The effects of exposure to ozone (O3) on concentrations of serum lipids and lipoproteins were investigated. Male and female guinea pigs were exposed to O3 at 1 ppm for two weeks. Serum concentrations of cholesterol, triglycerides, low density (LDL) and very low density (VLDL) lipoproteins were elevated after O3 exposure, particularly in males. During O3 exposure the food intake per day decreased (for a constant body weight), suggesting that metabolic rate and possibly basal metabolic rate was lower. Lung wet weights increased during O3 exposure by 87% for males and 45% for females. When individual lung weight/body weight ratios were correlated with cholesterol and LDL values from the same animal, a high correlation is found for males (r = 0.81, P less than 0.05), suggesting that there may be a relationship between lipoprotein elevations and lung damage for males. Because elevated concentrations of lipids and lipoproteins in humans increase the risk of coronary heart disease (CHD), the lipoprotein results suggest that an epidemiological study of the incidence of CHD with metropolitan O3 levels may be warranted.

Sodium dodecylsulphate precipitates very low density lipoproteins (VLDL and chylomicrons) rich in triglyceride and a narrow correlation (r = 0.9) was found between the turbidimetric index SDS and triglyceridemia. Heparin in calcium medium acts in the same way and precipitates also low density lipoproteins (LDL) rich in cholesterol. A correlation (r = 0.875) was drawn up between the cholesterol LDL and the difference between the turbidimetric indices (heparin Ca -- SDS). In the first case, we were thus measuring by turbidimetry a VLDL + chylomicron index and, in the second case, an LDL index which permits one to obtain simplified typing of the hyperlipoproteinemias. A nomogram linking the two indices of hyperlipoproteinemia type was drawn up experimentally. This orientation analysis may be completed by electrophoresis on polyacrylamide gel used in concentration gradient and pH. In the system proposed, the lipoproteins were previously stained with tetrazolium nitroblue and clearly shown up. The chylomicrons in particular, become separated from the VLDL, the sinking pre-beta-lipoprotein or Lp (a) was identifiable and the type III hyperlipemia was easily diagnosed.

OBJECTIVE

Determining the prevalence and estimating the risk of obesity for dyslipidemia and hyperinsulinemia in adolescents. The existence of a linear association betweenanthropometric measures, lipids and insulin was also evaluated.

METHODS

A comparative study was carried out amongst obese (body mass index=BMI >95th percentile for age and gender; n=120) and non-obese adolescents (BMI <85th percentile for age and sex; n=120) aged 10-19. A structured questionnaire was used for collecting anthropometric and demographic data. Glucose, insulin and lipid profiles were obtained for each adolescent.

RESULTS

Prevalence of at least one dyslipidemia was 56,6 % among obese adolescents and 20,8 % amongst non-obese ones (p<.001). The former registered 50 % prevalence of hyperinsulinemia, the latter 4 % (p<.001). Obesity increased hyperinsulinemia risk having a 23 odds ratio (8.3-68.9 95 % CI) and for at least one dyslipidemia (OR=5,0; 2,7-9,2 95 % CI). Insulin level significantly correlated with BMI (r=0,57), triglycerides (r=0,57), VLDL (r=0,57), HDL (-0,37), waist-hip circumference index (r=0,29), cholesterol (r=0,22), and LDL (r=0,13).

CONCLUSIONS

Obesity can be considered to be a risk factor for developing metabolic disorders in adolescents. In fact, there was a linear relationship between anthropometric measurement, lipids and insulin. Prevention should focus on improving predisposing environments for obesity amongst families having children and teenagers. Emphasising life-styles and healthy behaviour is essential, as well as training and treatment options for complete care of individuals in this age-group.

Nine non-diabetic, non-obese, normocholesterolemic normal male subjects with varied triglycerides levels were subjected to a simultaneous infusion test with a synthetic somatostatin analogue [des(Ala1, Gly2)-D-Trp8, D-Asn3, 14-somatostatin], insulin and glucose under ambulatory conditions. The levels of C-peptide reactivity, immunoreactive glucagon and growth hormone were reduced, and the level of immunoreactive insulin remained constant during the infusion. The blood glucose reached a constant value at 110-120 minutes (steady state blood glucose, SSBG) after the commencement of the infusion. The total cholesterol (TC) levels decreased slightly in the 30 minutes after the experiments were begun, and the triglycerides (TG) levels decreased gradually throughout the infusion period, due mainly to the reduction of very low density lipoprotein (VLDL). The most striking finding was the highly significant positive correlation (p less than 0.005, r = 0.868) between SSBG and the serum TG level prior to the infusion. These results indicate an important relationship between insulin sensitivity and serum TG level. High TG level may be regarded as one of the indices of insulin resistance.

