Fasting Triglyceride Concentrations Research Articles

Prevalence of subclinical hypothyroidism in patients with chronic kidney disease.

Subclinical primary hypothyroidism is highly prevalent in the general population, especially in the elderly. However, the prevalence of subclinical primary hypothyroidism in persons with chronic kidney disease (CKD) not requiring chronic dialysis is not well defined. Cross-sectional data from 3089 adult outpatients, who were consecutively referred by general practitioners for routine blood testing over the last two years, were analyzed. Glomerular filtration rate (GFR) was estimated by the abbreviated Modification of Diet in Renal Disease equation. Multivariable logistic regression was used to evaluate the independent association between prevalent subclinical primary hypothyroidism and estimated GFR. Among 3089 adult participants, 293 (9.5%) had subclinical primary hypothyroidism and 277 (9%) had an estimated GFR <60 ml/min per 1.73 m(2). The prevalence of subclinical primary hypothyroidism increased from 7% at an estimated GFR >or=90 ml/min per 1.73 m(2) to 17.9% at an estimated GFR <60 ml/min per 1.73 m(2) (P < 0.0001 for trend). Compared with participants with an estimated GFR >or=60 ml/min per 1.73 m(2), those with estimated GFR <60 ml/min per 1.73 m(2) had an increased odds of subclinical primary hypothyroidism after adjusting for age, gender, fasting plasma glucose, total cholesterol, and triglyceride concentrations. These findings suggest that subclinical primary hypothyroidism is a relatively common condition ( approximately 18%) among persons with CKD not requiring chronic dialysis, and it is independently associated with progressively lower estimated GFR in a large cohort of unselected outpatient adults.

Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function.

Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m(2)) were randomized to "control (CO)" = 100% energy requirements; "CR" = 25%; "caloric restriction and increased structured exercise (CR+EX)"= 12.5% CR + 12.5% increase in energy expenditure through exercise; or "low-calorie diet (LCD)" = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD.

High Plasma Retinol Binding Protein-4 and Low Plasma Adiponectin Concentrations Are Associated with Severity of Glucose Intolerance in Women with Previous Gestational Diabetes Mellitus

Women with previous gestational diabetes mellitus (pGDM) are at high risk of developing type 2 diabetes mellitus in the future. The role of adipokines in women with pGDM has not been established. We investigated whether circulating adipokine concentration is associated with abnormal glucose homeostasis in women with pGDM. DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURES: We measured the plasma concentrations of retinol-binding protein-4 (RBP4), transthyretin (TTR), and adiponectin and metabolic parameters in four groups of women who exhibited normal glucose tolerance (NGT) during a previous pregnancy (NP, n = 17), NGT after GDM (GDM-NGT, n = 72), impaired glucose tolerance after GDM (GDM-IGT, n = 60), and type 2 diabetes after GDM (GDM-DM, n = 8). Plasma RBP4 concentration was significantly higher in women with GDM-DM, GDM-IGT, and GDM-NGT than in those with NP. RBP4 concentration correlated positively with TTR concentration; fasting plasma glucose, insulin, and triglyceride concentrations; blood pressure; abdominal fat area; and homeostasis model assessment of insulin resistance. Plasma TTR concentration was elevated in women with GDM-DM compared with other groups. In contrast, adiponectin concentration was lowest in the GDM-DM group and correlated inversely with parameters of insulin resistance. Resistin concentration was higher only in the GDM-NGT and GDM-IGT groups, whereas leptin did not differ between groups. Plasma RBP4 and adiponectin concentrations were inversely correlated. The severity of glucose intolerance in women with pGDM is associated with high RBP4 and low adiponectin concentrations.

