60- and 120-min postoxidative stress, respectively. We did not find differences in the conjugated diene production kinetics between patients and controls. CONCLUSIONS: The enrichment in triglycerides and the high apoB/ cholesterol ratio suggest the presence of an abnormal LDL particle in normolipidemic and dyslipidemic patients. This LDL particle was more susceptible to oxidation. In the ROC analysis, the TBARS plot at 120 min exhibited greater accuracy and better performance than the other LDL oxidability markers.

VLDL compositional changes and plasma levels of triglycerides and high density lipoprotein.

VLDL chemical composition is related to plasma levels of triglycerides and HDL-cholesterol. We evaluated patients with primary hypertriglyceridemia with or without hypoalphalipoproteinemia and subjects with normotriglyceridemia with hypoalphalipoproteinemia. The pattern observed in all the groups was an enrichment in the triglyceride content of VLDL and in apo B-VLDL. Compared to controls, LpC-III:B levels were higher in hypertriglyceridemic patients with low or normal HDL-cholesterol levels (7.3 +/- 0.6 vs. 14.9 +/- 1.8 and 12.3 +/- 2.8 mg/dl; P < 0.005 and P < 0.01, respectively) and LpE:B concentration was only increased in patients with hypertriglyceridemia and normal HDL-cholesterol levels (3.1 +/- 0.5 vs. 6.3 +/- 1.0 mg/dl; P < 0.01). The activity of the cholesteryl ester transfer protein was higher in hypertriglyceridemic patients with low HDL-cholesterol levels than in controls (380 +/- 25 vs. 262 +/- 14% cholesteryl esters/ml.h; P < 0.001). The most atypical VLDL particle was found in patients who combined an accumulation of VLDL particles and a reduction in HDL-cholesterol concentration. These two parameters represent both ends of the cholesteryl ester-triglyceride transfer, a crucial factor for VLDL chemical composition and HDL levels.

Abnormal capacity to induce cholesterol efflux and a new LpA-I pre-beta particle in type 2 diabetic patients.

In this study, we first characterized the lipoprotein components of serum samples obtained from a group of well-controlled diabetic patients and from healthy subjects in fasting and postprandial states. We then explored some aspects of reverse cholesterol transport in the same population. Patients showed high levels of fasting triglycerides, postprandial triglyceride responses and LpC-III levels (3.18+/-0.86 vs 2.17+/-0.54 mg/dl, P < 0.001). There were also positive correlations between LpC-III and fasting triglycerides (r = 0.82, P < 0.001), total triglyceride area (r = 0.75, P < 0.001) and incremental triglyceride area (r = 0.54, P < 0.001). HDL-C and apo A-I were significantly decreased in diabetic patients due to a selective reduction in LpA-I subfraction, whose antiatherogenic role is generally accepted (37.4+/-8.0 vs 49.2+/-12.5 mg/dl, P < 0.001). In addition, HDL from patients proved to be triglyceride enriched and cholesteryl ester depleted, alterations which were further amplified in the postprandial state. The molar ratio HDL-C/apo A-I + apo A-II, already defined as a predictor of apo A-I fractional catabolic rate, was significantly diminished in the patient group (15.1+/-2.2 vs 20.8+/-3.3, P < 0.001), thus suggesting an accelerated catabolism of apo A-I. For the first time, we describe here the presence of a small apo A-I-containing particle, isolated by two-dimensional electrophoresis and characterized by immunoblotting, only in samples from diabetic patients. This particle that we named pre-beta0, has an apparent molecular weight of 40 kDa. As regards the capacity of serum samples to promote cholesterol efflux from [3H]cholesterol-labeled Fu5AH rat hepatoma cells, patient samples were found to induce significantly lower cholesterol efflux than controls only in the postprandial state (21.2+/-3.3 vs 23.8+/-1.8%, P = 0.012). The presence of pre-beta0 in samples from diabetic patients might therefore be associated to an altered capacity of these serum samples to promote cellular cholesterol efflux. Overall, these abnormalities may contribute to a delay in the reverse cholesterol transport pathway in type 2 diabetic patients.