Decreased circulating levels of free thiols (R-SH, sulfhydryl groups) reflect enhanced oxidative stress, which plays an important role in the pathogenesis of cardiometabolic diseases. Since hyperglycemia causes oxidative stress, we questioned whether plasma free thiols are altered in patients with type 2 diabetes mellitus (T2DM) without cardiovascular disease or renal function impairment. We also determined their relationship with elevated triglycerides and very low density lipoproteins (VLDL), a central feature of diabetic dyslipidemia. Fasting plasma free thiols (colorimetric method), lipoproteins, VLDL (nuclear magnetic resonance spectrometry), free fatty acids (FFA), phospholipid transfer protein (PLTP) activity and adiponectin were measured in 79 adult non-smoking T2DM subjects (HbA1c 51 ± 8 mmol/mol, no use of insulin or lipid lowering drugs), and in 89 non-smoking subjects without T2DM. Plasma free thiols were univariately correlated with glucose (r = 0.196, p < 0.05), but were not decreased in T2DM subjects versus non-diabetic subjects (p = 0.31). Free thiols were higher in subjects with (663 ± 84 µmol/L) versus subjects without elevated triglycerides (619 ± 91 µmol/L; p = 0.002). Age- and sex-adjusted multivariable linear regression analysis demonstrated that plasma triglycerides were positively and independently associated with free thiols (β = 0.215, p = 0.004), FFA (β = 0.168, p = 0.029) and PLTP activity (β = 0.228, p = 0.002), inversely with adiponectin (β = -0.308, p < 0.001) but not with glucose (β = 0.052, p = 0.51). Notably, the positive association of free thiols with (elevated) triglycerides appeared to be particularly evident in men. Additionally, large VLDL were independently associated with free thiols (β = 0.188, p = 0.029). In conclusion, circulating free thiols are not decreased in this cohort of non-smoking and generally well-controlled T2DM subjects. Paradoxically, higher triglycerides and more large VLDL particles are likely associated with higher plasma levels of thiols, reflecting lower systemic oxidative stress.

Postheparin plasma (PH)-lipoprotein lipase (LPL) activity has been reported to be a significant correlate of plasma triglyceride and high-density lipoprotein cholesterol (HDL-C) levels. However, some studies have failed to observe these associations. In this regard, apolipoprotein (apo) E polymorphism may play an important role, since the apo E2 isoform has unfavorable effects on the catabolism of triglyceride-rich lipoprotein particles. We have thus examined the relationships between PH-LPL activity and plasma lipoprotein-lipid levels within groups of men classified on the basis of apo E phenotypes, to verify whether apo E polymorphism could alter these associations. In men carrying the apo E2 isoform (n = 12), PH-LPL activity showed a strong negative correlation with plasma triglyceride (r = -.72, P < .01), very-low-density lipoprotein (VLDL) triglyceride ([VLDL-TG] r = -.83, P < .001), and VLDL cholesterol ([VLDL-C] r = -.57, P < .05) levels and a positive correlation with plasma HDL-C (r = .87, P < .001) and HDL2-C (r=.90, P < .001) concentrations. These correlations were also noted for plasma apo B levels (r = -.65, P < .05), VLDL-apo B concentrations (r= -.76, P < .01), and the HDL-C to cholesterol ratio (r = .85, P < .001). In contrast, none of these associations were found in men carrying the apo E4 isoform (n = 11). In men homozygous for the apo E3 isoform (n = 29), PH-LPL activity was only significantly correlated with plasma HDL2-C levels (r = .46, P < .01). Results of the present study indicate that PH-LPL activity is related to plasma triglyceride, VLDL-TG, VLDL-C, VLDL-apo B, apo B, and HDL-C levels and the HDL-C to cholesterol ratio in men carrying the apo E2 isoform, but not in men homozygous for the apo E3 isoform or among apo E4 carriers. Thus, apo E polymorphism appears to modulate the effect of variation in PH-LPL activity on the plasma lipoprotein profile.

Peroxisome proliferators (PxPs) induce peroxisomal beta-oxidation (Px-ox) in the liver of rodents and have a hypolipidemic function. To investigate hypolipidemic effect of PxPs, the relationship between TG fluctuation and Px-ox activity, as an indicator of the function of PxPs, was studied in primary cultured rat hepatocytes. Nafenopin (Nf) treatment of hepatocytes caused an increase in Px-ox activity in association with cellular TG accumulation in a time-dependent manner with a coefficient of r=0.918. This relationship between the activity and cellular TG were obtained using structurally diverse PxPs with a correlation coefficient of r=0.747. Treatment of the hypolipidemic drug, but non-PxP Pravastatin, decreased TG in the medium, but did not have the effects on cellular TG and Px-ox activity. The total amount of TG and diacylglycerol acyltransferase activity, the last enzyme in the TG de novo synthesis pathway, were not affected by Nf treatment. When hepatocytes were cultured with Brefeldin A, cellular TG was accumulated, the same as with Nf, however, Px-ox activity was not enhanced. Nf treatment markedly decreased the level of apolipoprotein B (apo B) in very low density lipoprotein (VLDL) fractions prepared from conditioned media and increased that of cellular apoB by Western blot analysis. Microsomal triglyceride transfer protein activity was not influenced by Nf. Together, with regards to TG lowering effect of PxPs, it is suggested that PxPs cause hepatocellular accumulation of TG without effects on TG biosynthesis and VLDL construction, and they might have inhibitory effect on VLDL secretion process.

