Normotriglyceridemic Group Research Articles

The Effect of Sex Differences on Endothelial Function and Circulating Endothelial Progenitor Cells in Hypertriglyceridemia.

Background Men have a higher risk and earlier onset of cardiovascular diseases compared with premenopausal women. Hypertriglyceridemia is an independent risk factor for the occurrence of ischemic heart disease. Endothelial dysfunction is related to the development of ischemic heart disease. Whether sex differences will affect the circulating endothelial progenitor cells (EPCs) and endothelial function in hypertriglyceridemia patients or not is not clear. Methods Forty premenopausal women and forty age- and body mass index (BMI)-matched men without cardiovascular and metabolic disease were recruited and then divided into four groups: normotriglyceridemic women (women with serum triglycerides level <150 mg/dl), hypertriglyceridemic women (women with serum triglycerides level ≥150 mg/dl), normotriglyceridemic men (men with serum triglycerides level <150 mg/dl), and hypertriglyceridemic men (men with serum triglycerides level ≥150 mg/dl). Peripheral blood was obtained and evaluated. Flow-mediated dilatation (FMD), the number and activity of circulating EPCs, and the levels of nitric oxide (NO), vascular endothelial growth factor (VEGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in plasma and culture medium were measured. Results The number and activity of circulating EPCs, as well as the level of NO in plasma or culture medium, were remarkably increased in premenopausal females compared with those in males both in the hypertriglyceridemic group and the normotriglyceridemic group. The EPC counts and activity, as well as the production of NO, were restored in hypertriglyceridemic premenopausal women compared with those in normal women. However, in hypertriglyceridemic men, the EPC counts and activity, as well as levels of NO, were significantly reduced. The values of VEGF and GM-CSF were without statistical change. Conclusions The present study firstly demonstrated that there were sex differences in the number and activity of circulating EPCs in hyperglyceridemia patients. Hypertriglyceridemic premenopausal women displayed restored endothelial functions, with elevated NO production, probably mediated by estradiol. We provided a new insight to explore the clinical biomarkers and therapeutic strategies for hypertriglyceridemia-related vascular damage.

Dislipidemia aterogénica en pacientes con diabetes mellitus tipo 1

Background and objectiveTo assess the prevalence of lipid abnormalities, with special emphasis on atherogenic dyslipidemia and its relationship with chronic complications in patients with type 1 diabetes mellitus (T1DM). Patients and methodCross-sectional study including all patients aged 18 and over, diagnosed of T1DM attending the outpatient clinic at Hospital del Mar and Hospital de Granollers, in Barcelona, during 2008. ResultsOf the 291 enrolled patients, 17.2 and 7.9% had high density lipoproteins (HDL) cholesterol<40mg/dL (men) or<50mg/dL (women) and triglycerides>150mg/dL, respectively. Hypoalphalipoproteinemic patients had a higher prevalence of peripheral neuropathy (28 vs. 7.1%, P<.001), macroalbuminuria (14 vs. 2.5%, P<.001) and higher concentrations of triglycerides (107.5 [55.8] vs. 82.7 [36] mg/dL, P<.0001) compared with those with normal/high HDL cholesterol levels. Hypertriglyceridemia was associated with increasing age (43.6 [11.2] vs. 37.6 [11.8] yr, P<.02), higher prevalence of hypertension (47.8 vs. 22.8%, P<.008), metabolic syndrome (82.6 vs. 22%, P<.001) and microangiopathic complications, lower insulin sensitivity (6.75 [2.1] vs. 8.54 [2.6] mg/Kg−1/min−1, P<.004) compared with the normotriglyceridemic group. ConclusionOne in 5 patients with T1DM has hypoalphalipoproteinemia or hypertriglyceridemia and these conditions are associated with 3 fold-increase microangiopathy. Thus, in these patients glycemic and blood pressure but also lipid profile control must be optimum.