A comparative study of two hormone replacement therapy regimens on safety and efficacy variables.

OBJECTIVE: To assess the effect of tibolone on endometrial safety, plasma estradiol concentrations, lipid metabolism and climacteric symptoms in comparison to sequential conjugated equine estrogens and medroxyprogesterone acetate in postmenopausal women. METHODS: In a randomised, open-label, 6-cycle, group-comparative study, the effects on the aforementioned parameters were studied with tibolone 2.5 mg/day (N = 13) continuously, and with conjugated equine estrogens 0.625 mg/day continuously, combined with medroxyprogesterone acetate 5 mg/day (N = 11) (CEE/MPA) sequentially, during 12 days of each 28-day cycle. Within-group statistical analysis was performed with Student's t-test for paired samples, whereas between-group statistics were performed using the Student's t-test for independent groups. RESULTS: Cytological evaluation revealed no endometrial stimulation in either group. In the tibolone group, there were no effects on estradiol levels, whereas in the CEE/MPA group, an increase in total and non-SHBG-bound estradiol plasma levels was reported. In the tibolone group, there were significant decreases in plasma total cholesterol, triglycerides, HDL-cholesterol and VLDL-cholesterol, whereas no significant changes in LDL-cholesterol and IDL-cholesterol were reported. In the CEE/MPA group there were significant decreases in plasma total cholesterol, HDL-cholesterol and LDL-cholesterol, whereas there were no significant changes in triglycerides, IDL-cholesterol and VLDL-cholesterol. Climacteric symptoms, particularly vasomotor episodes, decreased similarly in both groups. CONCLUSIONS: Both tibolone and CEE/MPA were safe with respect to effects on the endometrium and both treatments induced changes in the plasma profiles of certain lipid and lipoprotein parameters. However, the overall clinical implications of these changes are unknown. Finally, both regimens were equally effective in the treatment of climacteric symptoms.

Premenopause contraception with monthly injectable Mesigyna with special emphasis on serum lipid and bone density patterns.

This 2-year study compared Mesigyna(R) administered to 49 pre-menopausal women between 38 and 50 years, to 99 women fitted with an IUD (Nova-T). A complete lipoprotein assessment was carried out before treatment and at 6, 12, and 24 months of treatment. A bone densitometry was performed on half of the women, and an endometrial biopsy was taken from half of the Meisgyna group before and at the end of the first and second year. No pregnancy occurred with Mesigyna use while three pregnancies were observed with the IUD. The incidence of bleeding anomalies was higher in the Mesigyna group, with a discontinuation rate for these reasons of 20% versus 4% for IUD (p <0.05). The duration of bleeding days as well as dysmenorrhea were less with Mesigyna. No differences were seen in the pattern of intermenstrual bleeding and spinal bone density between both groups. No patient developed endometrial hyperplasia after treatment, thus endometrial risk seemed not to be increased. Total and LDL cholesterol, and apolipoproteins did not show modifications. A slight decrease in total triglycerides, HDL and HDL(2) cholesterol, and IDL lipoproteins was observed with Mesigyna. The present study appears to be the first using a monthly injectable hormonal contraceptive and monitoring its influence on lipid patterns in premenopausal women. Mesigyna proved to be a highly effective and low risk agent for premenopausal users.

[Very low density lipoproteins and subclasses of intermediate density lipoproteins in postmenopausal women]. / Lipoprotéinas de muy baja densidad y subespecies de liproprotéinas de densidad intermedia en mujeres postmenopáusicas.