BACKGROUND

Lipid emulsions given i.v. are normally rapidly metabolized by apoprotein recruited from high-density lipoprotein (HDL) particles in the blood. Very low-birthweight infants (VLBWI), however, have a low rate of lipid clearance from the blood, and therefore lipid emulsions must be given carefully to minimize the risk of hyperlipidemia. The purpose of this study was to evaluate the influence of i.v. lipid emulsion on lipoprotein subclass profile in VLBWI during the early postnatal period.

METHODS

Forty-six VLBWI who had been given different doses of lipid emulsion in the first few days after birth were enrolled in the present study. Triglyceride and cholesterol content of each lipoprotein subclass was measured at 3 weeks after birth, and their correlation with the total dose of lipid emulsion was calculated.

RESULTS

There was no correlation between the total dose of lipid emulsion and the triglyceride and cholesterol content in any subclasses of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). There was a significant negative correlation between the total dose of lipid emulsion and the triglyceride content in very large (P < 0.05, r = -0.32), large (P < 0.01, r = -0.47) and medium HDL (P < 0.05, r = -0.34) particles; and the cholesterol content in large (P < 0.01, r = -0.47) and medium HDL (P < 0.01, r = -0.4) particles.

CONCLUSIONS

Lipid emulsion influenced the triglyceride and cholesterol content of HDL particles in VLBWI, suggesting that lipid emulsion can affect lipid metabolism in this infant population in the early postnatal period.

In order to evaluate the influence of serum insulin levels on serum lipoprotein composition, 62 randomly selected healthy males were studied. All of them had a normal glucose tolerance. The Insulin Response to a bolus of intravenous glucose (0.50 g/kg) was significantly correlated with VLDL-Triglyceride (p less than 0.01), VLDL-Cholesterol (p less than 0.01) and with the "Atherogenic Index" (Formula: see text) (p less than 0.01). Moreover, stratifing the all population in quartiles according to the Insulin Response distribution, the highest quartile had a significant increase in Total and VLDL-Cholesterol levels (p less than 0.02), as well as in Total (p less than 0.02), VLDL (p less than 0.02) and LDL (p less than 0.01) Triglyceride, in comparison with the lowest quartile. The Atherogenic Index was also significantly elevated in the high Insulin Response group (p less than 0.005). The influence of serum insulin on lipoprotein metabolism was also evaluated by a stepwise multiple regression analysis. Body weight, Insulin Response and Exogenous Triglyceride removal were independently correlated with VLDL-Triglyceride concentration (r = 0.58, p less than 0.001). VLDL cholesterol concentration and fasting serum insulin levels were inversely correlated with HDL-Cholesterol (r = 0.49, p less than 0.001). In conclusion, in absence of any metabolic derangement, high insulin levels are associated with multiple lipoprotein abnormalities. Insulin might act as a risk factor for arterial disease through its influence on serum lipoproteins.

BACKGROUND

Animal studies suggest that liver weight is directly related to hepatic very low-density lipoprotein-triglyceride (VLDL-TG) secretion, independently of body size. This relationship has never been examined in humans.

METHODS

We measured VLDL-TG secretion rate by using stable isotope-labelled tracers in 21 healthy, non-obese men (age: 25 +/- 3 years; body mass index: 24.8 +/- 1.6 kg m(-2)), and evaluated the relationship between VLDL-TG secretion and indices of total and regional adiposity (body mass index, total body fat, trunk fat), metabolic parameters (free fatty acid, glucose, and insulin concentrations, homeostasis model assessment index of insulin resistance, resting energy expenditure), and estimated liver weight.

RESULTS

Correlation analysis showed that estimated liver weight was positively associated with total VLDL-TG secretion rate (r = 0.722, P < 0.001), VLDL-TG secretion rate per liter of plasma (r = 0.562, P = 0.008), VLDL-TG secretion rate per kilogram of body weight (r = 0.555, P = 0.009), and VLDL-TG secretion rate per kilogram of liver weight (r = 0.620, P = 0.003). In multiple regression analysis, estimated liver weight was the only significant predictor of VLDL-TG secretion rate regardless of units of expression, explaining 31-52% of total variance; none of the metabolic parameters and indices of body fatness entered the regression models.

CONCLUSIONS

We conclude that estimated liver weight is directly related to hepatic VLDL-TG secretion rate in healthy non-obese men; this relationship is likely not mediated by interindividual variation in body size.