Omega-3 fatty acid containing diets decrease plasma triglyceride concentrations in mice by reducing endogenous triglyceride synthesis and enhancing the blood clearance of triglyceride-rich particles

Intake of n-3 fatty acids can reduce both fasting and postprandial triglyceride (TG) concentrations in humans as well as in experimental animals, but the mechanisms by which this occurs are not completely known. We investigated in mice the effects of dietary fish oil (a source of n-3 fatty acids) on endogenous TG synthesis and exogenous TG-rich particle removal. C57 BL/6J mice were fed for 4 months with three types of high-fat diets (18% fat wt/wt) - soy oil, fish oil and a mixture of soy oil and fish oil (soy/fish) (5:1 wt/wt), and a chow diet with 6% fat from soy oil (wt/wt) served as a control. Plasma TG and apolipoprotein B (apoB) concentrations and lipoprotein lipase (LPL) activity were measured. Triton WR 1339 was used to assess hepatic synthesis of very low density lipoprotein, and intravenous injection of chylomicron-like lipid emulsions was conducted to determine the effects of dietary fish oil n-3 fatty acids on exogenous TG clearance. Both fish and soy/fish oil diets reduced plasma TG levels in fed and fasted states compared to soy oil alone. Plasma pre- and post-heparin LPL activities were significantly higher with fish and soy/fish oil diets than soy oil diet in fed mice. No differences in plasma TG levels and LPL activity were shown among groups of fish oil, soy/fish oil and normal chow diets. Levels of hepatic TG and apoB synthesis were 30-50% and 42% lower in mice fed with the fish oil diet compared to the other three diets. In addition, compared to soy oil diet, fish oil feeding significantly increased blood clearance of chylomicron-like lipid emulsions by 21-26%. Our data suggest that reduced endogenous TG synthesis, increased LPL activities and more rapid blood clearance of TG-rich particles all distinctly contribute to the TG-lowering effects of fish oil n-3 fatty acids.

Abdominal Obesity and the Metabolic Syndrome: Contribution to Global Cardiometabolic Risk

There is currently substantial confusion between the conceptual definition of the metabolic syndrome and the clinical screening parameters and cut-off values proposed by various organizations (NCEP-ATP III, IDF, WHO, etc) to identify individuals with the metabolic syndrome. Although it is clear that in vivo insulin resistance is a key abnormality associated with an atherogenic, prothrombotic, and inflammatory profile which has been named by some the "metabolic syndrome" or by others "syndrome X" or "insulin resistance syndrome", it is more and more recognized that the most prevalent form of this constellation of metabolic abnormalities linked to insulin resistance is found in patients with abdominal obesity, especially with an excess of intra-abdominal or visceral adipose tissue. We have previously proposed that visceral obesity may represent a clinical intermediate phenotype reflecting the relative inability of subcutaneous adipose tissue to act as a protective metabolic sink for the clearance and storage of the extra energy derived from dietary triglycerides, leading to ectopic fat deposition in visceral adipose depots, skeletal muscle, liver, heart, etc. Thus, visceral obesity may partly be a marker of a dysmetabolic state and partly a cause of the metabolic syndrome. Although waist circumference is a better marker of abdominal fat accumulation than the body mass index, an elevated waistline alone is not sufficient to diagnose visceral obesity and we have proposed that an elevated fasting triglyceride concentration could represent, when waist circumference is increased, a simple clinical marker of excess visceral/ectopic fat. Finally, a clinical diagnosis of visceral obesity, insulin resistance, or of the metabolic syndrome is not sufficient to assess global risk of cardiovascular disease. To achieve this goal, physicians should first pay attention to the classical risk factors while also considering the additional risk resulting from the presence of abdominal obesity and the metabolic syndrome, such global risk being defined as cardiometabolic risk.

Markedly Blunted Metabolic Effects of Fructose in Healthy Young Female Subjects Compared With Male Subjects

To compare the metabolic effects of fructose in healthy male and female subjects. Fasting metabolic profile and hepatic insulin sensitivity were assessed by means of a hyperglycemic clamp in 16 healthy young male and female subjects after a 6-day fructose overfeeding. Fructose overfeeding increased fasting triglyceride concentrations by 71 vs. 16% in male vs. female subjects, respectively (P < 0.05). Endogenous glucose production was increased by 12%, alanine aminotransferase concentration was increased by 38%, and fasting insulin concentrations were increased by 14% after fructose overfeeding in male subjects (all P < 0.05) but were not significantly altered in female subjects. Fasting plasma free fatty acids and lipid oxidation were inhibited by fructose in male but not in female subjects. Short-term fructose overfeeding produces hypertriglyceridemia and hepatic insulin resistance in men, but these effects are markedly blunted in healthy young women.