Post menopausal women present an increase of cardiovascular risk associated with the atherogenic plasma lipoproteins IDL and LDL. Our purpose was to study the composition of VLDL, IDL and the subfractions IDL-1 and IDL-2, and the Lipoprotein Lipase and Hepatic Lipase activities in a group of twelve healthy post menopausal women as compared with eleven fertile controls. The mean values of total cholesterol and LDL cholesterol were significantly increased in the post menopausal group compared to the controls (p < 0.005 and p < 0.001 respectively). The contribution of the HDL-cholesterol plasma concentration to total cholesterol was lower in the postmenopausal women (p < 0.02) although no one had HDL-cholesterol lower than 35 mg/dl and the mean value was 50 mg/dl. Postmenopausal women had increased concentrations of VLDL, total IDL and IDL-2 compared to controls (p < 0.05, p < 0.005 and p < 0.001 respectively). Plasma concentrations of total IDL was increased in postmenopausal women (33.6 +/- 3.4 vs 22.6 +/- 0.8 mg/dl, p < 0.005). The increase in total IDL was due to IDL-2 (19.9 +/- 1.7 vs 11.5 +/- 0.8 mg/dl, p < 0.001, in postmenopausal women vs controls). The IDL-2 subfraction was 60 +/- 2.6% of total IDL in postmenopausal women and 51 +/- 2.0% in controls (p < 0.02). In postmenopausal women and in controls the ratio triglyceride/protein (which indicates particles size) was significantly higher in IDL-1 than in IDL-2 (p < 0.005 and p < 0.01 respectively), but this ratio did not show differences when VLDL, total IDL and IDL-2 were compared between postmenopausal and control women. Then, the increased plasma concentration of these lipoproteins would show an increased number of particles in the postmenopausal women vs controls. There were no differences in the Lipoprotein Lipase and Hepatic Lipase activities between both groups. Lipoprotein Lipase vs total IDL-triglycerides and IDL-2-triglycerides showed a significant inverse correlation in controls (p < 0.05) but not in postmenopausal women. We conclude that the qualitative and quantitative study of the lipoproteins shows a more atherogenic profile in the postmenopausal group, with an increase in the concentration and number of particles of VLDL, total IDL and IDL-2.

Evaluation of the blood components considered as risk predictors in coronary heart disease.

The study included 249 patients two days before cardiovascular surgery and 73,915 control subjects. Results obtained were analyzed by grouping the individuals according to sex and age. In coronary heart disease (CHD) in males, total cholesterol was found higher than in controls (mean +/- D.S.: 241.9 +/- 44.7 vs 223.6 +/- 43.0 mg/dl, p < 0.01) between 25 and 49 years of age, this significance being lost with age. Triglycerides were also higher (197 +/- 107.3 vs 161.6 +/- 97.7 mg/dl, p < 0.01) in the CHD male population between ages 25 and 69. In CHD females, triglycerides were higher (116.9 +/- 56.2 vs 91.5 +/- 43.3 mg/dl, p < 0.05) between ages 25 and 49; cholesterol showed no difference at any of the ages studied. HDL-C was much lower in both sexes of CHD patients at all ages studied (p < 0.001). Uric acid was higher in CHD males between ages 25 and 49 (p < 0.05), this significance being lost in the older age CHD group. Other components such as glycated hemoglobin, glucose and ionized calcium, were not different from those of the control group.

[Incorporation of squid oil fatty acids to plasma lipoproteins in rats]. / Incorporación de ácidos grasos de aceite de calamar a lipoproteínas plasmáticas en ratas.

There is clinical and epidemiologic evidence that long chain polyunsaturated fatty acids of the n-3 series, (AGPI n-3): eicosapentaenoic acid (EPA 20:5 n-3) and docosahexaenoic acid (22:6 n-3) decrease the incidence of heart attack, coronary restenosis and also platelet aggregation, leukotriene synthesis and arterial pressure. They also decrease significantly the severity of atherosclerosis in hyperlipidemic models. Some of these results are obtained after daily intake of 3g or more of AGPI n-3. Marine oils are very rich in AGPI n-3 but rarely the amount is larger than 20%. Due to this fact there is great interest in the possibility of obtaining concentrates of AGPI n-3 with a high coefficient of intestinal absorption. EPA and DHA ethyl esters are able to be concentrated over 90% but their absorption is incomplete. For the moment AGPI n-3 can be concentrated as free fatty acids (AGL). Squid oil (Illex argentinus) is one of the natural oils with the highest concentration of AGPI n-3 (31 to 34%). In this paper, we have studied the incorporation of AGPI n-3 to plasmatic lipoproteins of rats fed during 28 days with diets supplemented with squid oil (Ac) or AGL obtained from the same oil. Both groups were compared with a control group (C, n = 5) fed on a standard diet. The composition of oil fatty acids and of AGL is almost identical: EPA 13.6% and DHA 17.7% (Table 1). Daily intake of AGPI n-3 was very similar: in the Ac group (n = 7) 80 mg/day and in the AGL group (n = 7) 90 mg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