BACKGROUND

Serum very low density lipoprotein (VLDL) levels increase during the early stages of insulin resistance; therefore, determination of VLDL levels would be useful for evaluating the progression of metabolic syndrome and diabetes mellitus. The aim of this study was to clarify the clinical utility of triglyceride in VLDL (VLDL-TG) level, determined using a homogeneous assay kit (Shino-test Corporation, Tokyo, Japan), as an index of insulin resistance.

METHODS

We enrolled 74 subjects in this study (diabetic subjects, n = 42; nondiabetic subjects, n = 32). The levels of VLDL-TG, remnant-like lipoprotein particle cholesterol, preheparin lipoprotein lipase mass, and other biochemical markers were determined.

RESULTS

VLDL-TG levels were significantly higher in the diabetic group (1.04 ± 0.84 mmol/l vs. 0.64 ± 0.42 mmol/l, P < 0.01) than in the nondiabetic group. In the nondiabetic group, VLDL-TG was significantly correlated with the homeostasis model assessment of insulin resistance (HOMA-IR), the index for insulin resistance (r = 0.513, P = 0.003). VLDL-TG levels, but not TG levels, were higher in the highest quartile (HOMA-IR) of the nondiabetic group.

CONCLUSIONS

VLDL-TG level was a useful early marker for insulin resistance, especially in nondiabetic subjects. The homogeneous VLDL-TG assay is a simple, low-cost method for determining insulin resistance.

Insulin resistance and hyperinsulinemia can induce overproduction of triglyceride (TG) rich VLDL in the liver by increasing the availability of free fatty acids (FFA). Conversely, apolipoprotein C-III (apoC-III) is an inhibitor of the catabolism of TG-rich lipoproteins. To explore the relationship among FFA, apo C-III and TG in hyperinsulinemic subjects, we studied 103 individuals (63 women and 40 men) with a body mass index (BMI) 25 Kg/m2: 59 subjects with normal glucose tolerance (NGT), and 44 with newly diagnosed type 2 diabetes. After adjustment for age, BMI, fasting insulin and TG, FFA were significantly higher in women than in men and in subjects with diabetes compared with NGT. Subjects with diabetes had higher apo C-III levels compared to NGT, adjusted for age, sex and BMI, and that was largely accounted for by differences in insulin and TG levels. In addition, regression analysis in subjects with diabetes showed that TG were strongly associated with apo C-III in both men and women (r = 0.90 and 0.79, respectively; p < 0.001), while the association tended to be smaller between TG and FFA (r = 0.48, p < 0.05 in men and r = 0.45, p = 0.06 in women). Conversely, in individuals with NGT fasting TG was strongly associated with apo C-III in men (r = 0.83, p < 0.01) but not with FFA, while in women TG was associated with FFA (r = 0.39, p < 0.05) but not with apo C-III. In summary, elevated apo C-III was a predominant factor associated with elevated TG levels in NGT men and all subjects with type 2 diabetes, while FFA were more closely related with TG levels in NGT women.

Tissue factor pathway inhibitor (TFPI), a kunitztype inhibitor of the extrinsic coagulation pathway, factor VII coagulant (FVIIc), FVIIa, and the fibrinolytic factors plasminogen activator inhibitor-1 (PA1-1) and tissue plasminogen activator (TPA) have been studied in various hyperlipidemias. Compared with a normal lipidic group, mean TFPI activity was 70% higher (P < .001) and 36% higher (P < .001) in type IIa and IIb hyperlipidemias, respectively, and was lower by 13% in type IV hyperlipidemia (P = .05). TFPI was correlated with LDL cholesterol (P < .001), total cholesterol (P < .001), HDL cholesterol (P < .01), apolipoproteins (apo) AI (P < .001) and B (P < .001) and lipoprotein a (P < .01). TFPI was negatively correlated with the triglyceride level (P < .05); the correlation was dependent on LDL cholesterol and HDL cholesterol levels, which were decreased in type IV hyperlipidemia. FVIIc activity (P < .001) was increased by 30% in both type IV and type IIb hyperlipidemia and was correlated with triglyceride levels. FVIIa was not significantly increased in any group compared with control group. FVIIc was correlated with triglyceride level (P < .001), while FVIIa was not. Interestingly, FVIIa was correlated with FVIIc (r = .5, P < .001) in the control group as well as in the hyperlipidemic groups (r = .32, P < .01). These results favor the hypothesis that higher FVIIc concentrations in hyperlipidemic patients are likely due to enhancement of synthesis of FVII and that a part of this FVII circulates in an activated chemical form. Compared with the control group, PAI-1 activity was twofold higher (P < .08) in type IIa hyperlipidemia, threefold higher (P < .001) in type IIb hyperlipidemia, and fourfold higher in type IV hyperlipidemia (P < .001). PAI-1 activity correlated with triglyceride levels (P < .001), apoB levels (P < .001) and total cholesterol levels (P < .05). These correlations were dependent on apoB and probably reflect the correlation between PAI-1 and VLDL. In contrast, TPA level was normal in the different hyperlipidemias. No correlation was found between TFPI, FVIIc, and PAI-1. Variation of TFPI activity appears to be related to the variations of its main lipoprotein carriers: LDL, HDL, and Lp (a). The association in hypertriglycemic patients of hypercoagulability (increased FVIIc and decreased TFPI) and hypofibrinolysis (increased PAI-1) may explain thrombosis predisposition of some of these patients. However, it would be interesting to study the increased levels of endothelium-derived TFPI in plasma induced by the injection of heparin.