Low level of Lemon Balm (Melissa officinalis) essential oils showed hypoglycemic effects by altering the expression of glucose metabolism genes in db/db mice

The effects of the lemon balm essential oils (LBEO) in the db/db mice were examined. Mice were divided into four groups and the LBEO was orally administered for 6 weeks: saline, control; 0.15mg/d, LBEO1; 0.05mg/d, LBEO2; 0.0125mg/d, LBEO3. The LBEO showed biphasic effects on plasma glucose levels; the low level feeding was hypoglycemic but the medium and the high levels exerted hyperglycemic effects. The LBEO3 group showed reduced fasting glucose (65%, P&lt;0.05) and triglyceride concentrations compared with the controls. Glucose tolerance, assessed by oral glucose tolerance test, was improved in this group accordingly. However, in the LBEO1 and the LBEO2 groups, glucose tolerance was worsened according to the elevated fasting glucose levels compared with the controls (33% and 27% elevation in the LBEO1 and the LBEO2, respectively P&lt;0.05). Plasma GOT and GPT levels were elevated in these groups as well. The hypoglycemic mechanism of low level feeding of the LBEO was further investigated with quantifying the expression of the glucose metabolism genes by real time PCR. The glucokinase and the GLUT 4 gene expressions were significantly upregulated, however, the expression of glucose‐6‐phosphase and phosphoenolpyruvate carboxykinase were downregulated in the mouse livers of the LBEO3 group. The results suggest that the LBEO may be hypoglycemic when administered at low concentration. These effects may be due to the enhanced glucose uptake and the inhibition of gluconeogenesis in the livers.

Association of Circulating Lactoferrin Concentration and 2 Nonsynonymous LTF Gene Polymorphisms with Dyslipidemia in Men Depends on Glucose-Tolerance Status

Lactoferrin, an innate immune protein with antiinflammatory properties, shows considerable antiatherosclerosis activity in animal studies. We investigated the relationship between circulating lactoferrin, lactoferrin gene (LTF, lactotransferrin) polymorphisms, dyslipidemia, and vascular reactivity in the context of glucose-tolerance status in men. We evaluated 2 nonsynonymous LTF polymorphisms (rs1126477 and rs1126478) and measured circulating lactoferrin concentrations by ELISA under nonstressed conditions in healthy Caucasian men (n = 188) and male patients with an altered glucose tolerance (n = 202). We also studied the association of lactoferrin concentration with vascular reactivity via high-resolution ultrasound analysis of the brachial artery in a subsample of study participants. Circulating lactoferrin concentration was inversely associated with fasting triglyceride concentration (r = -0.24; P = 0.001), body mass index (BMI) (r = -0.20; P = 0.007), waist-to-hip ratio (r = -0.35; P <0.001), and fasting glucose concentration (r = -0.18; P = 0.01), and directly correlated with HDL cholesterol concentration (r = 0.21; P = 0.004). Control AG heterozygotes for rs1126477 had significantly decreased fasting triglyceride concentrations (P = 0.001). Similarly, control individuals who were G carriers for rs1126478 had significantly lower fasting triglyceride concentrations (P = 0.044) and significantly higher HDL cholesterol concentrations (P = 0.028) than AA homozygotes. These associations remained significant after controlling for age, BMI, waist-to-hip ratio, fasting glucose concentration, smoking status, and alcohol intake. Circulating lactoferrin concentration was not significantly associated with endothelium-dependent vasodilatation (EDVD) in the individuals studied (n = 95); however, lactoferrin was positively associated with EDVD in obese participants with an altered glucose tolerance (r = 0.54; P = 0.04). We have identified associations among LTF polymorphisms, circulating lactoferrin concentration, fasting triglyceride concentration, and vascular reactivity in humans.