A hypertriglyceridemic state increases high sensitivity C-reactive protein of Japanese men with normal glucose tolerance

Both fasting and postprandial hypertriglyceridemia have been identified as risk markers for cardiovascular disease. High-sensitivity C-reactive protein (hs-CRP), known to independently predict future cardiovascular disease, has also been reported to be a direct participant in the progression of atherosclerosis. We evaluated whether or not fasting and/or postprandial hypertriglyceridemia influence hs-CRP of men with normal glucose tolerance. According to the triglyceride (TG) level, measured before and 1 and 2 h after a meal tolerance test, subjects were classified into a normotriglyceridemic (NTG) group (n = 86), a postprandial hypertriglyceridemia (PHTG) group (n = 50), or a fasting hypertriglyceridemia (FHTG) group (n = 53). Hs-CRP and HOMA-R were significantly higher in the FHTG group than in the other groups (P < 0.01). The PHTG group had higher hs-CRP than the NTG group (P < 0.05). No significant differences in age, BMI, LDL cholesterol, or carotid intima-media thickness were found in comparison of the three groups. Multivariate linear regression analysis showed that the area under the TG curve (AUC-TG), HbA1c, and BMI were independently correlated with hs-CRP (P < 0.001, P = 0.016, P = 0.032, respectively). Our data suggests that a hypertriglyceridemic state is associated with hs-CRP irrespective of BMI, LDL-C, and HDL-C, indicating that hs-CRP might represent chronic inflammation induced by hypertriglyceridemia in Japanese men with normal glucose tolerance.

Impaired Hepatic Ketogenesis in Moderately Obese Men With Hypertriglyceridemia

BackgroundSeveral studies suggest that increased nonesterified fatty acid flux and increased de novo lipogenesis may contribute to hypertriglyceridemia, but few studies have examined fatty acid oxidation as a factor.RationaleEndogenous hypertriglyceridemia...

食後高血糖と食後高脂血症を同時に観察するテストミールＡについて

It is now well recognized that both Postprandial hyperglycemia and postprandial hyperlipidemia contribute to the development of atherosclerosis. Both an impaired glucose tolerance (IGT) and hyperglycemia after glucose loading have been reported to be risk factors for coronary arterial disease. Postprandial hyperlipidemia, or an increase in remnant lipoproteins in the plasma after a meal has been recognized as atherogenic. It therefore becomes important to establish an international standard test meal for simultaneously assessing both postprandial hyperglycemia and postprandial hyperlipidemia. Test meal A was developed for this purpose by the Working Group for Test Meals under the Committee of Laboratory Testing for Diabetes Mellitus of the Japan Diabetes Society. Test meal A contains total energy of 450 kcal with 51.4% of carbohydrate, 33.3% of fat and 15.3% of protein. Eighteen diabetics, 12 IGTs and 29 subjects with normal glucose tolerance were enrolled for this study. An oral glucose tolerance test was performed one week after loading with the test meal. There was a close correlation between the blood glucose values 120min. after glucose loading and 120min. after test meal loading. A blood glucose value of 200mg/dl 2 hour after glucose loading corresponds to 150mg/dl at the same sampling point after test meal loading, and a blood glucose value of 140mg/dl 2 hour after glucose loading corresponds to 10mg/dl at the same sampling point after the test meal loading. No significant increase in plasma triglyceride was apparent in the hypertriglyceridemic subjects, while the normotriglyceridemic group showed a significant rise in plasma triglyceride after the test meal loading. The results indicate that test meal A can be applied as a pilot model for the simultaneous assessment of both postprandial hyperglycemia and hyperlipidemia in diabetic subjects.

Evaluation of the effect of tibolone and transdermal estradiol on triglyceride level in hypertriglyceridemic and normotriglyceridemic postmenopausal women

The objective of the present study was to quantify the magnitude of the association between the change in triglycerides and high-density lipoprotein (HDL) cholesterol levels with the use of tibolone and transdermal estrogen in postmenopausal women with hypertriglyceridemia and normotriglyceridemia. This prospective randomized study enrolled 140 postmenopausal women who had all been hysterectomized for almost a year or more. All subjects completed the 3-month follow-up. The 140 patients were divided into two groups: 70 were given transdermal 17β-estradiol 0.05 mg/day, and 70 were given tibolone 2.5 mg/day. We compared the effects of tibolone and transdermal 17β-estradiol on lipids and climacteric symptoms of the patients. To evaluate the effects of tibolone and transdermal estrogens on triglycerides and HDL cholesterol in postmenopausal women with normotriglyceridemia and hypertriglyceridemia, the women were assigned to five groups according to triglyceride levels (0-100, 101-200, 201-300, 301-400 and ⋛ 401 mg/dl). We compared changes in the triglyceride and HDL cholesterol levels of each group after treatment. All 140 postmenopausal women completed the trial. No significant differences were found in baseline characteristics of the patients. The tibolone group showed a 22.6% decrease whereas the transdermal estrogen group had a 10.9% decrease in the mean triglyceride levels after 3 months of treatment. The mean decrease of triglyceride level with transdermal estradiol was approximately 11% in normotriglyceridemic and hypertriglyceridemic postmenopausal women. The mean decrease of triglyceride level was 17% in the normotriglyceridemic group and 22-30% in the hypertriglyceridemic groups with tibolone. While the mean HDL cholesterol level increased in the transdermal estrogen group (3.6%), it decreased in the tibolone group (9.3%). We found that tibolone decreased triglyceride levels much more than did transdermal estradiol. However, HDL cholesterol was decreased by tibolone and increased by transdermal estradiol. Tibolone had a more marked decreasing effect in postmenopausal women who had higher initial triglyceride levels. It is suggested that the beneficial effect of tibolone on the cardiovascular system might be greater in women with a high level of triglycerides.