This study assessed serum lipid, lipoprotein and apolipoprotein changes during one year in 3 groups of nonsmoking women: 1) Triphasil(R); 2) Ortho(R) 7/7/7; 3) Controls. Both oral contraceptives contain the estrogen, ethinyl estradiol(EE), in combination with a progestin in three different ratios during each cycle. The progestin in Triphasil is d-norgestrel, as the dl-racemate norgestrel (NG), whereas that in Ortho 7/7/7 is norethindrone(NE). Total plasma triglycerides were elevated significantly from baseline (p < 0.001) with Ortho 7/7/7 at 3, 6 and 12 months, but only at 3 months with Triphasil, p = 0.047. Triglycerides were elevated in the LDL fraction with Ortho 7/7/7 at 3 months (p = 0.001), 6 months (p = 0.018) and 12 months (p = 0.010). In contrast, LDL triglycerides were not significantly elevated with Triphasil. Similarly, IDL triglycerides were elevated only in the Ortho 7/7/7 group at 6 months (p = 0.002) and 12 months (p = 0.001). Plasma cholesterol was elevated only in the Ortho 7/7/7 group at 3, 6 and 12 months with p values of 0.009, 0.005 and 0.010, respectively. Cholesterol in the LDL fraction was elevated with Ortho 7/7/7 at 12 months (p = 0.002). Plasma apolipoprotein B (apo B) increased at least 24% from baseline for both the Triphasil and Ortho 7/7/7 groups at 3 and 12 months (p < 0.001). However, at 6 months, apolipoprotein B increased only 17.7% (p = 0.008) with Triphasil compared to 29.7% (p < 0.001) with Ortho 7/7/7 at 6 months. Apo B was increased (p < 0.001) in LDL with Triphasil at 3 months only, whereas LDL apo B was increased at 3, 6 and 12 months with Ortho 7/7/7 (p < 0.001, p = 0.020 and p = 0.012, respectively). Apo B increased dramatically in the IDL fraction of both oral contraceptive user populations, with the range of increases being between 48% and 87% during the year (p < 0.001 at all times). Significant elevations in VLDL apo B ranged from 71% to 106% (p < 0.001) with Triphasil and from 42.4% (p < 0.005) to 72.6% (p < 0.001) with Ortho 7/7/7. In conclusion, norethindrone- and dl-norgestrel-formulations have divergent effects on several components of plasma lipoprotein and lipid metabolism, but both products increase plasma and IDL apo B.

We report here a new formula for estimating apolipoprotein (apo) B concentration in the low-density lipoprotein (LDL) fraction from measurements of plasma triglyceride and apoB. ApoB in plasma and in the triglyceride-rich lipoprotein fraction (VLDL, d less than 1.019) and plasma triglyceride were measured in 112 subjects, including 56 diabetics. There was a significant correlation between VLDL-apoB and plasma triglyceride (Y = 0.07X + 1, r = 0.73, P less than 0.001). We calculated LDL-apoB according to this formula: LDL-apoB = total apoB - (0.07 x total triglyceride + 1). We found an excellent relationship between LDL-apoB (total apoB - VLDL-apoB) and calculated LDL-apoB (Y = 1.0X + 1, r = 0.96, P less than 0.001). This new formula will enable us to estimate the apoB concentration in the LDL fraction without ultracentrifugation.