Postprandial lipaemia, metabolic syndrome and LDL particle size in urbanised South African blacks with and without coronary artery disease

Postprandial lipaemia, characterised by a rise in triglycerides (TG) after eating, is associated with coronary artery disease (CAD) and metabolic syndrome (MetS). Small, dense, low-density lipoprotein (LDL) particles are implicated in atherogenesis. Little is known about postprandial lipaemia or small, dense LDL particles in urbanised black South Africans. Assess postprandial lipaemia in black CAD patients with and without MetS and measure their fasting and postprandial lipid profiles and LDL particles. Anthropometric data, biochemical variables and LDL particles were measured in 40 patients and 20 control subjects. Twenty three patients met International Diabetes Federation criteria for MetS and were subdivided according to fasting TG concentration either < or > or = 1.7 mmol/l. Postprandial lipaemia was assessed by an oral fat tolerance test (OFTT) and area under the curve (AUC). CAD patients with and without MetS had similar fasting lipid profiles, postprandial responses during OFTT and AUCs. MetS patients with fasting TG > or = 1.7 mmol/l had greater postprandial responses (P < 0.001) and higher AUC (P < 0.0001) than patients with TG < 1.7 mmol/l. AUC was higher in all patients than controls (P < 0.03). The most significant correlation was between fasting TG and AUC (r = 0.8703; P < 0.0001). Small, dense LDL particles were present in 29 patients (72.5%) and 3 controls (15%) (p = 0.0001). Postprandial lipaemia was common in black CAD patients, including patients with MetS. Fasting TG concentration was the strongest determinant. Small, dense LDL particles were highly associated with CAD.

The apolipoprotein A5 gene –1131T→C polymorphism affects vitamin E plasma concentrations in type 2 diabetic patients

Variations of the apolipoprotein A5 (APOA5) gene are strongly associated with hypertriglyceridemia. Vitamin E is transported in triglyceride (TG)-rich lipoproteins and therefore could also be modulated by apoAV. Patients with type 2 diabetes have a tendency towards high TG values and increased oxidative stress. We examined the impact of genetic APOA5 variation (-1131T-->C) on vitamin E and oxidative status in 169 non-smoker type 2 diabetic patients. Plasma samples were analyzed for lipids, lipoproteins, vitamin E, oxidized low-density lipoprotein (oxLDL), lipoperoxides, autoantibodies against oxLDL and diene formation of LDL. Vitamin E concentrations were higher in TC carriers compared with TT carriers (45.48+/-8.20 micromol/L vs. 40.32+/-10.47 micromol/L; p=0.02). The prevalence of the TC genotype was 2.6-fold higher among individuals with high vitamin E concentrations (p=0.02). The APOA5 polymorphism did not determine any differences in oxidative status. Fasting TG concentration was a significant 21% higher in carriers of the TC genotype (p=0.04) due to higher TG concentrations in very-low-density lipoprotein (VLDL) and high-density lipoprotein. The APOA5-1131T-->C polymorphism is associated with both higher vitamin E concentrations and higher VLDL-TGs in diabetic patients.

Impact of testosterone treatment on postprandial triglyceride metabolism in elderly men with subnormal testosterone levels

Objective. To investigate the impact of testosterone supplementation on postprandial triglycerides in elderly men with subnormal endogenous testosterone. Material and methods. Twenty‐six men with subnormal testosterone levels (⩽11.0 nmol/L) were randomly assigned to treatment with intramuscular testosterone or placebo for one year in a double‐blinded study. The participants underwent an oral fat load before and after the treatment period, and serum and chylomicron triglyceride levels were measured fasting and 2, 4, 6 and 8 h afterwards, together with total fat mass and fat‐free mass. Results. Total testosterone rose to low‐normal levels in the testosterone‐treated group. No differences in waist circumference, body mass index, serum levels of total cholesterol, low‐density lipoprotein cholesterol, high density lipoprotein cholesterol, fasting triglyceride concentrations or lipase activity between the groups were observed during testosterone treatment. Testosterone treatment did not affect postprandial serum and chylomicron triglyceride levels assessed by area under the curve, incremental area under the curve or triglyceride response. Total fat mass was significantly reduced (p<0.001) while fat‐free mass was significantly increased (p<0.001) in the testosterone‐treated group. Conclusion. Normalizing testosterone levels in elderly men does not seem to affect the postprandial lipid metabolism to any great extent, but has favourable effects on body composition.