[Intermediate-density lipoproteins and liver lipase in postmenopausal women]. / Lipoproteínas de densidad intermedia y lipasa hepática en mujeres post-menopáusicas.

In order to evaluate atherogenic lipoproteins in post-menopause, we studied 73 healthy women, 49 to 65 years old (Post-menopausal Group), with 1 to 10 years of amenorrhea and body mass index below 27 Kg/m2, and 20 young women (Control Group). We have determined plasma cholesterol concentration in the lipoproteins of intermediate density in addition to the classical lipoprotein parameters: total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and fractionation of lipoproteins by electrophoresis. In 63 women from the Post-menopausal Group and 16 from the Control Group we studied the activity of hepatic lipase. Among these patients we selected at random 25 post-menopausal women and 13 controls to add measurements of triglycerides in the lipoproteins of intermediate density. Table 1 shows that the average plasma concentration of total cholesterol in the Post-menopausal Group was higher than that of the Controls (p < 0.001). The same was found for LDL-cholesterol (p < 0.001) and for triglycerides (p < 0.001) whereas the average concentration of HDL-cholesterol did not show significant differences. The Post-menopausal Group had high values of plasma lipoproteins of intermediate density, even with normal phenotypes (Table 2). Cholesterol but also triglycerides (Fig. 1) were responsible for this increase. A triglyceride rich lipoprotein subspecies of intermediate density was predominant in 73% of Post-menopausal women vs 23% of the Controls (p < 0.01, Table 3). No differences in hepatic lipase activity were seen between the two groups (Table 4), and non statistic correlation between the enzyme activity and IDL-triglycerides or HDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

[Partial lecithin-cholesterol acyltransferase (LCAT) deficiency syndrome]. / Síndrome de deficiencia parcial de lecitina-colesterol aciltransferasa (LCAT).

This syndrome is a pathological entity of low incidence which mainly affects high density lipoprotein (HDL) metabolism. We here show the first case reported in our country, observed in a 63-year-old woman who showed bilateral corneal opacity and eruptive xanthomas in both arms. The lipoprotein profile disclosed severe hypertriglyceridemia and normocholesterolemia, although the percentage of cholesteryl esters was low. Plasma levels of HDL-cholesterol and HDL major apolipoproteins, A-I and A-II, were markedly decreased. The patient also showed glucose intolerance and hematological alterations related to abnormal lipid composition of erythrocyte membranes. As evaluated by the exogen substrate method, LCAT activity proved to be 82% lower in the patient than in a control subject. It is noteworthy that the patient had experienced cardiac events and presented hypertension, neither of which has been commonly documented in partial LCAT deficiency syndromes.

[Low density lipoprotein rich in triglycerides and hepatic lipase activity in insulin-dependent diabetic patients]. / Lipoproteína de baja densidad rica en triglicéridos y actividad de lipasa hepática en pacientes diabéticos insulino-dependientes.