Family history of atherosclerosis has been recognised as an nonmodifiable cardiovascular risk factor. Lipid levels, together with hypertension and diabetes, appear to have an inheritable component. The aim of the study was to ascertain whether lipoprotein abnormalities of 169 adult patients with non-coronary atherosclerosis were associated with a family history of atherosclerosis. Besides intermediate density lipopoprotein composition and Lp(a) levels, we focused on apo(a) and apo E phenotypes, LDL cholesterol/apo B ratio, VLDL triglyceride/HDL cholesterol ratio, and environmental factors. We found that patients with a family history of atherosclerosis had a higher prevalence of VLDL triglyceride/HDL cholesterol ratio above 1.8 (51.3% vs 34.7%) than patients without. Similarly, there was a significant inverse correlation between both considered ratios (r = -0.24, p < 0.05). The odds ratio of the presence of both abnormal ratios (4.60, 95% CI, 1.41-15.00) and low molecular weight apo(a) isoforms (3.30, 95% CI, 1.05-10.30 and family history of atherosclerosis was independent of smoking and hypertension. Apo(a) isoform size seems to be more important than Lp(a) concentrations in the family history of atherosclerosis risk determination. Subsequent analysis showed that patients with a family history of atherosclerosis had a greater-than-fourfold increased risk of having one or both abnormal ratios reflecting metabolic disturbances which probably constitute a combined trait. Family history of atherosclerosis may constitute a specific lipoprotein-related marker of atherosclerosis. Such a marker often precedes the onset of overt disease and may contribute to identifying patients with an atherogenic lipoprotein profile even in the absence of classical lipid risk factors.

The purpose of this study was to determine the relationship between insulin resistance and apoB100 metabolism in African American males. Fifteen subjects, 33 +/- 7.6 years old, were divided into two groups, insulin-resistant (IR) or insulin-sensitive (IS), based on the sum of the plasma insulin concentrations during an oral glucose tolerance test. The IR group (n = 8) differed significantly from the IS group (n = 7) with respect to body mass index (BMI) (30.1 vs 23.1 kg/m2; P = 0.0003), fasting triglycerides, (118 vs 54 mg/dl, P = 0. 013), and total plasma apolipoprotein B100 (80 vs 59 mg/dl, P = 0.014). Significantly elevated apoB100 levels in the IR group were seen in very low density lipoprotein (VLDL) (5.1 vs 3.4 mg/dl, P = 0.045) and intermediate density lipoprotein (IDL) (18 vs 12 mg/dl, P = 0.017) but not in low density lipoprotein (LDL) (57 vs 46 mg/dl, P = 0.19). Total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A-I, and blood pressure were not significantly different between the two groups. There was a high correlation between the sum of insulins during the oral glucose tolerance test and the BMI (rho = 0.88, P = 0.0001). In five IR and five IS subjects, apoB100 kinetics were determined in the fasting state using a bolus dose of deuteroleucine and multicompartmental modeling. IR subjects had significantly lower fractional catabolic rates (FCR) in the larger VLDLVLDLVLDLrho = -0.65, P = 0.05) and of IDL (rho = -0.85, P = 0.004). The correlation coefficient of the sum of insulins and the FCR of VLDLVLDL and IDL and elevated plasma levels of apoB and triglycerides (TG). These changes might be explained by decreased clearance of the TG-rich lipoproteins. We postulate that this may reflect decreased lipoprotein and/or hepatic lipase activity related to insulin resistance and its association with obesity.

The LCAT rate, VLDL triglyceride turnover, and bile acid kinetics were determined under standardized conditions in 10 patients with primary type IV HLP. Bile acid and plasma VLDL triglyceride kinetics were determined with the aid of [14C]-labeled cholic and chenodeoxycholic acid and [3H]glycerol, respectively. The LCAT rate was simultaneously determined in fasting-state plasma. The mean values of total bile acid formation (21.2 +/- 2.6 mumol kg-1 day-1), apparent VLDL triglyceride production (19.6 +/- 2.0 mumol kg-1 hr-1), and LCAT rate (6.0 +/- 0.6 mumol kg-1 hr-1) exceeded those reported previously for healthy controls. Plasma LCAT rate correlated positively with bile acid synthesis (R = 0.85, p less than 0.01) and with apparent plasma VLDL triglyceride production (R = 0.75, p less than 0.02). The results suggest that parallel disturbances in the regulation of cholesterol, bile acid, and lipoprotein metabolism occur in some patients with type IV HLP.

OBJECTIVE

Objective of the study is to identify the predictors of plasma triglycerides.

METHODS

A stratified random sample of university staff categories underwent measurements of anthropometry, blood pressure, and fasting blood glucose, insulin, lipids, CRP and homocysteine. Dietary intakes were assessed using duplicate 24h recalls. HOMA-IR was calculated. Stepwise, multivariate regression analysis was performed with TAG as the dependent variable.

RESULTS

The sample (n=251) was 55% females with a mean age of 44.9±9.7 years. African ancestry comprised 43%, followed South Asian 30% and mixed ethnicity 27%. Prevalence of obesity was 19.4%, insulin resistance 22.7% and metabolic syndrome 21.6%. Males had significantly higher (p<0.01) triglycerides and VLDL and lower HDL than females. Africans had significantly lower triglycerides and cholesterol than South Asians and Mix. Triglycerides were significantly (p<0.01) correlated with glucose, cholesterol, insulin, CRP, systolic, diastolic blood pressure, WC, BMI, age and components of MS. Glucose, cholesterol, insulin and total energy intake predicted TAG, to varying extents, in all participants (R(2)=45.1%), males (R(2)=40.3%), females (R(2)=56.0%), Africans (R(2)=35.0%), TSA (R(2)=31.5%) and mix (R(2)=51.0%).