Fasting versus Nonfasting Triglycerides and the Prediction of Cardiovascular Risk: Do We Need to Revisit the Oral Triglyceride Tolerance Test?

Historically, triglycerides have been measured in the fasting state for 2 reasons. First, because of the marked increase in triglycerides after fat ingestion, the variability in triglyceride measurements is much smaller in the fasting state. Second, before the availability of direct assays for LDL cholesterol (LDL-C),1 estimation of LDL-C was performed in clinical practice almost exclusively by use of the Friedewald equation, which requires that both the HDL-C concentration and the fasting triglyceride concentration divided by 5 be subtracted from the total cholesterol concentration. The recommendations to measure triglycerides in the fasting state did not, however, derive from a consistent set of prospective cohort studies showing that fasting concentrations were superior to nonfasting concentrations for the detection of cardiovascular risk. Instead, following screening guidelines, most epidemiologic investigations simply relied on fasting triglycerides. Taken as a whole, such studies indicate that fasting triglycerides are a univariate predictor of vascular disease. Controversy exists, however, regarding the clinical usefulness of fasting triglycerides as an independent predictor of risk, because adjustment for other covariates—in particular HDL-C—markedly decreases both the magnitude and significance of observed epidemiologic effects (1). The extent to which investigators have sought to avoid nonfasting triglycerides as a method for risk detection is evident in a recent metaanalysis that limited evaluation only to those epidemiologic studies that measured fasting triglycerides, specifically “to exclude the possibility of postprandial effects” (2). Is it possible, then, that recommendations to measure triglycerides in the fasting state have systematically underestimated the impact of hypertriglyceridemia in clinical practice? Atherosclerosis has long been hypothesized to be a disorder influenced by postprandial effects. As early as 1950, J. R. Moreton, writing in the Journal of Laboratory and Clinical Medicine , suggested a linkage between chylomicronemia, fat tolerance, and atherosclerosis (3). A major source of circulating triglycerides is dietary …

Effect of hypocaloric diet plus sibutramine treatment on hormonal and metabolic features in overweight and obese women with polycystic ovary syndrome: a randomized, 24-week study

To examine the effect of hypocaloric diet plus sibutramine on body composition, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS). Open-label, randomized study at an outpatient clinic. A total of 59 overweight and obese (18-39 years old) women with PCOS. All patients were placed in a hypocaloric diet plus sibutramine (10 mg per day) for the first month and then on a hypocaloric diet plus sibutramine (10 mg per day, group S) or hypocaloric diet only (group D) for the subsequent 6 months. Body composition, hormonal and metabolic features and insulin sensitivity (oral glucose tolerance test, OGTT) were evaluated at baseline and at 3 and 6 months of treatment. Body weight reduced in both groups but the reduction was greater with sibutramine (-15.4+/-1.1 vs -11.1+/-1.9% in groups S and D, respectively, P<0.05). At 6 months, a greater percent of patients lost more than 10% of initial body weight in group S than D (81 vs 52.9%). In both groups, all women with abnormal OGTT at baseline presented normal glucose tolerance after 6 months. Free androgen index (FAI), glucose area under the curve and fasting triglyceride (TG) concentration were reduced after 6 months in group S only (P<0.05). No changes in cardiovascular risk factors, prolactin and hepatic enzymes levels were observed in both groups. A hypocaloric diet and a diet plus sibutramine both result in significant weight loss in overweight and obese women with PCOS. Patients who received sibutramine showed a greater weight loss and improvement in hyperandrogenemia and insulin sensitivity after 6 months of treatment. The amelioration of insulin resistance in this group could not be totally explained by weight loss. Total testosterone, FAI and TG levels reduction could be a possible mechanism. Finally, sibutramine increased compliance to diet and it was well tolerated from these patients.