Genetic hepatic lipase (HL) deficiency is associated with low density lipoprotein (LDL) rich in triglycerides (TG), whose affinity for B:E receptors is decreased. In rats, experimental hypoinsulinemia produces HL deficiency. However, the relation between human insulin-dependent Diabetes Mellitus (IDDM), HL activity and the characteristics of LDL have not been studied. The objective of our study is to evaluate the relation between HL activity and the chemical composition of LDL in treated IDDM patients. Subjects were 15 IDDM patients and 15 controls (C), matched for sex and body mass index (BMI). The IDDM patients were classified by the WHO criteria, were free of nephropathy and hypothyroidism, and received no medication except insulin. Controls were clinically healthy and normolipidemic with no family history of diabetes. The IDDM group was divided into two subgroups: subgroup IDDM-A (n = 9) with HL values > or = 4.3 and IDDM-B (n = 6) with HL < or = than 4.2 mumoles glycerol/ml h. the HL in IDDM was lower than in C (p < 0.001). Table 1 shows clinical data. Blood samples were drawn after 12 h fasting. Percentage of HbA1c and plasma concentrations of glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and TG were assayed. LDL was separated by sequential ultracentrifugation at densities of 1.019-1.063 g/ml and its chemical composition was analyzed. The most relevant results were: plasma TG concentration was higher in IDDM than in C (p < 0.05) (Table 2), although average values DMID not exceed the reference values of 200 mg/dl. The TG-LDL were higher in IDDM than in C: 24.8 +/- 2.7 vs 17.5 +/- 1.1 mg/dl plasma, media +/- SE, (p < 0.02). This difference reflected the values of IDDM-B, whose plasma concentrations of TG-LDL were higher than in C: 32.3 +/- 3.6 vs 17.5 +/- 1.1 mg/dl (p < 0.001), and also higher than in IDDM-A (p < 0.02). (Table 3). The chemical composition of LDL in IDDM-B contained a higher percentage of TG than C: 8.5 +/- 0.7 vs 6.8 +/- 0.3% (p < 0.05), a lower percentage of cholesterol than IDDM-A: 39.0 +/- 1.7 vs 45.2 +/- 2.2% (p < 0.05) and also a larger percentage of proteins than IDDM-A: 28.9 +/- 1.9 vs 20.8 +/- 1.0% (p < 0.01). The correlations between TG/cholesterol and HL activity in IDDM were r = -0.53 (p < 0.05) and in IDDM-B, r = -0.81 (p = 0.05). The noteworthy result of this study is the modification of the LDL particle in IDDM, rich in TG in patients with low HL activity. Anomalies in the chemical composition of LDL like those described decrease the uptake of this particle by its physiological B:E receptors. It has recently been demonstrated that LDL is an indisoluble association of lipids and apoproteins, and that both act simultaneously to hold the apoB in a spatial position that expresses normal epitopes. It has been described that particles of LDL rich in TG and poor in cholesterol, shows low affinity for LDL receptors in human fibroblasts. Also in IDDM the interaction of LDL rich in TG with B:E receptors is decreased. This might be one more mechanism contributing to the accelerated atherosclerosis of these patients. Our results suggest that there may be a threshold of HL activity for the complete hydrolysis of the TG of LDL, for the normalization of the TG/cholesterol relation and for the conformation of typical LDL particles.

[Acquired partial lipodystrophy. Insulin resistance, hepatic lipase activity and small and dense LDL particles]. / Lipodistrofia parcial adquirida. Resistencia insulínica, actividad lipasa hepática y partículas LDL pequeñas y densas.

Partial lipodystrophy (PLD) is an infrequent condition characterized by symmetric loss of subcutaneous adipose tissue in the upper or lower part of the body, although occasionally it affects only the extremities. In all cases it appears along with acantosis nigricans (AN), insulin resistance and impairment in the metabolism of lipids and carbohydrates. The case depicted pertains to a 49 year old female with no family history involving loss of adipose tissue in face and upper body. No fat in lower part of body was observed. The patient showed facial thinning at age 8, AN at 11 and gestational diabetes during her fourth pregnancy at 33. At present, the patient presents severe hyperglycemia and hyperinsulinemia with a marked insulin resistance. Type IV hyperlipoproteinemia (OMS), declined C-HDL and Apo A1 and low C-LDL but with a high proportion of small and dense LDL particles were present. Non esterified fatty acids were high. Lipoprotein lipase and hepatic lipase activities are in the lower limit and increased respectively. Fraction C3 of the complement was diminished. No mutations were observed either in codons 170, 809 and 972 of the IRS-1 receptor or in codon 276 of the adrenergic beta 2 gene.