Studies in hypertriglyceridaemia. VI: Serum lathosterol concentration is raised in hypertriglyceridaemic non-diabetic males with hyperinsulinaemia.

To assess the cholesterol synthesis rate in primary hypertriglyceridaemia using the serum unesterified lathosterol concentration as an indicator. A cross-sectional, case-control study. The Karolinska Hospital, Stockholm. Randomly selected hyper- (n = 53) and normotriglyceridaemic (n = 57) males, 40-50 years, with a fasting serum triglyceride concentration (mean +/- SD) of 3.81 +/- 1.65 and 1.28 +/- 0.53 mmol L-1, respectively. The exclusion criterion was diabetes mellitus, defined according to the World Health Organization (WHO) guidelines. To compare the fasting serum concentration distributions of lathosterol, a cholesterol precursor, in hyper- and normotriglyceridaemic groups. Thirty-six per cent of the hypertriglycerdaemic group had raised serum lathosterol concentrations, based on the 90th percentile of the lathosterol distribution of the normotriglyceridaemic group. In the hyper- but not in the normotriglyceridaemic group, lathosterol concentration was directly correlated with serum insulin responses to oral (r = 0.38; P = 0.007) and intravenous (r = 0.41; P = 0.005) glucose challenges. One-third of a randomly selected non-diabetic hypertriglyceridaemic population had an increased serum lathosterol concentration and this might indicate an increased cholesterol synthesis rate compatible with increased production of VLDL particles, possibly as the result of chronic hyperinsulinaemia.

Alterations of VLDL composition during alimentary lipemia

Apoliprotein (apo) B-100-containing very low density lipoprotein (VLDL) particles secreted from the liver accumulate in plasma during alimentary lipemia. To determine whether changes of VLDL composition occur in the postprandial state that may render these lipoproteins more atherogenic, apoE, C-I, C-II, and C-III, and lipids (triglycerides, phospholipids, and cholesterol) were measured in Svedberg flotation (Sf) 60-400 (large) and Sf 20-60 (small) VLDL before and after an oral fat load. Ten normotriglyceridemic (NTG) and three hypertriglyceridemic (HTG) healthy men were given a fat-rich mixed meal (1,000 kCal with 60.2 E% from fat). Triglyceride-rich lipoproteins were isolated by density gradient ultracentrifugation from plasma samples obtained before (fasting) and at 2-h intervals after the meal. VLDL was then separated from chylomicrons and their remnants by immunoaffinity chromatography using monoclonal antibodies 4G3 and 5E11, recognizing apoB-100, but not apoB-48 epitopes. Large and small VLDL isolated from the NTG group were enriched with apoE and C-I, and cholesterol, but depleted of apoC-II in the postprandial state, whereas the apoC-III, triglyceride, and phospholipid contents were essentially unchanged. The compositional changes of VLDL in HTG subjects were similar but more pronounced compared with NTG subjects. We conclude that postprandial lipemia in healthy men induces transient compositional alterations of VLDL that link these lipoprotein species to the formation of atherosclerosis.

Relationship of plasma cholesteryl ester transfer protein to HDL cholesterol. Studies in normotriglyceridemia and moderate hypertriglyceridemia.