Carotid artery wall hypertrophy in children with metabolic syndrome

Preclinical vascular changes (increased stiffness and/or wall thickness) have been observed in children with known metabolic risk factors. Aim of the present study was to evaluate different carotid parameters, representative of vascular health, in children with and without metabolic syndrome (MS). We studied 38 children with MS (mean age 9.6+/-2.6 years; range 6-14 years) and 45 healthy age-matched subjects. Children who met three or more of the following criteria qualified as having the MS: fasting glucose >110 mg dl(-1), fasting triglyceride concentration >100 mg dl(-1), fasting high-density lipoprotein cholesterol concentration <50 mg dl(-1) for females or <45 mg dl(-1) for the males, waist circumference >75th percentile for age and gender and systolic or diastolic blood pressure >90th percentile for age, gender and height. Carotid B-mode ultrasound examinations were performed and intima-media thickness and diameters were measured in all subjects. Arterial geometry was further characterized by calculation of carotid cross-sectional area. Carotid intima-media thickness and lumen diameters were increased in children with MS as compared to children without MS. Moreover, carotid cross-sectional area was significantly higher in the group of children with MS 9.83+/-1.86 mm(2) [mean+/-s.d.] compared with the control group: 7.77+/-1.72 mm(2), P<0.001, even after adjustment for age, gender and height. Carotid hypertrophy is already detectable in children with MS. High-resolution B-mode ultrasound could provide a valuable tool for the cardiovascular risk stratification of children.

Neonatal dietary supplementation of arachidonic acid increases prostaglandin levels in adipose tissue but does not promote fat mass development in guinea pigs

The role of arachidonic acid (AA) on the development of adipose tissue is still controversial since its metabolites, i.e., prostaglandins, can either stimulate or inhibit preadipocyte differentiation in vitro. In the present study, we evaluated the effects of early postnatal supplementation of AA on body weight and adipose tissue development in guinea pigs. Male newborn guinea pigs were fed for 21 days (day 21) with diets (milk and pellet) supplemented (+AA) or not (-AA) with 1.2% (total fatty acids) AA. From day 21 to day 105 both groups were fed a chow diet. The 21-days-old +AA pups showed a twofold higher AA accretion in phospholipids associated with a two- to sixfold increase in several prostaglandins, such as 6-keto PGF(1alpha) (the stable hydrolysis product of PGI(2)), PGF(2alpha), PGE(2), and PGD(2) in adipose tissue, compared with the -AA group. No difference in fat pad and body weight, aP2, and leptin gene expression in adipose tissue, fasting plasma glucose, free-fatty acids, and triglyceride concentration was observed between groups at day 21 or day 105. These results show that dietary supplementation of AA during the suckling/weaning period increases prostaglandin levels in adipose tissue but does not influence early fat mass development in the guinea pig.

Elevation of Low-Density Lipoprotein Cholesterol Concentration with Over-the-Counter Fish Oil Supplementation

To report a case of elevated low-density lipoprotein cholesterol (LDL-C) concentration in a patient taking fish oil supplements for hypertriglyceridemia. A 63-year-old white woman had been taking 2.7 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily in 9 g of over-the-counter (OTC) fish oil capsules for triglyceride lowering. Prior to the adverse event, she had baseline fasting triglyceride (TG) and LDL-C concentrations of 278 mg/dL and 106 mg/dL, respectively. After 6 weeks of treatment with fish oil, fasting TG levels decreased by 47.5% (-132 mg/dL) and the LDL-C increased by 75% (+80 mg/dL). Discontinuation of therapy for 6 weeks resulted in TG returning to high concentrations (334 mg/dL; +56 mg/dL change from baseline) and LDL-C decreasing toward baseline (143 mg/dL; +37 mg/dL change from baseline). Fish oil, an omega-3 polyunsaturated fatty acid, consists of EPA and DHA. EPA and DHA are thought to inhibit the synthesis of triglycerides in the liver. Type IV dyslipidemic patients may develop increased LDL-C levels while taking fish oil to lower triglycerides due to possible down-regulation of the LDL-C receptor in hepatic cells and formation of larger LDL particles. Use of the Naranjo probability scale indicates a probable relationship between elevations in LDL-C from baseline and initiation of fish oil treatment for hypertriglyceridemia. It is unknown whether any component within this particular product could have contributed to such an unusual elevation in LDL-C. This case documents a much higher LDL-C elevation associated with OTC fish oil supplementation than has been previously identified in the literature. Healthcare providers should be advised that LDL-C levels may increase with use of OTC fish oil and should monitor patients periodically for such elevations. The significance of this increase on clinical outcomes is not known.