CONCLUSIONS

Africans have lower triglycerides and cholesterol than South Asians and mix. Major predictors of triglycerides were fasting glucose and cholesterol independent of gender and ethnicity.

Anthropometric data, plasma lipoprotein lipid levels, and post-heparin lipoprotein lipase (PHLPL) activity were measured in nine patients with type III hyperlipoproteinemia (HLP) and two hypocholesterolemic subjects with the apo-E2/2 phenotype. Five type III HLP patients were treated with clofibrate. Log PHLPL activity was inversely correlated (r = -0.667, p less than 0.05) and age was positively correlated (r = 0.706, p less than 0.05) with cholesterol levels in the VLDL fraction of plasma from type III HLP patients. The correlation between log PHLPL and VLDL cholesterol levels remained significant when age was held constant in partial correlation analysis. Together age and log PHLPL activity accounted for 77% of individual variation in VLDL cholesterol levels in the type III patients. Clofibrate treatment raised PHLPL activity (+48%, p less than 0.05) and reduced the levels of VLDL cholesterol (-67%, P less than 0.05), VLDL triglycerides (-40%, P less than 0.02), and the ratio cholesterol/triglyceride in VLDL (-50%, P less than 0.05) in five type III HLP patients. Mean PHLPL activity was higher in the hypocholesterolemic subjects with the apo-E2/2 phenotype compared to the type III HLP patients. These results suggest that lipoprotein lipase activity and factors associated with age modulate the levels of abnormal and atherogenic remnant particles (beta-VLDL) in the VLDL plasma fraction of type III HLP patients.

We showed previously that hypertriglyceridaemia, but not hypercholesterolaemia, is correlated with increases in cholesterol synthesis and apolipoprotein B secretion in patients with secondary hypertriglyceridaemia. The aim of the present study was to compare the rate of cholesterol synthesis, using fasting plasma mevalonic acid (MVA) as an index, in patients with primary mixed hyperlipidaemia (type IIb phenotype, n=45) and primary hypercholesterolaemia (type IIa phenotype, n=92). LDL cholesterol was significantly higher in types IIa (6.38+/-0.18 mmol/l) and IIb (5.89+/-0.25 mmol/l) compared to 40 normolipidaemic controls (2. 99+/-0.1 mmol/l, P<0.0001), whereas serum triglyceride was higher in type IIb (2.62 (range 2.2-3.0) mmol/l) than type IIa (1.22 (range 0. 85-1.60) mmol/l, P<0.001) and controls (0.90 (range 0.68-1.24) mmol/l, P<0.001). Similarly, MVA was higher in type IIb (7.0+/-0.46 ng/ml) than IIa (5.6+/-0.23 ng/ml, P<0.0) and controls (5.6+/-0.36 ng/ml, P<0.05). Plasma MVA correlated positively with serum triglyceride (r=0.22, P=0.004) and negatively with LDL cholesterol (r=-0.21, P=0.014). These results are in accordance with previous observations that VLDL-apolipoprotein B secretion and cholesterol synthesis are linked and demonstrate that the latter is increased in mixed hyperlipidaemia.

A quantitative assay, based on endpoint immunonephelometry, was developed for human apolipoprotein C-III (Apo C-III) in plasma and lipoprotein fractions. The standard curve was constructed either with purified Apo C-III2 as a primary standard or with plasma as a secondary standard. It was linear between 50 and 400 ng Apo C-III per sample, corresponding to 1 microliter undiluted plasma. The intra- and interassay coefficients of variation (CV values) were 2.2 and 6.3%, respectively. The Apo C-III immunoreactivity was not influenced by detergents, denaturants nor by delipidation. The use of a non-ionic detergent (Apovax, 0.1 g/l) avoided the need for organic solvent extraction for plasma containing up to 4 g of triglycerides/l by reducing the sample turbidity. As measured in 126 normolipidemic subjects, the plasma Apo C-III concentration was 0.118 +/- 0.028 g/l (mean +/- SD). Apo C-III concentrations were only slightly elevated in patients with Fredrickson type IIa hyperlipoproteinaemia. The Apo C-III levels were nearly 3 times higher in type I, IIb, III and IV patients, while subjects with type V hyperlipaemia had about a 5-fold increase in Apo C-III compared to the healthy. The plasma Apo C-III values were strongly correlated with the plasma triglyceride concentrations (r = 0.80, n = 201). The Apo C-III distribution among the various lipoprotein fractions showed a higher proportion of Apo C-III in VLDL in hypertriglyceridaemic subjects compared to normolipaemic subjects.