To evaluate the independent effect of cholesteryl ester transfer protein (CETP) on HDL concentrations in humans, we measured lipids, lipoproteins, postprandial lipemia after an oral fat load, CETP mass, and the activities of CETP, lipoprotein lipase (LPL), and hepatic lipase in 16 healthy, normotriglyceridemic men and in 23 men with moderate, primary hypertriglyceridemia on an American Heart Association Step I diet. Fasting triglycerides and postprandial lipemia were increased and HDL cholesterol (HDL-C) was decreased in hypertriglyceridemic men compared with control subjects (P < .001). In the normotriglyceridemic group, CETP mass (P < .001) and activity (P < .005) were directly related to LPL activity After statistical adjustment for this close association, no significant relationship of CETP to HDL-C independent of LPL activity could be demonstrated in the normotriglyceridemic subjects. In contrast, CETP was unrelated to LPL activity in the hypertriglyceridemic subjects, but CETP concentrations showed a close inverse relationship to HDL-C (r = -.504, P = .014). Structural equation modeling of the association structures between HDL and fasting and postprandial triglycerides, endothelial lipases, and CETP in both groups indicated that the overall regression models for the two groups differed (P < .05). Specifically, the associations between CETP mass and activity and HDL-C differed between both groups (both P < .01). We conclude that high-normal CETP levels lower HDL-C in nonsmoking, nonobese men with moderate, primary hypertriglyceridemia on a hypolipidemic diet, but not in healthy, normotriglyceridemic men on an unrestricted diet. Thus, variation in CETP plasma concentrations may contribute to the high-triglyceride, low-HDL phenotype.

Studies in hypertriglyceridaemia, III: glucose tolerance, insulin sensitivity and indices of adipose tissue lipolysis in randomly selected non‐diabetic hypertriglyceridaemic Swedish men

Hypertriglyceridaemia, insulin resistance and glucose intolerance are conditions associated with an increased risk of coronary heart disease. In this study we have examined randomly selected nondiabetic hypertriglyceridaemic (HTG) males, 40-50 years (n = 65) and age-matched normotriglyceridaemic (NTG) controls (n = 61). The (mean +/- SD) insulin sensitivity index, as assessed by the Minimal Model method, was significantly lower in the HTG compared with the NTG group (3.69 +/- 2.96 vs. 6.29 +/- 3.38 x 10(-4) min-1 per mUL-1; P < 0.001). Thirty-eight per cent of the HTG group was glucose intolerant, compared with 8% in the NTG group (X2 = 13.16; P < 0.001). The glucose intolerant HTG sub-group had, when compared with the glucose tolerant one, significantly higher serum concentrations of apoB (1318 +/- 284 vs. 1094 +/- 312 mg L-1; P < 0.01) and glycerol (84 +/- 26 vs. 65 +/- 22 nmol L-1; P < 0.01). Serum FFA concentrations were, irrespective of glucose tolerance/intolerance, higher in the HTG than in the NTG group. By logistic regression analysis with the HTG/NTG state as the dichotomous variable, it was found that neither a low insulin sensitivity, nor glucose intolerance were independently linked with the HTG state. Instead, the lower insulin sensitivity of the HTG group was related to their higher body mass index. The higher frequency of glucose intolerance in the HTG group was explained by their higher mean serum apoB concentration, when compared with the NTG group. In conclusion, this study of a randomly selected of HTG group has confirmed the frequent coexistance of HTG, insulin resistance and glucose intolerance. The new important finding was that neither of these two latter conditions appear to be of direct pathogenetic importance for HTG.

Relationship between insulin resistance and risk factors for cardiovascular disease in Japanese non-insulin-dependent diabetic patients

To investigate whether a resistance to insulin-stimulated glucose uptake (IR) is associated with the risk factors (RF) for cardiovascular disease (CVD) in non-insulin-dependent diabetic (NIDDM) patients, we determined the degree of IR in 135 adult NIDDM patients who had no advanced diabetic complications. The euglycemic (80 mg/dl) hyperinsulinemic clamp (insulin infusion rate 1.12 mU/kg per min) was performed and the average glucose infusion rate (GIR) during a steady-state euglycemia was determined as a measure of IR. Hypertension was more common among NIDDM patients with an increased IR and was highest in the group of patients with CVD. CVD-RF such as hypertension, hypertriglyceridemia, low HDL-cholesterol and obesity tended to cluster in the NIDDM patients who had lower GIR values and higher fasting IRI levels. GIR values were compared between a set of groups extracted from the 135 NIDDM patients that were matched for age, sex, body mass index and HbA 1c levels. The CVD-positive group had the significantly lower GIR value than the CVD-negative group (2.06 ± 0.66 vs. 3.45 ± 1.75, P < 0.005). The GIR value was also significantly lower in the hypertriglyceridemic group compared with the normotriglyceridemic group (2.50 ± 1.36 vs. 4.03 ± 1.82, P < 0.0005). However, there was no significant difference between the hypertensive and normotensive groups and between the high cholesterol or low HDL-cholesterol groups and their respective control groups. In conclusion, these results suggest that IR contributes to the clustering of CVD-RFs which may accelerate the development of CVD in the subgroup of Japanese NIDDM patients.