Cardiovascular Disease Under the Influence of Excess Visceral Fat

Diabetes and cardiovascular disease have emerged as major threats to human health, and the risk of developing these chronic conditions is increased in individuals with abdominal obesity and the metabolic syndrome. Excess visceral abdominal tissue (VAT) accumulation appears to be a key feature of abdominal obesity contributing to the development of the metabolic syndrome. For instance, excess VAT is accompanied by elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, elevated blood pressure, and/or elevated fasting plasma glucose. In addition, the rather normal or only marginally elevated low-density lipoprotein (LDL) cholesterol concentrations in patients with excess VAT could provide misleading information as viscerally obese patients have an increased plasma concentration of small, dense LDL particles. Prospective studies have suggested that even among patients with LDL cholesterol concentrations within normal limits, an increased concentration of small LDL particles is associated with higher risk of cardiovascular disease. With the treatment of abdominal obesity and excess VAT, an increase in patients' LDL particle size and improvements in other cardiovascular risk factors (eg, insulin levels, glucose tolerance, HDL, C-reactive protein [CRP], and adiponectin levels) can be achieved. Waist circumference can be used in clinical practice as a first approach and as a crude index to identify patients who have excess VAT, particularly when the elevated waistline is accompanied by the clinical features of the metabolic syndrome, among which an elevated fasting triglyceride concentration appears to be predictive of a reduced LDL particle size and of further metabolic abnormalities frequently referred to as the metabolic syndrome. Lifestyle changes, including more physical activity and healthier nutritional habits, are the cornerstone of therapy for high-risk abdominally obese patients with an excess of VAT. In addition, results from the RIO-Lipids study, which was conducted in high-risk obese, dyslipidemic patients, have provided evidence that CB1 receptor blockade with rimonabant can induce significant weight loss, and, more importantly, improve the cardiometabolic risk profile beyond what could be explained by the weight loss effects of the drug.

Corticosteroid-induced lipodystrophy is associated with features of the metabolic syndrome

Familial and HIV-associated lipodystrophies are associated with metabolic disorders and elevated blood pressure. Whether corticosteroid-induced lipodystrophy (CIL) is also associated with features of the metabolic syndrome is unknown. We conducted a prospective study in two French tertiary centres and enrolled all consecutive patients starting long-term (> or = 3 months), high dosage (> or = 20 mg/day) systemic corticosteroid therapy. Three investigators assessed the development of CIL from standardized head and neck photographs. Arterial blood pressure and fasting blood glucose levels were assessed at baseline and then every three months until month 12. Total, HDL- and LDL-cholesterol and triglycerides were recorded at baseline, month 3 and month 12. Eighty-eight patients were enrolled (women: 75%, mean age: 57.4 +/- 17.9 yrs, mean baseline dosage of prednisolone: 56 +/- 15 mg/day). Sixty-four patients still received corticosteroids at month 12 (mean prednisolone dosage: 11 +/- 4 mg/day). In intention-to-treat analysis, the cumulative incidence rate of CIL at months 3 and 12 was 61 +/- 8% and 69 +/- 9%, respectively. Baseline characteristics were similar in patients who developed CIL and patients who did not develop CIL during follow-up except with regard to baseline body mass index, which was higher in patients who develop CIL (24.3 +/- 3.7 kg/m2 vs 21.4 +/- 3.2 kg/m2, P= 0.02). Blood pressure was significantly higher in CIL+ patients at month 9 (135/78 mmHg vs 127/73 mmHg) and month 12 (141/81 mmHg vs 128/72 mmHg) visits. Moreover, compared with CIL- patients, CIL+ patients had significantly higher plasma concentrations of fasting blood glucose, triglycerides and total cholesterol and lower HDL-cholesterol concentration during follow-up. CIL is associated with features of the metabolic syndrome and should then not be considered only as an aesthetic challenge. Further studies are required to test the relation between CIL and cardiovascular events.