<Abst<em>r</em>actText>Plasma apolipop<em>r</em>otein C3 (ApoC3) is associated with highe<em>r</em> plasma t<em>r</em>iglyce<em>r</em>ide and type 2 diabetes incidence. We evaluated whethe<em>r</em> body mass index (BMI) o<em>r</em> glucose metabolism we<em>r</em>e associated with ApoC3 in healthy monozygotic (MZ) twins.</Abst<em>r</em>actText><p><div><b>METHODS AND RESULTS</b></div>Fo<em>r</em>ty-seven MZ twin-pai<em>r</em>s (20 man, 27 women), aged 23-42 yea<em>r</em>s, we<em>r</em>e divided in subg<em>r</em>oups acco<em>r</em>ding to disco<em>r</em>dance o<em>r</em> conco<em>r</em>dance fo<em>r</em> (a) BMI (within-pai<em>r</em> diffe<em>r</em>ence (Δ) in BMI≥3.0 o<em>r</em><3.0 kg/m²), o<em>r</em> (b) 2-h glucose iAUC, du<em>r</em>ing o<em>r</em>al glucose tole<em>r</em>ance test (ΔGlucose iAUC ≥97.5 o<em>r</em><97.5 mmol × 120 minutes). Within these disco<em>r</em>dant o<em>r</em> conco<em>r</em>dant subg<em>r</em>oups, we tested (Wilcoxon signed-<em>r</em>ank test) co-twin diffe<em>r</em>ences in ApoC3, adiposity measu<em>r</em>es, insulin-<em>r</em>esistance and beta-cell function indices, and plasma and lipop<em>r</em>otein lipids. In BMI-Disco<em>r</em>dant (p = 0.92) o<em>r</em> BMI-Conco<em>r</em>dant (p = 0.99) subg<em>r</em>oups, ApoC3 did not diffe<em>r</em> between leane<em>r</em> and heavie<em>r</em> co-twins. In the Glucose-Disco<em>r</em>dant subg<em>r</em>oup, ApoC3 was significantly highe<em>r</em> in twins with highe<em>r</em> Glucose iAUC than in thei<em>r</em> co-twins with the lowe<em>r</em> Glucose iAUC (10.03 ± 0.78 vs. 8.48 ± 0.52 mg/dl; M ± SE; p = 0.032). Co-twins with highe<em>r</em> Glucose iAUC also had highe<em>r</em> waist ci<em>r</em>cumfe<em>r</em>ence, body fat pe<em>r</em>centage, live<em>r</em> fat content, wo<em>r</em>se insulin-sensitivity and beta-cell function and highe<em>r</em> choleste<em>r</em>ol and t<em>r</em>iglyce<em>r</em>ide in plasma <em>VLDL</em>, IDL, and LDL. In Glucose-Conco<em>r</em>dant twin-pai<em>r</em>s, no significant diffe<em>r</em>ences we<em>r</em>e obse<em>r</em>ved in the explo<em>r</em>ed va<em>r</em>iables. In all twin-pai<em>r</em>s, ΔApoC3 co<em>r</em><em>r</em>elated with Δ in lipids and glucose metabolism va<em>r</em>iables, the closest <em>r</em>elationship being between ΔApoC3 and Δ<em>VLDL</em> t<em>r</em>iglyce<em>r</em>ide (<em>r</em> = 0.74, p < 0.0001).</p><Abst<em>r</em>actText>While ApoC3 was not <em>r</em>elated to acqui<em>r</em>ed diffe<em>r</em>ences in BMI, it associated with ea<em>r</em>ly dys<em>r</em>egulation of glucose metabolism independently of obesity and genetic backg<em>r</em>ound.</Abst<em>r</em>actText>

BACKGROUND

Glucose effectiveness (SG) is a parameter that indicates the glucose ability to clearing itself from the plasma independently of insulin's action. Our purpose was to analyze the cluster characteristics associated with the metabolic syndrome in a group of non-obese, recent-onset hypertensives and to test if there was a correlation with SG and the effectiveness of glucose at basal insulin point (GEZI).

METHODS

We studied 36 patients with mild hypertension with normal basal glucose levels. We determined plasma lipid subfractions, apolipoproteins and urate levels. An intravenous glucose tolerance test (TTGI) and minimal model analysis according to Bergman was performed and SG, GEZI and insulin sensitivity (SI) were calculated.

RESULTS

Patients with lower SG and GEZI had higher levels of total triglycerides (Tg) (r = 0.42; p = 0.01 and r = 0.48; p = 0.002, respectively) and triglycerides bind to VLDL (Tg-VLDL) (r = 0.40; p < 0.01 and r = 0.49; p = 0.002, respectively). When the cluster of metabolic syndrome was analyzed, SG was inversely related to uric acid levels and to the waist-hip index. However, SI was only related to the uric acid levels (r = 0.38; p = 0.01).

CONCLUSIONS

In non-obese, recently diagnosed hypertensive patients, the SG parameter seems to be an early marker for the development of metabolic syndrome.