Relationship between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, insulin levels and insulin sensitivity: studies in randomly selected normo- and hypertriglyceridaemic men

Impaired fibrinolytic function secondary to elevated plasma plasminogen activator inhibitor-1 activity, hypertriglyceridaemia and hyperinsulinaemia are frequent findings in patients with coronary heart disease. It has been debated whether VLDL or insulin is the major regulator of plasma plasminogen activator inhibitor-1 activity. This study examines the relationships between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, fasting and post-oral glucose load insulin levels and insulin sensitivity, as estimated by the minimal model method. Subjects studied were randomly selected hypertriglyceridaemic (n = 65) and age-matched normotriglyceridaemic (n = 61) men, aged 40-50 years, recruited in a population survey. Plasma plasminogen activator inhibitor-1 activity was higher in the hypertriglyceridaemic than in the normotriglyceridaemic group (21 +/- 14 vs 10 +/- 8 mU/l; p < 0.01). The hypertriglyceridaemic group had higher serum insulin, basal as well as 2 h after intake of the oral glucose load, and a lower insulin sensitivity index. In univariate analysis, plasma plasminogen activator inhibitor-1 activity correlated positively with VLDL triglycerides in both the hyper- and normotriglyceridaemic groups (r = 0.43 r = 0.60, respectively) and negatively with the insulin sensitivity index (r = -0.35 r = -0.44, respectively). In multivariate analysis, VLDL triglyceride levels were found to be independently related to plasma plasminogen activator inhibitor-1 activity in both groups, whereas insulin sensitivity/serum insulin levels were not. An unexpected finding was that the serum activity of the enzyme gamma glutamyl transpeptidase appeared to influence the relationships for plasma plasminogen activator inhibitor-1 in the hypertriglyceridaemic group.(ABSTRACT TRUNCATED AT 250 WORDS)

High density lipoprotein (HDL) subfractions in cardiovascular patients with low levels of HDL-cholesterol: Influence of hypertriglyceridaemia on subfraction concentration and composition

The major high density lipoprotein (HDL) subfractions were examined in angiographically defined cardiovascular patients with low HDL-cholesterol (HDL-C) levels. The aims were to study subfraction concentration and composition, and the extent to which hypertriglyceridaemia (HTG) modified these variables. Normotriglyceridaemic (NTG)-low HDL-C patients showed similar subfraction composition to age-matched healthy controls. However, these groups showed notable differences in subfraction composition compared to HTG-low HDL-C patients, particularly with regard to the HDL 2 subfraction. HDL subfraction mass was significantly reduced in both cardiovascular groups; the HTG group showed a greater reduction in HDL 2, whilst the NTG group showed a greater reduction in HDL 3. The major HDL apoprotein (apo A-I) was lower in both subfractions of the cardiovascular patients. Apo A-II showed significant reductions only in the HTG patients.

The esterification of exogenous fatty acids by adipose tissue of hypertriglyceridaemic subjects with or without diabetes mellitus.

1. The esterification of exogenous palmitate to diglyceride and triglyceride in adipocytes was studied in obese and diabetic patients with and without hypertriglyceridaemia. The rate of esterification correlated significantly with the triglyceride content of adipocytes. 2. In diabetic patients with hypertriglyceridaemia, the rate of esterification to triglyceride was significantly greater than in diabetic patients with normotriglyceridaemia. This difference could not be attributed to differences in glucose tolerance or to the degree of obesity. 3. Fasting plasma insulin levels were greater in the hypertriglyceridaemic group than in the normotriglyceridaemic group. The difference in esterification rates could have been due to differences in adipocyte size. 4. The esterification of fatty acid in adipose tissue of diabetic patients was lower than in non-diabetic subjects and this difference could not be accounted for by differences in adipocyte size or differences in the intracellular pools of fatty acid in adipose tissue. 5. The role of esterification of exogenous fatty acids in adipose tissue as a possible determinant of the uptake of glyceride fatty acids from plasma is discussed.

Seasonal variation of lipoprotein lipase activity in human subcutaneous adipose tissue.

1. In 126 normotriglyceridaemic and in seventy-three hypertriglyceridaemic subjects there was a similar seasonal variation of adipose tissue lipoprotein lipase activity, the lowest activity being noted during the summer months. 2. There was no seasonal variation of the serum triglyceride or free fatty acid concentrations in the normotriglyceridaemic group. 3. In the same group the highest blood acetoacetate concentration was noted in March–April, the lowest in November–December. 4. There was no seasonal variation of the blood glucose concentration for women, but for men the lowest concentration was noted in July–August.