Increased plasma levels of visfatin/pre-B cell colony-enhancing factor in obese and overweight patients with metabolic syndrome

Visfatin [pre-B cell colony- enhancing factor (PBEF)] is a cytokine highly expressed in visceral fat that exhibits insulin-mimetic properties. However, its role in insulin-resistant states, such as in metabolic syndrome (MetS), remains largely unknown. To investigate the possible differences of plasma visfatin levels between obese and overweight subjects with and without MetS. Plasma visfatin concentrations were measured with enzyme-linked immunosorbent assay (ELISA) in 28 overweight and obese [body mass index (BMI)>28 kg/m2] subjects with Mets and 28 age- and sex-matched overweight and obese (BMI>28 kg/m2) individuals without MetS (control group). Patients with MetS exhibited significantly elevated waist circumference (WCR ) values, higher blood pressure readings, higher fasting glucose and triglyceride concentrations as well as lower levels of HDL cholesterol (HDL-C) compared with controls. Total and LDL cholesterol (LDL-C) concentrations did not differ significantly between the two groups. Plasma visfatin concentrations were significantly higher in subjects with MetS compared with controls [27 (16- 65) ng/ml vs 19 (10-47) ng/ml, p<0.05]. The same results were observed even after adjustment for age, sex and BMI. Plasma visfatin levels were positively correlated with age (r=0.32, p<0.05), WCR (r=0.31, p<0.05), triglyceride (r=0.59, p<0.01) and glucose (r=0.33, p<0.05) levels and were negatively correlated with HDL-C levels (r=-0.38, p<0.05). Multiple linear regression analysis revealed similar results. Plasma visfatin levels are increased in overweight and obese subjects with MetS compared with those individuals who do not fulfil the criteria for the diagnosis of MetS.

An Examination of the Relationship Between Normal Range Thyrotropin and Cardiovascular Risk Parameters: A Study in Healthy Women

To investigate the relationship between thyrotropin concentrations within the accepted reference range and cardiovascular risk. Initially, 728 women aged 45-60 years were enrolled over a 12-month period. All participants underwent full cardiovascular assessment, including detailed health questionnaire, sphygomanometry, body mass index (BMI) calculation, fasting glucose and lipid profiling, and measurement of serum thyrotropin concentrations. Patients whose thyrotropin concentrations were within the reference range (0.5-4.5 mU/L) were divided into quartiles (n = 629). The means of cardiovascular risk parameters between the first (n = 158) and fourth (n = 157) quartile were compared. Subsequently, the relationships between thyrotropin concentration and risk parameters for cardiovascular disease were examined. This study demonstrates that, within the reference range, increasing thyrotropin concentrations are associated with increasing risk parameters for the development of cardiovascular disease. Subjects with thyrotropin concentrations within the uppermost quartile of the reference range had significantly increased waist circumference, BMI, glucose, triglyceride, and systolic blood pressure measurements when compared to those in the lowermost quartile. Furthermore, significant relationships between thyrotropin and waist circumference, BMI, and fasting glucose and triglycerides concentrations were demonstrated. Finally, independent relationships between thyrotropin and both fasting glucose and triglyceride concentrations were demonstrated. Within the reference range, increasing thyrotropin concentrations are associated with increasing cardiovascular risk parameters. Fasting glucose and triglycerides have been shown to be independently associated with thyrotropin concentration.